Preparation Of Salviae Miltiorrhiza And Ligustrazine Hydrochloride Nasal Thermosensitive In Situ Gel

Objective: To prepare the nasal gel for the preparation of ligustrazine hydrochloride. At the same time, its release rate in vitro and mucosal permeability were investigated, and the nasal ciliary toxicity and mucosal irritation of the preparation were investigated preliminarily.Methods: Salviae miltiorrhizae and ligustrazine hydrochloride injection was taken as the research object to prepare the preparation of Salviae miltiorrhizae and ligustrazine hydrochloride nasal temperature sensitive in situ gel. Based on L9(34) orthogonal experimental design, the DSS extraction rate as index, the optimal extraction process of DSS from Radix Salvia was selected. With gelling temperature as dependent variable, the contents of P407, P188 and PEG-6000 as independent variables, blank prescription was optimized by central composite design-response surface methodology, and the optimal prescription was predicted by response surface method, and finally verified. And the in vitro release was evaluated in Franz diffusion cell to optimal formula of the matrix further; with the preparation of DSS and LH transdermal permeation as index, the gel penetration enhancers was optimized. To investigate and analyze the drug release pattern of the gel in vitro, the method of free film dissolution was taken. NA, VE and other auxiliary materials added, the final prescription of the preparation was determined. The toxicity and safety of the cilia were studied in parallel. To study the irritation of the nasal mucosa of the gel, SD rats were taken intranasal administration many times. The ciliotoxicity of the preparation was taken on toad palate.Results: The optimal extraction process of DSS obtained as follows: 12 times of water soaking 12 h, and in decoction for 2 h. the optimal formulation composed with P407, P188 and PEG-6000 were18%, 7% and 1% respectively. The cumulative release was detected to be over 70% after 12 h, and the release curve conforms to the first-order kinetic equation. The cumulative release rate equations in vitro of DSS and LH were Ln(100-Qt) =-0.3491t+4.6231 and Ln(100-Qt) =-0.5979t+4.3582. The cumulative permeation of LH and DSS in the gel were 2649.77 μg?cm-2 and 119.72 μg?cm-2 after 12 h. The release in vitro and permeability curves were both in accord with the first order kinetic equation, which indicated that the preparation had obvious sustained-release characteristics. In parallel, compared the in vitro release and transdermal permeation equation, the mucosa was the main rate limited step to restrict the entry of drugs into the body. Mucosal toxicity test showed that the preparation was almost no irritation. The ciliary toxicity test showed that the gel has no toxic and side effect on the cilia.Conclusion: It was stable and reliable to optimal the extraction method of DSS with the orthogonal experiment method. The model built by the central composite design and response surface method can better optimize the prescription of Salviae miltiorrhizae and ligustrazine hydrochloride nasal temperature sensitive in situ gel. The preparation process has the advantages of simple, reasonable and feasible. The gel has sustained release effect, and better mucosal permeability. The preparation of stability and safety are in line with the requirements.