OPTIMIZATION AND FORMULATION DEVELOPMENT OF PROMETHAZINE THEOCLATE ORODISPERSIBLE LIQUISOLID COMPACT TABLETS USING DIRECT COMPRESSION

Abstract

This study aimed to formulate and optimize promethazine theoclate orodispersible liquisolid compact tablets to achieve improved flowability, rapid disintegration, and enhanced early drug release. The objectives were to develop liquisolid systems using microcrystalline cellulose (carrier) and Aerosil 200 (coating material), apply factorial design for optimization, and evaluate micromeritic, mechanical, dissolution, and morphological characteristics. A full factorial design was employed using Design-Expert® software with microcrystalline cellulose (X1) and Aerosil 200 (X2) as independent variables. Responses included angle of repose, cumulative drug release at 15 minutes, and disintegration time. Promethazine theoclate was dispersed in PEG 400, converted into liquisolid powders with carrier–coating blends, mixed with superdisintegrants and excipients, and compressed by direct compression. Pre-compression parameters such as bulk density, tapped density, Carr’s index, and Hausner’s ratio were evaluated. Post-compression studies included hardness, friability, thickness, weight variation, drug content, wetting, dispersion, and dissolution. Surface morphology was examined by FE-SEM. Powder blends showed acceptable flow with angles of repose between 22–30°. Drug release at 15 minutes ranged from 95–99%, and disintegration occurred within 30–35s. Statistical analysis demonstrated significant influence of formulation variables with strong model fitting (R² > 0.9). Tablets exhibited hardness around 3.8–4.1 kg/cm², friability below 1%, and drug content of 97–99%. Microscopy confirmed predominantly amorphous drug distribution within the matrix, favoring rapid wetting and dissolution. The optimized liquisolid approach successfully produced robust orodispersible tablets with fast disintegration and high early drug release, offering a promising strategy to enhance dissolution performance and patient compliance.