Development, Optimization and Evaluation of Naproxen Amorphous ASDs Tablets for Enhanced Solubility and Dissolution Using Hydrophilic Polymers
DOI:
https://doi.org/10.66220/75p78209Keywords:
Amorphous solid dispersion, Dissolution study, Factorial design, Naproxen, Response surface methodology, Solubility enhancement, Solvent evaporation, Tablet formulationAbstract
Naproxen is a widely prescribed non-steroidal anti-inflammatory drug (NSAID) belonging to Biopharmaceutical Classification System (BCS) Class II, exhibiting high permeability but poor aqueous solubility, which limits its dissolution rate and oral bioavailability. The present study aimed to develop, optimize, and evaluate amorphous solid dispersions (ASDs) of naproxen using hydrophilic polymers to improve its solubility and dissolution characteristics. Preformulation studies including melting point determination, Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), UV spectrophotometric analysis, and solubility studies confirmed the identity, purity, and crystalline nature of naproxen. ASDs were prepared by the solvent evaporation method using PVP K30, PEG 6000, HPMC E5, and Poloxamer 188 individually and in combinations. Preliminary screening demonstrated that PVP K30 exhibited the highest solubility enhancement, while the combination of PVP K30 and PEG 6000 showed synergistic improvement. Formulation variables were optimized using response surface methodology (RSM) based on a factorial design with polymer concentration and ethanol volume as independent variables. The optimized formulation (F6) exhibited a production yield of 95.40%, drug content of 86.23%, and 95.68% cumulative drug release within 60 minutes. FTIR and DSC analyses confirmed the absence of significant drug–polymer interactions and indicated successful formation of the ASDs. The optimized dispersion was compressed into tablets that demonstrated acceptable pre- and post-compression characteristics, including hardness, friability, weight variation, and drug content. The tablet formulation released 96.23% of drug within 60 minutes and followed the Korsmeyer–Peppas kinetic model, suggesting anomalous drug release behavior. Accelerated stability studies conducted for three months revealed no significant changes in physicochemical properties or dissolution profile. The findings demonstrate that the developed ASDs tablet effectively enhances the solubility and dissolution of naproxen and represents a promising strategy for improving its oral bioavailability.
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