Investigation of polymeric excipients for dutasteride solid dispersion and its physicochemical characterization
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- 作者：Nam Ah Kim (1)
Du Hyung Choi (2)
Jun Yeul Lim (1)
Ki Hyun Kim (1)
Dae Gon Lim (1)
Eunhee Lee (3)
Eun-Seok Park (4)
Seong Hoon Jeong (1) - 关键词：Dutasteride ; Solubility ; Glass transition temperature (T g ) ; Attenuated total reflection Fourier ; transform infrared spectroscopy (ATR FT ; IR) ; Solid dispersion
- 刊名：Archives of Pharmacal Research
- 出版年：2014
- 出版时间：February 2014
- 年：2014
- 卷：37
- 期：2
- 页码：214-224
- 全文大小：868 KB
- 作者单位：Nam Ah Kim (1)
Du Hyung Choi (2)
Jun Yeul Lim (1)
Ki Hyun Kim (1)
Dae Gon Lim (1)
Eunhee Lee (3)
Eun-Seok Park (4)
Seong Hoon Jeong (1)
1. College of Pharmacy, Dongguk University-Seoul, Donggukro 32, Ilsandonggu, Gyeonggi, Goyang, 410-820, Republic of Korea
2. College of Pharmacy, Pusan National University, Busan, 609-735, Republic of Korea
3. College of Pharmacy, Korea University, Chungnam, 339-700, Republic of Korea
4. School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea - ISSN：1976-3786
文摘
To investigate the effects of polymeric excipients for dutasteride solid dispersion, experimental approaches together with physical interactions at molecular level were evaluated. The drug and various polymers (anionic, amphiphilic, and hydrophilic) were mixed physically into different ratios and their thermodynamic and physical properties were analyzed by differential scanning calorimetry and Fourier transform-infrared spectroscopy, respectively. The enhanced equilibrium solubility of dutasteride was also investigated. Dutasteride is non-ionic and showed low solubility in the tested pH ranges (lower than the detection limit of 20?ng/mL). Kollidon? MAE 100P, an anionic polymer, showed enhanced dutasteride solubility in aqueous solution followed by hydrophilic Kollidon? SR and the amphiphilic polymer, Soluplus?. Melting point (T m ) of dutasteride was 249.7?°C and was decreased to 229.84?°C when mixed evenly with Kollidon? MAE 100P. However, the melting point was not detected at a ratio of 1:4 since it fully dissolved or dispersed in the polymer. Glass transition temperature (T g ) of different compositions exhibited strong interaction of polymer and drug. The result was supported by spectra evidence that Kollidon? MAE 100P forms hydrogen bonds with dutasteride presenting strong physical interaction with the primary amine group of dutasteride. This study supports a convenient method that together with microscopic observation can perform polymer selection and characterize solid dispersions.