Probing the mechanism of bupivacaine drug release from multivesicular liposomes
| Autor: | Yixuan Dong, Yong Wu, Jiwen Zheng, Lynn Chen, Darby Kozak, Soumyarwit Manna, Yan Wang, Berk Oktem, Stephanie Choi, Bonhye Koo, Peter Petrochenko, Xiaoming Xu |
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| Rok vydání: | 2019 |
| Předmět: |
Multivesicular liposomes
Pharmaceutical Science 02 engineering and technology Dosage form law.invention 03 medical and health sciences law medicine Anesthetics Local 030304 developmental biology Bupivacaine 0303 health sciences Liposome Chemistry Vesicle 021001 nanoscience & nanotechnology Drug Liberation Membrane Liposomes Microscopy Electron Scanning Biophysics Particle size Electron microscope 0210 nano-technology medicine.drug |
| Zdroj: | Journal of Controlled Release. 294:279-287 |
| ISSN: | 0168-3659 |
| Popis: | The mechanism of drug release from complex dosage forms, such as multivesicular liposomes (MVLs), is complex and oftentimes sensitive to the release environment. This challenges the design and development of an appropriate in vitro release test (IVRT) method. In this study, a commercial bupivacaine MVL product was selected as a model product and an IVRT method was developed using a modified USP 2 apparatus in conjunction with reverse-dialysis membranes. This setup allowed the use of in situ UV–Vis probes to continuously monitor the drug concentration during release. In comparison to the traditional sample-and-separate methods, the new method allowed for better control of the release conditions allowing for study of the drug release mechanism. Bupivacaine (BPV) MVLs exhibited distinct tri-phasic release characteristics comprising of an initial burst release, lag phase and a secondary release. Temperature, pH, agitation speed and release media composition were observed to impact the mechanism and rate of BPV release from MVLs. The size and morphology of the MVLs as well as their inner vesicle compartments were analyzed using cryogenic-scanning electron microscopy (cryo-SEM), confocal laser scanning microscopy and laser diffraction, where the mean diameters of the MVLs and their inner “polyhedral” vesicles were found to be 23.6 ± 11.5 μm and 1.52 ± 0.44 μm, respectively. Cryo-SEM results further showed a decrease in particle size and loss of internal “polyhedral” structure of the MVLs over the duration of release, indicating erosion and rearrangement of the lipid layers. Based on these results a potential MVL drug release mechanism was proposed, which may assist with the future development of more biorelevant IVRT method for similar formulations. |
| Databáze: | OpenAIRE |
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