Correlation of urinary excretion with in vitro dissolution using several dissolution methods for hydrochlorothiazide...

Area of Science:

• Pharmaceutical Sciences
• Pharmacokinetics
• Drug Formulation

Background:

• Hydrochlorothiazide is a widely prescribed diuretic.
• Ensuring consistent bioavailability across different formulations is crucial for therapeutic efficacy.
• In vitro dissolution testing is a key predictor of in vivo drug performance.

Purpose of the Study:

• To compare the in vivo performance of four hydrochlorothiazide formulations.
• To evaluate the ability of various in vitro dissolution methods to predict in vivo drug excretion.
• To identify the optimal dissolution method for assessing hydrochlorothiazide formulation quality.

Main Methods:

• Four hydrochlorothiazide formulations were prepared.
• A crossover study in six volunteers assessed cumulative urinary hydrochlorothiazide excretion (in vivo).
• Dissolution studies utilized flask, USP basket, and magnetic basket methods at varying agitation speeds (50-150 rpm).

Main Results:

• Formulation D exhibited significantly different in vivo urinary excretion profiles compared to other formulations at multiple time points.
• Specific in vitro dissolution conditions, notably the USP basket method at 150 rpm and the flask method at 100/150 rpm, differentiated Formulation D.
• Significant correlations between in vitro dissolution and in vivo excretion were established via regression analysis and F test.

Conclusions:

• Formulation D demonstrated distinct in vivo pharmacokinetic behavior.
• The USP basket method at 150 rpm emerged as the most reliable in vitro predictor of urinary hydrochlorothiazide excretion.
• This finding supports the use of specific dissolution parameters for quality control of hydrochlorothiazide formulations.