Formulation Optimization and Evaluation of Aprepitant Orally Disintegrating Tablets

Abstract

The present investigation was undertaken to develop and evaluate orally disintegrating tablets (ODTs) of Aprepitant as a rapid and patient-friendly dosage form for the management of chemotherapy-induced nausea and vomiting. Preformulation studies involving drug identification, solubility assessment, melting point determination, spectral characterization, and drug–excipient compatibility studies established the physicochemical characteristics of Aprepitant. The drug exhibited a high melting point of 254–256°C and poor aqueous solubility, being soluble in methanol, sparingly soluble in phosphate-buffered saline (PBS, pH 6.8), and practically insoluble in water. To overcome the solubility limitation, solid dispersions were prepared using PEG 4000, PEG 6000, and β-cyclodextrin as hydrophilic carriers. The prepared systems exhibited a substantial improvement in drug solubility and dissolution characteristics. Among the investigated formulations, SD4 containing Aprepitant and PEG 6000 in a 1:2 ratio demonstrated the most favorable characteristics, with a drug content of 99.31%, solubility of 3.91 mg/mL, and 97.17% drug release within 15 min. The optimized solid dispersion was subsequently incorporated into ODTs containing different superdisintegrants, namely crospovidone, sodium starch glycolate (SSG), and croscarmellose sodium (CCS). The prepared tablets were evaluated for hardness, friability, weight variation, thickness, drug content, disintegration time, wetting time, and in vitro drug release. All formulations demonstrated satisfactory pharmaceutical characteristics. Among the formulations, F3 containing crospovidone exhibited the fastest disintegration, with a disintegration time of 21 s, together with rapid drug release. Comparative assessment of the superdisintegrants indicated the dissolution performance order of crospovidone > sodium starch glycolate > croscarmellose sodium. Stability assessment of F3 under refrigerated, room-temperature, and accelerated conditions for three months showed no significant change in appearance or drug content. The findings indicate that the developed Aprepitant ODT formulation may provide a promising approach for rapid drug delivery and improved patient convenience in chemotherapy-induced nausea and vomiting.