Effect of Lipid Composition in Propofol Formulations: Decisive Component in Reducing the Free Propofol Content and Improving Pharmacodynamic Profiles
Autor: | Sharad Darandale, Ganesh Shevalkar, Pradeep R. Vavia |
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Rok vydání: | 2016 |
Předmět: |
Male
Chemistry Pharmaceutical Glyceride Lipid composition Pain Pharmaceutical Science 02 engineering and technology Aquatic Science Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Drug Discovery medicine Animals Rats Wistar Propofol Triglycerides Ecology Evolution Behavior and Systematics Anesthetics Loss of righting reflex Ecology Triglyceride Chemistry General Medicine 021001 nanoscience & nanotechnology Lipids Rats Pharmacodynamics Anesthetic Nanoparticles Emulsions 0210 nano-technology Agronomy and Crop Science medicine.drug |
Zdroj: | AAPS PharmSciTech. 18:441-450 |
ISSN: | 1530-9932 |
Popis: | Current endeavor was aimed towards studying significance of lipid composition on free propofol concentration in aqueous phase and associated pain on injection. Three different nanoformulations, namely long-chain triglyceride (LCT)/medium-chain glyceride (MCG)-based nanoemulsion (ProNano), MCG-based self-nanoemulsifying formulation (PSNE), and lipid-free nanoformulation (PNS) were accessed for the same. In vitro and in vivo performances of developed formulations were compared with Diprivan®. ProNano showed minimum free propofol concentration (0.13%) and hence lower pain on injection (rat paw-lick test, 6 ± 2 s) compared to Diprivan®, PSNE, and PNS (0.21%, 0.23%, and 0.51% free propofol, respectively, and rat paw-lick test; 12 ± 3, 14 ± 2, and 22 ± 3 s, respectively). These results conjecture the role of MCG in effective encapsulation of propofol. Anesthetic action assessed by measuring duration of loss of righting reflex (LORR), which was found similar in case of ProNano and PSNE (14 ± 3 and 15 ± 3 min, respectively) compared to Diprivan® (13 ± 3 min). In case of lipid-free formulation, PNS, extended anesthetic action (21 ± 2 min) was observed which may be due to sustained release of propofol from nanosponges. Studies on effect of lipoproteins on propofol release highlighted significance of HDL (100% release with maximum concentration of about 1.2 μg/ml of HDL) from all three formulations. |
Databáze: | OpenAIRE |
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