Microwave-Assisted Wet Granulation for Engineering Rice Starch–Mannitol Co-Processed Excipients for Direct Compression of Orally Disintegrating Tablets

Abstract

Background/Objectives: Enhancing excipient functionality through environmentally friendly and scalable processing methods is essential for improving the manufacturability and performance of orally disintegrating tablets (ODTs). Microwave-assisted wet granulation enables controlled microstructural modification without chemical alteration of excipient components. This study aimed to develop and evaluate a rice starch (RS)–mannitol co-processed excipient using microwave-assisted wet granulation for direct compression of ODTs. Methods: RS and mannitol were co-processed by wet granulation followed by microwave treatment under varying power levels and irradiation times. The effects of processing conditions on granule morphology, solid-state properties, porosity, powder flow, compressibility, wettability, and disintegration behavior were systematically investigated. The optimized excipient was further evaluated in ODT formulations containing chlorpheniramine maleate and piroxicam and benchmarked against a commercial co-processed excipient (Starlac^®). Results: Microwave treatment generated internal vapor pressure that promoted pore formation and particle agglomeration, resulting in enhanced powder flowability (compressibility index 8.4–10.8%). Partial crystallinity reduction and microstructural modification improved compressibility and surface wettability compared with non-microwave-treated materials. The optimized formulation (MW-RM-H-30) exhibited rapid wetting (25 s), high water absorption (90.5%), low contact angle (42°), and fast tablet disintegration (31 s). ODTs prepared with MW-RM-H-30 showed rapid disintegration (42 s for chlorpheniramine maleate and 32 s for piroxicam) and dissolution behavior comparable to Starlac^®. Conclusions: Microwave-assisted wet granulation provides an efficient, scalable, and environmentally friendly strategy for engineering starch-based co-processed excipients with enhanced functionality for direct compression ODT applications. The developed excipient demonstrates strong potential for solid dosage form manufacturing.

1. Introduction

Orally disintegrating tablets (ODTs) are solid dosage forms designed to disintegrate rapidly in the oral cavity without the need for water, offering improved patient compliance, especially for pediatric, geriatric, and dysphagic populations [1]. Rapid disintegration and fast drug release are the key performance attributes of ODTs, and these properties are strongly influenced by the choice of excipients and manufacturing techniques [2]. Among the various manufacturing approaches, direct compression (DC) is widely preferred due to its simplicity, cost-effectiveness, minimal processing steps, and compatibility with heat- and moisture-sensitive drugs. However, successful DC of ODTs requires excipients with carefully balanced functional properties such as good flowability, adequate compressibility, and the ability to promote rapid tablet disintegration [3].

To achieve these requirements, co-processed excipients have emerged as a promising strategy. Co-processing improves the functionality of individual components without altering their chemical structure, producing composite particles with synergistic behavior [4]. A common design principle for direct compression is to combine a plastic deforming material with a brittle fracturing material. Plastic excipients undergo extensive deformation under pressure, enabling strong interparticulate bonding and high tablet tensile strength. However, their compressibility is often highly sensitive to magnesium stearate, because the formation of a lubricant film reduces interfacial bonding. In addition, plastic materials tend to exhibit decreased tablet hardness at high tableting speeds, as slower stress relaxation limits bond formation [5]. In contrast, brittle materials fragment upon compression, generating fresh surfaces that contribute to bonding and thus reduce sensitivity to lubricants. Their fragmentation mechanism also allows more consistent compressibility at high tableting speeds, providing improved robustness during industrial-scale manufacturing [6]. Combining these two deformation mechanisms within a single co-processed system therefore offers a balanced approach, yielding an excipient with enhanced compressibility, adequate flowability, and improved performance under varying manufacturing conditions [7].

Starch is commonly characterized as a plastically deforming material with limited fragmentation, yet it exhibits good swelling and wicking properties that contribute effectively to tablet disintegration [8]. In contrast, sugars such as lactose and mannitol behave as brittle materials and typically enhance packing efficiency and flowability due to their higher density [9]. They also improve patient acceptability, as these sugars contribute to a more pleasant taste profile, particularly mannitol which imparts a mild sweetness and a characteristic cooling sensation that is desirable in ODT formulations [10]. These complementary mechanical and functional attributes make starch–sugar combinations well suited for direct compression and ODT applications, as demonstrated by several commercially available co-processed excipients [11].

While existing co-processed systems perform effectively in many formulations, opportunities remain to further tailor particle porosity, wetting behavior, and microstructural design for enhanced ODT performance. Many traditional manufacturing techniques such as spray drying or conventional drying of wet granules provide limited control over internal pore architecture or require energy-intensive processing [12,13]. Optimizing the balance between granule hardness, porosity, and disintegration efficiency can therefore be challenging, especially when attempting to optimize excipient performance across a broader range of formulation needs or APIs.

Microwave-assisted wet granulation offers additional advantages as a flexible and efficient method for engineering excipient functionality. Wet granulation improves powder cohesiveness, enhances flowability, and promotes uniform distribution of moisture, producing granules with better packing and compressibility [14]. When combined with microwave irradiation, the technique provides rapid and accelerated moisture evaporation inside the granules, which generates internal vapor pressure that promotes controlled pore formation and microstructural expansion [15]. This mechanism is particularly beneficial for starch-based systems, as microwave-induced vapor channels can create porous starch structures that enhance water uptake and accelerate disintegration [15,16]. Through this combined effect can be effectively adjusted in a single processing step. In addition, the technique is considered a green technique, offering reduced processing times and compatibility with commercial-scale continuous or batch microwave systems.

Therefore, this study aimed to develop and characterize a microwave-assisted wet-granulated co-processed excipient composed of rice starch (RS) and mannitol for direct compression of ODT formulations. The effects of microwave energy and processing duration on physicochemical properties, powder functionality, and excipient performance were systematically investigated. Furthermore, the optimized formulation was incorporated into ODTs containing chlorpheniramine maleate and piroxicam, representing BCS class I and class II drugs, respectively, and its performance was compared with a commercial co-processed excipient (Starlac^®) and physical mixture controls. Altogether, the findings highlight the promise of microwave-assisted co-processing as a green, efficient, and scalable approach for producing high-performance excipients tailored for direct compression in ODT manufacturing.

2. Materials and Methods

2.1. Materials

Native rice starch (RS) (Lot No. 709161) was obtained from Thai Flour Industry Co., Ltd. (Bangkok, Thailand). Mannitol (CAS No. 1344-09-8; Product Code 2305169781) was sourced from Kemaus (Cherrybrook, NSW, Australia). Chlorpheniramine maleate (CPM) (Lot No. SLL/C/0624070) was purchased from S. Tong Chemicals Co., Ltd. (Nonthaburi, Thailand), and piroxicam (Lot No. PRAH0360518) was supplied by Apex Healthcare Limited (Gujarat, India). Starlac^® (Meggle GmbH, Wasserburg, Germany) (Lot No. L104262421A535) was supplied by Thai Meochems Co., Ltd. (Bangkok, Thailand).

2.2. Preparation of Co-Processed Rice Starch with Mannitol Using Microwave-Assisted Wet Granulation Technique (MW-RM)

RS and mannitol were co-processed using a microwave-assisted wet granulation technique. RS and mannitol powders at a weight ratio of 1:2 were blended using a mortar and pestle following the geometric dilution method. The batch size for each preparation was 50 g. Deionized (DI) water was gradually added to the mixture (0.3 mL/g of dry powder) and mixed until a suitable wet mass was formed. The wet mass was passed through a No. 16 sieve to produce wet granules. The wet granules were then subjected to microwave treatment using a microwave oven (model: R-219EX(K), Sharp Thai, Bangkok, Thailand) under varying conditions of microwave power (440, 620, and 800 W) and treatment time (15, 30, 45, and 60 s) (

Table 1. Materials composition and microwave-assisted wet granulation conditions.

Samples	RS (%)	Mannitol (%)	Microwave Treatment
			Energy (W)	Time (s)
RS	100	-	-	-
W-RM	33.34	66.67	-	-
MW-RS-L-15	100	-	440	15
MW-RS-H-60	100	-	800	60
MW-Man-L-15	-	100	440	15
MW-Man-H-60	-	100	800	60
MW-RM-L-15	33.34	66.67	440	15
MW-RM-L-30	33.34	66.67	440	30
MW-RM-L-45	33.34	66.67	440	45
MW-RM-L-60	33.34	66.67	440	60
MW-RM-M-15	33.34	66.67	620	15
MW-RM-M-30	33.34	66.67	620	30
MW-RM-M-45	33.34	66.67	620	45
MW-RM-M-60	33.34	66.67	620	60
MW-RM-H-15	33.34	66.67	800	15
MW-RM-H-30	33.34	66.67	800	30
MW-RM-H-45	33.34	66.67	800	45
MW-RM-H-60	33.34	66.67	800	60

). During microwave treatment, the wet granules were uniformly spread as a thin powder bed on a flat glass plate to ensure homogeneous microwave exposure, and no mechanical mixing or agitation was applied during irradiation. The microwave-treated granules were subsequently dried in a hot air oven for 6 h, passed through a No. 20 sieve, and stored in an airtight container until further analysis. The control samples were prepared, which included pure RS and mannitol granules prepared under the lowest (440 W, 15 s) and highest (800 W, 60 s) microwave conditions, as well as co-processed RS–mannitol (1:2) prepared by conventional wet granulation without microwave treatment (W-RM). In addition, the commercial co-processed excipient Starlac^®, composed of approximately 85% alpha-lactose monohydrate and 15% native maize starch (w/w), was included as a positive control.

2.3. Scanning Electron Microscope (SEM)

Morphological analysis was carried out with a CLARA field emission scanning electron microscope (FESEM; TESCAN, Brno, Czech Republic). Samples were pretreated at 60 °C for 24 h prior to observation. Imaging was performed under low-vacuum conditions (0.7–0.8 Torr) using an accelerating voltage between 10 and 20 kV.

2.4. Particle Size and Size Distribution

Particle size and distribution were analyzed using a laser diffraction method (Malvern Mastersizer S, Malvern Instruments, Malvern, UK). Before measuring, samples were dried at 60 ± 5 °C for 24 h. The analysis was conducted by wet dispersion in methanol (refractive index 1.33), with starch assigned a refractive index of 1.53. Particle size parameters (D₁₀, D₅₀, D₉₀, D_4,3, and span) were recorded, and span values were calculated according to Equation (1). All measurements were carried out in triplicate.

2.5. Fourier Transform Infrared (FT-IR) Spectroscopy

FT-IR spectra were recorded using an Invenio R spectrophotometer (Bruker, Billerica, MA, USA). The samples were dried at 60 °C for 24 h before measurement and subsequently mixed with potassium bromide (KBr) powder to obtain a fine dispersion. The analysis was carried out in attenuated total reflectance (ATR) mode.

2.6. X-Ray Diffraction (XRD)

The crystallinity of the samples was evaluated using X-ray diffraction (XRD). Diffraction patterns were recorded on a Miniflex II diffractometer (Rigaku, Tokyo, Japan) operated in reflection mode. Data were collected over a 2θ range of 5–60° at a scan speed of 2.5°/min to obtain the characteristic diffraction profiles.

2.7. Differential Scanning Calorimetry (DSC)

Differential scanning calorimetry (DSC) was performed using a DSC-1 instrument (Mettler-Toledo, Greifensee, Switzerland). Samples were heated from 25 to 250 °C at a rate of 10 °C/min. The characteristic transition temperatures, including onset (T_o), peak (T_p), and end (T_e), as well as the peak area, were recorded. The enthalpy change (ΔH) was calculated and expressed in J/g of sample weight.

2.8. Powder Density

Powder bulk and tapped densities were determined using the graduated cylinder method in accordance with the standard USP method [17]. Sample powder (50 g) was gently poured into a graduated cylinder (1 mL readability), and the initial volume was recorded as the bulk volume. Bulk density was calculated as the ratio of powder mass to bulk volume. For tapped density, the cylinder was placed on a jolting volumeter (Stav 2003, Erweka, Langen, Germany) and tapped repeatedly for 1250 times to obtain the final tapped volume was then used to calculate tapped density. The test was repeated in triplicate.

True density was measured with an Accupyc II 1340 pycnometer (Micromeritics, Norcross, GA, USA) based on the principle of helium gas displacement. The sample powder was weighed into a sample cup, and measurements were performed at 25–30 °C over ten cycles. The instrument automatically calculated true density from the powder mass and the displaced volume. The test was repeated ten times.

2.9. Surface Area, Pore Volume, and Pore Size Analysis

The surface and pore characteristics of the samples were determined using a nitrogen adsorption–desorption method on a BET surface analyzer (Nova2200e, Quantachrome, Boynton Beach, FL, USA). All samples were degassed under vacuum at 80 °C for 5 h to remove adsorbed gases. The specific surface area (SSA) was calculated using the multipoint Brunauer–Emmett–Teller (BET) equation, while pore characteristics were determined according to BJH method.

2.10. Moisture Content and Hygroscopicity

Moisture content was measured using a moisture analyzer (MX-50, A&D, Tokyo, Japan). Sample powder (1.000 g) was accurately weighed and analyzed at 105 °C until a constant mass was achieved, indicating complete removal of volatile components. The moisture content was expressed as the percentage mass loss, and each determination was conducted in triplicate.

Hygroscopicity was evaluated following a pre-drying step in a hot-air oven at 80 °C for 12 h to eliminate residual moisture. Subsequently, 250 mg of the dried sample was transferred into a pre-weighed sample cup (2.5 cm diameter). The cups were placed inside a sealed tight container containing a saturated sodium chloride solution to maintain a relative humidity of 75%. After storage for 7 days, the samples were re-weighed, and hygroscopicity was calculated as the percentage increase in mass. All measurements were conducted in triplicate.

2.11. Powder Flowability

Powder flowability was evaluated according to USP guidelines using the angle of repose (AR) and compressibility index (CI). The AR was measured using a fixed-funnel method with a funnel orifice diameter of 12 mm and a funnel height of 10 cm above the base. Sample powder (50 g) was allowed to flow freely through a funnel positioned at a constant height above a flat surface, forming a conical bulk without external vibration. The height (h) of the powder cone and the base radius (r) were measured, and the angle of repose (θ) was calculated using Equation (1). Bulk and tapped densities were measured as described previously, and the CI was calculated using Equation (2). The test was repeated in triplicate.

CI (%) = [(Tapped density − Bulk density)/Tapped density] × 100

(1)

AR (°) = tan⁻¹ (h/r)

(2)

2.12. Compression Behavior

The compaction performance of the powders was investigated with respect to plastic deformation, particle rearrangement, tensile strength, solid fraction, and resulting tablet porosity. For this purpose, tablets were prepared by compressing 250 mg portions of each sample using a hydraulic press (Model C, Carver, Wabash, IN, USA) equipped with an 8.4 mm flat-faced round die. To minimize sticking and lower ejection forces, pre-lubrication was performed by applying a thin layer of a 1% (w/v) magnesium stearate suspension in acetone to the punch faces and die wall using a cotton swab, followed by complete evaporation of the solvent prior to compression. Compression was carried out at four pressure levels (49, 98, 147, and 196 MPa), and the resulting tablets were evaluated for weight, thickness, and diameter. The test was repeated at least in triplicate.

2.12.1. Plastic Deformation Property

The plastic deformation of the powders was evaluated through Heckel analysis, which assumes that densification during compression follows first-order kinetics. According to this model, the relative density (D) of the compact increases proportionally with the applied pressure (P), as expressed in Equation (3). The material’s plasticity is characterized by its yield pressure (Py), derived from the slope of the Heckel plot, with lower Py values indicating greater plasticity [18].

In (1/1 − D) = kP + A

(3)

where D denotes the relative density at a given pressure P. The intercept (A) reflects initial particle rearrangement and volume reduction during die filling. The constant k, obtained from the linear regression slope of the Heckel plot, is used to calculate the yield pressure (Py), defined as the reciprocal of k.

2.12.2. Particle Rearrangement

Particle rearrangement during compaction was assessed using relative density parameters derived from compression data. The relative density at die filling (ρ₀) was defined as the ratio of bulk density to true density, representing the efficiency of initial packing under gravity. The relative density after the initial stage of compression (ρA) was calculated from the intercept (A) of the Heckel plot, as shown in Equation (4). A further parameter, ρB, was used to describe additional particle rearrangement and potential fragmentation occurring in the early phase of compression, as given in Equation (5).

$$\rho \mathrm{A}=1-e^A$$

(4)

ρB = ρA − ρ0

(5)

2.12.3. Tablet Tensile Strength, and Solid Fraction

Tablet hardness was measured using a PTB-311 hardness tester (Pharmatest, Hainburg, Germany) and the values were used to calculate tensile strength, solid fraction (SF), and porosity (ε) according to Equations (6)–(8).

σx = 2X/πdt

(6)

SF = Wt/(ρtrue × V)

(7)

ε = 1 − SF

(8)

where σx represents tablet tensile strength (Mpa), and X corresponds to the measured hardness (N). The parameters d and t denote tablet diameter (mm) and thickness (mm), respectively. Wt is the tablet weight, ρtrue is the true density of the powder, and V is the apparent tablet volume. The solid fraction (SF) reflects the relative density of the compact, while porosity (ε) represents the proportion of void space within the tablet structure.

2.12.4. Elastic Recovery

Elastic recovery (ER) was assessed based on the time-dependent relaxation of tablets following compression. Tablets were prepared according to the previously described procedure. The initial tablet volume was measured immediately after ejection and recorded as V_ej. Subsequently, the tablets were stored in a tightly sealed container for 24 h, after which the volume was remeasured and denoted as V_24h. The ER (%) was calculated using Equation (9). The test was repeated in triplicate.

ER (%) = [(V_24h − V_ej)/V_ej] × 100

(9)

2.13. Lubricant Sensitivity

The sample powders were blended with magnesium stearate powder (1% w/w) for 15 min to evaluate the effect of lubrication. Subsequently, 250 mg of each blend was compressed into tablets using a hydraulic press at a compression pressure of 98 MPa. The tablet hardness was determined using a tablet hardness tester, and the lubricant sensitivity ratio (LSR) was calculated according to Equation (10). The test was repeated at least in triplicate.

$$\mathrm{LSR}={\displaystyle \frac{{\mathrm{T}}_0-{\mathrm{T}}_1}{{\mathrm{T}}_0}}$$

(10)

where T₀ and T₁ represent the tablet hardness values of unlubricated and lubricated compacts, respectively.

2.14. Disintegration Property

Disintegration property of the samples was determined using disintegration test and wetting test. The sample powder (250 mg) was compressed into a tablet using a hydraulic press (Model C, Carver, Wabash, IN, USA) fitted with an 8.4 mm flat-faced round die under a compression pressure of 98 MPa.

2.14.1. Disintegration Test

The disintegration time was evaluated for six tablets using a basket-rack assembly of a disintegration tester (PTZ Auto 3, PharmaTest, Hainburg, Germany). Each tablet was placed in an individual tube of the basket, and the test was performed in 750 mL of distilled water maintained at 37 ± 0.5 °C. The time required for each tablet to disintegrate completely was recorded as the disintegration time. According to the European Pharmacopoeia (Ph. Eur.), tablets with a disintegration time of not more than 3 min are classified as ODTs [19]. Measurements were conducted using six tablets per formulation.

2.14.2. Wetting Test

The wetting time of the tablets was determined using a simple visual method. Three circular Whatman No. 5 filter papers (47 mm in diameter) were evenly placed in a watch glass, and 2 mL of distilled water was added to uniformly moisten the papers. Each tablet was carefully positioned on the filter paper, and the time required for the liquid to completely cover and moisten the upper surface of the tablet was recorded as wetting time. The test was repeated in triplicate.

2.14.3. Water Absorption Ratio

The water absorption ratio (%) was determined to evaluate the liquid uptake capacity of the tablets. Each tablet was initially weighed, and the dry weight was recorded as Wi. The tablets were then placed on Whatman No. 5 filter papers moistened with distilled water until complete wetting was achieved. Afterward, the filter papers containing the fully wet tablets were weighed to obtain the total wet weight (Ww). The weight of the dry filter paper (Wp) and the amount of water absorbed by the filter paper alone (Wwp) were determined separately under identical conditions. The water absorption ratio was calculated using the following Equation (11). The test was repeated in triplicate.

Water absorption ratio (%) = [(Ww − Wp − Wwp)/Wi] × 100

(11)

where Ww is the total weight of the filter paper and wetted tablet, Wp is the weight of the dry filter paper, Wwp is the amount of water absorbed by the filter paper, and Wi is the initial tablet weight.

2.15. Contact Angle Measurement

The surface wettability of the tablets was evaluated by measuring the static contact angle using an Optical Contact Angle Meter (Theta Flow, Biolin Scientific, Gothenburg, Sweden). The sample powder (250 mg) was compressed into tablets without lubricant using a hydraulic press (Model C, Carver, Wabash, IN, USA) equipped with an 8.4 mm flat-faced round die under a compression pressure of 98 MPa. A droplet of glycerol (5 µL) was carefully dispensed onto the tablet surface using an automated syringe system. The contact angle was recorded 10 s after droplet deposition using a high-resolution camera equipped with OneAttension software Version 4.2.1 (r10106) (Biolin Scientific). The contact angle was determined from the average of three independent measurements on different areas of tablet surface. The test was repeated in triplicate.

2.16. Formulation Study

The functionality of MW-RM as a direct compression excipient for orally disintegrating tablets (ODTs) was evaluated using two model drugs including chlorpheniramine maleate (CPM) and piroxicam. These model drugs represented BCS class I and class II drugs, respectively. Each model drug was incorporated at a fixed dose of 4 mg per tablet for CPM and 20 mg per tablet for piroxicam. Each model drug was blended with the excipient (MW-RM-H-30 or Starlac^®) for 15 min to ensure homogeneity, followed by the addition of magnesium stearate (1% w/w) and further mixing for 2 min. The resulting powder blend was then compressed into tablets using a single punch tablet press (CMT 12, Charatchai, Bangkok, Thailand). Flat faced punches with diameters of 6.3, and 8.0 mm were used for preparing CPM and piroxicam tablets, respectively. For comparison, physical mixture formulations were prepared by blending each model drug with RS and mannitol in the same proportion as used in the MW-RM composition.

The quality attributes of the CPM and piroxicam tablets which including weight variation, hardness, friability, and disintegration were evaluated in accordance with the United States Pharmacopeia (USP). Ten tablets were individually weighed to assess weight variation, and another ten tablets were tested for tablet breaking force using a tablet hardness tester. Approximately 6.5 g of tablets were used to determine friability with a friability tester (PTF 20ER, Pharmatest, Hainburg, Germany) [20]. Disintegration testing was performed on six tablets using a basket rack apparatus with purified water maintained at 37 ± 0.5 °C as the disintegration medium [21]. The drug content was determined in accordance with the USP specification, which requires the content to be within 90–110% of the labeled amount for CPM and piroxicam tablets [22], and within 92.5–107.5% for piroxicam tablets [23]. All analyses were at least conducted in triplicate.

2.17. In Vitro Release Study

The dissolution testing of CPM and piroxicam tablets was performed using a USP Apparatus II (SR8PLUS Dissolution Test Station, Hanson Research, Chatsworth, CA, USA) (paddle method) under standard conditions. For CPM, six tablets were tested in 500 mL of 0.01 N hydrochloric acid (pH approximately 2) maintained at 37 ± 0.5 °C with a paddle rotation speed of 50 rpm. At predetermined time points (1, 3, 5, 10, 15, and 30 min), 5 mL of dissolution medium was withdrawn and immediately replaced with fresh medium to maintain sink conditions. The samples were analyzed using a UV-Vis spectrophotometer (UV2600i, Shimadzu, Kyoto, Japan) at 265 nm. The release profile was assessed based on the USP requirement that not less than 80% (Q) of chlorpheniramine maleate should dissolve within 30 min. For piroxicam tablets, six units were evaluated in 900 mL of 0.01 N hydrochloric acid at 37 ± 0.5 °C and 50 rpm. Samples of 5 mL were collected at the same designated time points and replaced with fresh medium. The drug concentration was determined at 333 nm using the same spectrophotometric system. Compliance with the USP specification was established if not less than 75% (Q) of the labeled amount of piroxicam dissolved within 45 min.

2.18. Statistical Analysis

All experiments were performed at least in triplicate, and the results are presented as mean ± standard deviation. Statistical analysis was conducted using one-way analysis of variance (ANOVA) in SPSS software (Version 19.0; IBM Corp., Armonk, NY, USA). When significant differences were detected, post hoc comparisons were carried out using Tukey’s Honestly Significant Difference (HSD) test at a 95% confidence level (p < 0.05).

3. Results and Discussion

3.1. Particle Morphology

The SEM micrographs revealed distinct morphological differences among the raw materials, conventionally wet-granulated samples, and the microwave-assisted wet-granulated samples (Figure 1). RS particles exhibited an irregular polygonal shape with smooth surfaces, while mannitol displayed large, elongated crystals with well-defined edges. Starlac^® particles, which is spray-dried material, showed a spherical morphology with relatively smooth surfaces. The co-processed material through wet granulation (W-RM) formed irregular agglomerates with partially fused surfaces and visible interparticle voids. The crystalline structure of mannitol within the composite remained similar to that of untreated mannitol, indicating the preservation of its stable form, which was not altered by the co-processing technique. The microwave-assisted wet granulation produced more pronounced morphological modifications. Increasing microwave power markedly increased surface roughness and the presence of pores. However, the prolonged exposure to microwave heat (60 s) caused more particle fusion, reducing pore volume and increasing particle densification. On the other hand, intermediate conditions (moderate microwave power and treatment time) optimal, producing rough, porous agglomerates with interconnected pore networks. Overall, SEM observation demonstrated that both microwave power and exposure time critically influence granule microstructure. High power with moderate treatment durations promotes porosity, whereas prolonged heating increases densification, reducing porosity and could limit disintegration.

3.2. Particle Size and Size Distribution

The particle size characteristics of the samples are summarized in

Table 2. Particle size and size distribution of the samples.

Sample	Dx (10)	Dx (50)	Dx (90)	D [4, 3]	Span
RS	13.03 ± 001	36.71 ± 0.02	99.89 ± 0.35	48.27 ± 0.14	2.37 ± 0.01
Mannitol	43.22 ± 0.55	150.02 ± 1.93	387.69 ± 1.81	188.42 ± 0.47	2.30 ± 0.02
W-RM	12.71 ± 1.01	74.84 ± 2.69	368.65 ± 22.47	141.74 ± 5.34	4.77 ± 0.48
MW-RS-L-15	23.50 ± 0.08	69.03 ± 0.65	296.38 ± 4.95	118.13 ± 1.78	3.95 ± 0.03
MW-RS-H-60	24.45 ± 0.06	68.93 ± 0.40	277.14 ± 4.93	112.26 ± 1.53	3.67 ± 0.05
MW-Man-L-15	71.28 ± 0.30	208.09 ± 1.36	457.60 ± 0.64	240.46 ± 0.62	1.86 ± 0.01
MW-Man-H-60	67.39 ± 0.08	195.81 ± 0.71	414.79 ± 7.00	223.58 ± 0.77	1.77 ± 0.03
MW-RM-L-15	10.26 ± 0.30	50.87 ± 1.65	246.52 ± 4.13	92.17 ± 0.50	4.65 ± 0.23
MW-RM-L-30	10.71 ± 0.72	62.20 ± 6.20	335.91 ± 2.39	116.81 ± 3.19	6.88 ± 0.69
MW-RM-L-45	12.64 ± 0.78	64.83 ± 4.21	311.75 ± 6.74	118.95 ± 1.51	4.63 ± 0.40
MW-RM-L-60	13.61 ± 0.53	64.13 ± 1.66	337.81 ± 6.27	119.96 ± 1.97	4.86 ± 0.22
MW-RM-M-15	10.57 ± 0.37	55.43 ± 2.84	315.82 ± 7.90	114.03 ± 0.27	5.52 ± 0.44
MW-RM-M-30	10.59 ± 0.18	52.56 ± 1.20	277.84 ± 10.12	101.52 ± 3.40	5.08 ± 0.10
MW-RM-M-45	10.86 ± 0.18	52.50 ± 1.11	328.82 ± 3.50	112.69 ± 0.48	6.06 ± 0.20
MW-RM-M-60	11.14 ± 0.17	54.17 ± 1.11	302.12 ± 4.60	107.43 ± 2.08	5.37 ± 0.06
MW-RM-H-15	8.37 ± 0.13	41.49 ± 1.05	287.33 ± 2.33	96.22 ± 1.01	6.73 ± 0.22
MW-RM-H-30	8.92 ± 0.28	43.14 ± 2.12	298.29 ± 13.15	99.04 ± 5.64	6.71 ± 0.03
MW-RM-H-45	9.65 ± 0.21	47.63 ± 1.67	295.77 ± 6.08	101.83 ± 1.93	5.81 ± 0.06
MW-RM-H-60	9.07 ± 0.10	47.69 ± 0.94	307.41 ± 1.71	106.33 ± 0.52	6.26 ± 0.09
Starlac®	8.89 ± 0.04	24.14 ± 0.24	80.63 ± 2.38	37.62 ± 0.57	2.97 ± 0.07

. RS exhibited a relatively small particle size with an average particle diameter of 48 μm due to some aggregation that corresponded to the SEM image. In contrast, D-mannitol exhibited a much larger particle size (188 μm), which corresponded to its elongated crystalline morphology and limited agglomeration. Wet granulation notably increased the particle size of starch-based materials compared with RS, as reflected in the MW-RS (112 to 118 μm). Similarly, the co-processed W-RM formulation produced significantly larger granules (142 μm), confirming the particle growth effect induced by wet granulation.

The microwave-assisted wet granulation (MW-RMs) further influenced the particle size profile. The results revealed that granules subjected to microwave irradiation showed a reduction in particle size with the average particle size in the range of 92–119 μm, which was smaller compared to that of W-RMs. An overall trend toward smaller particle size was observed in MW-RM samples with increasing microwave power and treatment time. This reduction in granule size can be attributed to the rapid evaporation of water molecules under microwave irradiation, which promoted shrinkage stresses thereby producing smaller particles [24]. Starlac^® that is a spray-dried material, showed an average particle diameter of 38 μm, which was considerable smaller than MW-RMs. However, spray drying technique provided more uniformity of size distribution rather than the wet granulation technique [25].

3.3. Fourier Transform Infrared (FT-IR) Spectroscopy

The FTIR spectra of RS, D-mannitol, control samples, and W-RM is shown in Figure 2A. RS exhibited characteristic absorption bands corresponding to polysaccharide functional groups. A broad band around 3000–3600 cm⁻¹ was assigned to O–H stretching vibrations. The weak peak near 2930 cm⁻¹ corresponded to C–H stretching vibrations of the CH₂ groups. The band observed at approximately 1645 cm⁻¹ was attributed to the O–H bending vibration. In the fingerprint region, prominent absorption peaks were identified at 1149, 1053, and 999 cm⁻¹, which are characteristic of C–O–C stretching vibrations of the glycosidic linkages and C–O stretching of hydroxyl groups, confirming the polysaccharide backbone [26,27]. MW-RS series, which was RS underwent the microwave-assisted wet-granulated process, showed similar FT-IR spectra with that of RS, indicating the process did not change chemical structure of starch.

The FT-IR spectrum of D-mannitol showed distinct absorption bands consistent with its crystalline polyol structure. A broad band between 3000–3500 cm⁻¹ corresponded to O–H stretching vibrations. The peak at 2935 cm⁻¹ was attributed to C–H stretching of aliphatic CH₂ groups. In the fingerprint region, characteristic bands of mannitol were observed between 1200 and 900 cm⁻¹, corresponding to C–O–H bending and C–O stretching vibrations. In particular, the presence of sharp peaks at 958, 929, and 881 cm⁻¹ was corresponded of the β-polymorphic form of mannitol, consistent with previous reports [28]. MW-Man exhibited identical FT-IR spectra with D-mannitol, implying the microwave-assisted wet-granulated process did not affect mannitol polymorphism.

The FT-IR spectra of the co-processed materials (W-RM and MW-RS series) are presented in Figure 2A,B. All co-processed materials exhibited the characteristic absorption bands of RS and D-mannitol, confirming the preservation of their native functional groups. A broad band observed around 3000–3600 cm⁻¹ corresponded to O–H stretching vibrations, which appeared in both RS and D-mannitol. The peak near 2930 cm⁻¹ was attributed to aliphatic C–H stretching, while the weak band at 1645 cm⁻¹ was associated with the O–H bending vibration of the RS structure. In the fingerprint region, sharp peaks characteristic of the β-polymorph of mannitol were observed. Furthermore, the FT-IR spectra of all co-processed materials showed no shifts in peak position and no appearance of new peaks, indicating that RS and D-mannitol were compatible and that the co-processing technique did not alter their chemical structures.

3.4. X-Ray Diffraction (XRD)

The X-ray diffraction (XRD) patterns of RS and MW-RS series are shown in Figure 3A. RS and MW-RS series exhibited broad diffraction peaks at approximately 15.1°, 16.9°, 18.0°, and 22.9° (2θ), characteristic of the A-type crystalline structure of cereal starches [29]. However, XRD pattern of MW-RS series showed lower peak intensity than that of RS, indicating the microwave-assisted wet granulation partial disruption of the crystalline structure and an increase in amorphous character [30]. The A-type crystalline structure is more densely packed and exhibits higher crystallinity compared with other starch polymorphs, which contributes positively to its compression properties [31]. In contrast, D-mannitol exhibited sharp and intense diffraction peaks at 10.6°, 14.7°, 18.9°, 23.5°, and 29.5° (2θ), confirming its highly crystalline nature and consistent with the β-polymorph (Figure 3B) [32]. For MW-Man series, the characteristic peaks of β-mannitol were still present, but with reduction in peak intensity. This result is consistent with the XRD patterns, which indicate a partial reduction in crystalline order of the MW-RS series.

The XRD pattern of the co-processed materials (W-RM and MW-RM series) (Figure 3C) demonstrated diffraction pattern characteristic of crystalline mannitol superimposed with the small halo pattern of RS between 15–25° (2θ). In addition, they exhibited sharp and intense reflections at 14.7°, 16.9°, 18.9°, 21.3°, 23.6°, and 29.5 (2θ), corresponding to the β-polymorphic form of mannitol, confirming the predominance of its crystalline lattice. Compared with D-mannitol, the intensity of the diffraction peaks decreased in W-RM, indicating a reduction in crystallinity after the wet granulation process. A further decrease in peak intensity and broadening was observed in the MW-RM series, demonstrating that the microwave process disturbed disrupted the crystalline lattice of mannitol [33]. Therefore, this result confirmed that the microwave-assisted co-processing reduces the material crystallinity of RS and mannitol, while still preserving mannitol polymorph that corresponds to FT-IR and DSC results.

3.5. Differential Scanning Calorimetry (DSC)

The DSC thermograms and thermal parameters are summarized in Figure 4 and

Table 3. DSC thermal parameters of the samples.

Samples	To (°C)	Tp (°C)	Te (°C)	Enthalpy (J/g)
D-mannitol	166.52	170.83	174.60	291.53
W-RM	166.66	171.50	178.14	201.84
MW-RS-L-15	N/A	N/A	N/A	N/A
MW-RS-H-60	N/A	N/A	N/A	N/A
MW-Man-L-15	166.70	172.00	175.33	267.46
MW-Man-H-60	166.66	172.17	174.98	278.54
MW-RM-L-15	166.54	172.50	176.61	197.97
MW-RM-L-60	166.57	173.00	178.32	196.69
MW-RM-M-15	166.98	172.50	177.93	186.49
MW-RM-M-60	166.96	171.67	176.34	186.42
MW-RM-H-15	166.78	172.00	177.50	188.46
MW-RM-H-60	166.78	172.00	176.69	193.83

. D-mannitol exhibited a sharp endothermic event with an onset temperature of 166.52 °C with a high enthalpy value of 278.54 J/g. These values are consistent with the melting point of the β-polymorph of mannitol (166.5 °C) (Figure 4A), as previously reported, whereas the α form melts at 166 °C and the δ form at approximately 155 °C [34]. For MW-Man series, melting endotherms were still observed with onset temperature around 165.5 °C, confirming the presence of the β polymorph. However, their enthalpy values were lower than D-mannitol, suggesting reduced crystalline order due to the co-processing technique. The DSC thermogram of the MW-RS series showed no sharp melting peak typical of crystalline material. On the other hand, a broad endothermic transition was observed over an extended temperature range with T_p at 104 °C. This behavior reflects the largely amorphous nature of starch, in which the crystalline region was disrupted [35]. This result is consistent with the XRD patterns, which also demonstrated the predominance of amorphous characteristics in the MW-RS series.

The co-processed materials (W-RM and MW-RM series) exhibited melting peaks with T_o in the range of 166.66–166.98 °C, which is characteristic of the β-polymorphic form of mannitol (Figure 4B). This indicates that co-processing by either wet granulation or microwave treatment did not induce polymorphic transformation. However, the enthalpy values (ΔH) revealed a clear reduction in crystallinity relative to D-mannitol. After wet granulation (W-RM), the enthalpy decreased, confirming that the process reduced crystalline order. This reduction can be attributed to the partial dissolution of mannitol in water during the wet granulation process, followed by incomplete or disordered recrystallization upon drying. A further decline in ΔH was observed in the microwave-assisted wet-granulation process, indicating that microwave treatment caused additional disruption of the crystalline lattice. This result suggested that microwave treatment reduced the crystallinity of mannitol by disrupting its molecular bonding through rapid localized heating and by limiting the time available for recrystallization [36]. These findings were in accordance with the FT-IR and XRD results.

3.6. Powder Density

The density parameters of the samples are presented in

Table 4. Density, surface area, and porosity characteristics of the samples.

Samples	Density (g/cm3)			Surface Area (m2/g)	Pore Volume (cc/g)	Pore Radius (nm)	Moisture Content (%)	Hygroscopicity (%)
	Bulk Density	Tapped Density	True Density
RS	0.35 ±0.00 a	0.49 ± 0.00 a	1.5291 ± 0.0009 i	11.39	0.019	15.61	6.38 ± 0.25 d	4.04 ± 0.12 d
D-mannitol	0.66 ± 0.03 g	0.89 ± 0.01 i	1.4996 ± 0.0046 cd	10.10	0.016	19.59	0.36 ± 0.06 a	0.02 ± 0.01 a
W-RM-2	0.53 ± 0.00 cdef	0.59 ± 0.00 def	1.5026 ± 0.0004 fg	11.15	0.014	15.77	3.32 ± 0.77 b	1.39 ± 0.15 c
MW-RS-L-15	0.39 ± 0.00 b	0.49 ± 0.00 a	1.5126 ± 0.0009 h	19.19	0.034	18.73	7.82 ± 0.42 e	4.34 ± 0.24 d
MW-RS-H-60	0.41 ± 0.01 b	0.52 ± 0.00 ab	1.5117 ± 0.0005 h	67.66	0.099	18.71	8.30 ± 0.48 e	3.86 ± 0.39 d
MW-Man-L-15	0.53 ± 0.01 cdefg	0.61 ± 0.02 efg	1.4873 ± 0.0014 a	6.62	0.016	15.08	0.40 ± 0.10 a	0.02 ± 0.02 a
MW-Man-H-60	0.55 ± 0.01 fgh	0.64 ± 0.02 gh	1.4992 ± 0.0003 c	5.09	0.012	15.04	0.43 ± 0.06 a	0.07 ± 0.06 a
MW-RM-L-15	0.52 ± 0.01 cde	0.55 ± 0.01 cd	1.5026 ± 0.0003 de	10.70	0.015	15.05	3.61 ± 0.25 bc	1.44 ± 0.18 c
MW-RM-L-30	0.52 ± 0.01 cde	0.57 ± 0.01 cd	1.5032 ± 0.0006 g	10.12	0.018	15.06	3.22 ± 0.23 bc	1.42 ± 0.05 c
MW-RM-L-45	0.50 ± 0.01 c	0.55 ± 0.02 bc	1.4996 ± 0.0005 cd	11.27	0.019	15.00	3.15 ± 0.38 bc	1.33 ± 0.07 c
MW-RM-L-60	0.54 ± 0.01 defg	0.54 ± 0.01 de	1.5015 ± 0.0003 defg	11.79	0.022	15.08	3.93 ± 0.38 c	1.52 ± 0.11 c
MW-RM-M-15	0.51 ± 0.01 c	0.55 ± 0.01 bcd	1.5016 ± 0.0004 defg	11.54	0.021	16.74	3.22 ± 0.25 bc	1.50 ± 0.06 c
MW-RM-M-30	0.51 ± 0.00 cd	0.58 ± 0.01 bcd	1.5003 ± 0.0002 cde	11.98	0.022	21.18	3.58 ± 0.18 bc	1.57 ± 0.10 c
MW-RM-M-45	0.50 ± 0.00 c	0.58 ± 0.01 bcd	1.4991 ± 0.0003 c	10.70	0.021	21.15	3.35 ± 0.16 bc	1.51 ± 0.07 c
MW-RM-M-60	0.51 ± 0.00 c	0.59 ± 0.00 bcd	1.5025 ± 0.0003 efg	7.99	0.022	17.78	3.92 ± 0.51 c	1.58 ± 0.12 c
MW-RM-H-15	0.56 ± 0.01 gh	0.64 ± 0.01 efgh	1.5007 ± 0.0004 cdef	12.90	0.023	21.07	3.44 ± 0.37 bc	1.69 ± 0.10 c
MW-RM-H-30	0.54 ± 0.00 efgh	0.64 ± 0.01 efg	1.4990 ± 0.0020 c	15.96	0.027	29.72	3.76 ± 0.06 bc	1.73 ± 0.07 c
MW-RM-H-45	0.57 ± 0.00 h	0.65 ± 0.01 gh	1.4994 ± 0.0003 cd	13.15	0.024	23.96	3.44 ± 0.20 bc	1.72 ± 0.16 c
MW-RM-H-60	0.57 ± 0.00 h	0.63 ± 0.00 fgh	1.5011 ± 0.0002 cdefg	7.65	0.021	21.07	3.98 ± 0.10 c	1.89 ± 0.64 c
Starlac®	0.55 ± 0.01 fgh	0.65 ± 0.01 h	1.4950 ± 0.0003 b	12.18	0.022	15.63	2.26 ± 0.51 a	0.69 ± 0.12 b

A common letter (a–i) is not significantly different within group by Tukey HSD test at the 5% level of significance (p < 0.05).

. RS exhibited the lowest bulk (0.35 g/cm³) and tapped density (0.49 g/cm³), consistent with its loosely packed granules and high interparticle porosity due to poor packing efficiency. In contrast, D-mannitol powder showed the highest bulk (0.66 g/cm³) and tapped density (0.89 g/cm³), reflecting its compact crystalline morphology. The wet granulation technique, together with the incorporation of RS and D-mannitol, significantly enhanced the bulk density of the material. This improvement was attributed to particle agglomeration, which reduced interparticle spaces and promoted more efficient packing [37]. Moreover, microwave treatment further increased both bulk and tapped densities of the co-processed powders, as observed in the MW-RM series. Increasing the microwave treatment time (45–60 s) and energy (800 W) resulted in powder with high bulk density (0.57 g/cm³). This result was associated with rapid surface hardening and particle shrinkage, which yielded smoother, denser granules with fewer interparticle voids, as confirmed by SEM observations. Notably, the increased packing efficiency observed in MW-RM powders resulted in bulk and tapped density values that were comparable to those of Starlac^®, the commercial excipient. This indicates that the microwave-assisted wet granulation can improve particle packing behavior to a level similar to an established direct-compression material [13].

On the other hand, true density values revealed the opposite trend. RS showed the highest true density (1.5291 g/cm³), while D-mannitol demonstrated lower value (1.4996 g/cm³). The microwave-assisted wet granulation caused decreasing in true density starch-based material that noticeably observed in MW-RS series. The results showed that material true density proportionally decreased with increased microwave time and energy, while MW-RM-H series showed the lowest true density among the co-processed materials (1.4990–1.5011 g/cm³) that was comparable to Starlac^® (1.4950 g/cm³). This reduction suggests that microwave treatment induced structural loosening of the particle structure through the generation of microstructural pores and partially amorphous regions [38].

These findings demonstrated that the microwave-assisted wet granulation simultaneously enhanced powder bed packing while creating a loose particle structure. Such material characteristics were expected to promote downstream tableting performance, particularly compressibility and disintegration [15].

3.7. Surface Area, Pore Volume, and Pore Size Analysis

The specific surface area (SSA), pore volume, and pore radius of the sample powders are summarized in Table 4. The results demonstrated that the microwave-assisted processing markedly enhanced the SSA and pore volume of starch-based samples, with the most pronounced effect observed at high microwave energy (MW-RS-H-60). As bound water within the amorphous regions of starch granules absorbed microwave energy then rapidly vaporized, generating internal pressure that caused granule expansion and led to the formation of a porous structure [16]. On the other hand, pure mannitol samples (MW-Mans) exhibited low SSA and pore volume under microwave treatment due to their highly crystalline structure. Without sufficient bound water to generate internal pressure, the mannitol particles remained dense and non-porous despite microwave exposure.

For the co-processed materials (W-RM and MW-RM), both SSA and pore volume were lower than those of the pure starch samples (MW-RS), reflecting the influence of mannitol in the formulations. At low to moderate microwave energies (440–620 W), the SSA and pore volume of MW-RM were comparable to those of W-RM, which did not undergo microwave treatment. In contrast, exposure to high microwave energy (800 W) produced a marked increase in both SSA and pore volume, while pore size progressively increased with rising microwave energy from moderate to high levels (620–800 W). However, prolonged exposure at high microwave power (60 s) led to a notable reduction in SSA and pore volume, as observed in MW-RM-M-60 and MW-RM-H-60, suggesting partial pore collapse under these conditions. This reduction was attributed to starch gelatinization induced by extended microwave exposure, which caused granule swelling and structural collapse. The gelatinized network sealed or densified previously formed pores, thereby lowering the accessible SSA and pore volume of the co-processed materials [39].

All formulations exhibited average pore radii within the mesoporous range (2–50 nm) which is considered favorable for capillary-driven water uptake [40]. In the pure systems (MW-RS and MW-Man) variations in microwave power and irradiation time did not produce significant changes in pore size. In contrast, the MW-RM series demonstrated a clear dependence on processing conditions. Short irradiation at low power yielded narrower pores (~15.0 nm) comparable to those of the W-RM sample, whereas longer exposure or higher power generated larger mesopores reaching up to 29.7 nm (MW-RM-H30). This indicates that microwave treatment not only induced pore formation but also facilitated the widening of existing channels, particularly under more intense conditions. However, excessively long irradiation led to a reduction in pore size likely due to rupture and collapse of previously formed pores. Overall, the enlargement of pores within the mesoporous range is expected to enhance rapid water uptake and tablet disintegration by providing an optimal balance between capillary force and pore accessibility [41].

3.8. Moisture Content and Hygroscopicity

The moisture content and hygroscopicity of all samples are presented in Table 4. RS exhibited a moisture content of 6.38 ± 0.25% and relatively high hygroscopicity (4.04 ± 0.12%), which is consistent with its hydrophilic polysaccharide structure. The microwave-treated rice starch samples (MW-RS series) showed similarly elevated moisture contents (7.82–8.30%) and hygroscopicity values (3.86–4.34%). The slightly higher moisture uptake observed for the MW-RS samples compared with RS can be attributed to microwave-induced microstructural changes, such as increased porosity and surface exposure, which enhance water adsorption [42]. In addition, the moisture content of both RS and all MW-RS samples remained well within the acceptance criterion specified in the USP for RS, which limits moisture content to not more than 15% [43].

D-mannitol exhibited very low moisture content (0.36 ± 0.06%) and negligible hygroscopicity (0.02 ± 0.01%), consistent with its crystalline and non-hygroscopic nature. Similarly, the microwave-treated mannitol samples (MW-Man-L-15 and MW-Man-H-60) showed comparably low moisture content (0.40–0.43%) and minimal hygroscopicity (0.02–0.07%). All mannitol-based samples therefore complied with the USP specification for mannitol, which requires a moisture content of not more than 0.5% [44], indicating that microwave processing did not adversely affect the moisture stability of mannitol.

For the co-processed materials (W-RM and MW-RM series), moisture content ranged from 3.15 to 3.98% and hygroscopicity values from 1.39 to 1.89%. These intermediate values reflect the combined contribution of hydrophilic starch and moisture-resistant mannitol, resulting in substantially reduced moisture uptake compared with pure rice starch systems. The commercial co-processed excipient Starlac^® exhibited lower moisture content (2.26 ± 0.51%) and hygroscopicity (0.69 ± 0.12%) than the co-processed materials. This reduced moisture sensitivity can be attributed to the lower starch fraction in Starlac^® compared with the co-processed materials, which contain a higher proportion of starch.

3.9. Powder Flowability

The flow properties of the samples were evaluated using angle of repose (AR) and compressibility index (CI, %), and the results are summarized in

Table 5. Flowability, plastic deformation property, and particle rearrangement of the samples.

Samples	Flow Properties		Heckel Constant			Particle Rearrangement
	AR (°)	CI (%)	Py	A	r2	ρA	ρ0	ρB
RS	39.08 ± 0.52 g	27.16 ± 0.73 g	190.55	0.98	0.8978	0.63	0.23	0.39
D-mannitol	41.33 ± 0.80 h	25.41 ± 2.79 fg	506.59	1.74	0.4582	0.82	0.44	0.38
W-RM	22.92 ± 0.80 de	11.39 ± 0.20 abc	163.40	1.64	0.9957	0.79	0.35	0.44
MW-RS-L-15	26.00 ± 1.25 f	19.57 ± 0.95 de	182.08	1.21	0.9850	0.70	0.27	0.43
MW-RS-H-60	25.58 ± 0.52 f	20.74 ± 0.97 ef	178.00	1.31	0.9872	0.73	0.26	0.47
MW-Man-L-15	22.42 ± 0.63 cde	11.96 ± 0.95 abc	503.52	1.94	0.9917	0.86	0.36	0.50
MW-Man-H-60	22.92 ± 0.80 de	14.70 ± 0.58 bcd	281.69	1.78	0.8622	0.83	0.37	0.47
MW-RM-L-15	22.00 ± 1.56 bcde	8.86 ± 1.22 a	148.24	1.52	0.9936	0.78	0.34	0.44
MW-RM-L-30	21.17 ± 0.80 abcd	8.41 ± 1.25 a	146.26	1.50	0.9419	0.78	0.35	0.43
MW-RM-L-45	19.83 ± 1.26 ab	8.50 ± 1.53 a	138.66	1.31	0.9657	0.73	0.34	0.39
MW-RM-L-60	20.33 ± 0.80 abc	8.66 ± 3.89 a	137.89	1.38	0.9836	0.75	0.36	0.39
MW-RM-M-15	19.67 ± 0.58 a	8.33 ± 1.18 a	147.78	1.54	0.9673	0.79	0.34	0.45
MW-RM-M-30	22.33 ± 0.14 cde	9.35 ± 1.30 a	146.74	1.53	0.9507	0.78	0.34	0.44
MW-RM-M-45	22.25 ± 0.43 cde	9.29 ± 0.66 a	136.65	1.55	0.8981	0.79	0.34	0.45
MW-RM-M-60	22.25 ± 0.43 cde	9.37 ± 2.12 a	131.13	1.46	0.9662	0.77	0.34	0.43
MW-RM-H-15	20.75 ± 0.90 abcd	10.53 ± 0.68 abc	148.59	1.55	0.9632	0.79	0.37	0.42
MW-RM-H-30	21.50 ± 0.50 abcde	10.22 ± 2.33 ab	145.50	1.54	0.9605	0.78	0.36	0.42
MW-RM-H-45	19.25 ± 0.25 a	10.85 ± 0.95 abc	140.13	1.48	0.9306	0.77	0.38	0.39
MW-RM-H-60	21.25 ± 0.66 abcde	9.20 ± 0.60 a	135.63	1.45	0.9635	0.77	0.38	0.39
Starlac®	23.50 ± 0.66 e	15.36 ± 0.49 cd	154.18	1.57	0.9239	0.79	0.38	0.41

A common letter (a–h) is not significantly different within group by Tukey HSD test at the 5% level of significance (p < 0.05).

. The flowability of RS and D-mannitol was classified as fair, with high AR values of 39.08° and 41.33°, respectively. These findings were consistent with their high CI values (>25%), which categorize the powders as passable to poor flow materials [17]. The limited flowability can be attributed to their particle morphologies as shown in SEM images. RS exhibited small, irregular polyhedral granules, whereas mannitol displayed large, elongated, plate-like crystals with flat surfaces. Such shapes increase interparticle friction and mechanical interlocking, thereby restricting powder flow.

In contrast, the materials that underwent granulation demonstrated markedly improved flow characteristics. W-RM showed a substantial reduction in AR (22.92°) and CI (11.39%), indicating excellent to good flow compared with the parent excipients. This improvement was attributed to particle agglomeration, which increased particle size, reduced surface contact area, and thereby promoted flowability [45]. The microwave-assisted formulations further enhanced the flowability of the MW-RM series. They exhibited AR values in the range of 19.25–22.33° and CI values in the range of 8.33–10.85%, which also correspond to excellent flow properties. Their flow characteristics were comparable to those of Starlac^®, a commercial benchmark excipient that also demonstrated good flowability (AR 23.50° and CI 15.36%). These findings suggest that both W-RM and MW-RM provided comparably high flowability, with wet granulation being the primary contributor, while microwave treatment offered only a minor additional effect.

For MW-RS and MW-Man, flowability also improved following microwave treatment, although the effect was less pronounced than in the co-processed materials. MW-RS showed only moderate changes, with AR values remaining above 25° and CI values exceeding 20%, corresponding to fair flow. SEM analysis indicated that MW-RS formed agglomerates with irregular shapes, which limited flowability compared with co-processed materials. In contrast, MW-Man exhibited a clear improvement, with AR reduced to 22° and CI values below 15%, classifying it as a good flow material. This enhancement was attributed to microwave processing, which reduced particle elongation and promoted aggregation. These morphological modifications consequently improved powder flow.

3.10. Compression Behavior

3.10.1. Plastic Deformation Property

Plastic deformation property was determined using Heckel parameters that are summarized in Table 5. The lower yield pressure (Py) value indicated higher plastic deformation property. RS exhibited a moderate Py value (190.55), indicating limited plastic deformation and particle rearrangement in the early compression stage rather than by fragmentation [31]. In contrast, D-mannitol, a well-known brittle material, showed the highest Py (506.59) reflecting particle densification through fragmentation during compression [46]. In addition, the relatively low R² (0.4582) for D-mannitol suggested deviation from ideal Heckel behavior due to its brittle fracture mechanism.

The wet granulation process (W-RM) significantly reduced Py compared with the parent materials, indicating enhanced plastic deformation as a result of decreased crystallinity [47]. The reduction in Py became more pronounced when the materials were subjected to microwave treatment. The MW-RS series exhibited lower Py values than RS, suggesting that the microwave-assisted wet granulation further promoted plastic deformation by disrupting the crystalline structure, particularly under high microwave energy and treatment time. Similarly, MW-Man series showed a marked decrease in Py at higher treatment conditions, indicating that microwave exposure disrupted the crystal lattice [48]. This structural modification shifted densification mechanism of mannitol from predominantly brittle fragmentation toward a greater contribution of plastic deformation.

The MW-RM series demonstrated a consistent reduction in Py values compared with the parent materials and W-RM. The results indicated that microwave treatment duration played a predominant role in reducing Py (131–140 MPa), whereas treatment energy had only a minor influence (145–148 MPa). These findings suggest that the microwave-assisted wet granulation process decreased starch crystallinity and introduced lattice disruptions in mannitol, thereby facilitating greater plastic deformation of the composite materials. For the commercial excipient (Starlac^®), its Py value (154.18) was comparable to MW-RM formulations. This confirms that the microwave-assisted composites achieved plasticity and rearrangement properties similar to a commercial co-processed excipient.

3.10.2. Particle Rearrangement

The particle rearrangement of materials was represented as the relative density at die filling (ρ0), the initial compression stage (ρA), and the additional particle rearrangement (ρB), which are shown in Table 5. The ρ0 parameter reflected the initial packing efficiency of the materials. Rice starch (RS) exhibited the lowest ρ0 value (0.23), consistent with its small, irregular granules that restricted close particle packing [49]. The microwave-assisted wet granulation considerably increased the ρ0 values of the MW-RS series, indicating improved initial packing efficiency. In contrast, D-mannitol showed the highest ρ0 (0.44), attributed to its large, crystalline morphology that facilitated efficient die filling under gravity [9]. Interestingly, the MW-Man series exhibited slightly reduced ρ0 values (0.36–0.37) compared with untreated mannitol, suggesting that microwave processing disrupted its crystalline packing structure and diminished its natural packing efficiency. For the co-processed materials, W-RM exhibited a moderate ρ0 (0.35) that fell between its parent excipients, reflecting the effect of granulation in producing larger and more uniform agglomerates that improved packing. However, the MW-RM series further increased ρ0 values (0.34–0.38), which were comparable to the commercial excipient Starlac^® (0.38), confirming that the microwave-assisted wet granulation enhanced the initial die-filling properties of the co-processed materials.

The ρA values highlighted differences in densification behavior. RS showed the lowest ρA (0.63), reflecting limited plasticity, while mannitol exhibited the highest (0.82), indicating extensive fragmentation during early compression. Both MW-RS (0.70–0.73) and MW-Man (0.83–0.86) showed increased ρA compared with their parent excipients, demonstrating that the microwave-assisted wet granulation facilitated densification. W-RM (0.79) also improved densification relative to RS, and MW-RM (0.73–0.79) gave values comparable to W-RM and Starlac^®, suggesting that granulation itself had a greater impact than microwave processing.

The ρB values provided additional insight into early rearrangement. RS showed a moderate ρB, consistent with its low ρA and rearrangement-driven densification. MW-RS displayed higher ρB, confirming that microwave processing enhanced both rearrangement and plastic deformation. D-Mannitol, in contrast, exhibited high ρA but relatively low ρB, indicating densification dominated by fragmentation. MW-Man showed both the highest ρA and large ρB values (0.47–0.50), supporting the conclusion that microwave treatment introduced lattice defects and promoted densification through fragmentation. exhibited comparable ρA and ρB values that were higher than that of RS, indicating a balanced contribution of rearrangement and plastic deformation. These values closely matched those of Starlac^®, suggesting that the co-processed composites achieved rearrangement behavior comparable to a commercial excipient.

3.10.3. Tablet Tensile Strength, Porosity, and Solid Fraction

Tabletability describes the capacity of a material to produce tablets with sufficient tensile strength when subjected to compaction pressure, which are shown in Figure 5. Pure starch-based materials (RS and MW-RS) demonstrated the highest tabletability among all samples (Figure 5A). The microwave-assisted wet granulation promoted plastic deformation, enabling strong interparticulate bonding under compression and resulting in improved tabletability of the MW-RS series, particularly at lower compression pressures [50]. In contrast, pure mannitol-based materials (D-mannitol and MW-Man) exhibited very poor tabletability, with tensile strength values remaining below 0.5 MPa across all pressures. This confirmed the brittle nature of mannitol, which limited effective particle bonding [46]. Furthermore, the microwave-assisted wet granulation did not improve the tabletability of brittle mannitol. The co-processed materials (W-RM and MW-RM) showed moderate tabletability, falling between RS and mannitol. Their tensile strength increased proportionally with compression pressure, reaching a maximum at 149 MPa before slightly declining at higher pressures, suggesting a limited capacity for additional bond formation under excessive compaction. The MW-RM series exhibited consistent tabletability in all microwave processing conditions and was comparable to W-RM, indicating that the primary improvement resulted from the wet granulation process rather than microwave treatment. Notably, the MW-RM formulations achieved tensile strength values similar to those of Starlac^®, demonstrating that the microwave-assisted co-processed materials provided balanced tabletability comparable to a commercial co-processed excipient.

Material compressibility was evaluated by plotting tablet porosity against compression pressure (Figure 5B). RS exhibited the highest porosity across all compression pressures and among all samples, which can be attributed to the elastic recovery and limited plastic deformation of starch during compaction [51]. D-mannitol also showed relatively high porosity, consistent with its brittle nature and limited interparticulate bonding. In contrast, both MW-RS and MW-Man series demonstrated lower tablet porosity than their parent excipients, indicating that the microwave-assisted wet granulation enhanced packing efficiency by promoting greater plastic deformation in MW-RS and inducing lattice defects in MW-Man. The W-RM formulation exhibited the lowest tablet porosity, confirming that the granulation process significantly improved particle packing and compressibility. Conversely, microwave treatment moderately increased the tablet porosity of the MW-RM series due to the formation of microvoids and internal pores within the granule matrix. However, variations in microwave treatment conditions did not significantly affect the porosity of MW-RM tablets. The porosity values of MW-RM formulations were comparable to those of Starlac^®, suggesting that the co-processed composites achieved compressibility and packing characteristics similar to those of a commercial co-processed excipient.

The compactibility of the materials, expressed as the relationship between tablet tensile strength and solid fraction, is presented in Figure 5C. Most samples exhibited tensile strengths within the desirable range of 0.5–2.0 MPa, corresponding to solid fractions of 0.85–0.90, which are considered appropriate for achieving adequate mechanical strength. Pure starch-based materials showed lower solid fractions than the other samples, primarily due to partial elastic recovery during decompression, which caused re-expansion of the tablet structure and consequently reduced the final solid fraction [52]. The MW-RM formulations exhibited a noticeable decrease in tablet solid fraction compared with W-RM, likely resulting from microwave-induced structural porosity that enhanced water penetration and promoted faster disintegration [53]. Overall, the MW-RM series achieved solid fractions within the optimal range, providing a balance between compact strength and porosity conducive to rapid disintegration while maintaining tablet integrity.

3.10.4. Elastic Recovery

The elastic recovery (ER) values of the samples are summarized in

Table 6. Elastic recovery, lubricant sensitivity, and disintegration properties of the samples.

Samples	Elastic Recovery (%)	LSR	Disintegration Properties
			Disintegration Time (s)	Wetting Time (s)	Water Absorption Ratio (%)
RS	1.89 ± 0.27	23.45	142.67 ± 5.03 k	126.33 ± 7.23 h	132.67 ± 2.45 j
D-mannitol	0.27 ± 0.21	4.26	21.67 ± 2.52 a	24.67 ± 0.58 b	11.64 ± 2.35 a
W-RM	1.65 ± 0.28	33.01	74.00 ± 4.36 i	59.67 ± 2.52 f	52.21 ± 6.66 cd
MW-RS-L-15	2.86 ± 0.18	29.14	92.33 ± 1.15 j	70.67 ± 1.53 g	127.55 ± 3.96 j
MW-RS-H-60	3.28 ± 0.07	33.26	90.00 ± 2.00 j	60.67 ± 4.73 f	133.23 ± 5.57 j
MW-Man-L-15	0.49 ± 0.19	6.88	22.33 ± 1.53 a	13.67 ± 0.58 a	27.95 ± 6.27 b
MW-Man-H-60	0.56 ± 0.69	9.04	19.00 ± 1.00 a	7.00 ± 1.00 a	39.52 ± 5.36 bc
MW-RM-L-15	1.56 ± 0.21	29.33	60.33 ± 4.73 gh	46.33 ± 0.58 e	62.65 ± 4.73 de
MW-RM-L-30	1.53 ± 0.19	31.43	57.00 ± 1.00 fg	42.67 ± 5.51 de	61.75 ± 2.03 de
MW-RM-L-45	2.38 ± 0.76	31.75	61.00 ± 1.00 gh	47.00 ± 1.00 e	64.15 ± 4.21 def
MW-RM-L-60	2.97 ± 0.60	45.17	68.33 ± 3.06 hi	55.00 ± 4.36 f	71.89 ± 4.04 efg
MW-RM-M-15	2.20 ± 0.49	34.49	40.67 ± 4.16 cd	30.67 ± 1.53 bc	80.28 ± 1.28 ghi
MW-RM-M-30	2.23 ± 0.53	32.49	42.00 ± 2.65 cd	34.67 ± 2.89 cd	72.68 ± 4.58 efg
MW-RM-M-45	2.79 ± 0.17	38.81	45.67 ± 4.04 de	34.00 ± 2.65 c	73.20 ± 2.53 efgh
MW-RM-M-60	2.86 ± 0.86	47.05	57.00 ± 2.65 fg	38.00 ± 3.61 cd	62.93 ± 6.72 de
MW-RM-H-15	2.47 ± 0.30	32.19	35.00 ± 4.58 bc	30.00 ± 2.65 bc	84.11 ± 2.58 ghi
MW-RM-H-30	2.45 ± 0.27	31.91	31.33 ± 1.53 b	25.67 ± 1.15 b	90.47 ± 4.49 i
MW-RM-H-45	2.65 ± 0.24	45.23	36.00 ± 2.65 bc	32.00 ± 1.00 bc	86.23 ± 3.68 hi
MW-RM-H-60	2.77 ± 0.18	46.49	51.00 ± 2.65 ef	38.00 ± 3.46 cd	77.32 ± 1.34 fghi
Starlac®	2.94 ± 0.43	39.92	39.00 ± 4.58 bcd	11.67 ± 0.58 a	35.96 ± 3.89 b

A common letter (a–k) is not significantly different within group by Tukey HSD test at the 5% level of significance (p < 0.05).

. Typically, starch exhibits elastic behavior upon decompression, which can limit tablet tensile strength [31,54]. However, the small particle size and irregular shape of RS granules mitigate this phenomenon [55]. In this study, RS showed an ER value of 1.89%, indicating a moderate ability to store and release elastic strain energy after compression. In contrast, D-mannitol exhibited the lowest ER (0.27%) due to its brittle nature, which promotes fragmentation and the formation of new surfaces during compression, thereby limiting its capacity for elastic deformation [56]. The microwave-assisted wet granulation markedly increased the ER of the MW-RS series (2.86–3.28%), with values rising progressively with microwave energy and treatment time. This enhancement was attributed to the partial disruption of crystalline regions and increased amorphous content, which enhanced molecular mobility and viscoelastic recovery. Conversely, the MW-Man series showed only a slight increase in ER (0.49–0.56%) compared with untreated mannitol. These minor changes suggest that microwave exposure had negligible influence on the elastic recovery of mannitol, and its brittle characteristics remained dominant.

The wet-granulated composite (W-RM) exhibited a lower ER (1.65%) than RS, reflecting the influence of mannitol in reducing the overall viscoelastic response. The MW-RM series displayed slightly higher ER values (1.53–2.97%) than W-RM, indicating that microwave irradiation improved molecular mobility within the co-processed matrix. Notably, increasing microwave energy and treatment time beyond 30 s led to a pronounced rise in ER. The commercial excipient (Starlac^®) also showed a high ER (2.94%), consistent with its partially amorphous lactose–starch composition, which provides viscoelastic behavior comparable to that of the MW-RM series. Overall, these findings indicate that the microwave-assisted treatment markedly enhances elastic recovery, whereas co-processing with a brittle component such as mannitol reduces it. Thus, the combination of a plastic material (starch) with a brittle material (mannitol) results in a balanced viscoelastic response that is suitable for tablet compression, as the brittle component promotes surface area formation for interparticulate bonding while simultaneously limiting the release of stored elastic energy [57].

3.11. Lubricant Sensitivity

The lubricant sensitivity ratios (LSR) of the samples are summarized in Table 6. A higher LSR value indicates a greater reduction in tablet tensile strength caused by over-lubrication, reflecting the stronger adverse effects of hydrophobic lubricants on interparticulate bonding during compression. The formation of a hydrophobic lubricant film over particle surfaces interferes with bonding sites, thereby reducing tablet tensile strength and consequently prolonging tablet disintegration and dissolution times [58,59]. The result revealed that D-mannitol exhibited the lowest LSR (4.26), confirming its brittle–fragmentation mechanism that generated new surfaces during compression. Thus, it was less affected by surface coverage of the lubricant [60]. On the other hand, RS showed a higher LSR (23.45), suggesting that its plastic and viscoelastic deformation behavior was more sensitive to lubricant and easier to be covered by hydrophobic film of lubricant. The MW-RS series displayed moderate sensitivity, with LSR values ranging from 29.14 to 33.26, reflecting that microwave treatment slightly increased plasticity and molecular mobility without substantially increasing lubricant susceptibility. Conversely, the MW-Man series showed low LSR values (6.88–9.04), consistent with the dominance of brittle fracture and limited plastic deformation of mannitol.

The W-RM demonstrated a substantially higher LSR (33.01) than its parent excipient, indicating that wet granulation promoted plastic deformation property, which was more readily covered by magnesium stearate. The MW-RM series exhibited LSR values between 29.33 and 47.05, suggesting that microwave irradiation enhanced material plasticity and surface cohesiveness, leading to greater sensitivity to lubricant film formation [61]. Notably, increasing microwave energy and treatment time correlated with higher LSR values. The commercial excipient Starlac^® also showed high lubricant sensitivity (39.92), attributed to its partially amorphous lactose–starch composition and plastic deformation mechanism. These findings indicate that the microwave-assisted wet granulation increased lubricant sensitivity, especially for starch materials, due to enhanced plastic deformation. In contrast, brittle materials such as mannitol remained relatively insensitive to lubricant effects, reinforcing the advantage of blending brittle and plastic materials to balance lubrication behavior for direct compression of tablets [4].

3.12. Disintegration Property

3.12.1. Disintegration Test

The disintegration times of the tablet samples are presented in Table 6. According to the European Pharmacopoeia (Ph. Eur.), tablets that completely disintegrate within 180 s are classified as orally disintegrating tablets (ODTs). The results showed that RS tablets exhibited the longest disintegration time (143 s), while still complied with the Ph. Eur. specification. RS is generally recognized as an effective disintegrant when used at high concentrations, primarily due to its swelling-driven disintegration mechanism [62]. For D-mannitol, it disintegrated rapidly within 22 sec owing to its high solubility and brittle fracture behavior, which facilitated rapid breakup of the compact [34]. The application of microwave-assisted wet granulation markedly reduced the disintegration time of the MW-RS series. This improvement was attributed to the increased pore volume that enhanced liquid uptake and dispersion. However, MW-Man series showed comparable disintegration time to that of D-mannitol.

The wet-granulated formulation (W-RM) disintegrated more rapidly (74 s) than RS, indicating that co-processing with mannitol enhanced disintegration through the combined effects of mannitol’s brittle fracture behavior and high solubility. The microwave-assisted co-processed tablets (MW-RM) exhibited further improvement, with disintegration times ranging from 31 to 68 s, depending on the applied microwave power and exposure duration. Increasing microwave power significantly shortened disintegration time, likely due to the generation of a more porous structure that facilitated liquid penetration. In contrast, prolonged exposure (60 s) resulted in a notable delay in disintegration, which may be attributed to partial fusion of mannitol and starch that reduced internal pore connectivity. Among all formulations, MW-RM-H-30 showed the fastest disintegration, demonstrating a marked improvement over both RS and W-RM tablets and exhibiting performance comparable to the commercial excipient.

3.12.2. Wetting Test

The wetting times of the prepared tablets are summarized in Table 6. A strong correlation was observed between wetting and disintegration time, indicating that faster wetting facilitated quicker tablet breakup. Among all samples, RS tablet exhibited the longest wetting time (126 s) because it absorbed water and formed a hydrated layer that reduced the liquid penetration rate into the tablet core. In contrast, D-mannitol showed a shorter wetting time (25 s), consistent with its high solubility that enhanced capillary uptake of water. The microwave-assisted wet granulation significantly decreased wetting of materials. MW-RS tablets exhibited considerably shorter wetting time (61–71 s) compared to RS, indicated the formation of micro-pores that facilitated limited liquid penetration into the tablet core. In addition, MW-Man tablets showed remarkably shorter wetting times (7–14 s) and was comparable to Starlac^® (12 s), which was attributed to partial disruption of the crystalline lattice induced by microwave heating. This enhanced surface wettability and accelerated capillary absorption, resulting in the most rapid wetting time.

For co-processed materials, W-RM demonstrated improved wetting (60 s) compared with RS, confirming that co-processing with mannitol enhanced surface wettability. The microwave-assisted tablets showed further improvement, with wetting times ranging from 26–55 s depending on the applied microwave power and exposure duration. The results revealed that increase in microwave power generally reduced wetting time that was consistent with the increase in pore volume of materials that facilitated water penetration. However, prolonged irradiation (60 s) produced a slight increase in wetting time in all tested microwave power that caused particle fusion and densification, which hindered water penetration. Among MW-RM tablets, MW-RM-H-30 exhibited the shortest wetting time. The overall findings indicate that the microwave-assisted co-processing substantially improved liquid uptake and wetting kinetics, contributing to the enhanced disintegration performance of the MW-RM tablets.

3.12.3. Water Absorption Ratio

The water absorption ratios (WAR) of the sample tablets are summarized in Table 6. The RS tablets exhibited the highest water absorption ratio (132%), reflecting the strong swelling ability of starch granules upon hydration. When starch came into contact with water, hydroxyl groups within the amorphous regions formed hydrogen bonds with water molecules, leading to water uptake and granule expansion [63]. Although this high swelling capacity promoted liquid uptake, it also slowed overall penetration due to the gradual expansion of the hydrated surface layer. The MW-RS tablets exhibited comparable WAR values (128–133%) to RS, confirming that the microwave-assisted wet granulation process preserved the swelling character of starch. In contrast, D-mannitol tablets displayed the lowest WAR value (12%) because mannitol dissolves rapidly without significant swelling. Meanwhile, the MW-Man tablets showed higher WAR values (28–40%) than untreated D-mannitol, which can be attributed to partial amorphization induced by microwave processing, which enhanced liquid retention.

The W-RM tablet showed an intermediate WAR value (52%), indicating improved liquid uptake compared with D-mannitol but less than RS, consistent with its mixed composition and moderate porosity. The MW-RM tablets showed WAR values ranging from 62–90%, depending on the microwave power and exposure duration. Increasing microwave power generally improved water uptake, whereas prolonged exposure (60 s) slightly reduced it possibly due to particle fusion and partial pore collapse under these conditions. Among MW-RM tablets MW-RM-H-30 showed the highest WAR (90%), implying optimal pore formation and efficient capillary water absorption. These results aligned with the wetting and disintegration test, confirming that enhanced liquid uptake contributed to the superior disintegration performance of the MW-RM tablets. In comparison, the commercial co-processed excipient (Starlac^®) exhibited a considerably lower WAR (36%) than MW-RM series, likely due to its high lactose content (~85%) which limited water absorption despite its good wettability [64].

3.13. Contact Angle Measurement

The surface wettability of tablets was characterized by the contact angle (CA) formed between a liquid droplet and the solid surface. A lower contact angle denotes enhanced wettability, indicating greater liquid spreading and stronger solid–liquid interactions, which reflect the hydrophilic nature and porosity of the material. Thus, a lower contact angle is highly desirable for ODTs, as it promotes rapid water penetration into the tablet matrix, facilitating faster disintegration and drug release (ODT) [65]. As shown in Figure 6, RS exhibited a moderate contact angle of 47.19°, indicating moderate surface hydrophilicity due to the presence of hydroxyl groups on the starch granule surface [66]. Mannitol displayed a slightly lower CA (41.99°), suggesting higher wettability associated with its crystalline, water-soluble nature. In contrast, the wet-granulated sample (W-RM) exhibited the highest contact angle (67.19°), indicating reduced surface wettability. This behavior can be attributed to surface densification that occurred during the granulation process, which decreased surface roughness and granule porosity, thereby limiting liquid penetration across the tablet surface. In contrast, the microwave-assisted wet-granulated material (MW-RM-H-30) exhibited a considerably lower CA (42.19°) than W-RM and was comparable to that of mannitol. This result suggested the microwave-assisted process successfully improved material porosity relative to conventional wet granulation, resulting in enhanced liquid spreading and faster wetting. The improved wettability of MW-RM-H-30 was beneficial for ODT formulations, as it facilitated rapid water uptake and promoted tablet disintegration upon contact with saliva [67]. The commercial excipient, Starlac^®, showed the lowest CA (33.89°), demonstrating the highest wettability among all samples. Overall, MW-RM presented wettability characteristics approaching those of Starlac^®, suggesting its suitability for direct compression of ODTs, where rapid wetting is essential to promote tablet disintegration. The original, unprocessed contact angle images corresponding to Figure 6 are provided in the supplementary data to support image clarity and measurement transparency.

3.14. Formulation Study

The formulation outcomes are summarized in

Table 7. Tablet properties of chlorpheniramine maleate and piroxicam formulations prepared using different excipients.

Formulations	Tablet Weight (mg)	Breaking Force (N)	Friability (%)	Disintegration Time (s)	Drug Content (%)
Chlorpheniramine maleate
Physical mixture	101.6 ± 1.01	29.8 ± 1.88	1.24	61.00 ± 6.56	101.64 ± 4.95
MW-RM-H-30	101.4 ± 0.96	56.4 ± 3.74	0.28	42.17 ± 7.49	102.40 ± 1.16
Starlac®	101.0 ± 1.32	56.2 ± 4.49	0.40	46.17 ± 5.00	96.64 ± 2.67
Piroxicam
Physical mixture	151.0 ± 1.59	36.2 ± 3.69	1.38	38.67 ± 3.51	101.56 ± 2.95
MW-RM-H-30	150.7 ± 1.48	62.0 ± 4.97	0.20	32.00 ± 3.61	96.47 ± 2.03
Starlac®	150.6 ± 1.10	69.1 ± 4.52	0.64	28.67 ± 2.08	97.92 ± 2.08

. Evaluation of both CPM and piroxicam tablets clearly demonstrated that the MW-RM formulations possessed excellent functionality as direct-compression excipients for orally disintegrating tablets (ODTs). The MW-RM tablets exhibited performance comparable to the commercial excipient (Starlac^®) while fully meeting pharmacopeial requirements for uniformity of dosage units, friability (<1%), and drug content within the USP-specified limits for both drug models. In contrast, the physical-mixture formulations failed to comply with friability specifications owing to insufficient mechanical strength, as correspond with their low breaking force (<40 N). Regarding disintegration behavior, the MW-RM tablets displayed rapid disintegration time comparable to Starlac^® (42–46 s for CPM and 28–32 s for piroxicam formulations), whereas the physical-mixture tablets disintegrated significantly more slowly. Collectively, these findings confirm that the MW-RM excipient provided an optimal balance between mechanical robustness, friability resistance, and fast disintegration, establishing its suitability for the direct compression of ODTs.

3.15. In Vitro Release Study

The dissolution profiles of CPM and piroxicam tablets formulated with MW-RM-H-30 were compared with those prepared using Starlac^® and the corresponding physical mixture (Figure 7). For CPM tablets, Starlac^® and MW-RM-H-30 formulations exhibited very rapid dissolution, achieving more than 80% drug release within the first 5 min, consistent with their short disintegration times and adequate mechanical strength. In contrast, the physical mixture tablets showed a slightly faster initial release due to their low mechanical strength and high friability (>1%). However, as the test progressed, their dissolution rate became slower than MW-RM-H-30 and Starlac^®, reflecting limited wettability and reduced disintegration efficiency compared to the optimized formulations.

For piroxicam tablets, the distinction between formulations became more evident, owing to the poor aqueous solubility of piroxicam [68]. MW-RM-H-30 demonstrated high dissolution efficiency throughout the test and reached more than 80% of the drug release within 10 min, which was comparable to Starlac^®. This behavior is well correlated with its fast disintegration, which facilitated rapid water penetration and drug dissolution. Conversely, the physical mixture formulation exhibited the slowest release behavior after the initial phase, attributed to its inferior mechanical properties and longer disintegration time, resulting in delayed water penetration and dissolution [69]. Overall, the results indicate that MW-RM-H-30 provided dissolution performance comparable to the commercial benchmark Starlac^®, confirming its suitability as an effective co-processed excipient for ODT manufacturing.

4. Conclusions

This study successfully developed a novel co-processed excipient composed of rice starch (RS) and mannitol (MW-RM series) using a microwave-assisted wet granulation technique. The approach effectively combined the plastic deformation behavior of starch with the brittle fracture characteristics of mannitol, while microwave treatment introduced particle porosity that enhanced its performance as a direct-compression excipient for ODT formulations. The influence of microwave energy and treatment duration was systematically evaluated to optimize functional properties of the co-processed materials.

SEM analysis showed the transformation of irregular starch granules and elongated mannitol crystals into a more spherical, and cohesive agglomerated of materials. Particle size analysis demonstrated granule enlargement following wet granulation and subsequent size reduction due to microwave-induced structural shrinkage. True density and porosity data confirmed the formation of internal porous structures in the MW-RM-H series, which is favorable for rapid liquid penetration during disintegration. FTIR and DSC analyses demonstrated no chemical interactions and preserved thermal properties, while XRD results indicated partial amorphization that may further promote fast wetting and dissolution.

These physicochemical improvements indicated excellent manufacturability of the MW-RM powders. The optimized formulation, MW-RM-H-30, exhibited superior flowability, appropriate compressibility, and rapid disintegration as confirmed by standardized disintegration testing. In addition, MW-RM-H-30 demonstrated short wetting time, high water absorption capacity, and reduced contact angle compared with the non-microwave-treated material, indicating enhanced surface wettability and more efficient liquid penetration into the tablet matrix. When formulated into ODTs containing CPM and piroxicam as model drugs, MW-RM-H-30 enabled the production of tablets meeting pharmacopeial criteria for friability, content uniformity, and drug content, while maintaining rapid disintegration performance. Dissolution studies further confirmed that MW-RM-H-30 tablets achieved similar release profiles to Starlac^®, a commercial benchmark excipient, and significantly faster dissolution than the physical mixture. These findings confirm that MW-RM-H-30 fulfills essential requirements for direct-compression ODT applications.

Overall, the microwave-assisted wet granulation represents an efficient and promising manufacturing strategy for producing rice starch–based co-processed excipients with enhanced pharmaceutical performance. Nevertheless, potential scale-up challenges related to non-uniform microwave energy distribution and moisture gradients should be considered. Future work will therefore focus on long-term stability studies, systematic scale-up evaluation, and broader API compatibility to support the industrial translation of this excipient platform.