Preparation And Pharmacokinetics In Rats Of Nano-carvedilol Tablets

Carvedilol is a vasodilator drug used to treat hypertension and coronary heart disease.Carvedilol is a class II drug in the biopharmaceutics classification system,with poor water solubility and low bioavailability.In this thesis,carvedilol was made into a nanosuspension.Based on the optimized formulation and process of blank tablet cores,the active ingredient coating technology was used to obtain nano-carvedilol tablets,and the quality evaluation and pharmacokinetics study were performed.The purpose of study was to improve drug dissolution and bioavailability.In this thesis,ultraviolet spectrophotometry was established as an analytical method for the dissolution of nano-carvedilol tablets,and high performance liquid chromatography was used as an analytical method for the content of nano-carvedilol tablets.The experimental results showed that the established methods were accurate and reliable,and both met the requirements for determination of nano-carvedilol tablets.Carvedilol nanosuspension was prepared by media grinding method.The formulation of carvedilol nanosuspension was determined:the stabilizer was 8%PVPK30,the drug concentration was 200 mg/m L,and the grinding medium was zirconia beads（φ0.8 mm）40 g,the ball mill speed was 500 r/min,the grinding time was 6 h.Screening and optimizing of the formulation and process of blank tablet cores were carried out.The blank tablet cores were compressed by wet granulation and were formulated with 35%starch,29%lactose,35%microcrystalline cellulose,1%magnesium stearate,and a suitable amount 10%starch slurry.The blank tablet cores were coated by a roll coating method,and the coating liquid was formulated with a solid content of 15%and a ratio of the drug to the coating powder of 1:1.The quality of homemade nano-carvedilol tablets was evaluated.The tablet weight difference,friability,content,and content uniformity all met the requirements of the 2015Chinese Pharmacopoeia;the dissolution studies were performed on homemade nano-carvedilol tablets,the results of three batches of tablets showed that the dissolution of tablets had uniform release within batches and similar releases between batches.In four dissolution media of p H 1.2 hydrochloric acid solution,p H 4.0 acetate buffer solution,p H 6.8 phosphate buffer solution and distilled water,the dissolution of homemade nano-carvedilol tablets was measured and compared with physical mixture and commercially available tablets.The results indicated that the dissolution rate of nano-carvedilol tablets was significantly improved.The pharmacokinetic study of nano-carvedilol tablets in rats was carried out.The method of administration:fasting and feeding.The plasma concentration of carvedilol was determined by HPLC,and the pharmacokinetic parameters were calculated using DAS 3.0.The results showed that,whether fasted or eaten,the C_maxand AUC_0-∞of homemade nano-carvedilol tablets were significantly greater than those of physical mixtures and commercially available tablets;under fasting conditions,compared with physical mixtures and commercially available tablets,the relative bioavailability of homemade nano-carvedilol tablets was 224.49%and 153.89%respectively;under the feeding conditions,compared with physical mixtures and commercially available tablets,the relative bioavailability of homemade nano-carvedilol tablets was 248.39%and180.81%respectively.The results showed that nano-carvedilol tablets could significantly improve drug absorption and bioavailability.