Enhancement of Aceclofenac Dissolution Rate via Solid Dispersion with Hydroxypropyl Methylcellulose
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Abstract
Aceclofenac, a widely used NSAID for managing osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, faces bioavailability challenges due to its poor water solubility, classifying it as a BCS Class II drug. This limits its dissolution and absorption, necessitating higher doses, which increase the risk of side effects. This study aimed to enhance aceclofenac's solubility and dissolution rate by formulating solid dispersions with hydroxypropyl methylcellulose (HPMC), a hydrophilic polymer. Solid dispersions were prepared via freeze-drying at drug-to-polymer ratios of 1:1, 1:2, and 2:1 Solid-state characterization was performed using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Solubility and in vitro dissolution profiles were compared to those of pure aceclofenac. DSC and PXRD analyses confirmed a significant reduction in crystallinity, evidenced by the absence of characteristic crystalline peaks and endothermic transitions, indicating transformation into an amorphous state. Reduced crystallinity is associated with weaker lattice energy, which enhances the dissolution process. FTIR analysis revealed no chemical interactions between aceclofenac and HPMC. The solubility of the 1:2 solid dispersion formulation was significantly higher (p < 0.001), achieving a 2.73-fold increase compared to pure aceclofenac. Dissolution testing showed almost complete drug release within 60 minutes, highlighting the formulation’s superior performance. These findings suggest that the 1:2 aceclofenac-HPMC solid dispersion holds promise for improving the solubility, dissolution rate, and overall bioavailability of aceclofenac, thereby enhancing its therapeutic efficacy.
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