It is well recognized that the active pharmaceutical ingredient (API) can exist in different crystalline forms, and therefore differ in their bioavailability, stability and physical properties. Characterization of polymorphism of drug substances is required by the ICH Q6A guideline [1].

     Dutasteride is a 5α-reductase inhibitor. It is mainly used in treatment of benign prostatic hyperplasia (BPH) and prostate cancer [2]. Dutasteride is also used in treating the male pattern hair loss [3].

     The patent and scientific literature reveal two polymorphic forms of dutasteride known as form I [4,5] and form II [5,6], form III called hemihydrate [7,8] as well as the amorphous dutasteride [5].

     We present physicochemical characterization of dutasteride polymorphs, involving analytical techniques such as X-ray powder diffraction (XRPD), IR and Raman spectroscopy as well as thermal analysis (differential scanning calorimetry and thermogravimetry). These studies proved that form II is a pseudopolymorph. Additional XRPD temperature measurements showed phase transitions in the dutasteride forms II and III.

Acknowledgement

Research Project has been supported by INNOTECH No. INNOTECH-K2/IN2/65/182982/NCBR/13 ,,Synthesis and new technology of manufacturing drug containing an inhibitor of 5α- reductase”

References:

[1] Guideline ICH Q6A, „Specifications: test procedures and acceptance criteria for new drug substances and new drug products: chemical substances”.

[2] Slater S., et al., „Dutasteride for the treatment of prostate-related conditions", Expert Opinion on Drug Safety, 2012, 11, 325-330.

[3] Eun H. C., et al., „Efficacy, safety, and tolerability of dutasteride 0.5 mg once daily in male patients with male pattern hair loss: A randomized, double-blind, placebo-controlled, phase III study”, Journal of the American Academy of Dermatology, 2010, 63, 252-258.

[4] Batchelor K.W., Frye S.V., „Androstenone derivative”, WO 95/07 927, 23.03.1995.

[5] (a) Reddy M. S., et al., „Forms of dutasteride and methods for preparation thereof”, US 2004/0 077 673 A1, 22.04.2004; (b) Reddy M. S , et al., „Forms of dutasteride and methods for preparation thereof”, US 7,022,854 B2, 04.04.2006.

[6] Katkam S. et al., „Preparation of dutasteride”, WO 2007/120 263 A2, 25.10.2007.

[7] (a) Vecchiolli A. , et al., „Solid and crystalline dutasteride and processes for preparation thereof”, WO 2009/083 258 A2, 09.07.2009; (b) Tombardi D. G., et al., „Solid and crystalline dutasteride and processes for preparation thereof”, US 8,153,648 B2, 10.04.2012.

[8] Jagadesh B. N., et al., Cryst. Eng. Comm., 2012, 14, 2571-2578.

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