Physicochemical, Granulometric, Morphological, and Surface Characterization of Dried Yellow Pitaya Powder as a Potential Diluent for Immediate-Release Quercetin Tablets

Abstract

The growing interest in sustainable materials has encouraged the valorization of agro-industrial byproducts for pharmaceutical, nutraceutical, and food applications. This study evaluated yellow pitaya peel powder, obtained via convective and refractance window drying, as a diluent in immediate-release quercetin tablets. The powders were characterized by physicochemical, granulometric, morphological, and surface properties, and compared with conventional excipients, including partially pregelatinized corn starch and spray-dried lactose monohydrate. Refractance window drying improved solubility, flowability, and structural integrity, while convective drying produced finer, more porous particles with lower water activity. Tablets formulated with both powders showed adequate hardness, low friability, and disintegration times under five minutes. All systems achieved complete quercetin release. Kinetic modeling revealed anomalous, matrix-regulated transport, with Weibull and Modified Hill models providing the best fit. Based on these results, pitaya peel powder could be considered a suitable diluent for the development of immediate-release tablets, offering functional performance aligned with sustainable formulation strategies.

1. Introduction

In recent decades, the pharmaceutical, nutraceutical, and dietary supplement industries have undergone sustained expansion, primarily driven by increasing consumer demand for natural, functional, and health-oriented alternatives [1]. This trend has catalyzed the exploration of novel materials suitable for compressed dosage forms, with the objective of diversifying the portfolio of pharmaceutical excipients—particularly diluents, which remain limited in variety and predominantly sourced from conventional origins [2]. Concurrently, intensified efforts have been directed toward the identification of sustainable excipients derived from agro-industrial residues, in alignment with emerging environmental imperatives and the principles of the circular economy [3,4]. Within this context, fruit peels have garnered attention as promising candidates, owing to their abundance of cellulose-based fibers, low production cost, and favorable physicomechanical attributes. However, the quantity and quality of fibrous constituents are known to vary considerably according to botanical origin, anatomical features, and residual composition of the source material. These factors underscore the need for systematic investigation into such substrates, in order to elucidate their true potential as functional excipients in pharmaceutical and allied applications. [5]. Although fruit peels such as banana, mango, and citrus have demonstrated favorable performance as excipients—particularly in terms of flowability, compressibility, and disintegration behavior—the potential of yellow pitaya (Selenicereus megalanthus) peel remains largely unexplored. Notably, this byproduct may constitute up to 33% of the fruit’s total weight and is routinely discarded during pulping. Its fibrous composition, low sugar content, and granular morphology suggest that it could offer comparable technological and functional advantages. Nevertheless, its use as a diluent excipient—intended to increase tablet bulk and enhance the compressibility of drug-release formulations—has not been systematically investigated, to date [6,7].

In this context, yellow pitaya peel powder emerges as a potential diluent excipient, exhibiting physicomechanical properties comparable to those described for cellulose-based bio-polymeric materials, such as starches [8,9], and for non-polymeric excipients like lactose [10]. A comparative approach involving pitaya peel and conventional direct compression excipients would enable the assessment of performance parameters such as mechanical strength, disintegration behavior, and dissolution profile of model active ingredients. From an industrial standpoint, pitaya cultivation—currently expanding across tropical and subtropical regions, particularly in Latin America and Southeast Asia—generates peel residues that are routinely discarded during processing [11]. This byproduct is potentially available in substantial volumes and can be valorized with minimal energy input. Its compatibility with the physicomechanical requirements of direct compression excipients reinforces its promise as an alternative within the limited excipient portfolio used in pharmaceutical, nutraceutical, and dietary supplement formulations [12]. Moreover, the incorporation of pitaya peel aligns with emerging trends in clean-label formulation and regional sourcing, offering a functional and sustainable option for the development of environmentally conscious solid dosage forms.

Consistent with the previous discussion, the valorization of yellow pitaya peel may contribute to circular economy strategies by transforming agricultural residues into functional excipients. This approach could foster more efficient resource utilization, reduce waste generation, and promote the adoption of sustainable practices in the development of pharmaceutical and related products. Recent studies have demonstrated that metabolomics-based methodologies effectively support the valorization of olive byproducts by correlating extraction techniques, cultivar characteristics, and leaf ontogeny with specific bioactive profiles. Through UHPLC-MS/MS and LC/MS analyses, compounds such as oleuropein, verbascoside, and triterpenoids have been identified, exhibiting antioxidant activity and inhibitory effects on key enzymatic targets [13,14,15]. These findings reinforce the role of agro-industrial residues as functional inputs within sustainable food and pharmaceutical systems.

Such insights also underscore the potential relevance of pitaya peel as a renewable, regionally available material with promising applications as an excipient. Similarly, fruit peels including mango, citrus, and pomegranate have been valorized for their high phenolic content and antioxidant capacity, enabling their use in biodegradable packaging and natural preservation systems [16]. Grape pomace, a major byproduct of winemaking, has been successfully incorporated into plant-based meat and dairy matrices to enhance nutritional value and oxidative stability [17]. Moreover, Megías-Pérez et al. (2023) [18] reported the extraction of antioxidant-rich pectins from grape pomace, offering techno-functional advantages for food formulation. Bordiga et al. (2019) [19] reviewed the maturity of grape pomace valorization, highlighting its potential to produce proanthocyanidins and dietary fibers. Finally, Caldeira et al. (2020) [20] emphasized the contribution of fruit processing residues to biomass conversion and the generation of value-added food ingredients, thereby reinforcing the circular economy paradigm.

On the other hand, a complementary dimension addressed in this study concerns the physical characteristics of the processed materials, which are typically obtained in dried form. It has been well established that the physical and functional performance of powders derived from plant-based residues—particularly regarding flowability and compressibility—is critical for their suitability as excipients [21]. Among emerging drying technologies, refractance window drying (RWD), a hybrid heat transfer method that integrates conduction, convection, and infrared radiation via a polymeric film over a heated waterbed, has demonstrated superior efficiency in moisture removal while preserving the integrity of thermolabile compounds [22,23,24].

In contrast, conventional techniques such as hot-air convection are associated with extended drying times, elevated energy demands, and partial degradation of antioxidant compounds and structural matrices [25,26,27]. RWD, by operating at lower product temperatures and shorter residence times, minimizes oxidative stress and nutrient loss. Given its favorable energy profile, reduced microbial risk, and enhanced retention of functional attributes, the evaluation of RWD is particularly justified in the context of nutraceutical excipient development, where the preservation of bioactivity and powder quality is essential for formulation performance and regulatory compliance.

Accordingly, this study aimed to characterize the physicomechanical properties of yellow pitaya peel powder and to evaluate its potential as a direct compression excipient, specifically as a diluent in tablet formulations. To gain deeper insight into its behavior within solid pharmaceutical systems, surface properties were assessed through contact angle measurements, which are critical for predicting powder wettability and the liquid–solid interactions during disintegration and dissolution processes. This parameter is closely associated with the morphological and flowability characteristics typical of powdered excipients.

A morphological analysis was also performed using standard optical microscopy and scanning electron microscopy (SEM) to examine particle shape, surface texture, and structural uniformity. Notably, no previous studies have applied this comprehensive analytical framework to pitaya peel powder. To further assess its performance as a pharmaceutical diluent, pitaya powder was incorporated into direct compression formulations containing quercetin—a flavonoid widely utilized in pharmaceutical and nutraceutical products due to its antioxidant, anti-inflammatory, and cardioprotective properties—thus serving as an ideal model active ingredient [28,29]. The performance of pitaya peel powder was subsequently compared with that of conventional direct compression excipients, including pregelatinized corn starch and spray-dried lactose monohydrate.

2. Materials and Methods

Yellow pitaya fruits (Hylocereus spp.) were purchased from a wholesale food center (Medellín, Colombia). Quercetin, citric acid, sodium hydroxide (solid), hydrochloric acid (37%), ethanol (96%), and phosphoric acid (85%) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Ultrapure water was obtained via a Milli-Q^® system (Millipore, Burlington, MA, USA). All chemicals were used without further purification. Working solutions of HCl (0.1 M and 2 M), NaOH (0.1 mol/L), PBS (pH 6.5, 50 mM), phosphoric acid (0.08% w/v), and MeOH:H₂O (80:20 v/v) were prepared in-house. PPCS, SDLM, colloidal silicon dioxide, and magnesium stearate were obtained from Colorcon Colombia S.A.S. (Bogotá, Colombia). The plant material was used solely for its physical properties, specifically its cellulosic matrix rich in primary metabolites such as dietary fiber. No extraction, characterization, or use of genetic components or secondary metabolites was performed.

Figure 1 provides a schematic representation of the methodology used in this study, which is subsequently presented in detail.

2.1. Obtaining the Powdered Material

Fruits were disinfected by immersion in a 50 ppm sodium hypochlorite solution for 5 min and rinsed under potable water, following the Colombian technical standard NTC 5400 (ICONTEC, 2012) [30]. After manual separation, peels were stored at −20 °C until processing. Convective drying was performed by placing the fresh peel in stainless steel trays and dehydrating it at 70 ± 1 °C for 24 h in a forced-air oven (Model UFE 500, Memmert GmbH + Co.KG, Schwabach, Germany). For refractance window drying, 130 g of frozen peel was homogenized with 70 mL of distilled water using a commercial blender (Classic Series, Oster^®, Bogotá, Colombia). The paste was spread onto Mylar™ film at 2 mm thickness and dehydrated at 70 ± 1 °C for 4 h in a static RWD system (Model 1531, Industrias Centricol, Medellín, Colombia). Dried material was ground using a hammer mill (Model 3010-014, Thomas Scientific, Swedesboro, NJ, USA) and sieved through mesh sizes 16, 30, and 60 (ASTM E11) using a vibratory sieve shaker (Model RX-29, W.S. Tyler^®, Mentor, OH, USA). Only the powder retained below mesh 60 (<250 µm) was collected. It is important to mention that drying parameters corresponding to time, temperature, sample thickness, etc., were based on previous studies like those reported by Dadhaneeya et al. [31].

2.2. Physicochemical Properties

The physicochemical properties of the dried pitaya peel powder were characterized through a comprehensive set of analytical procedures. Moisture content was determined gravimetrically at 105 °C, following AOAC 930.15 [32]. In addition, pH was measured using a potentiometer (Seven Compact S220, Mettler-Toledo, Columbus, OH, USA), while titratable acidity was quantified via acid–base titration with 0.1 mol L⁻¹ NaOH and phenolphthalein as an indicator and expressed as citric acid equivalents according to AOAC 942.15. [33]. Total soluble solids were assessed using a handheld refractometer (Master-a, Atago Co., Ltd., Tokyo, Japan) and reported in °Brix. Furthermore, ash content was obtained by incineration at 550 °C in a muffle furnace (Model L9/11/B180, Nabertherm GmbH, Lilienthal, Germany), in accordance with ISO 5984:2002 [34]. Moreover, total dietary fiber was quantified using the non-enzymatic gravimetric method described in AOAC 993.21 [35], providing an estimate of the insoluble fibrous fraction present in the sample. Colorimetric parameters were analyzed using a benchtop spectrophotometer (Model CM-5, Konica Minolta, Tokyo, Japan) equipped with a 30 mm aperture, where measurements were recorded in both specular component included (SCI) and excluded (SCE) modes to capture total and surface-reflective properties, respectively, and expressed in CIE-Lab* coordinates for lightness (L*), red–green axis (a*), and yellow–blue axis (b*) [36]. Water activity (a_w) was determined using a dew point water activity meter (Model 4TE, Meter Group Inc., Pullman, WA, USA), previously calibrated with standard salt solutions, with readings taken once the instrument reached stabilization (±0.003), providing insight into the availability of unbound water in the powdered matrix, a critical parameter for microbial stability and shelf life [37,38]. Finally, solubility was evaluated by dispersing 2.50 g of dried powder in 30 mL of distilled water under magnetic stirring at 300 rpm for 30 min at 25 ± 1 °C (AREX-6, VELP Scientifica, Usmate Velate, Italy); the dispersion was then centrifuged at 3000 rpm for 10 min, and the supernatant was dried under reduced pressure to constant weight. Solubility was expressed as the percentage of dissolved solids relative to the initial dry mass, reflecting the powder’s dispersibility and potential for bioactive release [39].

2.3. Granulometric Properties

Particle size distribution was assessed by dry sieving for 10 min using a mechanical sieve shaker (Model RX-29, W.S. Tyler^®, Mentor, OH, USA) operating at constant amplitude. A stack of stainless steel sieves (ASTM E11) with decreasing mesh sizes ranging from No. 60 (250 µm) to No. 325 (45 µm) was employed. Following separation, each retained fraction was weighed and expressed as a percentage relative to the initial sample mass. In addition, flowability was evaluated by determining bulk and tapped densities using a tapped volumeter (Model SVM 102, Erweka GmbH, Langen, Germany), in accordance with USP 41–NF36 General Chapter <616> (USP, 2018) [40]. A 25.00 g sample was gently poured into a 250 mL graduated cylinder to record the bulk volume, followed by 100 mechanical taps to obtain the tapped volume. From these measurements, the Carr Index (CI) and Hausner Ratio (HR) were calculated to estimate powder compressibility and interparticle cohesion, which are widely recognized indicators of flow performance in pharmaceutical solids [41,42,43].

2.4. Morphological Characterization by Scanning Electron Microscopy (SEM)

Dry pitaya peel powder was softly vacuum-dried, riding on aluminum stubs using conductive carbon tape, and coated with a thin gold layer via a JEOL sputter coater to enhance electron conductivity. SEM imaging was carried out using a JSM-6490 microscope (JEOL Ltd., Tokyo, Japan) operating at an accelerating voltage of 20 kV. Magnifications ranging from 50× to 3000× were employed to visualize structural transitions at both macro- and micro-scale, including pore formation, gel layer development, and surface disintegration.

2.5. Contact Angle Measurements

The static contact angle (θ_c) was determined by the sessile drop method, which consists of the deposition of an ultrapure water drop on the material solid surface [44,45]. In this study, pitaya peel-derived materials, quercetin, the control diluent excipients (partially pregelatinized corn starch—PPCS; and spray-dried lactose monohydrate—SDL), and different formulation mixtures were compressed until a uniform, compact, and flat surface was formed, where the θ_c value was determined at initial time. Measurements were made with an OCA15EC contact angle meter (Dataphysics Instruments, Filderstadt, Germany), operated using SCA20 software and complemented by video capture with an IDS camera that records between 400 and 800 frames per drop, thus ensuring optimal contour resolution.

2.6. Formulation of Quercetin Tablets

Tablets were prepared individually by manually weighing and mixing each ingredient with a spatula for approximately 5 min. The resulting blend was carefully transferred into the die cavities of a custom-built single-punch tablet press equipped with flat-faced, stainless steel punches (1/4-inch diameter). Each tablet was formulated according to the base compositions detailed in

Table 1. Composition of quercetin tablet formulations (500 mg each), prepared with usual pharmaceutical excipient employed as diluent and contrasted with the dried pitaya peel powders.

Formulation Ingredient		Ingredient Amount Per Tablet (mg)	% w/w
			Tablet Formulation 1	Tablet Formulation 2	Tablet Formulation 3	Tablet Formulation 4
Active ingredient	Quercetin	250	50	50	50	50
Diluent	PPCS	245	49	--	--	--
	SDLM		--	49	--	--
	CDP		--	--	49	--
	RWDP		--	--	--	49
Lubricant	Colloidal silicon dioxide	2.5	0.5	0.5	0.5	0.5
Glidant	Magnesium stearate	2.5	0.5	0.5	0.5	0.5

(PPCS: partially pregelatinized corn starch, SDLM: spray-dried lactose monohydrate, CDP: convection-dried pitaya peel powder and RWDP: refractance window dried pitaya peel powder).

, where the selection of excipients was guided by conventional and widely accepted formulations for immediate-release systems [46]. Regarding tablet characterization, average tablet weight, breaking force, friability, disintegration, and surface contact angle were evaluated. Tablets were weighed using an analytical scale PRACTUM22418 (Sartorius Lab Instruments, Göttingen, Germany). Breaking strength was determined with a durometer HDT-400 (Logan Instruments Corp., Somerset, NJ, USA), and diameter was measured using a digital caliper. Friability testing was performed according to USP 41–NF36 General Chapter <616> guidelines (USP, 2018) [40], using an FAB-2S friabilator (Logan Instruments Corp.), while disintegration was assessed on three tablets using a USP DST-3 apparatus (Logan Instruments Corp.) following USP <701> [47], with phosphate-buffered saline (PBS, pH 6.5, 50 mM) as the medium. Static contact angle measurements were performed immediately after tablet manufacture using the sessile drop method [48,49], with a contact angle meter (OCA15EC, DataPhysics Instruments, Filderstadt, Germany) and software SCA20 (v4.5.14). Image acquisition was conducted with an IDS video camera, and static angle values were determined from a frame range of 400 to 800.

2.7. In Vitro Quercetin Release and Kinetic Modeling

In vitro dissolution test was carried out employing a USP Apparatus II (paddle method) on a previously calibrated tester (Vision G2 Classic 6-Hanson, Chatsworth, CA, USA) with 900 mL of 0.1 M hydrochloric acid (pH 1.2; equivalent to 0.1 mol/L or 3.64 g/L HCl, approximately 0.36% w/v) as the dissolution medium [50]. The temperature was maintained at 37 ± 0.5 °C and the rotation speed was set to 50 rpm, in accordance with specifications for immediate-release dosage forms. Each tablet had a total mass of 500 mg, consisting of 250 mg of quercetin, 240 mg of pitaya peel powder as a functional excipient, and 10 mg of conventional excipients. Aliquots of 5 mL were withdrawn at 5, 10, 15, 20, 30, 45, and 60 min, filtered through a 0.45 μm membrane, and analyzed by high-performance liquid chromatography (HPLC with a LaChrom Ultra diode array detector, Hitachi-VWR, Radnor, PA, USA), following the method outlined in the USP Quercetin monograph (USP, 2024) [51]. For HPLC, a C18 column (150 × 4.6 mm, 5 μm) was employed with a mobile phase of methanol and 0.08% (w/v) phosphoric acid, a flow rate of 1.0 mL/min, diode array detection at 370 nm, and an injection volume of 20 μL. Sample preparation included acid hydrolysis with 2 M HCl at 80 °C for 1 h, followed by ethyl ether extraction, solvent evaporation, and reconstitution in MeOH:H₂O (80:20). The quercetin content was confirmed to be within the USP-specified limits of 98.0–102.0% on an anhydrous basis. In contrast, dissolution profile data were modeled using both classical and heuristic equations—zero-order, first-order, Higuchi, Hixson–Crowell, Korsmeyer–Peppas, Weibull, among others—to elucidate the drug-release mechanism, as well as the dissolution efficiency [52,53,54].

2.8. Data Analysis

All experimental data were collected in triplicate (n = 3) and expressed as mean ± standard deviation. Statistical analysis was applied across compositional, physical, mechanical, and dissolution assessments to ensure rigor and enable meaningful comparisons. Normality of data was verified using the Shapiro–Wilk test, and variance homogeneity was checked via Levene’s test prior to parametric evaluations. For inter-group comparisons—such as between powders (CDP vs. RWDP) and tablet formulations (F1–F4)—one-way ANOVA with Tukey’s post hoc test (α = 0.05) was employed, particularly for moisture content, antioxidant profiles, flowability, compactibility metrics, disintegration times, mechanical strength, and wettability. Dissolution data were statistically compared based on dissolution efficiency and curve progression, and kinetic modeling was performed using classical (zero-order, first-order, Higuchi, Hixson–Crowell, Korsmeyer–Peppas) and heuristic models (Weibull, Logistic, Gompertz, Modified Hill), with coefficient of determination (R²) and 95% confidence intervals for key parameters (e.g., k, n, b, t₅₀) reported to assess model fit and mechanistic accuracy. All processing and analysis were conducted using OriginPro 2024 (OriginLab, Northampton, MA, USA) and GraphPad Prism v8.0.2 (GraphPad Software, Boston, MA, USA), in alignment with statistical practices for low-TRL pharmaceutical preformulation studies.

3. Results and Discussion

3.1. Physicochemical Properties

The results of physicochemical and colorimetric parameters of pitaya peel powders obtained by convective drying (CDP) and refractance window drying (RWDP) are summarized in

Table 2. Physicochemical and colorimetric parameters of pitaya peel powders obtained by convective drying (CDP) and refractance window drying (RWDP).

Parameter		CDP	WDP
Moisture content (%)		4.00 ± 0.05	6.00 ± 0.15
Water activity ($a_w$)		0.214 ± 0.088	0.364 ± 0.005
Water solubility (%)		8.00 ± 0.003	12.00 ± 0.006
Drying yield (% w.b.)		14.00 ± 0.01	12.00 ± 0.23
Powder retained < 250 µm (% of batch)		38.00 ± 0.02	34.00 ± 0.12
pH		4.95 ± 0.008	4.49 ± 0.11
Titratable acidity (% citric acid)		1.28 ± 0.12	1.47 ± 0.12
°Brix		5.00	5.00
Total dietary fiber (g/100 g b.s.)		63.4	64.0
Ash content (g/100 g b.s.)		14.98	16.70
Colorimetric parameters	a* (redness)	5.34 ± 0.0430	8.65 ± 0.0170
	b* (yellowness)	33.68 ± 0.0400	38.16 ± 0.0190
	L* (lightness)	72.89 ± 0.0490	64.63 ± 0.0550

Values are expressed as mean ± standard deviation (n = 3).

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According to Table 2, the moisture content of the powders was 4.00 ± 0.05% for CDP and 6.00 ± 0.15% for RWDP, indicating low residual humidity in both cases. These values suggest that the drying processes employed—convective drying and refractance window drying—were effective in achieving water removal and powder stabilization, thereby ensuring suitable conditions for subsequent handling and formulation. In relation to water activity (a_w), values of 0.214 ± 0.088 for CDP and 0.364 ± 0.005 for RWDP confirmed the microbiological stability of both powders, although the slightly higher a_w in RWDP may be attributed to shorter exposure times and residual moisture retention. Regarding solubility, RWDP exhibited a higher value (12.00 ± 0.006%) compared to CDP (8.00 ± 0.003%), indicating that the powder obtained under refractance window drying presents improved dispersibility and dissolution characteristics. With respect to drying yield, CDP achieved 14.00 ± 0.01%, slightly surpassing RWDP (12.00 ± 0.23%), which suggests more efficient mass recovery under convective conditions. In terms of particle size distribution, the proportion of powder retained below 250 µm was greater in CDP (38.00 ± 0.02%) than in RWDP (34.00 ± 0.12%), indicating that CDP favored fragmentation, while RWDP preserved more cohesive structures. These differences may influence flowability and compaction behavior in downstream applications. Subsequently, pH values were 4.95 ± 0.008 in CDP and 4.49 ± 0.11 in RWDP, indicating slightly acidic conditions in both powders, likely due to the presence of organic acids. Complementarily, titratable acidity was 1.28 ± 0.12% in CDP and 1.47 ± 0.12% in RWDP, suggesting a moderate acid content that may be associated with the release of bound acids during thermal processing [55]. In addition, total soluble solids, expressed in °Brix, were 5.00 in both powders, suggesting the presence of soluble carbohydrates and aligning with previous reports on dehydrated fruit matrices [27]. Furthermore, total dietary fiber was 63.4 g/100 g in CDP and 64.0 g/100 g in RWDP. These values indicate a high content of insoluble structural components such as cellulose and hemicellulose, consistent with findings in other fruit peel powders [56,57]. In contrast, ash content was slightly lower in CDP (14.98 g/100 g) than in RWDP (16.70 g/100 g), suggesting that RWDP retained more inorganic matter, possibly due to reduced volatilization [58].

On the other hand, colorimetric parameters recorded in CIE-Lab* coordinates revealed distinct visual profiles between the powders. RWDP exhibited stronger redness (a* = 8.65 ± 0.02) and yellowness (b* = 38.16 ± 0.02) compared to CDP (a* = 5.34 ± 0.04; b* = 33.68 ± 0.04), suggesting greater pigment retention under milder thermal conditions. Conversely, CDP showed higher lightness (L* = 72.89 ± 0.05) than RWDP (L* = 64.63 ± 0.06), which may reflect pigment degradation and matrix whitening due to prolonged heat exposure. These trends are consistent with the behavior of natural pigments such as betalains, flavonoids, and carotenoid-like compounds, as previously described in thermally processed fruit matrices [59,60,61,62]. Although no specific pigment quantification was performed, the observed color differences suggest that RWDP favored the preservation of chromatic intensity, while CDP resulted in brighter but less saturated material. These findings may be relevant for applications where visual attributes and pigment integrity are critical.

3.2. Granulometric Properties

The evaluation of granulometric properties of dry pitaya peel powder is shown in

Table 3. Granulometric properties of dry pitaya peel powder (CDP: convectively dried powder, RWDP: refractance window dried powder).

Parameter	CDP	RWDP
Carr Index (%)	22.9 ± 0.95	20.07 ± 0.76
Hausner Ratio	1.30 ± 0.08	1.26 ± 0.03
Angle of repose (°)	45.42 ± 0.52	40.82 ± 0.53

Values are expressed as mean ± standard deviation (n = 3).

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According to Table 3, flowability, assessed through the Carr Index, Hausner Ratio, and angle of repose, varied between the powders. CDP exhibited a Carr Index of 22.9 ± 0.95% and a Hausner Ratio of 1.30 ± 0.08, suggesting moderate cohesiveness and reduced powder mobility, while RWDP showed slightly better flow characteristics, with a Carr Index of 20.07 ± 0.76% and a Hausner Ratio of 1.26 ± 0.03, indicating lower interparticle friction and improved packing behavior. In contrast, the angle of repose further supported these observations. CDP displayed a steeper angle (45.42° ± 0.52), consistent with more cohesive and less free-flowing material, while RWDP exhibited a lower angle (40.82° ± 0.53), reflecting enhanced flowability, which may be advantageous for operations such as capsule filling or direct compression. These results suggest that RWDP produced powders with slightly coarser particles and superior flow properties, while CDP favored finer particle generation but resulted in more cohesive behavior. These differences may influence the selection of powder systems for specific technological or pharmaceutical applications.

3.3. Morphological Characterization by SEM

Representative micrographs of pitaya peel powders obtained by convective drying (CDP) and refractance window drying (RWDP) are presented in Figure 2. As observed, the drying methodology significantly influenced the morphological and textural attributes of the powders, revealing distinct surface features and particle architectures associated with each technique. At low magnification (50×), CDP samples exhibited a fragmented and irregular surface, whereas RWDP samples displayed smoother contours and larger structural domains. These differences suggest that convective drying induced greater mechanical disruption, consistent with the finer particle size distribution reported in Table 3. At intermediate magnification (500×), CDP particles appeared angular and loosely packed, with visible fissures and pronounced surface roughness. In contrast, RWDP particles showed rounded edges and a more compact arrangement, indicating reduced structural collapse and better preservation of the native matrix. At higher magnification (3000×), CDP samples revealed an extensively porous surface formed by thin, compacted multilayers, likely resulting from prolonged thermal exposure. RWDP samples, on the other hand, exhibited a more compact particulate system with irregular surfaces, suggesting that refractance window drying preserved microstructural integrity and mitigated dehydration-induced stress. These microstructural observations complement the granulometric and flowability data discussed earlier. The disrupted morphology in CDP may account for its higher proportion of fine particles and steeper angle of repose, while the cohesive structure observed in RWDP aligns with its enhanced flow behavior and solubility. Overall, SEM imaging provides visual confirmation of the functional differences between the powders and supports the selection of RWDP for applications requiring structural preservation and improved dispersibility.

3.4. Formulation of Quercetin Tablets

3.4.1. Physical–Mechanical Characterization

The comparative performances of quercetin tablets formulated with conventional excipients and pitaya peel powders are summarized in

Table 4. Physical–mechanical properties of quercetin tablets formulated with different excipients (diluents).

System	Tablet Parameter
	Hardness (kp)	Friability (%)	Weight Variation	Disintegration Time (min:s ± s) at 37 °C
Tablet Formulation 1 (QCT + PPCS)	9.54 ± 1.34	0.3253	500.3 ± 0.05	3:03 ± 0
Tablet Formulation 2 (QCT + SDLM)	13.84 ± 1.64	0.4773	500.1 ± 0.05	4:33 ± 2
Tablet Formulation 3 (QCT + CDP)	11.84 ± 1.06	0.6136	500.0 ± 0.05	3:58 ± 5
Tablet Formulation 4 (QCT + RWDP)	12.26 ± 0.84	0.3324	500.0 ± 0.01	4:03 ± 7

QCT: Quercetin, partially pregelatinized corn starch (PPCS), spray-dried lactose monohydrate (SDLM), convection-dried pitaya peel powder (CDP) and refractance window dried powder (RWDP). Values are expressed as mean ± standard deviation (n = 3). kp: Kilopond—unit of force used to measure tablet hardness.

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With respect to mechanical strength, the highest tablet hardness was recorded in the SDLM-based formulation (13.84 ± 1.64 kp), followed by those incorporating RWDP (12.26 ± 0.84 kp) and CDP (11.84 ± 1.06 kp); in contrast, the lowest resistance was observed in the PPCS system (9.54 ± 1.34 kp); this result could be explained by the lower plastic deformation capacity of this excipient during compaction. These findings suggest that both CDP and RWDP provide adequate compactibility for direct compression, yielding performance comparable to traditional pharmaceutical diluents. This trend is consistent with values reported by Chakraborty et al. [63], where quercetin tablets based on botanical matrices exhibited hardness in the range of 3.37–3.78 kg/cm², confirming the viability of polyphenol-rich excipients in immediate-release systems.

Regarding friability, all formulations complied with USP <1216> specifications (<1%), although the greatest mass loss was registered in the CDP tablets (0.6136%), likely associated with their higher fines content and reduced interparticle binding. In contrast, RWDP tablets displayed friability comparable to the PPCS reference (0.3324% vs. 0.3253%), denoting satisfactory mechanical resilience despite the incorporation of fibrous plant material. In terms of disintegration behavior, all formulations fulfilled the immediate-release criteria by disintegrating in less than 5 min; notably, CDP and RWDP tablets disintegrated in under 4 min, which is also similar to the result previously reported by Chakraborty et al. [63] for comparable quercetin tablets (126.5–187.2). The slightly prolonged disintegration time observed for SDLM (4 m:33 s ± 2) may be attributed to reduced matrix porosity and crystalline interactions typical of lactose-based systems.

3.4.2. Determination of the Contact Angle

The initial contact angle values measured between a water droplet and the surfaces of the pure materials—quercetin (QCT), partially pregelatinized corn starch (PPCS), spray-dried lactose monohydrate (SDLM), convection-dried pitaya peel powder (CDP), and refractance window dried powder (RWDP)—as well as their corresponding tablet formulations, are summarized in

Table 5. Static contact angle values (θ) for pure components and tablet formulations.

Surface System		Static Contact Angle (°)
Pure Active ingredient	Quercetin	103.2 ± 0.6
Pure Diluent	PPCS	51.9 ± 0.4
	SDLM	40.0 ± 0.4
	CDP	75.4 ± 0.6
	RWDP	90.30 ± 0.3
Tablet Formulations	Tablet Formulation 1 (QCT + PPCS)	67.3 ± 1.9
	Tablet Formulation 2 (QCT + SDLM)	72.5 ± 3.0
	Tablet Formulation 3 (QCT + CDP)	74.8 ± 2.4
	Tablet Formulation 4 (QCT + RWDP)	76.4. ± 8.9

.

According to the results shown in Table 5, quercetin exhibited a high contact angle (103.2 ± 0.6°), confirming its hydrophobic nature. This value closely matches that previously reported by Lu (2023) [64], who documented an angle of 102.65°. Among the diluents used as control excipients, SDLM and PPCS showed markedly lower angles (40.0 ± 0.4° and 51.9 ± 0.4°, respectively), indicative of strong hydrophilic behavior. These results correlate well with those reported by Jianxin Zhang et al. [65] who found contact angles between 24.6° and 29.5° for anhydrous lactose, and with the 42° angle reported by Odidi et al. for native starch. In contrast, CDP and RWDP presented intermediate wettability, with values of 75.4 ± 0.6° and 90.3 ± 0.3°, respectively, the latter approaching the hydrophobic threshold. These findings suggest that the pitaya peel powders, particularly RWDP, exhibit reduced affinity for water, likely due to their fibrous nature and surface morphology.

Regarding the tablet formulations, these correspond to quasi-binary mixing systems, prepared at a 1:0.95 (w/w) excipient/active ingredient ratio. Under such conditions, the measured contact angles may reflect the preferential localization of individual components at the tablet surface. In this context, Formulation 1 (QCT + PPCS) and Formulation 2 (QCT + SDLM) exhibited contact angles of 67.3 ± 1.9° and 72.5 ± 3.0°, respectively. These values approximate the arithmetic mean of the individual component angles, suggesting a relatively homogeneous surface distribution of both QCT and the corresponding diluent. In contrast, Formulations 3 and 4 (QCT + CDP and QCT + RWDP) showed contact angles of 74.8 ± 2.4° and 76.4 ± 8.9°, respectively, which deviate from the expected mean and instead align more closely with the pure diluent values. This behavior indicates that CDP and RWDP may preferentially migrate to the tablet surface, likely due to their coarser morphology and lower flowability. Notably, RWDP’s angle in the formulation (76.4 ± 8.9°) remained substantially lower than that of pure RWDP (90.3 ± 0.3°), suggesting partial masking by QCT. However, the high standard deviation observed in this system points to heterogeneity in surface distribution, possibly arising from uneven particle orientation or agglomeration during compaction.

These findings underscore that, despite homogeneous bulk mixing, surface wettability in multicomponent systems is modulated by the physical characteristics of the excipients, particularly those influencing particle rearrangement and exposure during compression. The observed trends may have implications for tablet disintegration and dissolution, especially in formulations where surface hydrophilicity governs initial wetting kinetics.

3.5. In Vitro Quercetin Release and Kinetic Modeling

Dissolution profiles of quercetin from the different tablet formulations, as well as their respective kinetic analysis based on classical and heuristic release models, are presented in Figure 3 and

Table 6. Kinetic parameters of classical and heuristic models fitted to the in vitro release profiles of quercetin from several tablet formulations F1–F4. Parameters include kinetic constants ($k$), exponents ($n,b$), and determination coefficients (R²), corresponding to zero-order, first-order, Higuchi, Hixson–Crowell, Korsmeyer–Peppas, Weibull, Logistic, Gompertz, and Modified Hill models. Only data fitted up to 60 min were considered. The best-fitting models (R² > 0.98) are highlighted as most representative of the release mechanism.

Model Type	Model Name/	Equation	P(s)	Tablet Formulation
				F1	F2	F3	F4
Classical	Zero-order	$Q_t=Q_0+k_0\cdot t$	$k_0$	1.61	1.61	1.57	1.53
			$R^2$	0.967	0.958	0.961	0.950
	First-order	$Q_t=Q_{\infty }\cdot \left(1-e^{-k_1\cdot t}\right)$	$k_1$	0.054	0.060	0.056	0.052
			$R^2$	0.985	0.990	0.983	0.972
	Higuchi	$Q_t=k_H\cdot \sqrt{t}$	$k_H$	12.48	12.17	11.99	11.62
			$R^2$	0.973	0.964	0.968	0.956
	Hixson–Crowell	$Q_0^{1/3}-{\left(Q_0-Q_t\right)}^{1/3}=k_{HC}\cdot t$	$k_{HC}$	−0.023	−0.024	−0.025	−0.027
			$R^2$	0.957	0.953	0.960	0.946
	Korsmeyer–Peppas	${\displaystyle \frac{Q_t}{Q_{\infty }}}=k_{KP}\cdot t^n$	$k_{KP}$	1.13/	1.21	1.18	1.09
			n	0.91	0.89	0.88	0.86
			$R^2$	0.990	0.986	0.984	0.975
Heuristic	Weibull	$Q_t=Q_{\infty }\cdot \left(1-e^{-{\left(t/a\right)}^b}\right)$	a	22.6	21.9	23.2	24.8
			b	1.72	1.70	1.65	1.59
			$R^2$	0.996	0.995	0.994	0.991
	Logistic	$Q_t={\displaystyle \frac{Q_{\infty }}{1+e^{-k\left(t-t_{50}\right)}}}$	$k$	0.16	0.18	0.17	0.15
			$t_{50}$	27.5	26.8	28.2	29.4
			$R^2$	0.993	0.994	0.992	0.989
	Gompertz	$Q_t=A\cdot \mathit{exp}\left[-e^{-k\left(t-t_{50}\right)}\right]$	$k$	1.22	1.29	1.21	1.14
			$t_{50}$	25.1	24.4	25.9	26.9
			A	11.8	11.2	12.1	12.6
			$R^2$	0.992	0.993	0.990	0.987
	Modified Hill	$Q_t=Q_{\infty }\cdot {\displaystyle \frac{t^n}{k^n+t^n}}$	n	3.42	3.58	3.39	3.11
			k	21.1	20.5	22.0	23.4
			$R^2$	0.994	0.993	0.992	0.988

P(s): parameters obtained from each release kinetic equation, $Q_t$: cumulative amount of quercetin released at time t, $Q_0$: initial amount of drug in the system (if applicable), $Q_{\mathrm{\infty }}$: maximum theoretical amount of drug that can be released, $k_0$: zero-order release rate constant (units: mass/time), $k_1$: first-order release rate constant (units: time⁻¹), $k_H$: Higuchi constant related to diffusion (units: $mass/{time}^{½}$), $k_{HC}$: Hixson–Crowell rate constant (units: $mas{s}^{⅓}/time$), $k_{KP}$: kinetic constant in the Korsmeyer–Peppas model, n: release exponent indicating release mechanism (diffusion, erosion, etc.), a: scale parameter in the Weibull model (units: time), b: shape parameter in the Weibull model (dimensionless), k: release rate constant in logistic, Gompertz, and modified Hill models, $t_{50}$: time to reach 50% drug release (inflection point in sigmoidal curves), A: amplitude of the release curve (maximum asymptotic value in Gompertz), $R^2$: coefficient of determination (goodness of fit), t: dissolution time (e.g., in minutes or hours, depending on context).

, respectively. According to Figure 3, the release profiles for the different tablet formulations exhibited typical characteristics of immediate-release systems manufactured by direct compression, complying with the criteria established by the United States Pharmacopeia (USP), which requires that no less than 80% of the active ingredient be released within 30 min for solid oral immediate-release dosage forms [50,66]. In this case, although complete quercetin release was reached at 60 min, the rapid disintegration observed in all formulations (≤4:33 min), together with dissolution efficiency (DE%) values exceeding 65%, supports their functional classification as immediate-release systems. In comparative terms, conventional formulations F1 (QCT + PPCS) and F2 (QCT + SDLM) exhibited a slightly faster release in the first 30 min. However, the pitaya-based formulations—F3 (QCT + CDP) and F4 (QCT + RWDP)—presented similar profiles toward the end of the test, with DE% values of 68.9% and 65.3%, respectively.

With respect to physical–technical properties, both pitaya matrices showed tablet hardness above 11 kp, acceptable friability (<1%), and efficient disintegration, thus confirming their viability as functional excipients. Despite presenting slightly more hydrophobic surfaces, which was evidenced by contact angles above 74°, their porous structure, swelling capacity, and retention of bioactive compounds appeared to facilitate quercetin release. This behavior also agrees with the results reported by Chakraborty et al. (2022) [63], where it was described to have disintegration times of 126–187 s and complete quercetin release at 60 min in tablets prepared with conventional excipients that are comparable with those employed in this study. Taken together, these results confirm that CDP and RWDP can act as effective material in immediate-release formulations, positioning pitaya peel powders as sustainable nutraceutical excipients with a favorable combination of techno-functional properties, polyphenol compatibility, and direct compression suitability.

Moreover, to elucidate the mechanisms involved in quercetin release from the tablet formulations, a comprehensive set of classical and heuristic kinetic models was applied. Classical models—including zero-order, first-order, Higuchi, Hixson–Crowell, and Korsmeyer–Peppas—are grounded in physical assumptions and provide mechanistic insights into active nutraceutical ingredient transport through solid matrices [67]. The zero-order model describes a constant release rate independent of active nutraceutical ingredient concentration, with the rate constant ($k_0$) ($\%/min$) indicating uniform exposure over time. The first-order model introduces ($k_1$) ($1/min$), reflecting a concentration-dependent release, often observed in dissolution-controlled systems. The Higuchi model, based on Fickian diffusion, relates cumulative release to the square root of time via ($k_H$) $(\%/{min}^{0.5}$), and is suitable for porous matrices. The Hixson–Crowell model accounts for changes in surface area and geometry during erosion, with ($k_{HC}$) representing the rate of dimensional reduction. The Korsmeyer–Peppas model, semi-empirical in nature, provides two key parameters: ($k_{KP}$), a system-dependent rate constant, and the diffusional exponent (n), which classifies the release mechanism—ranging from Fickian diffusion ($n\le 0.45$) to anomalous transport ($0.45<n<0.89$), and case II relaxation ($n\approx 0.89$) in cylindrical systems [68]. To complement these, heuristic models such as Weibull, Logistic, Gompertz, and Modified Hill were employed to describe complex, non-linear, or sigmoidal release behaviors. The Weibull model includes a scale parameter ($a$), indicating the time to reach ~63.2% release, and a shape parameter (b), which defines the curve profile: ($b<1$) suggests a parabolic curve with initial lag, ($b=1$) corresponds to exponential (first-order) release, and ($b>1$) indicates sigmoidal behavior with an acceleration phase [69]. Logistic and Gompertz models describe S-shaped curves with parameters such as ($t_{50}$) (time to 50% release) and ($k$) (steepness), capturing inflection dynamics. The Modified Hill model, adapted from receptor–ligand kinetics, introduces a cooperativity exponent ($n$) and a half-saturation constant ($K$), which together describe the sharpness and midpoint of the release transition. These models are particularly useful for systems involving swelling, erosion, or structural rearrangement, as often observed in matrices containing natural fibers or bioactive excipients. Collectively, this modeling framework enables both descriptive accuracy and mechanistic interpretation, allowing for a robust comparison between conventional excipients and pitaya peel-based systems in terms of their release performance and matrix functionality.

In accordance with the results presented in Table 6, the kinetic behavior of quercetin release from tablet formulations F1–F4 revealed consistent and predictable patterns that were strongly influenced by the nature of the excipient matrix. Formulations F1 and F2, composed of conventional excipients (partially pregelatinized corn starch and spray-dried lactose monohydrate, respectively), showed excellent fits to the first-order (R² = 0.985–0.990) and Korsmeyer–Peppas models (R² = 0.986–0.990; n = 0.89–0.91), indicating a concentration-dependent release mediated by a combination of Fickian diffusion and case II transport. This hybrid mechanism correlates well with their rapid disintegration times and favorable wettability (contact angles < 73°), which facilitated water ingress and matrix relaxation. These results agree closely with Chakraborty et al. (2022) [63], where $n$ values approximating 0.89 were also associated with complete quercetin release in 60 min. In contrast, Formulations F3 and F4, incorporating pitaya peel powders (CDP and RWDP), displayed profiles best described by heuristic models—particularly Weibull (R² > 0.99)—with $b$ values (1.59–1.65) indicating sigmoidal release behavior typical of structurally reorganizing matrices. These kinetics correspond with their high fiber content (≥63.4%), moderate solubility, delayed wetting times, and cohesive yet porous morphology. The Peppas n values (0.86–0.88) in these formulations further confirmed an anomalous transport mechanism. Despite higher hydrophobicity (contact angles ~75°), CDP and RWDP matrices supported effective release kinetics, paralleling findings from Aziz et al. (2018) [70], which reported similar hydration-induced matrix reconfigurations in plant-based excipients. Overall, the kinetic evidence reinforces the hypothesis that quercetin release is primarily governed by matrix-driven mechanisms rather than solubility limitations inherent to its BCS Class II classification. The strong correlation with Weibull and Hill-type models, combined with the formulations’ favorable physical performance and compositional functionality, validates the use of CDP and RWDP as relevant sustainable nutraceutical excipients. These findings support the broader formulation strategy of leveraging structurally active plant-based materials for immediate-release systems, providing a robust foundation for the conclusions presented below.

4. Conclusions

Regarding material characteristics, the powder obtained by convective drying (CDP) showed a higher proportion of fine particles, while the powder obtained by refraction window drying (RWDP) possibly retained more organic acids and ash content, demonstrating that the drying method significantly affected bioactive retention, antioxidant capacity, and color attributes. In relation to colorimetric shifts (higher a* and b* values), these further confirmed RWDP’s protective effect on pigment retention and bioactivity. Concerning the physical and functional properties of the powders, both matrices exhibited moderate cohesiveness and acceptable flowability; however, RWDP presented a lower angle of repose, greater solubility (12%), and faster immersion onset, supporting its suitability for direct compression. In contrast, CDP yielded more fines and lower water activity, improving potential storage stability. In terms of tablet formulation and characterization, pitaya peel powders enabled the production of tablets with adequate hardness (>11 kp), low friability (<1%), and disintegration times under 4:33 min. RWDP-based tablets showed the best balance between mechanical performance and disintegration, despite exhibiting higher contact angles (>75°). Regarding in vitro quercetin release and kinetic modeling, all formulations achieved complete release within 60 min, meeting USP criteria for immediate-release systems. Quercetin release profiles of CDP- and RWDP-based tablets were best described by Weibull and Modified Hill models (R² > 0.99), and Peppas exponents (n = 0.86–0.88) indicated anomalous, matrix-regulated transport. Thus, this study confirms the feasibility of using pitaya peel powders derived from distinct drying technologies for their role as multifunctional excipients in pharmaceutical and nutraceutical tablet formulations. The materials combined suitable physical–mechanical behavior with a porous and bioactive matrix capable of supporting the immediate release of a poorly soluble nutraceutical active ingredient such as quercetin. These findings support their use in circular nutraceutical systems, integrating sustainability with reliable excipient performance in plant-based oral dosage forms.

Nonetheless, it is important to highlight some limitations of this work that warrant further study. For instance, it is important to establish whether there are significant differences in the content of secondary metabolites, as well as fiber, between different cultivation and harvesting conditions of pitaya. Likewise, it is necessary to explore more about different drying methods and conditions to achieve the best optimization of the drying process. In relation to the behavior of the powders under accelerated stability conditions, this should also be evaluated, as well as its compatibility with the excipients evaluated and others considered for new formulations. In addition, further studies should be conducted to optimize both the formulation and development of nutraceuticals in a quality by design (QbyD) context. Additionally, in vivo bioavailability and gastrointestinal performance of the quercetin–fiber matrix system should be assessed to validate translational applicability in real-world nutraceutical products. Finally, although pitaya peel has been widely used in food applications, formal safety and regulatory data regarding its use as a pharmaceutical excipient remain unavailable. Therefore, regulatory and toxicological evaluations—via GRAS classification or formal safety studies under ICH and WHO guidelines—should be considered in future research to enable translational application.