An integrated QbD based approach of SMEDDS and liquisolid compacts to simultaneously improve the solubility and processability of hydrochlorthiazide

Abstract

Hydrochlorothiazide (HCTZ) is a class IV BCS drug that exhibits varying bioavailability due to poor solubility and low permeability. The first part of the present investigation was aimed to prepare liquid self-microemulsifying drug delivery system (SMEDDS) of HCTZ to improve its dissolution properties. The liquid SMEDDS was subsequently converted to self-microemulsifying tablets (SMETs) by using the liquisolid technique to facilitate the manufacturing process. Based on the solubility study and ability to form transparent microemulsion upon dilution, oleic acid, tween-20, and propylene glycol were selected as oil, surfactant, and co-surfactant respectively to form liquid SMEDDS. The central composite design was used to investigate the effect of changes in formulation composition on critical product characteristics and to optimize the SMEDDS formualtion. Neusilin US2 and Aerosil-200 were selected as carrier and coating material to prepare SMETs as they displayed the highest flowable liquid potential among all tested excipients. The prepared SMETs have acceptable tableting properties (flowability, compressibility, and compactibility) and were able to preserve self microemulsifying properties of entrapped SMEDDS formulation. The results of DSC and XRD studies suggested that better dissolution properties of SMETs formulation compared to pure drug and marketed products was possibly due to the drug either being molecularly dispersed form or presence in the amorphous state within the formulation.