Abstract
Background: Polymorphism in drugs is a common phenomenon which can lead to compromised quality due to changes in their physicochemical properties and may impact therapeutic efficacy.
Objective: The main objective of the present study is to investigate the polymorphic behaviour of Pioglitazone Hydrochloride (PGH) under different preparative conditions and to evaluate the solid forms.
Method: The solid-state forms of PGH were developed under different preparative conditions like solvent addition, neat grinding, solvent assisted grinding, cooling, slurrying etc. Which were characterized by Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Powder Diffraction (XRPD), Scanning Electron Microscopy (SEM) and Differential Scanning Calorimetry (DSC).
Results: Solid forms D and E, crystallized from cooling and solvent evaporation methods exists in Form I of PGH, while solid form A obtained from antisolvent method underwent solid-solid transition from Form I to Form II. Form G obtained by slurrying in dimethylformamide contains Form II with trace amount of Form I. Grinding did not show any effect on polymorphic nature of PGH. The dissolution behaviour of these solid Forms reveals that solid Form A containing Form II showed improved dissolution (92.6 %). No significant difference in anti-diabetic activity was observed between Form I and Form II of PGH.
Conclusion: PGH readily undergoes polymorphic transitions under certain preparative and processing conditions. However, no significant difference in anti-diabetic activity was observed between Form I and Form II of solid form of PGH.
Keywords: Pioglitazone hydrochloride, polymorphism, solid-state, crystallization, fourier transform infrared spectroscopy, powder X-ray diffraction.
Graphical Abstract
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