A Dissolution Test for Finasteride in Immediate-Release Capsules

Abstract

In vitro dissolution tests for solid oral dosage forms are extremely important to ensure the quality of these products. However, no dissolution test has been reported for finasteride (FNS) in immediate-release capsules. The aims of this work were to optimize a dissolution method for FNS capsules, validate the analytical method, and evaluate three different commercial products. The best in vitro dissolution profile was achieved using water as the dissolution medium with a basket stirrer at 100 rpm. The quantitative determination was performed by high performance liquid chromatography (HPLC) at 210 nm. All validation parameters were satisfactory. The application of the method to commercial products showed the discriminatory power of the dissolution method. Because there is no monograph for FNS in capsules, this study illustrates the importance of an official dissolution test for FNS in capsules and the need to standardize the composition of the excipients contained in these commercial products. INTRODUCTION In vitro dissolution tests for immediate-release solid oral dosage forms, such as tablets and capsules, are extremely important because these tests are essential to evaluate the lot-to-lot quality of a drug product, to guide the development of new formulations, and to ensure continuing product quality and performance after certain changes (e.g., formulation, manufacturing process, site of manufacture, and scale-up of the manufacturing process) (1). For these reasons, progressively more emphasis has been placed on dissolution testing within the pharmaceutical industry and by regulatory authorities (2). Despite the importance of dissolution tests in ensuring the quality of medicines, several drug products that are widely commercialized throughout the world lack official dissolution tests. Finasteride (FNS) is a relevant example because no dissolution test is reported in the literature or in pharmacopeias for immediate-release capsules of this medication. FNS capsules are widely marketed and are prepared for medical reasons (e.g., avoiding an excipient to which a patient is allergic or obtaining a dosage level that is not marketed). FNS is N-(1,1-dimethylethyl)-3-oxo-4-aza-5α-androst1-ene-17β-carboxamide (Figure 1), a specific competitive inhibitor of steroid type-II 5α-reductase, an intracellular enzyme that converts testosterone to dihydrotestosterone (DHT) and is widely used for the treatment of benign prostatic hyperplasia (BPH) (3), prostate cancer (4), and androgenetic alopecia (5–8). A daily dose of 5 mg has been used for the treatment of BPH and prostate cancer, and a 1-mg dose has been used for the treatment of androgenetic alopecia. FNS has a molecular formula of C23H36N2O2, a molecular weight of 372.6, and a log Po/w of 3.03. According to the Biopharmaceutics Classification System (BCS), FNS is a Class 2 drug having low solubility and high permeability (9). Multiple analytical procedures have been reported for the analysis of FNS in pharmaceutical preparations when it is present as a single active ingredient or in combination dosage forms, using spectrophotometry (10–12), thin-layer chromatography (13, 14), infrared spectrophotometry (15), polarography (16), voltammetry (17), gas chromatography (18), gas chromatography–mass spectrometry (19), high performance liquid chromatography (HPLC) (20–23), and ultra-high performance liquid chromatography (UHPLC) (24, 25). Because of the importance of in vitro dissolution tests for immediate-release solid oral dosage forms and the lack of a dissolution test for FNS compounded capsules, the aims of this work were to optimize a dissolution method *Corresponding author. e-mail: olimpia_martins@yahoo.com.br Figure 1. Chemical structure of finasteride. dx.doi.org/10.14227/DT200313P25