The development and validation of a dissolution method for clomipramine solid dosage forms

Abstract

Dissolution testing has emerged in the pharmaceutical field as a very important tool to characterize drug product performance. Clomipramine HCl as a frequently used antidepressant has no dissolution method in its monograph in BP or USP. In vitro dissolution tests of solid oral dosage forms of clomipramine were performed by various methods using different test conditions but always under “sink”conditions. Release profiles of different dosage forms of clomipramine show that release rate from capsules is much faster than from film coated tablet and that release from film coated tablet is faster than from the sugar-coated tablet. Dissolution of almost all forms was complete at 45 minutes.The in vitro release profiles of various tests were compared for their similarity using the f2 test. Results of this test indicate that in most cases dissolution profiles of the different products were significantly different from each other. Under certain conditions,tablets had a more discriminating profile than capsules under the same test conditions. A method using HCl as the dissolution medium in USP Apparatus 2 and stirring speed of 75 rpm,for all solid oral dosage forms of clomipramine could reliably discriminate among different products, if they are truly different. With these conditions,more than 80% of the label amount is released over 30 minutes.