Font Size: a A A

Technological Improvement On Lidocaine-PLGA-loaded Microspheres Prepared With Double Emulsion Solvent Evaporation Method

Posted on:2016-02-16Degree:MasterType:Thesis
Country:ChinaCandidate:J H LiFull Text:PDF
GTID:2334330485459749Subject:Pharmaceutical engineering
Abstract/Summary:PDF Full Text Request
Water-in-oil-in-water(W/O/W)double emulsion solvent evaporation method is a mature technology to prepare water-soluble drug sustained-release microspheres for its simple operation. But for the good water soluble and small molecular weight drugs, microspheres prepared with this technology would result in low encapsulation efficiency and large burst release. In order to overcome these disadvantages, this study explored the effect of PLGA molecular, oil phase volume, sonic power,high-speed stirring speed and time on the characteristics and in vitro release behavior of microspheres prepared with W/O/W double emulsion solvent evaporation method.In addition, this paper has made improvement to the double emulsion solvent evaporation method. The innovation of this experiment is adding pH sensitive in situ chitosan and temperature sensitive in situ poloxamer 407 into the inner water phase to increase the viscosity of the inner water phase according to the combination of experimental conditions and the characteristics of in situ gel. If the viscosity of the inner water phase improved the protective layer which was around the drug would be thicker. And the thicker protective layer could not only increase the drug loading and encapsulation efficiency, but also prevent the drug from leaking out. Then the slow and stable drug release would be achieved. The encapsulation efficiency and in vitro release assay showed that: the drug loading of lidocaine hydrochloride microspheres prepared with traditional way was( 0.55±0.03) %, encapsulation efficiency was(6.09±0.28) %, burst release rate was( 19.31±1.58) %. But after added 3.0%chitosan to the inner water phase, the drug loading was(1.47±0.09)%, encapsulation efficiency was(16.57±1.05)%, burst release rate was(9.07±1.94)%. On the other hand, when 30% poloxamer 407 joined the inner water phase the drug loading was(1.18±0.26)%, encapsulation efficiency was(16.48±3.63)%, burst release rate was(8.05±0.99) %. What's more, when the inner water phase was filled with 2.0%chitosan and 20% poloxamer 407 mixtures the drug loading was(1.25±0.09)%,encapsulation efficiency was( 16.49±1.21) %, burst release rate was(11.54±3.21)%. The results showed that: after the in situ gel added into the inner water phase, the drug loading and encapsulation efficiency was obviously improved, and the burst release rate would be lower.Regarding the drug loading, encapsulation efficiency, burst release and yield as the evaluating index, single factor tests were executed to investigate the preparation of lidocaine hydrochloride microspheres. The optimal prescription was determined by orthogonal experiment and the best prescription was: molecular weight of PLGA was 30 000 Da, oil phase volume was 2.5ml, ultrasonic power was 475 W, stirring rate was 3400 rpm, stirring time was 3min and the concentration of chitosan was 3.5%.The average particle size of microspheres prepared with the optimal prescription and preparation was 50.03?m, the drug loading was 1.80%, encapsulation efficiency was20.43%, burst release was 12.34%, and in vitro release profiles could be fit well by Higuchi equation.
Keywords/Search Tags:lidocaine hydrochloride, emulsion solvent evaporation method, in situ gel, sustained-release microspheres, PLGA
PDF Full Text Request
Related items