| Glucosamine hydrochloride is extracted from natural chitin,clinical trials show that glucosamine hydrochloride will not only improve the symptoms of osteoarthritis,but also effectively control the development of osteoarthritis.At present,the dosage form of glucosamine hydrochloride approved for launching conclude tablets,capsules and granules at home and abroad.But the drug concentration in articular cartilage will lead to a decline in the transportation of drug by oral administration.In order to improve the concentration of glucosamine hydrochloride in inflammatory bone joints,a cataplasm of high local drug concentration and good transdermal absorption is chosen,and the formulation,preparation technology and quality of glucosamine hydrochloride cataplasm are studied by following work:1.An analytical method of glucosamine hydrochloride in vitro was established.According to USP36-NF31,the content of glucosamine hydrochloride was determined by HPLC method.The results showed that glucosamine hydrochloride concentration had a good linear relationship in the range of 2.52 ?g·mL-1?503.50 ?g·mL-1,the regression equation was A = 0.7637C + 1.0871,(R2 = 0.9998).The limit of quantitation(LOQ)and the limit of detection(LOD)of glucosamine hydrochloride were 2 ?g·mL-1 and 0.6 ?g·mL-1 respectively.The relative standard deviation(RSD)of recovery rate was 1.59%,and the stability and intra and inter day precision met the requirements.2.The oil-water distribution of glucosamine hydrochloride was investigated.The solubility of glucosamine hydrochloride was determined by 0.9%normal saline,purified water and phosphate buffer and the optimum solvent was purified water.The oil-water partition coefficient of glucosamine hydrochloride was 0.0123,LogP value was-1.91,the results showed that the glucosamine hydrochloride was highly hydrophilic,needed to take appropriate way to improve the percutaneous absorption of glucosamine hydrochloride.3.The penetration enhancer of glucosamine hydrochloride was determined.Using Franze diffusion cell as a simulated drug diffusion system,mouse skin as transdermal barrier,azone,dimethyl sulfoxide and 1,2-propylene glycol were screened.The results showed that the permeation effect of azone on the glucosamine hydrochloride was good.4.The prescription of glucosamine hydrochloride cataplasm was screened by orthogonal test.Partially neutralized polyacrylate NP-700 was chosen as the framework material,on the basis of single factor test,the initial adhesion,viscosity and sensory evaluation as index,orthogonal test was used to determine the optimun dosage of the matrix:NP-700 was 1.2 g,carboxymethylcellulose sodium was 0.15 g,dihydroxyaluminium aminoacetate was 0.2 g,glycerin was 10 g.With the cumulative penetration amount per unit area of glucosamine hydrochloride as index,the azone dosage was 1 g,glucosamine hydrochloride was 150 mg.The final prescription of glucosamine hydrochloride cataplasm was drawn up(according to 1000 g paste meter):glucosamine hydrochloride was 3.46 g,NP-700 was 27.63 g,carboxymethylcellulose sodium was 3.45 g,plasdoneK90 was 9.21 g,EDTA-2Na was 1.15 g,dihydroxyaluminium aminoacetate was 4.60 g,glycerin was 230.26 g,azone was 23.03 g and tartaric acid was 3.45 g,twain80 was 2.30 g,ethyl 4-hydroxybenzoate was 0.69 g,water was 690.77 g.5.The preparation process of glucosamine hydrochloride cataplasm was investigated.The peeling strength of paste as index,the formability of glucosamine hydrochloride cataplasm was investigated by adding carboxymethylcellulose sodium and plasdoneK90 to water phase or oil phase,addition order of water phase and oil phase and the stirring speed and stirring time.The final process was determined as follows:adding azone and ethyl 4-hydroxybenzoate to glycerin,followed by NP-700,dihydroxyaluminium aminoacetate and tween80,mixing evenly as an oil phase.Dissolving EDTA-2Na to distilled water,after adding Plasdone K90,carboxymethylcellulose sodium as the water phase 1.Tartaric acid and glucosamine hydrochloride were dissolved in distilled water as the water phase 2,water phase 1 and water phase 2 were mixed into the oil phase,the stirring speed was 20 r/min and the stirring time was 4min.The prepared paste was coated with a coating machine at room temperature,and the coating speed was 10 mm/s,the thickness of the paste was 1.5 mm,then the glucosamine hydrochloride cataplasm was prepared,which specification was 10 cm×15 cm each patch,with 100 mg glucosamine hydrochloride contained in 30 g paste.6.The quality of glucosamine hydrochloride cataplasm was studied.The identification method,content,shape,adhesiveness and weight difference of glucosamine hydrochloride cataplasm were examined.The content of glucosamine hydrochloride cataplasm was determined by HPLC,and the specificity experiment showed that the excipients had no effect on the measurement of glucosamine hydrochloride.The relative standard deviation(RSD)was 0.11%for recovery of low,medium and high concentrations of glucosamine hydrochloride.The average content of glucosamine hydrochloride cataplasm was 104.14 mg/plaster,and the average labeled content was 104.14%.According to the penetration rate of glucosamine hydrochloride,the penetration behavior of glucosamine hydrochloride cataplasm in vitro was studied.The cumulative penetration amount of glucosamine hydrochloride within 12 h was 84.59 mg,accounting for 84.59%of the total.The permeation rate equation was y=47.115t + 36.433(R2 = 0.9753),consistented with zero order kinetics.Through the long-term test:at 250C ± 2?,relative humidity of 60%± 10%for 3 months and accelerated tests:at 40? ± 20C,the relative humidity of 75%± 5%for 1 months,with the initial adhesion,viscosity and the content of glucosamine hydrochloride as index,the stability of glucosamine hydrochloride cataplasm was investigated,the results showed that glucosamine hydrochloride cataplasm had good stability.7.The quality standard of glucosamine hydrochloride cataplasm was studied out.According to the general inspection items of Chinese Pharmacopoeia in 2010? edition appendix to the preparation and quality standard of patch,the properties,methods of identification,content determination and cumulative permeation amount of glucosamine hydrochloride cataplasm were proposed. |
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