Abstract

VALIDATED BCS COMPARATIVE DISSOLUTION METHOD FOR HYDROCHLOROTHIAZIDE TABLETS

Jenaé Van Wyk, Joe M. Viljoen and Marius Brits*

ABSTRACT

Hydrochlorothiazide (HCTZ) is a globally used thiazide diuretic forthe treatment of hypertension and edema. It has been classified as aClass I/III drug according to the biopharmaceutical classificationsystem (BCS), thus potentially qualifying for BCS based biowaiverdissolution studies, waiving the regulatory requirement for in vivobioavailability (BA) and/or bioequivalence (BE) studies whendeveloping a generic immediate release solid oral dosage form.Regulatory guidelines require the use of validated analyticalprocedures during the performance of such comparative dissolutionstudies. A review of the available literature indicated that no validatedanalytical method has thus far been published for the quantification ofHCTZ release from conventional immediate release tablets during BCSbased biowaiver dissolution studies. Therefore, the aim of this studywas to develop and validate an analytical method for BCS comparativedissolution testing in accordance with the WHO and ICH guidelinesfor HCTZ. The developed and validated UV/Vis method quantifies the release of HCTZ at271 nm in the three biorelevant dissolution media. The method revealed acceptable accuracyraging between 99–101% over a linear working range of 1.4–17.0 μg/mL. Using method ofstandard addition the absence of excipient interferences was illustrated. The limit of detectionand quantification limit of the method were found to range between 0.120–0.350 μg/mL and0.364–1.061 μg/mL respectively. The stability of analytical solutions under normal analyticalconditions and the suitability of the filter-material were investigated and reported. Thisanalytical method will thus support generic medicine manufacturers and medicines regulatory authorities in their respective mandates, to ensure the availability of safe and efficaciousmedicines to the public.

Keywords: Hydrochlorothiazide, analytical method, validation, drug dissolution, spectrophotometry.