Preparation Of D-929 Nasal Thermosensitive Gel

D-929 is an oily substance that is insoluble in water and developing its preparation has a relatively large limitation,so the current clinical formulations are soft capsule and injection.The bioavailability of oral administration is not ideal and there is a first-pass effect,and injection compliance is poor.Based on those reasons,this research uses the approach of nasal delivery.The research uses new solubilizers and gel matrix and combines with thermo-sensitive gel technology to prepare thermo-sensitive gel with high dose and good stability.That solves the problems that the D-929 is insoluble and difficult to use drugs and other issues.The preparation takes methyl cellulose as gel matrix.The rheological characteristics of the methyl cellulose solution were examined with the gel phase transition temperature,viscosity,and fluidity,and the effect of additive on the rheological properties of methyl cellulose solution.Finally,the blank gel is prescribed as "methyl cellulose-polyethylene glycol-citric acid sodium".D-929 is an oily substance that is insoluble in water,and it can not be evenly dispersed in the aqueous medium.So it is necessary to screen suitable solubilizers,and make them into micelles and soluble in methyl cellulose matrix.Finally,we are sure that the solubilizer is polyethylene glycol-12-hydroxy stearate which is got by the solution clarification degree and compatibility.This experiment uses the method of the membrane free dissolution,that is similar to the nasal environment,to simulate and analyze the release of drugs and to optimize the prescription.Finally,the prescription of thermo-sensitive gel for D-929 nasal is determined: the concentration of methyl cellulose is 1.5%,the concentration of polyethylene glycol is 8.0%,the concentration of sodium citrate is 3.5%,the concentration of polyethylene glycol-12-hydroxy stearate is 2.0%,the concentration of D-929 is 0.2%.Evaluating the quality of the final prepared gel,the final determination of the gel phase transition temperature is 34.3?±0.5?,the flow distance that is measured by porcine nasal mucosa is 0.1-0.3 cm,the viscosity of 6-9 Pa.S,the cumulative release rate reached more than 93.8%±4.04% after D-929 gel releases 8 h in vitro,and D-929 releases completely.The stability of D-929 nasal temperature sensitive gel is studied.The pH range of this preparation is set between 5.0 and 7.0.With respect to in vitro pharmacodynamic studies,this experiment uses the nasal mucosa permeability test of isolated animals and bases on the permeability andsteady-state flow inspection targets,we make sure that the final determination of the beat location of the medicine is the upper turbinate and the dosage is about 50 ?L-100 ?L.