FORMULATION AND COMPARATIVE EVALUATION OF VARIOUS NATURAL POLYMER-BASED SOLID DISPERSIONS OF NAPROXEN FOR ENHANCED SOLUBILITY AND DISSOLUTION

Abstract

Background: Naproxen, a propionic-acid-derived non-steroidal anti-inflammatory drug (NSAID), is classified under Biopharmaceutics Classification System (BCS) Class II, meaning it is highly permeable across the intestinal membrane but poorly soluble in aqueous media, so its rate-limiting step for oral absorption is dissolution rather than membrane transport. This solubility bottleneck contributes to slow and variable release from conventional dosage forms, which in clinical practice can encourage higher or more frequent dosing and, in turn, a greater burden of NSAID-related gastrointestinal adverse effects.

Objective: The present investigation was undertaken to formulate solid dispersions of naproxen using three hydrophilic natural polysaccharide gums — guar gum (GG), xanthan gum (XG) and gum acacia (GA) — and to comparatively evaluate their capacity to enhance aqueous solubility and in-vitro dissolution relative to one another and to the unprocessed drug.

Methods: Twenty-seven formulation batches were generated by fully crossing the three carriers, three preparation techniques (solvent evaporation, fusion/melt, and kneading) and three drug-to-polymer ratios (1:1, 1:2 and 1:3 w/w). Pre-formulation studies — organoleptic evaluation, melting-point verification, equilibrium solubility profiling and FTIR-based drug–polymer compatibility screening — preceded formulation. Every batch was assessed for drug content, equilibrium solubility (in water and pH 6.8 phosphate buffer) and USP Apparatus II dissolution behaviour; the best-performing batch was further characterised in-house by FTIR and differential scanning calorimetry (DSC), compared against powder X-ray diffraction (XRD) data reported in the literature for analogous systems, and subjected to a 90-day accelerated stability study conducted in line with ICH Q1A(R2).

Results: Every natural-gum carrier improved both solubility and dissolution relative to pure naproxen (p < 0.001). The guar-gum system prepared by solvent evaporation at a 1:3 ratio (GG-SE3) was clearly the most effective, releasing 94.82 ± 3.1% of the drug within 60 minutes against only 28.6 ± 1.8% for the unprocessed drug, together with a 4.6-fold increase in phosphate-buffer solubility. DSC (this study) and XRD (compared from the literature for analogous systems) confirmed that this improvement coincided with a substantial reduction in naproxen crystallinity, consistent with conversion of the drug to a largely amorphous, molecularly dispersed state within the guar-gum matrix. The optimised batch retained the great majority of its performance across 90 days of accelerated storage (40 °C ± 2 °C / 75% RH ± 5%), with no statistically significant change in drug content, dissolution or solubility (p > 0.05).

Conclusion: Natural polysaccharide gums, and guar gum in particular, represent an inexpensive, biocompatible and technically effective platform for improving the dissolution behaviour — and, by extension, the likely oral bioavailability — of naproxen and potentially other BCS Class II NSAIDs.