Enhanced intestinal lymphatic absorption of saquinavir through supersaturated self-microemulsifying drug delivery systems
| Autor: | Prakash Khadka, Kanghee Jo, Soo Jin Kim, Jaehwi Lee, Taejun Jang, Hyeongmin Kim, Seong-Ha Hwang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Drug
media_common.quotation_subject viruses Pharmaceutical Science 02 engineering and technology Absorption (skin) 010402 general chemistry 01 natural sciences Lymphatic drug delivery chemistry.chemical_compound Research article medicine Self-microemulsifying drug delivery system Solubility Saquinavir media_common Pharmacology Chromatography Chemistry lcsh:RM1-950 biochemical phenomena metabolism and nutrition 021001 nanoscience & nanotechnology 0104 chemical sciences Bioavailability Supersaturation lcsh:Therapeutics. Pharmacology Methyl cellulose Drug delivery Precipitation inhibitor 0210 nano-technology medicine.drug Lipid-based formulation |
| Zdroj: | Asian Journal of Pharmaceutical Sciences, Vol 15, Iss 3, Pp 336-346 (2020) Asian Journal of Pharmaceutical Sciences |
| ISSN: | 1818-0876 |
| Popis: | 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 self-microemulsifying 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 SMEDDS. Through 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 self-microemulsification 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 SMEDDS. Therefore, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system. Graphical abstract Supersaturated self-microemulsifying drug delivery systems designed in this study were demonstrated to enhance the intestinal lymphatic absorption of saquinavir in vivo through inhibiting the drug precipitation in gastrointestinal fluid. Image, graphical abstract |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|