Formulation and Evaluation of Mouth Dissolving Tablet Containing Aprepitant for Chemotherapy Induced Nausea and Vomiting

Abstract

Objectives: Aprepitant is a poorly soluble BCS Class IV NK₁ receptor antagonist that causes chemotherapy-induced nausea and vomiting (CINV). The purpose of this research was to develop and optimize Aprepitant mouth dissolving tablets (MDTs) to improve its dissolution and compliance, especially in cancer patients with dysphagia.

Methods: Preformulation studies such as solubility, FTIR, and DSC were conducted to understand the drug-excipient compatibility. A 3² full factorial design was used to optimize the formulations (KF1-KF9) of MDTs, considering Kollidon® VA64 (A) and Crospovidone XL-10 (B) as independent variables and disintegration time (Y₁) and in vitro drug release after 15 min (Y₂) as responses. Following direct compression, tablets were tested for pre- and post-compression features, dissolution (PBS pH 6.8) and accelerated stability (40 ± 2 °C / 75 ± 5% RH, 90 days).

Results: Powder blends showed good flowability (Carr's index < 13.5%). All batches had post-compression parameters within pharmacopoeial limits. Quadratic polynomial was the optimal model for both responses (R² = 0.9982 for Y₁; R² = 0.9991 for Y₂). Kollidon® VA64 had the greatest impact on both responses. Batch KF9 with the highest excipient concentrations was identified as the optimal formulation due to the shortest disintegration time (37.2 sec), highest Q₁₅ (93.4 ± 2.6%) and almost complete drug release (99.3 ± 2.9%) within 45 min. Stability tests revealed no significant drug loss (98.63 ± 0.74%) or change in dissolution for up to 90 days.

Conclusion: The KF9 formulation had short disintegration time and enhanced dissolution, providing clinically relevant benefits for CINV treatment in dysphagia patients. These results suggest the clinical feasibility of developing Aprepitant MDTs and its in vivo pharmacokinetics should be evaluated.