| Meloxicam is a novel non-steroidal anti-inflammatory drugs (NSAIDs), a new and safe anti-inflammatory drug, The mainly dosage form of meloxicam is the immediate-release at present, however, the oral absorption is incomplete, which limited its clinical application. In order to extend the release time of Meloxicam, to extend the dosing interval, and to maintain the effective therapeutic concentrations, the poly-lactic acid prepared by melting can be used as a carrier material of the release microspheres of meloxicam, which can help to achieve the purposes of long-term sustained-release which can help to achieve the purposes of long-term sustained-release.The polylactic acid carrier material can be prepared by melt polymerization, inoder to get the best optimization process and conditions, the catalyst, temperature, reaction time on the impact of the product are studied, and then the polylactic acid carrier material will be analysed and characterized by means of the infrared (IR), nuclear magnetic resonance ('H-NMR), gel permeation chromatography (GPC), The optimum conditions are as follows:the stannous octoate was added in the amount of 0.6%(w/w) of the lactic acid, the reaction temperature was kept at 170℃,and the condensation time was 10 hours. The product of number average molecular weight of polylactic acid and quality-average molecular weight were measured by the gel permeation chromatography (GPC),and the former was about 6000 and the latter was about 17000.The microspheres were prepared by solvent evaporation, and the polylactic acid was used as a carrier, methylene chloride was used as the organic solvent, polyvinyl alcohol was used as dispersant. The factors which impact on the microspheres during preparation are as follows:methylene chloride used as the organic solvents have the highly volatile; polyvinyl alcohol (PVA) used as the emulsifier, the microspheres can obtained the good surface morphology, and the particle size distribution is more uniform; the average particle size of microspheres decreased with the stirring speed increases. The optimization process and conditions of drug-loaded microspheres'preparation can be decided by single factor and orthogonal experiments:the concentration of PVA was 2%, the concentration of PLA was 0.04 g/mL, MLX:PLA was 1:6 (mass ratio), water-oil ratio of 250:1, the magnetic stirring speed was 800 rpm, and the time of solvent evaporation was 3 hours, the surface morphology and the particle size distribution of the microspheres were observed by microscope and scanning electron microscopy. The microspheres were monodisperse, and the particle size was between 100μm～150μm. The result of drug loading and encapsulation efficiency showed that the drug loading was (11.39±0.83)%, the encapsulation efficiency was (71.86±0.1)%.The in vitro release properties was studied by UV spectrophotometry with phosphate buffer solution as the release medium. In vitro release, the experiments showed that the obtained microspheres have some burst release phenomenon in the first four hours and the burst release is about 30%, and then drug-loaded microspheres shouwed a slow release, the cumulative release rate was about 68% on the 4th day, and was about 85% on the 10th day, what mentioned above indicated that the meloxicam/PLA microspheres has good sustained-release effect. The research showed that the release time increases with the increases of microspheres'particle size and medium pH value, while decreases with the increases of the polyvinyl alcohol concentration. |
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