Formulation and Evaluation of Nanocrystals of Hydrochlorothiazide

Aim/Background: Hydrochlorothiazide (HTZ) is a diuretic derivative and used as an antihypertensive agent with low bioavailability (around 60%) due to impaired dissolution rate. Further, excretion of HTZ is high due to rapid renal clearance (~ 320 mL/min). Objectives: Aim of the current study to improve dissolution rate of HTZs through nanocrystals technology. Materials and Methods: Nanocrystals (NC) were prepared by controlled precipitation method varying two different approaches. From the first aspect NC were prepared without stabilizer, and from the second aspect NC were prepared using different stabilizer. NC formulations were physically characterized, in vitro dissolution rate and assessment of storage stability. Results: Physical characterization of HTZ NC using FTIR, DSC, and SEM revealed no changes took place in the drug quality attributes. The particle size, zeta-potential, and PDI measurement of NC exhibited their nano-size range in 252 nm, -15.5 mV, and 0.230 respectively. Dissolution rate of NCs were significantly improved in comparison to pure drug. The optimized batch AF2 was stable at room temperature (25±0.5ºC) and elevated temperature (40±1ºC) with 75±5% RH over the period of 60 days. However, drug assay of AF2 showed a slight decrease over the time at room temperature (25±0.5ºC), while degradation rate was enhanced at the elevated temperature (40±1ºC) with 75±5% RH. Based on physical characterization, in vitro release and stability studies, it can be concluded that NCs of HTZ (AF2) was stable for an extended period of time and provides improved dissolution rate. Conclusion: Nanocrystals of hydrochlorothiazide were successfully formulated by using different stabilizer which leads to the enhancement of dissolution rate and storage stability.