The Combination of Liqui-Mass System and Pelletization to Improve Pharmaceutical Properties of Hydrochlorothiazide

Liqui-Pellet technology has recently been developed and has shown to be promising in achieving a rapid drug release rate with water insoluble drugs. At present, only naproxen and ketoprofen have been applied to an oral solid dosage form for immediate release. The present investigation aims to explore the drug release performance of the poorly water-soluble hydrochlorothiazide (HCTZ) using the Liqui-Pellet technology. Various non-volatile co-solvents such as Tween 80, PG, Kolliphor EL, and PEG 200 were used to make HCTZ Liqui-Pellet formulations to investigate the influence of Liqui-Pellet technology on the drug release profile. Saturation solubility studies showed HCTZ was most soluble in PEG 200 (156 mg/mL), which is also reflected in the drug release data where HCTZ Liqui-Pellet containing PEG 200 had the most enhanced drug dissolution profile. A binary mixture of carriers consisting of Avicel PH-101 and Neusilin US2 was investigated, as this mixture has been shown to improve drug release rate in a previous study. Surprisingly, the binary mixture of carriers did not improve the drug release rate in this study. The best formulation reached 100% drug release at approximately 40 min. Other physicochemical analysis tests showed the Liqui-Pellets’ flow property, robustness, and size distribution are generally acceptable and pose no major issue in terms of manufacturing. In conclusion, the Liqui-Mass system combined with extrusion-spheronization is a viable approach to enhance HCTZ dissolution.