Evaluation the Preparation Methods of Pioglitazone / Cyclodextrin Inclusion Complex

• Main Authors: HSIUNG, YU-CHEN, 熊玉真
• Other Authors: HSIEH, WEI-HSIEN
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/bb56w5

碩士 === 元培醫事科技大學 === 生物科技暨製藥技術系碩士班 === 107 === Pioglitazone (PE) is a poor water soluble drug categorized as BCS class II for the treatment of type 2 diabetes. Physically the hydrochloride salt of PE is a white crystalline powder with no odor and has a molecular formula of C19H20N2O3S·HCl. The molecular weight is 392.90 Dalton. The water insolubility of PE results in highly inconsistent and poor dissolution profile in gastrointestinal fluids that impact its bioavailability. The aim of this study is to evaluate the feasibility of inclusion complex formation with cyclodextrin (β-CD) via different preparation method including ultra-sonication, microwave heating, and ball mill to evaluation of the formed complex PE-β-CD increase the water solubility of PE. β-CD has the ability to form inclusion complexes with a wide variety of organic compounds, which enter partly or entirely into the relatively hydrophobic cavity. Kneading method that had been known could format inclusion complex was used as standard. In addition, Differential scanning calorimetry (DSC), fourier-transform infrared spectroscopy (FTIR), and X-ray powder diffraction were used to confirm the formation of inclusion complex. The results revealed that oscillating ball mill (molar ratio =1:1) for 120 min could format inclusion complex evidenced by vanishing the malting point peak of PE at 178.35 °C analyzed by DSC, peak shift analyzed by FTIR as well as 2 theta alteration analyzed by X-ray powder diffraction. The experiment showed β-CD concentration ranging form 0~15mM.The water solubility of PE was significantly improved with cyclodextrin formulation comparing to PE alone reaching 12.073mM. Phase solubility analysis used to assesses affinity between guest and host molecules in water shown linear increased with a gradient increase in concentrations of β-CDs. The phase solubility of this inclusion complex was classified as AL type (the solubility of the guest molecule was linear with the increase of the concentration of the host molecule. Increase). Linear character of the plots with a slope <1 propose 1:1 stoichiometric ratio of optimum complexation over the range of PE-β-CD concentration investigated.