Development Of Phenytoin Poly (Lactide-co-glycolide) Microspheres

Objective: To develop a new idea, new method and new technique for periodontitis drug treatment. Periodontitis seriously threaten human health and affect human quality of life. Phenytoin sodium can promote hyperostosis of alveolar bone and curing periodontitis thoroughly. The biodegradable poly (lactide-co-glycolide) was used as carrier and phenytoin sodium was selected as model drug. The surface morphology, diameter and size distribution of microspheres were studied. To establish the quality controll standard for Phenytoin sodium -PLGA-MS, the encapsulation efficiency, drug loading capacity, in vitro release and stability were also examined. We are trying to break through the limitation of drug treatments for periodontitis and expand original channel for clinical use of phenytoin sodium.Methods: The solvent evaporation method was used to prepare Phenytoin sodium -PLGA-MS. According to the results of the effects of different variables, the orthogonal design of 4 factors and 3 levels was applied to optimize the technology of preparation. The properties of microspheres (e.g. micrometric properties like bulk density, the angle of repose, diameter and size distribution, et al) were observed by scanning electron microscope and light microscope. In vitro release of phenytoin sodium from microspheres was performed by oscillating in constant temperature method. The encapsulation efficiency, drug loading capacity was assayed by high performance liquid chromatography (HPLC) method. Results: The drug content and properties of the microspheres was remarkably determined by concentration of gelatin, concentration of PLGA, volume of intra-aqueous phase and extra- aqueous phase. The optimization is as follows: concentration of gelatin was 4%; concentration of PLGAwas 40mg/mL, volume of intra-aqueous phase was 400μL and volume of extra- aqueous phase was 10mL. Three batches of microspheres were prepared using the optimized formulation. By investigating three batches of samples, it was found that the globular power obtained had good fluidity. Examination using scanning electron photomicrographs showed spherical particles with many pores. The average particle size was 3.93μm with 84.00% of the microspheres being in the range of 1-6μm. HPLC method was established as the quality controll standard, there was a good linearity within the range of 4-200μg/ml. The average recovery was 100.37% and the RSD (intra- and interday) were less than 2%. The average yield, drug loading and incorporation efficiency were 44.5%, 12.17% and 82.22% respectively.The phenytoin sodium release behavior from microspheres in vitro could be described by double phase dynamic model and could be expressed by the following equation: 100-R=51.74e^-0.1733t+30.09 e^-0.001t .The release mechanism was erosion and diffusion. ThePhenytoin sodium stuff release profiles in vitro could be described by first order dynamic model and could be expressed by the following equation: In (100-R)=-0.7364t+4.6616.During stored at 3-5â–¡or room temperature (15-25â–¡) for 3 months, surface morphology and drug content did not alter. The stability was not affected by light irradiation in 10 days. ⁶⁰Co radiation had no effect on surface morphology and content of Phenytoin sodium. Conclusion: phenytoin sodium has strong alkalinity and stimulation. Simple administration in periodontal pocket lead to short time of drug effective concentration, limited actification of paradentium. Following to slow-release adjuvant gradual degradation, Phenytoin sodium torpidity releases from phenytoin sodium -PLGA-MS, maintain effective generation concentration for a long time and promote generation of alveolar bone, availably heal peridentitis.