Preliminary observations on dissolution and bioavailability of triamterene–hydrochlorothiazide combination products

Abstract

The dissolution profiles of two brands of triamterene–hydrocholorthiazide (TRM–HCT) combination tablets and two brands of TRM–HCT combination capsules were studied using the USP paddle method at 100 rev min⁻¹ in acid medium (0·1 N). The tablets represent two products marketed in Germany, whereas the capsules represent the approved innovator's product and an unapproved generic product. The tablets dissolved almost 100 per cent in 15 min whereas the capsules dissolved less than 25 per cent in 60 min. A pilot bioavailability study was carried out in four normal healthy male volunteers. Urine samples were collected over a 48 h period and analysed for TRM, its major metabolite TRM‐sulfate, and HCT using HPLC methods. The dissolution characteristics of TRM can be associated with the total drug excretion (absorption) of the product. On the other hand, the excretion (absorption) of HCT was independent of dissolution characteristics of the products. However, in TRM–HCT combination product, there appears to be a 50 per cent reduction in HCT excretion (absorption) when compared to the reported excretion (absorption) from a marketed single‐entity product.