The porous structure of freeze-dried aerogels enables higher drug absorption and faster diffusion, making it an option for drug delivery systems.
The pharmaceutical industry faces dual challenges: managing production waste and improving the solubility of poorly water-soluble drugs like clotrimazole. These innovative aerogels (AG) significantly enhance drug dissolution rates while repurposing industrial waste into sustainable materials.
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The research team developed hybrid aerogels using surplus pharmaceutical-grade gelatin and chitosan, a biopolymer with antimicrobial properties and high reactivity. They mixed these materials at four volume ratios—1:1, 1:2, 1:3, and 1:4—and cross-linked them using glutaraldehyde (GA) at varying concentrations (10%–40%). The resulting hydrogels were solvent-exchanged with ethanol and freeze-dried to produce porous aerogels suitable for drug delivery applications.
The model drug used was clotrimazole, an antifungal compound known for its low water solubility. Researchers incorporated clotrimazole into the aerogels by soaking them in a drug-containing ethanol solution before drying. This process led to the formation of clotrimazole-loaded aerogels with varying drug content and release profiles.
% clotrimazole loading in aerogels prepared from various chitosan-to-gelatin ratios and % GA. Courtesy of Sustainable development of hybrid AG from surplus gelatin and chitosan for enhancing the dissolution rate of clotrimazole.
Table 1 showed that clotrimazole content in aerogels ranged from 15.3% to 24.3%, with the highest loading at a 1:4 ratio and 30% GA. Drug content increased with gelatin proportion, but excessive GA (40%) slightly reduced the efficiency. Aerogels cross-linked at 20% GA consistently demonstrated the most favorable drug release profiles.
% clotrimazole loading in aerogels prepared from various chitosan-to-gelatin ratios and % GA. Courtesy of Sustainable development of hybrid aerogels from surplus
gelatin and chitosan for enhancing the dissolution rate of clotrimazole.
Effect of %GA and volume ratio of chitosan to gelatin on the release of clotrimazole at 180 min.Courtesy of Sustainable development of hybrid aerogels from surplus gelatin and chitosan for enhancing the dissolution rate of clotrimazole.
Aerogels released up to 100% of clotrimazole within 180 minutes, while unprocessed drug reached only 24.2%. Among all formulations, the 1:4 chitosan-to-gelatin ratio with 20% GA achieved the highest release. Table 2 showed that xerogels contained less drug (12.5%–19.6%), confirming that freeze-drying improved drug incorporation. Table 3 confirmed aerogels cross-linked at 50°C had slightly higher drug content than those made at room temperature.
Aerogels clearly outperformed xerogels in drug loading and release. The porous structure of freeze-dried aerogels enabled higher drug absorption and faster diffusion. While xerogels improved clotrimazole dissolution over raw drug, their compact structure limited effectiveness. For instance, aerogels reached up to 100% dissolution, whereas xerogels peaked at 94.3%. Cross-linking temperature also played a role, as heat-assisted aerogels showed enhanced performance due to faster gelation and minimal shrinkage.
Furthermore, aerogels demonstrated superior amorphous drug dispersion, as confirmed by XRD and DSC analyses. Reduced crystallinity increased solubility, which enhanced the drug’s bioavailability.
SEM images at 3500 magnification showing aerogels produced at different chitosan-to-gelatin ratios: (A) 1:1, (B) 1:2, (C) 1:3, (D) 1:4. Additionally, images of clotrimazole-loaded AG at various chitosan-to-gelatin ratios are presented: (E) 1:1, (F) 1:2, (G) 1:3, (H) 1:4. Image (I) displays unprocessed clotrimazole. Courtesy of Sustainable development of hybrid aerogels from surplus gelatin and chitosan for enhancing the dissolution rate of clotrimazole.
Antifungal tests against Trichophyton mentagrophytes revealed inhibition zones of 82.5–83.5 mm for clotrimazole-loaded aerogels, close to 92.5 mm for pure drug. Unloaded aerogels also displayed antifungal activity due to chitosan, which inhibits microbial growth via membrane disruption.
BET analysis revealed mesoporous structures (average 31 Å) with reduced surface area upon drug loading. SEM imaging showed smoother surfaces due to direct freeze-drying without pre-freezing, yet internal pores supported drug entrapment. These properties make hybrid aerogels suitable for controlled-release pharmaceutical applications.
This study presents a sustainable innovation by upcycling one ton of monthly gelatin waste from soft capsule manufacturing. By transforming gelatin waste into biodegradable, biocompatible drug carriers, it addresses both environmental and pharmaceutical challenges. The use of natural polymers and low-energy freeze-drying aligns with green chemistry principles, offering scalability for commercial applications.
From an industrial perspective, this technology offers a dual advantage—cost-effective waste valorization and enhanced drug delivery performance. It enables circular production models that minimize resource loss while creating high-value medical products.
Hybrid aerogels synthesized from surplus gelatin and chitosan offer a sustainable, efficient platform for delivering poorly water-soluble drugs like clotrimazole. Their superior drug-loading capacity, enhanced dissolution rates, and antifungal properties outperform traditional formulations and demonstrate real-world potential. This approach aligns pharmaceutical innovation with environmental stewardship, advancing both human health and sustainable industry.
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