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Background: The limited aqueous solubility of basic drugs poses significant challenges for oral bioavailability, necessitating a different formulation approach. This study utilizes acidic or non-ionic polymers (its aqueous solution close to acidic-neutral pH) to stabilize a basic drug via drug-polymer interaction. Due to acid-base super solubilization effects, amorphous solid dispersions (ASDs) have good recrystallization inhibition, and improved dissolution and stability. Methods: To prepare nimodipine, a model drug, solid dispersion, spray–drying and melt–quenching techniques were used with carriers like HPC, HPMCAS, HPMCP, and PVP K25 polymers. Drug-polymer miscibility or interaction was carefully evaluated with different modeling to reduce processing temperature and inhibit recrystallization. Results: Based on preparation methods, there were two ASD types: one with a small particle size and low bulk density (spray–drying) and the other with big particle size and high bulk density, prepared at a low temperature to minimize degradation (melt–quenching). The solid–state analysis revealed a low glass transition temperature (Tg), suggesting amorphous forms. The surface morphology of nimodipine and its solid dispersions demonstrated a uniform and consistent system. Nimodipine with HPMCP via spray–drying (NIM.CP.SM) exhibited the highest drug release (89.51%) in phosphate buffer (pH 6.0) after 2 h without recrystallization. The in vivo pharmacokinetic profiles demonstrated a 33–fold increase in Cmax and a 15–fold increase in AUC0–∞ with NIM.CP.SM. Conclusions: These findings suggest that an HPMCP–based polymer combined with spray–drying technique produces a thermodynamically and physico-chemically stable ASD with enhanced in vitro and in vivo drug release.