Sustainable Pharmaceutical Development Utilizing Vigna mungo Polymer Microbeads ^†

Abstract

This study explores the potential of Vigna mungo gum as a sustainable and innovative natural polymer for developing microbeads for the controlled delivery of vildagliptin, a widely used antidiabetic agent. Unlike conventional natural polymers, Vigna mungo gum offers unique biocompatibility, biodegradability, and an eco-friendly production process, distinguishing it as a superior candidate for drug delivery systems. Microbeads were prepared by combining Vigna mungo gum with sodium alginate and inducing gelation using calcium carbonate. Scanning electron microscopy (SEM) revealed a rough, porous microbead surface, advantageous for drug encapsulation and controlled release. Drug release studies demonstrated sustained release kinetics, highlighting the effectiveness of this formulation. These findings underscore the novelty of Vigna mungo gum as a promising platform for antidiabetic drug delivery, providing a sustainable alternative to existing polymer systems.

1. Introduction

Diabetes mellitus represents a global health crisis, with its prevalence escalating at an alarming rate. It is a metabolic disorder characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. This condition is associated with severe long-term complications such as retinopathy, nephropathy, neuropathy, cardiovascular diseases, and lower-limb amputations. Despite the availability of various antidiabetic medications, achieving optimal glycemic control remains a challenge. The limitations of current therapies, including poor bioavailability, frequent dosing requirements, and systemic side effects, emphasize the urgent need for innovative drug delivery systems that can improve therapeutic efficacy, enhance patient compliance, and minimize adverse effects [1].

The application of natural polymers in drug delivery has gained considerable interest due to their inherent advantages such as biocompatibility, biodegradability, and ease of chemical modification. These materials are particularly suited for designing controlled drug delivery systems, as they offer versatility in formulation and the ability to tailor drug release profiles. Among the various natural polymers, Vigna mungo gum, derived from the seeds of the black gram plant, has shown great potential as a novel biomaterial in pharmaceutical formulations. Its high swelling capacity, gel-forming ability, and cost-effectiveness make it a promising candidate for sustained drug release applications [2].

In recent years, the development of microbeads has emerged as an effective strategy for controlled drug delivery. Microbeads are spherical particles with diameters in the micrometer range, capable of encapsulating drugs within a polymer matrix. These systems offer significant advantages, including prolonged drug release, improved stability, and reduced dosing frequency, making them ideal for managing chronic conditions like diabetes. Leveraging the unique properties of Vigna mungo gum, this study explores its application in developing microbeads for the controlled delivery of vildagliptin, a widely prescribed dipeptidyl peptidase-4 (DPP-4) inhibitor [3,4,5,6].

The ionotropic gelation method was employed to prepare the microbeads, utilizing Vigna mungo gum and sodium alginate as primary polymers. Calcium carbonate was used as a crosslinking agent to ensure the structural integrity of the microbeads. The study involved a comprehensive characterization of the formulated microbeads, including surface morphology analysis via scanning electron microscopy (SEM) and compatibility studies using Fourier-transform infrared spectroscopy (FTIR). Key performance metrics such as drug loading efficiency, floating lag time, buoyancy duration, and in vitro release kinetics were also evaluated under the simulated physiological conditions [7,8,9].

The findings demonstrated that Vigna mungo-based microbeads possess excellent buoyancy properties, with immediate floating capabilities and sustained drug release over 24 h. The SEM analysis revealed a porous surface morphology, which contributes to the prolonged release and enhanced buoyancy of the microbeads. The FTIR studies confirmed the stability of the drug within the polymer matrix, and the drug release studies showed controlled and predictable release patterns [10,11,12].

Diabetes mellitus continues to pose a significant global health challenge, with its prevalence rising at an alarming rate. According to the International Diabetes Federation (IDF), an estimated 537 million adults were living with diabetes in 2021, and this number is projected to reach 783 million by 2045 if current trends persist. The condition is responsible for approximately 6.7 million deaths annually and incurs substantial economic burdens, with global health expenditures related to diabetes reaching over USD 966 billion in 2021. The rapid increase in diabetes prevalence is driven by factors such as sedentary lifestyles, unhealthy diets, obesity, and aging populations. In low- and middle-income countries, where healthcare resources are often limited, the impact of diabetes is particularly severe, leading to increased morbidity and mortality rates. These alarming trends underscore the critical need for more effective therapeutic strategies to manage diabetes and prevent its complications.

Despite the availability of numerous antidiabetic medications, including insulin and oral hypoglycemic agents, achieving optimal glycemic control remains challenging. Poor bioavailability, frequent dosing requirements, and systemic side effects often hinder patient adherence and long-term efficacy. Current therapeutic approaches primarily focus on managing blood glucose levels rather than addressing the underlying causes of the disease, leading to a cycle of disease progression and complications such as retinopathy, nephropathy, neuropathy, and cardiovascular diseases. The need for innovative drug delivery systems that can enhance therapeutic efficacy, improve patient compliance, and reduce adverse effects is more urgent than ever. Controlled drug delivery systems, particularly those utilizing natural polymers, offer a promising solution by providing sustained drug release, minimizing side effects, and enhancing patient adherence to treatment regimens.

This study underscores the potential of Vigna mungo gum as an innovative and sustainable polymer for developing advanced drug delivery systems. By addressing critical challenges in diabetes therapy, this research contributes to the development of eco-friendly and effective therapeutic solutions. The use of natural polymers like Vigna mungo not only advances pharmaceutical technology but also aligns with the global emphasis on sustainability and green chemistry. The outcomes of this study hold promise for expanding the application of natural polymers in tackling other chronic conditions, offering a pathway for future research and innovation in drug delivery science.

2. Materials and Methods

2.1. Materials

Vigna mungo gum was extracted from black gram seeds procured locally. Sodium alginate (analytical grade) and calcium carbonate were obtained from HiMedia Laboratories (Mumbai, India). Vildagliptin was sourced from a certified pharmaceutical supplier. All chemicals and reagents used in this study were of analytical grade and used as received without further purification. Deionized water was used throughout the experiments.

Despite the promising potential of Vigna mungo gum in controlled drug delivery applications, there are certain limitations and challenges that need to be addressed. One of the key challenges is the variability in the quality and composition of the gum, which can affect the reproducibility and consistency of the microbead formulations. Additionally, the swelling behavior of Vigna mungo gum may be influenced by factors such as pH and ionic strength, which could lead to variability in drug release profiles. The gelation process also requires careful optimization to prevent over- or under-crosslinking, which may impact the structural integrity of the microbeads. Furthermore, while Vigna mungo gum offers cost-effectiveness, sourcing and large-scale production could face challenges related to availability and standardization. These factors should be considered when designing and scaling up formulations using Vigna mungo gum for drug delivery applications.

2.2. Preparation of Vigna mungo Gum Microbeads

The microbeads were prepared using the ionotropic gelation method. The steps involved are as follows:

• Preparation of polymer solutions: A measured quantity of Vigna mungo gum was dispersed in 100 mL of deionized water and soaked for 20 min. The mixture was stirred continuously for 40 min using a mechanical stirrer (IKA T25 digital ULTRA-TURRAX^®, Staufen, Germany) at 500 rpm to ensure complete dissolution. Microbead formulations were prepared by varying the mechanical stirrer speed at 200, 400, 600, and 800 rpm for a fixed stirring time of 40 min for optimization. Simultaneously, sodium alginate was dissolved in 1000 mL of deionized water to form a 2% (w/v) solution. The gum solution was then mixed with the sodium alginate solution and stirred for an additional 5 min to obtain a homogenous polymer blend [13,14,15,16,17,18,19,20,21,22].
• Drug dispersion: Accurately weighed vildagliptin was dispersed into the polymer blend with constant stirring for 15 min at 300 rpm to form a stable drug–polymer dispersion.
• Crosslinking and bead formation: Calcium carbonate was added to the prepared dispersion to initiate crosslinking. The resulting mixture was immediately extruded dropwise into 1% (w/v) calcium chloride solution using a syringe with a 22G needle. The beads were allowed to harden for 30 min under gentle stirring.
• Washing and drying: The formed microbeads were collected by filtration, washed three times with deionized water to remove excess calcium ions, and air-dried at room temperature for 24 h.

A formulation with only sodium alginate and a crosslinking agent, without the addition of Vigna mungo gum was also prepared in order to assess the role of the gum in the formation of microbeads, their size, morphology, drug loading, and release characteristics. A formulation without the drug was prepared to evaluate the structural and release properties of the microbeads in the absence of the active ingredient which helps to isolate the effects of the polymer blend and crosslinking agent on the overall performance of the microbeads.

2.3. Characterization of Microbeads

• Morphological analysis: The surface morphology of the microbeads was analyzed using scanning electron microscopy (SEM) (ZEISS EVO 18, Oberkochen, Germany). Samples were sputter-coated with gold before imaging [23,24,25].
• Fourier-transform infrared (FTIR) spectroscopy: FTIR analysis was performed using a Shimadzu FTIR-8400S spectrophotometer (Kyoto, Japan) to assess the compatibility between vildagliptin and the polymer matrix.
• Drug loading and encapsulation efficiency: The amount of vildagliptin encapsulated was determined by dissolving the microbeads in phosphate buffer (pH 7.4) and measuring the absorbance using a UV–visible spectrophotometer (Shimadzu UV-1800). Drug loading and encapsulation efficiency were calculated using the standard formulas.
• Buoyancy studies: The floating ability of the microbeads was evaluated in 0.1N HCl (pH 1.2) at 37 ± 0.5 °C. Floating lag time and duration were recorded.
• In vitro drug release: Drug release studies were conducted in a USP Type II dissolution apparatus (Electrolab, India) using 0.1N HCl (pH 1.2) as the dissolution medium at 37 ± 0.5 °C and 50 rpm. Samples were collected at predetermined intervals and analyzed spectrophotometrically.
• Statistical analysis: All experiments were performed in triplicate, and data were presented as the mean ± standard deviation (SD). Statistical analysis was performed using GraphPad Prism version 9.0 [26,27,28,29,30,31,32,33,34,35,36,37].

The formulations (F1 to F8) with varying concentrations of Vigna mungo gum, while keeping other parameters like drug amount, sodium alginate, calcium chloride solution, and calcium carbonate constant, are presented in

Table 1. Formulations with varying concentrations of Vingo mungo gum.

Formulation Code	Drug Amount (mg)	Sodium Alginate (%)	Vigna mungo Gum (%)	Calcium Chloride Solution (%)	Calcium Carbonate (%)
F1	100	1.00	0.50	5.00	0.75
F2	100	1.00	1.00	5.00	0.75
F3	100	1.00	1.50	5.00	0.75
F4	100	1.00	2.00	5.00	0.75
F5	100	1.00	0.50	5.00	0.75
F6	100	1.00	1.00	5.00	0.75
F7	100	1.00	1.50	5.00	0.75
F8	100	1.00	2.00	5.00	0.75

.

3. Results and Discussion

3.1. Design and Evaluation of Vildagliptin Floating Microspheres Using Vigna mungo Polymer

The physicochemical characteristics of vildagliptin were evaluated to ensure its suitability for incorporation into the floating microspheres (

Table 2. Physicochemical characteristics of vildagliptin.

Parameter	Observation
State	Solid
Color	White
Solubility	Soluble in ethanol, DMSO, and dimethyl formamide (DMF)
Melting Point	150 °C

). Vildagliptin is a white solid compound with notable physicochemical properties. It exhibits solubility in organic solvents such as ethanol, dimethyl sulfoxide (DMSO), and dimethyl formamide (DMF). The substance has a melting point of 150 °C, indicating its thermal stability up to this temperature. These properties are characteristic of its suitability for pharmaceutical formulation and handling

3.2. λ-Max Determination of Vildagliptin

The maximum absorbance (λ-max) of vildagliptin in pH 1.2 acidic buffer was determined spectrophotometrically and used for subsequent calibration curve studies. Figure 1 illustrates the λ-max.

3.3. Differential Scanning Calorimetry of Vildagliptin

The differential scanning calorimetry (DSC) analysis of vildagliptin revealed a sharp endothermic peak at 154.24 °C, indicating the drug’s crystalline nature and thermal stability. This analysis also confirmed the absence of significant impurities or degradation (Figure 2).

3.4. Standard Calibration Curve of Vildagliptin in 0.1N HCl

A calibration curve was constructed by measuring the absorbance of vildagliptin in pH 1.2 acid buffer at different concentrations (

Table 3. Calibration curve values of vildagliptin in pH 1.2 acid buffer.

Concentration (µg/mL)	Absorbance
0	0.000
10	0.516
12	0.614
14	0.720
16	0.810
18	0.910
20	0.990

and Figure 3).

The linear regression equation was determined, with a regression coefficient (R²) of 0.999, confirming the method’s reliability.

3.5. Characterization of Vigna mungo Polymer

3.5.1. Physicochemical Parameters

The Vigna mungo polymer was evaluated for its organoleptic properties to ensure its suitability for pharmaceutical formulations, as detailed in

Table 4. Organoleptic properties of the Vigna mungo polymer.

Physical Parameter	Observation
Color	Off-white/pale white
Odor	Odorless
Texture	Smooth

, and the results confirm that Vigna mungo gum possesses favorable physical characteristics for use in drug delivery systems (Table 4 and

Table 5. Physicochemical parameters of the Vigna mungo polymer.

Physical Parameter	Polymer Obtained Using Acetone (1:2—Slurry:Acetone)
Color	Pale white/white
Solubility	Soluble in hot water; insoluble in chloroform, ethanol, methanol, and ethyl acetate
% Yield	41 ± 0.02
pH	5 ± 0.12
% Swelling Index	150 ± 0.52
% Moisture Content	16.48 ± 0.11
Bulk Density	0.8 ± 0.214
Tapped Density	0.9 ± 0.22
% Carr’s Index	12.5 ± 0.587
Hausner’s Ratio	1.125 ± 0.15
Angle of Repose (°)	24.14 ± 4.94
Particle Size (µm)	140 ± 2.41

). The critical physicochemical parameters of the Vigna mungo polymer showcase its potential as an excipient in pharmaceutical applications. The polymer’s swelling index, pH, particle size, and flow properties make it suitable for controlled drug delivery systems.

The X-ray diffraction profiles calculated for the Vigna mungo polymer are shown in Figure 4. The X-ray profiles display peaks at two pinpoints at 2θ = 15.106°, 17.177°, 28.481°, 40.259°, 41.425°, and 44.157° for the Vigna mungo polymer samples. Both data sets were sharp and indicate crystalline materials, as seen in the diffractogram. Broad angles of XRD design have been used to measure the crystalline values. A strong crystallinity amount was discovered at 26.4 per cent.

3.5.2. DSC Analysis

DSC is used to measure the heat loss or heat gain as a function of the temperature. The physical and chemical changes in the sample can be measured. The findings of the DSC mucilage study revealed that the temperature of the glass transition was 277.01 °C. The major intense peak, recorded in the DSC thermograms, is an exothermic transition followed by (a) weaker exotherm(s), exhibiting two exothermic peaks at 185.14 and 459.16 °C (Figure 5).

Phytochemical screening revealed the presence of sugars and reducing sugars (Molisch’s, Fehling’s, and Benedict’s tests), but the absence of steroids, alkaloids, tannins, flavonoids, and glycosides in the Vigna mungo polymer (

Table 6. Phytochemical screening of the Vigna mungo polymer.

Test	Procedure	Inference
Salkowski Reaction	Add 2 mL of chloroform and 2 mL of concentrated sulphuric acid to the test sample; shake. Red color in chloroform layer indicates sterols.	No red color, absence of sterols
Liebermann’s Test	Add acetic anhydride and heat; cool and add concentrated sulfuric acid. Blue color indicates sterols.	No blue color, absence of sterols
Liebermann-Burchard’s Reaction	Add acetic anhydride and sulfuric acid to aqueous dispersion of gum. Color change from red to blue indicates sterols.	No color change, absence of sterols
Mayer’s Test	Add Mayer’s reagent to the sample. Yellow color indicates alkaloids.	No yellow color, absence of alkaloids
Wagner’s Test	Add Wagner’s reagent. Brown or reddish precipitate indicates alkaloids.	No reddish precipitate, absence of alkaloids
Dragendroff’s Test	Add Dragendroff’s reagent. Red precipitate indicates alkaloids.	No red precipitate, absence of alkaloids
Hager’s Test	Add Hager’s reagent. Yellow precipitate indicates alkaloids.	No yellow color, absence of alkaloids
Ferric Chloride Test	Add 5% ferric chloride solution to sample; dark green or blue color indicates tannins.	No dark color, absence of tannins
Lead Acetate Test	Add 10% lead acetate solution. Precipitate formation indicates tannins.	No precipitate, absence of tannins
Potassium Dichromate Test	Add potassium dichromate; dark color formation indicates tannins.	No dark color, absence of tannins
Gelatin Solution Test	Add 1% gelatin solution with 10% sodium chloride. White precipitate indicates tannins.	No precipitate, absence of tannins
Bromine Water Test	Add bromine solution; decolorization indicates tannins.	No discoloration, absence of tannins
Shinoda Test	Dissolve the sample in ethanol; add HCl and magnesium. Pink/crimson color indicates flavonoids.	No color change, absence of flavonoids
Alkaline Reagent Test	Add sodium hydroxide; intense yellow color indicates flavonoids.	No yellow color, absence of flavonoids
Lead Acetate Test	Add lead acetate solution; yellow precipitate indicates flavonoids.	No yellow precipitate, absence of flavonoids
Ninhydrin Test	Add ninhydrin reagent and heat; blue color indicates amino acids.	No blue color, absence of amino acids
Xanthoproteic Test	Add concentrated nitric acid; yellow color indicates proteins.	No yellow color, absence of amino acids
Molisch’s Test	Add Molisch’s reagent and sulfuric acid. Red-brown ring indicates sugars.	Red-brown ring, sugars present
Fehling’s Test	Add Fehling’s solution and heat; red precipitate indicates reducing sugars.	Red precipitate, reducing sugars present
Benedict’s Test	Add Benedict’s reagent and heat; greenish yellow precipitate indicates reducing sugars.	Greenish yellow precipitate, reducing sugars present
Selwinoff’s Test	Add Selwinoff’s reagent and heat; cherry red color indicates sugars.	Cherry red color, sugars present
Glycosides Test	Add dilute HCl to the sample and perform glycoside test.	No indication of glycosides
Modified Borntrager’s Test	Add ferric chloride solution, heat, and extract with benzene. Rose-pink color indicates anthranol glycosides.	No rose-pink color, absence of glycosides
Legal’s Test	Add sodium nitroprusside and sodium hydroxide; pink to blood-red color indicates cardiac glycosides.	No pink to red color, absence of glycosides
Sudan III Test	Add Sudan III dye to the sample; pink droplets indicate lipids.	No pink droplets, absence of lipids
Biuret Test	Add cupric sulfate and sodium hydroxide; violet color indicates proteins.	No violet color, absence of proteins
Millon’s Test	Add Millon’s reagent; pink color indicates phenolic compounds.	No pink color, absence of phenolic compounds
Ruthenium Test	Place powder on a slide with glycerin and observe under a microscope.	Pink color, presence of certain bioactive compounds

). These findings highlight the suitability of the Vigna mungo polymer for specific pharmaceutical applications, such as in the formulation of floating microspheres, where non-interference with active pharmaceutical ingredients is crucial.

3.6. Acute Toxicity Studies of the Vigna mungo Polymer

The acute toxicity study of the Vigna mungo polymer was conducted by administering a single oral dose of 2000 mg/kg body weight to rats, with observations made over a 14-day period. The study assessed body weight changes and organ weight alterations to evaluate the polymer’s potential toxic effects.

3.6.1. Body Weight Observations

The rats in the control group showed a gradual increase in body weight over the study period. The average weight gain was 2.27% during the first week and 5.04% during the second week. In contrast, rats treated with 400 mg/kg of the Vigna mungo polymer experienced a higher weight gain, with 5.56% in the first week and 5.48% in the second week.

For the rats treated with 2000 mg/kg of the polymer, the weight gain was lower—2.18% in the first week and 4.64% in the second week. While the weight gain was slightly reduced compared to the control and 400 mg/kg groups, there were no significant signs of toxicity, indicating that the Vigna mungo polymer did not cause any major adverse effects at this dose.

3.6.2. Organ Weight Observations

The absolute organ weights of rats treated with 2000 mg/kg of the Vigna mungo polymer were similar to those of the control group after 14 days of treatment. No significant changes in the weights of vital organs—such as the heart, liver, brain, or kidneys—were observed in the test group compared to the control group. The mean organ weights for both groups were consistent, indicating that the polymer did not cause any acute toxicity or organ damage at the administered dose.

The findings from this acute toxicity study suggest that Vigna mungo polymer is relatively safe at a dose of 2000 mg/kg. There were no significant changes in body or organ weights, and no signs of acute toxicity were observed throughout the 14-day study period. These results support the safe use of the Vigna mungo polymer in future applications.

The acute toxicity study of the Vigna mungo polymer, administered orally at a dose of 2000 mg/kg, focused on evaluating the effects on body weight and hematological parameters in rats over a 14-day period. The body weight data indicated no significant changes, as both the control and test groups exhibited typical weight gain over the study duration. After 7 and 14 days, rats treated with the polymer showed normal weight gain, with values falling within the expected ranges. The body weight change, assessed through two-way ANOVA, showed no significant differences between the test and control groups, confirming that the polymer did not induce toxicity.

The organ weight analysis of the heart, liver, brain, and kidneys showed no significant differences between the control and treated groups, suggesting that the Vigna mungo polymer did not cause any organ toxicity at the administered dose. The findings were consistent with previous studies on phytochemicals and their impact on organ weight. The histopathological examination of these vital organs also revealed no toxic or necrotic changes in the test group. The microscopic evaluation showed no alterations in the cell structure or arrangement in the treated rats, further supporting the safety profile of the Vigna mungo polymer at 2000 mg/kg.

The hematological analysis of parameters such as hemoglobin, total RBC count, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and total WBC count showed no significant differences between the control and test groups. The values for all hematological parameters remained within normal ranges, indicating no adverse effects on blood composition. The statistical evaluation via two-way ANOVA also confirmed that there were no significant differences, with p-values < 0.0001, suggesting that the polymer had no detrimental effects on the blood parameters.

The results of this study align with findings from other studies on natural polysaccharides, such as Hibiscus esculentus mucilage and Lavandula stoechas aerial mucilage, which have demonstrated the safety of plant-derived polymers in animals. The acute toxicity study confirms that the Vigna mungo polymer, derived from Vigna mungo seeds, is safe for use in animals at doses up to 2000 mg/kg, showing no significant signs of toxicity or abnormal physiological changes. Therefore, the Vigna mungo polymer can be considered safe for further research and potential applications.

3.6.3. Drug–Excipient Compatibility Study: FTIR

The standard IR spectrum of vildagliptin was comparatively studied, with the spectrum of vildagliptin, sodium alginate Vigna mungo excipients. The spectrum of vildagliptin is portrayed by the presence of a carbonyl, group (c = 0) at 1651.67 cm⁻¹. The peak of the carbonyl group of vildagliptin—Vigna mungo gum, sodium alginate—was found to be at 1651.05 cm⁻¹. It was predicted that the peak of the carbonyl group of vildagliptin—Vigna mungo, sodium alginate—was similar to the peak of standard IR spectra of vildagliptin (Figure 6). The nitrile group (C-N) in the spectrum of vildagliptin was presented at 4744.48 cm⁻¹. The peak of the nitrile, group in vildagliptin—Vigna mungo, sodium alginate—was found at 4742.58 cm⁻¹ and it was observed that the peak of the nitrile group of vildagliptin—Vigna mungo, sodium alginate—was similar to the peak of vildagliptin.

Thus, from the above observations using FTIR spectroscopy, it was concluded that, for the mixtures of drug and their excipients like sodium alginate and Vigna mungo gum, their combination was shown to be the most, compatible with the vildagliptin spectrum, with no well-defined chemical interactions, as no new peaks where observed. Hence, this mixture, was selected for the formulation of the sustained release drug delivery system.

4. Discussion

The yield of the microspheres prepared using the Vigna mungo polymer varied across different formulations. Among them, formulation F4, prepared with 1% Vigna mungo polymer and 2% sodium alginate, achieved the highest yield of 92.67%. This indicates that the combination of the Vigna mungo polymer and sodium alginate was optimal for maximizing the yield of the microsphere (

Table 7. Percentage yield of microspheres prepared using Vigna mungo.

Formulations	% Yield
F1	78.2 ± 0.91
F2	80.3 ± 0.21
F3	91.42 ± 0.83
F4	92.67 ± 0.43
F5	80.42 ± 0.42
F6	83.21 ± 0.21
F7	83.73 ± 0.64
F8	91.5 ± 0.90

).

The particle size distribution of Vigna mungo microspheres showed a wide range of sizes, with the average particle size being 25.4 µm. The largest proportion of particles fell within the 21–25 µm range, which is generally favorable for controlled drug release (

Table 8. Particle size distribution of Vigna mungo microspheres.

Size Range (µm)	Mean (d)	No. of Particles (n)	(n × d)
10–15	11.5	12	148
16–20	18	9	162
21–25	22.5	44	765
26–40	27.5	22	605
41–45	42.8	6	196.8
46–40	47.7	4	150.8
41–45	44.6	4	140.8
46–50	46.6	5	244
51–55	54.4	4	159.9
56–60	57	2	114
Total		100	2541
Average Particle Size	25.4 µm

). The range in particle sizes suggests that the microspheres can be tailored for different release profiles by adjusting the formulation parameters.

The swelling index data revealed that Vigna mungo microspheres exhibit significant variation in water uptake. Formulation F8 demonstrated the highest swelling index (62%), which suggests a higher capacity for water absorption and potential for sustained release. Formulations F1 and F5 showed lower swelling indices, indicating reduced water absorption and likely slower drug release compared to the higher swelling formulations (

Table 9. Swelling index of Vigna mungo microbeads.

Formulations	Swelling Index (%)
F1	41.2
F2	54.0
F4	49.0
F4	64.0
F5	48.2
F6	52.1
F7	56.0
F8	62.0

).

The swelling index is directly influenced by the hydrophilic nature of the polymers used in the formulation. Vigna mungo gum is known for its high swelling capacity, which likely contributes to the higher swelling observed in formulations containing more gum. Formulations with a higher proportion of Vigna mungo gum (e.g., F4, F7, F8) tend to show higher swelling indexes, as this gum can absorb water more efficiently, leading to the greater expansion of the microbeads. Sodium alginate, while also hydrophilic, does not swell as extensively as Vigna mungo gum. Therefore, formulations with a higher percentage of sodium alginate may exhibit lower swelling, as seen in formulations like F1 and F2.

The safety profile of Vigna mungo gum is generally favorable, especially when compared to other widely used polysaccharides like guar gum and xanthan gum. Vigna mungo gum is biocompatible and non-toxic, with limited reports of gastrointestinal discomfort or allergic reactions, making it suitable for pharmaceutical and food applications. While guar gum is also biocompatible, it can cause gastrointestinal issues such as bloating or diarrhea, particularly at high doses, and it may trigger allergic reactions in individuals sensitive to legumes. Xanthan gum, derived from bacterial fermentation, is considered to have a low allergenic potential and is typically well tolerated, though some individuals may experience mild gastrointestinal disturbances when consumed in large quantities. Compared to these two, Vigna mungo gum appears to have a more favorable safety profile, though it is less studied in long-term applications, particularly in human clinical trials. In general, all three gums are regarded as safe, with guar gum and xanthan gum having more extensive regulatory approval, while Vigna mungo gum may require more specific clearance depending on its intended use. Overall, the formulations of Vigna mungo microspheres exhibit favorable characteristics for controlled drug delivery, with high yields, appropriate particle size distributions, and varying swelling behaviors based on the formulation. The F4 formulation showed the best performance in terms of yield, while F8 demonstrated the best swelling index, making it a promising candidate for sustained release applications.

All the formulations of Vigna mungo microbeads exhibited excellent floating behavior, with no lag time in the floating process. The beads floated immediately and maintained buoyancy for more than 24 h, indicating the potential of these formulations for sustained drug delivery. The buoyancy of the microbeads is attributed to the equilibrium between swelling and water absorption, which plays a key role in ensuring flotation. The floating system incorporated calcium bicarbonate as a gas-forming ingredient. Upon interaction with hydrochloric acid in the stomach, calcium bicarbonate generates carbon dioxide, which is trapped inside the beads, ensuring their buoyancy. This approach is critical for achieving prolonged gastric retention time, which enhances the therapeutic efficacy of the drug over an extended period (

Table 10. Floating time of Vigna mungo microbeads.

Formulations	Floating Time (h)
F1	26
F2	25
F4	25
F4	24
F5	25
F6	25
F7	24
F8	24

).

The in vitro drug release studies demonstrated that the Vigna mungo microspheres could effectively control the drug release profile. One of the phenomena observed during the release was ‘burst release’, where a significant initial amount of the drug is released rapidly when the microspheres are placed in the release medium. This burst release is a common feature in controlled release formulations and can be a challenge, especially if it leads to toxic drug levels. The challenge in drug release studies is to manage this burst release and gradually achieve a safe and controlled release profile. By adjusting factors such as polymeric system composition and particle size, the burst release can be minimized, ensuring that the drug is released at a steady, controlled rate.

For the formulation of vildagliptin, a DPP-4 inhibitor used in the treatment of Type 2 diabetes, the burst release could potentially lead to high initial concentrations of the drug, which may reach toxic levels. However, by designing microspheres with an appropriate polymer blend and size, this burst effect can be mitigated, allowing for a controlled release and avoiding peak drug concentrations above therapeutic levels. The equilibrium between the initial burst and the controlled release is vital to achieve the desired therapeutic effect without causing any adverse reactions.

These findings suggest that Vigna mungo microspheres have promising potential in the formulation of sustained release drug delivery systems, with effective control over both the floating behavior and drug release profiles.

In the in vitro drug release study, the release profile of the microbeads was observed to depend significantly on the polymer ratio, specifically the combination of Vigna mungo and sodium alginate. The formulations with higher concentrations of Vigna mungo and sodium alginate exhibited a reduced drug release in the first hour, indicating a sustained release pattern. This is crucial for controlled drug delivery systems, as burst release is typically undesirable in formulations intended to provide prolonged drug release over 24 h.

The formulations F5 (1:0.5) and F6 (1:1) showed higher drug release in the initial hours, with F6 reaching around 94% cumulative release at 24 h. In contrast, formulations with higher polymer ratios, such as F7 (1:1.5) and F8 (1:2), showed more controlled release with a lesser initial burst and a steadier release pattern (

Table 11. In vitro drug release studies of microbeads prepared with calcium chloride.

Time (h)	1:0.5 (F5)	1:1 (F6)	1:1.5 (F7)	1:2 (F8)
1	4.78 ± 2.47	41.47 ± 0.84	10.98 ± 2.74	12.66 ± 2.48
2	9.56 ± 0.47	64.41 ± 1.48	20.90 ± 0.56	18.48 ± 0.46
4	18.56 ± 0.47	78.94 ± 2.84	44.28 ± 0.64	29.91 ± 2.74
6	28.79 ± 1.29	80.44 ± 0.46	42.44 ± 2.47	46.46 ± 0.94
8	47.56 ± 0.84	94.42 ± 4.67	50.64 ± 0.46	48.44 ± 1.27
10	46.67 ± 2.84	94.42 ± 0.27	55.84 ± 0.56	41.61 ± 2.48
12	59.76 ± 0.94	94.67 ± 2.47	64.78 ± 1.27	45.80 ± 2.84
24	90.67 ± 1.98	94.74 ± 0.94	94.08 ± 0.47	92.12 ± 0.74

). These findings suggest that formulations with higher polymer content lead to slower drug release, providing a more consistent therapeutic effect without the risk of toxic peaks in drug concentration.

The drug release rate is influenced by the swelling behavior of the microbeads. As the microbeads swell, they create a larger surface area that can facilitate drug release. In formulations with higher swelling indices (e.g., F4, F7, F8), there is likely a faster drug release in the initial hours, as the microbeads expand and release the drug more rapidly. Formulations with a lower swelling index (e.g., F1, F2) may show slower drug release due to less swelling, which limits the diffusion of the drug from the bead. This is consistent with the lower initial release rates observed for formulations like F5 and F6 compared to those with higher swelling indexes.

The mechanism of drug release is influenced by the crosslinking behavior of barium chloride and calcium chloride. These crosslinks reduce the porosity of the polymer matrix, slowing drug diffusion and extending the release time. In simulated gastric fluid (HCl buffer), calcium and barium ions are exchanged for H⁺ ions, leading to the swelling and diffusion of the drug through the polymer matrix.

The observed results support the development of Vigna mungo microspheres as a promising system for sustained release drug delivery, particularly for antidiabetic therapies like vildagliptin. This system can reduce the frequency of drug administration, offering improved patient compliance, and minimizing the risks associated with high concentrations of drugs due to burst release. The polymeric matrix’s swelling behavior and crosslinking contribute to a controlled release, ensuring the drug is delivered over an extended period, making it an effective strategy for chronic conditions like Type 2 diabetes.

The data for the in vitro drug release study were expressed as the mean ± standard deviation (SD) for each formulation at various time points. The percentage cumulative drug release was calculated for each formulation (F5, F6, F7, and F8) at 1, 2, 4, 6, 8, 10, 12, and 24 h.

To analyze the differences in drug release between the different formulations over time, one-way analysis of variance (ANOVA) was conducted. The ANOVA test was chosen because it allows for the comparison of multiple groups (formulations) to determine if there are statistically significant differences in the drug release profiles. At 1 h, the percentage cumulative drug release showed a significant difference (p < 0.05) between F5, F6, F7, and F8. F6 (1:1) exhibited the highest drug release (41.47 ± 0.84%), while F5 (1:0.5) demonstrated the lowest drug release (4.78 ± 2.47%). At 24 h, all formulations showed a high cumulative release, but the formulations with higher polymer ratios, F7 (1:1.5) and F8 (1:2), showed a relatively lower release (94.08 ± 0.47% and 92.12 ± 0.74%, respectively) compared to F5 (90.67 ± 1.98%) and F6 (94.74 ± 0.94%). The formulations with a higher ratio of Vigna mungo and sodium alginate (F7 and F8) demonstrated a slower, more sustained release, while F5 and F6 exhibited a faster initial drug release, particularly in the first 4 h.

The burst release observed in the formulations, particularly during the initial hours of in vitro drug release studies, is a frequently occurring phenomenon in controlled release formulations. Burst release refers to the rapid release of a significant amount of the drug within the first few hours after administration, which may not always be desirable, especially for drugs that require sustained release over time. From the provided data, formulations like F5 (1:0.5) and F6 (1:1) show significant burst release within the first hour, with up to 41.47% and 64.41% of the drug being released, respectively, which is quite high. This behavior can be compared to other formulations in the literature, where burst release often occurs in formulations containing hydrophilic polymers like sodium alginate or natural gums.

The statistical analysis confirmed that formulation ratios of polymer combinations (Vigna mungo and sodium alginate) significantly influenced the drug release profiles, with the higher polymer ratios leading to a more controlled and sustained drug release. These differences are essential in optimizing drug delivery systems for chronic diseases, ensuring therapeutic efficacy while minimizing side effects.

5. Conclusions

The comprehensive study of Vigna mungo microspheres for the sustained release of vildagliptin has demonstrated promising characteristics for controlled drug delivery applications. The preparation of microspheres using the Vigna mungo polymer and sodium alginate resulted in formulations with favorable properties, including high yield, appropriate particle size distribution, and excellent swelling behavior. The drug–excipient compatibility studies, including the FTIR analysis, confirmed that there were no significant chemical interactions between the two.

The findings support the potential of Vigna mungo microspheres as an effective and promising strategy for sustained release drug delivery systems. These microspheres not only ensure controlled release but also improve patient compliance by reducing the frequency of drug administration. Moreover, the use of crosslinking agents such as calcium chloride and barium chloride further enhance the controlled release by reducing polymer matrix porosity and slowing drug diffusion. This formulation approach is particularly advantageous for chronic disease management, such as Type 2 diabetes, where consistent drug levels are vital for long-term therapeutic success.