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Solid Dispersion of an HIV Protease Inhibitor
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  • Solid Dispersion of an HIV Protease Inhibitor
  • Solid Dispersion of an HIV Protease Inhibitor
저자명
Park. Jae-Hyeon,Lee. Sung-Hack,Lee. Yong-Hee,Kim. Ae-Ri
간행물명
Journal of pharmaceutical investigation
권/호정보
2011년|41권 2호|pp.75-82 (8 pages)
발행정보
한국약제학회
파일정보
정기간행물|ENG|
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기타
이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
서지반출

기타언어초록

LB71350 is an HIV protease inhibitor with poor aqueous solubility and extensive first pass effect. The purpose of the present study was to test the feasibility of solid dosage form of LB71350 with improved bioavailability utilizing solid dispersion. Three different compositions with varying ratio of (LB71350: Gelucire 44/14: Tween 20) were studied. Capsule filling of these solid dispersion compositions was tested using a semi-automatic capsule filling system. Oral bioavailability in dog was tested. Chemical and physical stability at 4, 25 and $40^{circ}C$ was monitored by HPLC assay, dissolution test, powder XRD and microscopy. The capsule filling system yielded uniform products of drug loading up to 10%. Oral bioavailability in dog was improved compared to the aqueous suspension of crystalline LB71350. Capsules were chemically stable for up to 6 months at $40^{circ}C$. However, there were temperature and composition dependent physical changes. Decrease in dissolution rates after storage at $40^{circ}C$ was due to the polymorphic change. In conclusion, manufacturing process, bioavailability, and physico-chemical stability have been considered to propose a solid dispersion capsule formulation for the HIV protease inhibitor with poor physico-chemical properties. A new less soluble crystalline form identified during the physical stability test warrants further study.