Probing the mechanism of bupivacaine drug release from multivesicular liposomes

被引：64

作者：

Manna, Soumyarwit ^{[1
,2
]}

Wu, Yong ^{[2
]}

Wang, Yan ^{[1
]}

Koo, Bonhye ^{[1
,2
]}

Chen, Lynn ^{[1
,2
]}

Petrochenko, Peter ^{[1
]}

Dong, Yixuan ^{[3
]}

Choi, Stephanie ^{[1
]}

Kozak, Darby ^{[1
]}

Oktem, Berk ^{[2
]}

Xu, Xiaoming ^{[3
]}

Zheng, Jiwen ^{[2
]}

机构：

[1] US FDA, Div Therapeut Performance, Off Res & Stand, Off Gener Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA

[2] US FDA, Div Biol Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA

[3] US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Qual,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA

来源：

JOURNAL OF CONTROLLED RELEASE | 2019年 / 294卷

关键词：

Bupivacaine; Multivesicular; Liposome; Cryo-SEM; IVRT; Reverse dialysis; SUSTAINED-DELIVERY; BLOOD PROTEINS; PH; DISSOLUTION; TECHNOLOGY; FORMULATIONS; DEPOFOAM(TM); TEMPERATURE; SYSTEMS; CARRIER;

D O I：

10.1016/j.jconrel.2018.12.029

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 mu m and 1.52 +/- 0.44 mu m, 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.

引用

页码：279 / 287

页数：9

共 40 条

[21] PH-DEPENDENT SOLUBILITY AND DISSOLUTION OF BUPIVACAINE AND ITS RELEVANCE TO THE FORMULATION OF A CONTROLLED RELEASE SYSTEM [J].