Preparation Of Temperature-Sensitive In Situ Gel Of Scopolamine Hydrobromide

Objective:to prepare nasal temperature-sensitive in situ gel of scopolamine hydrobromide.Methods:(1) To determine the detection wavelength of Scop by using UV scanning method.(2) Ultraviolet detection method is determined by drawing standard curve, investigating precision and stability of Scop(3) To determine gel temperature by measuring the viscosity of situ gel under different temperature.(4) To optimize the situ gel prescription by studying the effects of chitosan quality concentration, ratio of chitosan /β- glycerol sodium phosphate, pH, temperature, etc to GT and gel viscosity, and screening penetration enhancer, antioxidant and antiseptic.(5) To establish the HPLC content determination method of Scop.(6) To study drug-loaded situ gel release behavior in vitro by using diffusion pool method, membrane stripping and dialysis bag method.(7) to evaluate its safety by investigating the cilia toxicity and mucous membrane irritation of the preparation.(8) To investigate situ gel preliminary stability by observing reserved sample.(9) To study preliminary pharmacodynamics of the situ gel by investigating effect of SD rat resistance to motion sickness thorough different route of medication.Results:(1) The UV detection wavelength of Scop was 258 nm.(2) Scopolamine hydrobromide had good linear relationship between absorbance and concentration in which concentration range was 0.2-1.2 mg/ml; good instrument precision; At room temperature, Scopolamine hydrobromide was relatively stable in pH6.5～7.5 solution,In line with the requirements of nasal preparation pH5.5～7.5。(3) The gelation temperature was 34℃。(4) Optimizing the chitosan concentration was 2%; Chitosan/β-glycerin sodium phosphate volume ratio of 6:1; PH7.1 as the pH of the gel system; 3%1,2-propylene glycol as promoting permeability agent; 0.01%VE as antioxidant; 0.1% methyl p-hydroxybenzoate as preservative。(5) HPLC detection wavelength was 203 nm, mobile phase: methanol-0.001 mol/L (including 0.01 mol/L SLS) phosphate (70:30), the method was accurate, simple, easy, and could effectively measured the content of Scop in situ gel.(6) diffusion cells results showed that Drug biological membrane diffusion of temperature-sensitive situ gel containing scopolamine hydrobromide using as nasal drug dependent on the drug concentration gradient passive diffusion on both sides of the mucosa; membrane stripping method showed the main drug of drug-situ gel released by diffusion rather than dissolution way; dialysis bag method showed that the release curve was in conformity to the first-order kinetic equation.(7) Cilia toxicity test and mucous membrane irritation test showed that drug in situ gel were non-toxic to cilia,or almost no irritation to mucosa.(8) Stability test results showed that the preparation was suitable for low temperature preservation, preparation traits, pH, viscosity, drug content did not change significantly in 0-6 months, had good stability, and at room temperature, preparation can be as short-term carry medication.(9) The experimental group has less symptoms of motion sickness and less recovery time than that of the blank group, the drug loaded in situ gel has good effect for motion sickness.Conclusion:The preparation technology of temperature-sensitive situ gel containing scopolamine hydrobromide using as nasal drug is reasonable, reliable, quality control method is feasible; drug loaded in situ gel had non-toxic to cilia, small stimulation to mucous membrane, and had sustained-release effect,was a kind of nasal cavity drug delivery new formulation for resistance to motion sickness,it has potential value to effectively prevent and treat motion sickness, deserves further research and development.