Development of a Vegan Gummy Using Sustainable Plant Biopolymers for Anthelmintic and Expectorant Therapies: with Albendazole and Guaifenesin

Albendazole, classified as a benzimidazole derivative, functions as a broad-spectrum antiparasitic compound with the chemical name methyl [5-(propylthio)-1H-benzimidazol-2-yl] carbamate. It exhibits potent activity against a wide range of intestinal helminths and protozoans, including Ascaris lumbricoides (ascariasis), Enterobius vermicularis (pinworm infection), Ancylostoma duodenale and Necator americanus (hookworm infections), Trichuris trichiura (trichuriasis), Strongyloides stercoralis (strongyloidiasis), Taenia species (taeniasis), Clonorchis sinensis (clonorchiasis), Opisthorchis species (opisthorchiasis), Giardia lamblia (giardiasis), and Gnathostoma spinigerum (gnathostomiasis), as well as cutaneous larva migrans [1-4]. On the other hand, guaifenesin (glyceryl guaiacolate), an expectorant derived from guaiacol and glycerin, functions by reducing mucus viscosity in the respiratory tract, facilitating its expulsion and relieving chest congestion [1-4]. Conventional gummy bears, widely consumed across age groups for their soft and chewy texture, predominantly rely on gelatin—a collagen-derived animal protein—as their gelling agent, making them unsuitable for vegan consumers [5]. To address this limitation, the present study focuses on developing a plant-based "drugummy" formulation utilizing natural hydrocolloids such as agar agar (extracted from red algae) and guar gum (obtained from Cyamopsis tetragonoloba seeds). Agar agar undergoes thermoreversible gelation, imparting structural integrity and firmness, while guar gum acts as a viscosity modifier, enhancing chewiness, minimizing water separation (syneresis), and improving sensory attributes. The synergistic blending of multiple hydrocolloids—including pectin, carrageenan, starch, and gum arabic—can further refine texture and functional performance [6-8]. Critical parameters in vegan gummy formulation include optimizing gel strength, maintaining pH (typically 3-4) for drug stability, controlling water activity to prevent microbial growth, masking bitter drug flavors, ensuring compatibility between active ingredients and excipients, and achieving mechanical resilience for handling and storage. Citric acid is incorporated to provide a tangy flavor profile while acidifying the medium to enhance stability for pH-sensitive actives. Sucrose serves a dual role as a sweetener and humectant, reducing water activity to extend shelf life, while sodium benzoate acts as an antimicrobial preservative. This plant-based matrix is particularly suitable for hydrophilic drugs like guaifenesin, whereas lipophilic compounds such as albendazole may require micronization or solubilization techniques (e.g., solid dispersion) to ensure homogeneous distribution [9-11]. By modulating the gel’s rheological properties and the drug’s physicochemical characteristics, the release profile can be tailored for either immediate or sustained delivery. The ultimate goal of this research is to engineer a palatable, stable, and precisely dosed vegan gummy that aligns with the rising consumer preference for plant-based pharmaceuticals and nutraceuticals, without compromising therapeutic efficacy or sensory appeal.

2.  APPLICATIONS OF GUARGUM AND AGAR AGAR

As a natural polysaccharide obtained from Cyamopsis tetragonoloba, guar gum serves various functional purposes in gummy formulations. As a thickening agent, it improves texture by increasing viscosity, while its binding properties promote uniform dispersion of active pharmaceutical ingredients (APIs) and excipients. Due to its high water-binding capacity and pseudoplastic behavior, guar gum acts as an effective stabilizer, preventing phase separation and sedimentation during storage. Additionally, it enhances sensory attributes by imparting a smooth, non-adhesive mouthfeel and influences drug release profiles in the gastrointestinal tract through controlled hydration and matrix formation. Agar agar, extracted from marine red algae (Gelidium and Gracilaria spp.), is a thermoreversible gelling agent that forms rigid, translucent gels with high thermal stability. This property ensures prolonged shelf life under varying temperature conditions. When combined with guar gum, the gel network forms rapidly upon cooling, optimizing production efficiency. While agar alone yields brittle gels, its synergy with other hydrocolloids (e.g., guar gum) creates elastic, cohesive textures suitable for chewable dosage forms. Beyond texture modulation, agar agar acts as a protective matrix for APIs, safeguarding them from environmental degradation and improving bioavailability. Its low-calorie profile further makes it ideal for nutraceutical and pharmaceutical applications targeting health-conscious consumers [12–14].

3.  SYNERGISTIC USE OF GUARGUM AND AGAR AGAR

The combination of agar agar and guar gum produces a synergistic gel matrix that capitalizes on the distinct properties of both hydrocolloids. Agar agar contributes thermoreversible gelation with structural rigidity, while guar gum enhances binding capacity and sensory characteristics. This interaction yields an optimal texture - firm yet elastic - that improves chewability and consumer preference while mimicking gelatin's functional properties [15]. The composite gel system demonstrates superior moisture retention and colloidal stability, effectively minimizing syneresis and maintaining product consistency during storage. Guar gum's rheological properties contribute to the development of a diffusion-controlled network, rendering this matrix particularly effective for modified-release pharmaceutical applications [16]. Furthermore, this blend ensures uniform dispersion of bioactive components including vitamins, nutraceuticals, and flavor compounds while preserving their stability and organoleptic qualities [17]. As plant-derived, biodegradable polymers, both agar agar and guar gum comply with international safety regulations (FDA GRAS, EFSA) and cater to growing demands for vegan, clean-label, and sustainable formulations. Their versatility in incorporating functional ingredients and tolerance to various processing parameters establish them as a robust platform for innovative gummy applications across therapeutic, nutritional, and functional food sectors [18-20].

4. MECHANISM OF ACTION OF ALBENDAZOLE AND GUAIFENESIN

Albendazole exerts its antiparasitic effects through multiple mechanisms. The drug selectively binds to β-tubulin subunits in helminths, disrupting microtubule assembly in intestinal parasites. This binding exhibits preferential affinity for parasitic β-tubulin over mammalian isoforms, accounting for its selective toxicity. The inhibition of microtubule formation impairs cellular transport and structural integrity in worms. Concurrently, albendazole interferes with glucose absorption, causing ATP depletion and subsequent parasite immobilization and death. Furthermore, its active sulfoxide metabolite induces oxidative damage through free radical generation, compounding the parasiticidal effects [21]. Functioning as a respiratory expectorant, guaifenesin exhibits a different mode of action. The compound enhances vagally-mediated gastric reflexes while directly stimulating secretory cells in the bronchial epithelium. This dual action increases respiratory fluid production while reducing mucus viscosity, thereby improving mucociliary clearance and promoting productive cough. Unlike albendazole's cytoskeletal disruption in parasites, guaifenesin specifically targets respiratory secretory mechanisms [22,23].

fig1. Mechanism of action of albendazole

Fig2. Mechanism of action of guaifenesin

MATERIALS AND METHODS

5.1 Materials

The formulation utilizes purified water as the primary solvent for hydrating gelling agents and dissolving hydrophilic components. All excipients including sucrose, agar-agar, guar gum, citric acid, sodium citrate, and sodium benzoate were pharmaceutical-grade materials procured from Excel Biosciences. To improve patient compliance, lemon flavoring was added to effectively mask the inherent bitterness of active pharmaceutical ingredients. Certified food-grade colorants (FSSAI-approved) were included in minimal concentrations to enhance aesthetic appeal while maintaining safety standards. Albendazole was kindly supplied as a complimentary sample by Kaushik Therapeutics Ltd., while commercial-grade guaifenesin was purchased from Dhamtec Pharma Pvt. Ltd.

5.2  Preparation of Albendazole Gummies

The gummy formulations were manufactured through a controlled thermal gelation method. For albendazole-containing preparations, the process began by heating purified water to 60°C for 5 minutes before gradually incorporating agar under constant stirring. This agar-water suspension was then heated to 85±2°C for 10 minutes to ensure complete hydration. Sucrose was subsequently added and dissolved under continuous mixing. The temperature was carefully reduced to 70°C before systematically adding key functional excipients: citric acid (for pH modulation and flavor enhancement), sodium benzoate (as an antimicrobial preservative), sodium citrate (pH buffer), FSSAI-certified colorants, and lemon flavor (to counteract drug bitterness). Guar gum was then dispersed uniformly to achieve optimal hydration and viscosity. When the gel matrix reached 50±2°C, micronized albendazole was aseptically incorporated. The homogeneous molten gel was promptly transferred into silicone molds, allowed to solidify at ambient temperature (25±2°C) for 10 minutes, then subjected to a 10-minute drying phase. Final products were stored under refrigerated conditions (4±1°C) to maintain physicochemical stability and extend shelf life [24-26].

5.3  Preparation of Guaifenesin Gummies

The formulation of guaifenesin-containing gummies necessitated process optimization to accommodate the drug's solubility profile. As per USP specifications, guaifenesin demonstrates significant aqueous solubility (1:60-70 parts water) along with solubility in various organic solvents including ethanol, chloroform, glycerol, and propylene glycol. The manufacturing process mirrored the standard protocol with modifications: agar was hydrated at 85°C for 10 minutes followed by sucrose incorporation for 5 minutes. Excipients (citric acid, sodium benzoate, sodium citrate, colorants, and lemon flavor) were sequentially incorporated as previously described. To maintain drug integrity, guaifenesin was introduced into the warm gel base (50±2°C) under gentle mixing to achieve homogeneous dispersion. The molten formulation was cast into molds and subjected to a two-stage setting process: initial solidification at ambient temperature (25±2°C) for 10 minutes followed by a 10-minute drying period. Final products underwent refrigerated storage (4±1°C) to promote optimal gel matrix formation. Throughout production, both albendazole and guaifenesin formulations maintained stringent temperature control to preserve hydrocolloid functionality and active pharmaceutical ingredient stability [27-29].

Table1. Albendazole formulation table

Table2. Guaifenesin formulation table

6. EVALUATION METHODS

6.1 Preformulation studies

Comprehensive powder analysis was conducted before initiating gummy production to verify material quality. Key powder properties were evaluated, including bulk density, tapped density, Carr’s index, Hausner’s ratio, and angle of repose, to predict material handling and performance.

6.1.1 Bulk Density (ρbulk)

Bulk density represents the ratio between a powder's mass and its uncompacted volume, accounting for interparticle voids. For determination, a precisely weighed powder sample was gently transferred into a graduated cylinder under minimal compaction. The initial volume occupied by the powder was recorded immediately after pouring. The bulk density was then calculated using the relationship: 

ρbulk = Weight of powder / Bulk volume

Significance: Predicts packaging requirements and behavior during storage.

6.1.2 Tapped Density (ρtap)

Tapped density is the density obtained after mechanically tapping (500-1000 taps) a graduated cylinder containing the powder until little or no volume change is observed.

ρtap = Weight of powder / Tapped volume

Reflects how powders settle and compact under vibration, simulating transport or storage.

6.1.3  Carr’s Index (Compressibility Index)

A measure of powder compressibility and flowability. Carr's compressibility percentage is calculated using the formula:

Carr’s index = [(ρ_tapped - ρ_bulk)/ρ_tapped] × 100

Interpretation:

6.1.4  Hausner Ratio

The Hausner ratio serves as a flowability indicator, calculated by dividing the tapped density by the bulk density.

Hausner Ratio = ρ tap /ρ bulk

Interpretation:

6.1.5  Angle of Repose (θ)

The steepest angle at which a powder pile remains stable, indicating flowability.

tan(θ) = Height of pile / Radius of base

θ = arctan (Height / Radius)

Interpretation:

Method:
Powder was poured through a funnel to form a cone; (h) and (r) were measured.

6.2 Characterization (Post Formulation Studies)

6.2.1 Hardness

Texture analysis of the formulated gummies was performed using a TA.XT Plus texture analyzer (Stable Micro Systems) following established protocols with minor adaptations [47]. The instrument was equipped with a 5-mm cylindrical probe (P/5) and calibrated to compress test samples (n=6 per batch) to 50% deformation of their initial height. To replicate natural chewing dynamics, the analyzer was configured with a compression rate of 1 mm/s and an activation force threshold of 5 grams.To minimize experimental variability, all measurements were conducted under controlled temperature conditions (25±1°C), with each sample undergoing a 30-second equilibration period prior to testing to ensure proper probe contact, as per USP <1217> guidelines. The hardness values obtained were evaluated against literature-reported ranges of 1500-12000 g (14-117.6 N) for commercial gummy products [29]. This standardized approach allowed for objective quantification of the mechanical properties while maintaining relevance to actual consumption conditions.

6.2.2 Organoleptic Assessment

Taste and overall sensory quality were evaluated by 20 healthy volunteers using an organoleptic scoring system as given in Table3. Participants chewed the gummies and rated them based on appearance, flavors, texture, and acceptability on a grade scale of 5.

6.2.3 Weight Variation Test

Twenty individual gummies were weighed, and the average weight was calculated. The deviation of each gummy from the mean was expressed as:

Weight Variation (%) = (|Individual weight - Average weight| / Average weight) × 100

A batch passes if no more than two gummies exceed the acceptable range and none deviate beyond double the limit.

6.2.4 Moisture Content

Gummies (10 g) were ground, dried in a hot air oven at 70°C for 7hrs, and weighed to constant mass. Moisture content was calculated as:

% Moisture = (Weight loss due to drying / Final dry weight) × 100

6.2.5 pH Determination

Thin slices of gummy (0.5 g) were dissolved in 50 mL boiling water. Following equilibration to 25°C, pH measurements were obtained using a pre-calibrated micro-pH electrode. The acceptable pH range for gummies lies between 5.0 and 6.4 as described in literature [2].

6.2.6 In Vitro Dissolution Testing

Dissolution behavior was studied using USP/BP paddle apparatus maintained at 37 ± 0.5°C. Samples were withdrawn from the mid-point of the vessel and tested at predetermined intervals to evaluate the release rate.

6.2.7 Drug Release Kinetics

The release data was analyzed using various kinetic models: Zero-order model, First-order model, Higuchi model, Hixson-Crowell model, Korsmeyer-Peppas model.

These models helped determine the release mechanism and predict drug behavior from the gummy matrix.

6.2.8 Microbiological analysis

The mesophilic aerobic population was assessed according to the ISO 4833-1:2013 standard which was previously described in literature [50]. Gummy bear candies (1g of optimized formulation) were homogenized with an isotonic PBS buffer(9ml) solution to achieve a final dilution of 10^-1. Sequential ten-fold dilutions were created with the identical buffer solution. Mold and yeast, bacterial counts were determined by incubating on plate count agar at 30°C for 48hrs.

Table3. Hedonic scale

7.  RESULTS

7.1 Gummy bear preparation

Many formulations were carried out to find the best composition for gummy bear candies using albendazole and guaifenesin. The final composition of the gummy is the same as the study described in literature [29] and several excipients were additionally added to the composition to achieve desirable properties. Finally, the candies were made with agar agar and Guargum, it showed best results with desirable properties. Four runs were carried out for albendazole and seven runs were carried out for guaifenesin. Among all the batches, the successful formulations such as F3 of albendazole emerged as superior, combining high mechanical strength, dissolution efficiency, hardness, microbial stability, palatability meeting the requirements for anthelminthic therapies. Similarly, R2 of guaifenesin demonstrated exceptional dissolution efficiency, hardness, and microbial stability, meeting the requirements for expectorant therapies. It was observed that on increasing the concentration of agar agar, the hardness of the gummies increased as more galactan molecules tend to participate in the formation of gel matrix. Also, on increasing the concentration of the Guargum the chewability of the gummies increased due to intermolecular chain interaction of galactose side chain [29].

fig1. Guaifenesin gummy candy

fig 2. Albendazole gummy candy

7.2 Results of albendazole gummies

Albendazole gummy candies were successfully synthesized. Different evaluation tests were performed to assess the physiochemical characteristics of gummies, and the results obtained from various tests ensured that the gummies were stable, showing no physiochemical changes. All the formulations showed acceptable results with reference to hardness, weight variation, moisture content, ph. and drug release. Preformulation studies for albendazole was not conducted and formulation was guided by reported physicochemical properties.

POST FORMULATION STUDIES

7.2.1 Sensory analysis

For evaluating numerous sensory characteristics, including sweetness, appearance, taste, texture and chewability, albendazole gummy bear candies were provided to a panel of 20 participants. The product received a mean hedonic score of 4.0 out of 5.0 based on likeliness, indicating a favorable level of acceptability among panelists.

7.2.2 Weight variation

The weight variations of the formulations (F1-D1) are shown in table4. All the formulations show adequate percentage variations which lie within the range according to USP specifications.

7.2.3 Hardness

Hardness of the gummy bear candies were measured using the texture profile analyzer. Hardness determines the chewiness of the gummies. The hardness of the formulations (F1-D1) is shown in the table4. R2 and D1 are less hard due to high water content and water content increases the softness of the gummies.

7.2.4 Moisture content

Results for the moisture content of the gummies are given in table.  The moisture content was observed in the range of 17.5-18.5% which lies within the range as described in [29]. F3 has 18.5% which is slightly high compared to other formulations and R2 has 17.5% which is the least. Increased hydration levels in the formulation contribute significantly to the product's pliable consistency. Gummies with higher moisture content had a higher quantity of water and low concentration of polymers.

7.2.5 pH.

It was found that chewable Gummy bear candies have a pH. All the formulations F1 to D1 showed satisfactory results, and their pH values lies within the recommended range [2]. Table 4 presents the measured pH values for all gummy formulations.

7.2.6 In vitro dissolution

The percentage of drug release was observed for a period of 180mintues, as demonstrated in table. Dissolution studies were carried out for a duration of 3 hours. However, the gummy formulation demonstrated a prolonged release behavior, with complete drug release observed at approximately 8 hours in preliminary extended observations. This gradual release suggests that the gummy formulation exhibits characteristics of a sustained-release dosage form. Such a release profile could be beneficial in maintaining prolonged therapeutic levels of albendazole in systemic circulation, reducing dosing frequency, and potentially improving patient compliance, especially in pediatric populations. The formulation F3 showed the highest drug release within 180minutes; that’s why it is considered to be the best formulation and R2 showing the least amount of drug release. The pattern of release is shown in fig3 below. In future studies, a complete dissolution and drug release analysis should be performed to know the drug release profile for both gummy bear candies.

fig 3. Percentage drug release of albendazole

7.2.7 Release kinetics

During formulation kinetic data modelling, we concluded that (F1-D1) formulations were following first order because their R² is near 1. So, it was shown that the release of drugs is dependent on concentration, which explained the first order behaviour of the formulation and extended-release kinetics. The n value in Korsemeyer and peppas release kinetics model describes the formulation’s specified drug release through Fick’s law of diffusion. In this case, a transport mechanism that is Fickian diffusion corresponds to an n value less than 0.45. The release kinetics of 4 formulations are shown in table 6. 

Table 4. Results of albendazole gummy bear candies

Table 5. Dissolution test results of albendazole gummies

Table 6. Release kinetics results of albendazole gummies

7.3 Results of Guaifenesin gummies

Similarly, Guaifenesin gummy bear candies were successfully synthesized. Different evaluation tests were performed to assess the physiochemical characteristics of gummies, and the results obtained from various tests ensured that the gummies were stable, showing no physiochemical changes. All developed formulations demonstrated compliance with established quality parameters, including texture profile, weight uniformity, hydration levels, pH stability, and drug release characteristics.

7.3.1 Preformulation Studies

Before formulation development, guaifenesin powder underwent thorough material characterization to examine its physical and chemical attributes. Critical powder flow properties - comprising loose and packed density measurements, compressibility index, density ratio, and repose angle analysis - were assessed to verify compatibility with gummy production processes. The combined evaluation of these properties yields comprehensive understanding of the powder's behavior during processing and its uniformity. The results of these analyses are systematically compiled in Table 7, offering a comparative overview of the powder’s performance characteristics.

Table 7. Preformulation studies of guaifenesin

7.3.2 Post formulation studies

7.3.1 Sensory analysis

For evaluating numerous sensory characteristics, including sweetness, appearance, taste, texture and chewability, guaifenesin gummy bear candies were provided to a panel of 20 participants. The product received a mean hedonic score of 4.0 out of 5.0, indicating a favorable level of acceptability among panelists.

7.3.2 Weight variation

The weight variations of the formulations (F1-X1) are shown in table 8. All the formulations show adequate percentage variations which lie within the range according to USP specifications.

7.3.3 Hardness

Hardness of the gummy bear candies were measured using the texture profile analyzer. Hardness determines the chewiness of the gummies. The hardness of the formulations (F1-X1) is shown in table8.

7.3.4 Moisture content

Results for the moisture content of the gummies are given in table.  The moisture content was observed in the range of 15.5% to 16.5% which lies within the range (12-20%) as described in the literature [12].

7.3.5 pH.

It was found that chewable Gummy bear candies have a pH. All the formulations F1 to X1 showed satisfactory results, and their pH values lies within the recommended range [2]. Table 8 summarizes the pH characteristics of the developed gummy products.

7.2.6 In vitro dissolution

The percentage of drug release was observed for a period of 180mintues, as demonstrated in table. Dissolution studies were carried out for a duration of 3 hours. Similarly, drug release of guaifenesin was observed at approximately 6 hours in preliminary extended observations. This gradual release suggests that the gummy formulation exhibits characteristics of a sustained-release dosage form. The formulation R2 showed the highest drug release within 180minutes; that’s why it is considered to be the best formulation and X1 showing the least amount of drug release. The pattern of release is shown in fig4 below. Among the seven different formulations, best six formulations except D2 were taken for study of dissolution.

fig 4. Percentage drug release of guaifenesin

7.2.7 Release kinetics

During formulation kinetic data modelling, we concluded that (F1-X1) formulations were following first order because their R2 value is near 1. So, it was shown that the release of drugs is dependent of concentration, which explained the first order behaviour of the formulation. The n value in Korsemeyer and peppas release kinetics model describes the formulation’s specified drug release through Fick’s law of diffusion. In this case, a transport mechanism that is Fickian diffusion corresponds to an n value less than 0.45. The release kinetics of 6 formulations are described in table10. 

Table8.  Results of guaifenesin gummy bear candies

Table9. dissolution results of guaifenesin

Table 10. Release kinetics results of guaifenesin gummies