| The purpose of this research was to prepare submicron-emulsion nasal spray with Scutellaria-extracts phospholipid complex as a model drug to treat cerebral ischemic injury through nasal delivery. The main research content included pre-formulation study, prescription study, preparation technology study, quality standard study, stability study, etc.In the pre-formulation research, I confirmed the solubility of Scutellaria-extracts phospholipid complex in water, MCT,LCT were about84.7,1189.4,266.7μg/ml. It was shown significant improvements both in lipid solubility and water solubility after Scutellaria-extracts become phospholipid complex, and the change of lipid solubility was more apparent. I also explored that the aqueous solution, MCT solution, LCT solution of phospholipid complex would maintain stable after keep in the condition of60℃for24h.I worked out the prescription and preparation technologies for submicron emulsion were as follows:evaporated ethanol solution of Scutellaria-extracts phospholipid complex, which contained40g drugs, by vacuum concentration to appropriate amount, then added LCT80mL, MCT170mL, soybean phosphatide15g, oleic acid1mL, VE1g etc., and continued to evaporate it to without ethanol taste. Ultimately, the oil phase was prepared. Glycerin10g, poloxamer10g, sodium EDTA0.06g were dissolved in appropriate amount of warm-up distilled water, which was the aqueous phase. Two-phase was mixed hot, and then added distilled water to1000mL after it cooled to room temperature. Colostrum was sheared with high-speed for9min by19000r.min-1at60℃, and implemented homogenization in high pressure homogenizer for6times whole the homogenization pressure was600bar. Adjusted its pH to5.0, and filtrated, sterilized, repacked, nasal spray of Scutellaria-extracts phospholipid complex submicron-emulsion was finally prepared out. In addition, I validated the rationality and feasibility of prescription and preparation technologies through three batches of pre-production study, and I also confirmed the storage environment of this product was low temperature keeping away from direct sunlight through influence factors test.In the quality standard research, the character of this product and the safety of residue ethanol were explicit. The limits of pH, total spray times, the content of each spray were restricted. The methods for determination of free fatty acid, phosphorus, baicalin and phosphatidylcholine were established.In the stability research, accelerated test for6month and long-term test for12month had been conducted. The results showed that the major indicator of this preparation had no significant change, which meant the stability this preparation was good. |
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