DESIGN AND EVALUATION OF PANTOPRAZOLE-LOADED FLOATING MUCOADHESIVE MICROSPHERES FOR PROLONGED GASTRIC RETENTION

Khushboo Vyas, Ritika Parashar, Aman Kushwaha, Dilip Kumar, M. K. Gupta*

ABSTRACT

Objective: The present study aimed to design and evaluate pantoprazole-loaded floating mucoadhesive microspheres to overcome the challenges associated with conventional pantoprazole delivery, namely its acid-lability and narrow absorption window in the proximal small intestine, by achieving prolonged gastric retention and sustained drug release. Methods: Floating mucoadhesive microspheres were prepared using the ionotropic gelation technique with sodium alginate as the polymer matrix and calcium chloride as the cross-linking agent. Calcium carbonate was incorporated as a gas-forming agent to impart buoyancy. A 3² factorial design was employed to systematically evaluate the influence of polymer concentration (2-4% w/v) and cross-linker concentration (5-15% w/v) on critical formulation attributes. The prepared microspheres were characterized for micromeritic properties, surface morphology using Scanning Electron Microscopy (SEM), drug-excipient compatibility by FTIR and DSC, percentage yield, drug entrapment efficiency, in-vitro buoyancy, ex-vivo mucoadhesive strength, in-vitro drug release in simulated gastric fluid (pH 1.2), and drug release kinetics. Results: All formulations produced discrete, spherical microspheres with good flow properties (Carr's index 12.4-18.7%). Mean particle size ranged from 425 ± 12.5 µm to 680 ± 18.3 µm, showing a direct correlation with polymer concentration. FTIR studies confirmed the absence of drug-polymer interactions, while DSC analysis indicated amorphous dispersion of pantoprazole within the polymer matrix. Percentage yield ranged from 72.5% to 89.6%, and drug entrapment efficiency varied from 58.3% to 87.2%, with both parameters significantly influenced by polymer and cross-linker concentrations. All formulations exhibited excellent buoyancy with floating lag times of 2-8 minutes and total floating time exceeding 12 hours. Ex-vivo mucoadhesive strength ranged from 8.5 ± 0.8 g to 15.2 ± 1.2 g, increasing with higher polymer concentration. In-vitro drug release studies revealed a biphasic pattern with initial burst release (18-32%) followed by sustained release over 12 hours. Drug release kinetics followed the Higuchi model (R² > 0.96) with anomalous (non-Fickian) transport mechanism (n = 0.512-0.651), indicating diffusion coupled with polymer relaxation. Formulation F5 (3% sodium alginate, 10% calcium chloride) was identified as the optimized formulation, exhibiting highest entrapment efficiency (87.2%), minimal floating lag time (2 minutes), maximum mucoadhesive strength (15.2 g), and optimal sustained release (86.3% in 12 hours) with anomalous transport kinetics. Conclusion: The developed floating mucoadhesive microspheres successfully addressed the biopharmaceutical limitations of conventional pantoprazole delivery by combining buoyancy and mucoadhesion to achieve prolonged gastric retention. The optimized formulation (F5) demonstrated superior performance characteristics, offering a promising gastroretentive drug delivery system capable of enhancing the oral bioavailability and therapeutic efficacy of pantoprazole through sustained release at its absorption site, potentially enabling once-daily dosing and improved patient compliance in the management of acid-related disorders.

Keywords: Pantoprazole; Gastroretentive Drug Delivery System (GRDDS); Floating Microspheres; Mucoadhesive.