Study On Dutasteride Related Substance And Quality Standard Of Dosage Forms

To control the purity of the drug, the most important is analysis, detection, control related substance content. ICH clearly defined the limits of related substances, ensuring the related substances limit is the key in drug development, research and production. Materials having impact on the drug purity are considered as drug impurities, including inorganic impurities, organic impurities and residual solvents.Dutasteride, original research by US GSK, has been approved by the FDA in 2003 and put into clinical use, the chemical name: N-[2,5-bis(trifluoromethyl) phenyl]-3-carbonyl-4-aza-5α-androst-1-ene-17β-carboxamide. It is a dual 5α-reductase inhibitor, which can inhibit the 5α-reductase typeⅠ, typeⅡ, reducing dihydrotestosterone(DHT) significantly.Given the importance of the study of related substance, we must control dutasteride quality, and demarcate and characterize impurities, while also controlling the total content and the content of a single impurity to comply with pharmaceutical purity requirements according to ICH."European Pharmacopoeia" 8.0(EP 8.0) and "USP" 38(USP38-NF) and, etc. have introduced impurity detection conditions and categories of dutasteride in detail.In order to show more intuitively synthesis process related substances of dutasteride drug, we directionally synthesized impurity, and also demarcate impurities with external standard method, and demonstrated the limits of the content of impurities.Currently, we have synthesized eight impurities of dutasteride. They are impurity A, B, C, F, G, I, trimer(Trimer), dutasteride 5-β isomers as EP8.0 listed. impurity B is the substance that the related products A associated with dimethylamine hydrochloride; impurity C is the substance that the related products A associated with ethanol; impurity F is the substance that the related products A associated with SOCl2 and 2,5-bis(trifluoromethyl) aniline; impurity G is the substance that dutasteride associated with DDQ and BSTFA; impurity I is the polymerization of related substances A and dutasteride; Trimer is the polymerization of impurity A and dutasteride; Dutasteride 5-β isomer is a synthetic intermediate 8 by an addition reaction, namely 5-β-isomer 13.At the same time, we made a preliminary study in the quality standards of the dosage form of dutasteride soft capsule made by ourselves,investigating the appearance of the dosage form, BHT(antioxidants) checks,he stability of soft capsules, while also investigated materials compatibility of dutasteride soft capsule, release in vitro, comprising the dissolution profile of different SDS concentrations, and compared with dissolution of a commercial sample of dutasteride soft capsule.