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Enhanced intestinal lymphatic absorption of saquinavir through supersaturated self-microemulsifying drug delivery systems

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Asian Journal of Pharmaceutical Sciences 2020年第3期15卷 336-346页

作者： Kanghee Jo Hyeongmin Kim prakash khadka Taejun Jang Soo Jin Kim Seong-Ha Hwang Jaehwi Lee College of Pharmacy Chung-Ang UniversitySeoul 06974Republic of Korea

The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus(HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. Thus, we aimed to design a supersaturated selfmicroemulsifying drug delivery system(S-SMEDDS) that can maintain a high concentration of saquinavir in gastro-intestinal fluid thorugh inhibiting the drug precipitation to enhance the lymphatic transport of saquinavir and to increase the bioavailability of saquinavir considerably. Solubilizing capacity of different oils, surfactants, and cosurfactants for saquinavir was evaluated to select optimal ingredients for preparation of *** the construction of pseudo-ternary phase diagram, SMEDDS formulations were established. A polymer as a precipitation inhibitor was selected based on its viscosity and drug precipitation inhibiting capacity. The S-SMEDDS and SMEDDS designed were administered at an equal dose to rats. At predetermined time points, levels of saquinavir in lymph collected from the rats were assessed. SMEDDS prepared presented a proper selfmicroemulsification efficiency and dispersion stability. The S-SMEDDS fabricated using the SMEDDS and hydroxypropyl methyl cellulose 2910 as a precipitation inhibitor exhibited a signficantly enhanced solubilizing capacity for saquinavir. The drug concentration in a simulated intestinal fluid evaluated with the S-SMEDDS was also maintained at higher levels for prolonged time than that examined with the SMEDDS. The S-SMEDDS showed a considerably enhanced lymphatic absoprtion of saquinavir in rats compared to the ***, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system.

关键词： Lymphatic drug delivery Self-microemulsifying drug delivery system Saquinavir Precipitation inhibitor Supersaturation Lipid-based formulation

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Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability

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Asian Journal of Pharmaceutical Sciences 2014年第6期9卷 304-316页

作者： prakash khadka Jieun Ro Hyeongmin Kim Iksoo Kim Jeong Tae Kim Hyunil Kim Jae Min Cho Gyiae Yun Jaehwi Lee College of Pharmacy Chung-Ang UniversitySeoul 156-756Republic of Korea Department of Food Science and Technology Chung-Ang UniversityAnseong 456-756Republic of Korea

Pharmaceutical particle technology is employed to improve poor aqueous solubility of drug compounds that limits in vivo bioavailability owing to their low dissolution rate in the gastrointestinal fluids following oral *** particle technology involves several approaches from the conventional size reduction processes to the newer,novel particle technologies that modify the solubility properties of the drugs and produce solid,powdered form of the drugs that are readily soluble in water and can be easily formulated into various dosage *** review highlights the solid particle technologies available for improving solubility,dissolution and bioavailability of drugs with poor aqueous solubility.

关键词： Particle technology Drug solubility Poorly water soluble drug Solubility enhancement Dissolution

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