Study On Preparation And Release Mechanism Of Salvianolic Acid B Microporous Osmotic Pump Capsules

Salvianolic acid B(Sal B)is the most abundant and biologically active water-soluble compound in salvianolic acid.It is mainly used for the treatment of cardiovascular diseases and liver diseases.It has the characteristics of high potency and low probability of causing allergic reactions.Because of its instability in the gastrointestinal tract and the large first-pass effect of the liver,limiting the development of drugs.To meet the medical needs of patients with cardiovascular and cerebrovascular diseases,and to improve the problems of Sal B,this article used Sal B as a model drug to prepare microporous osmotic pump capsules,optimized the preparation process and prescription of capsule shells and contents,and studied the stability of the preparations.According to the accumulative releasing degree,electron micrograph and capsule shell morphology as evaluation indicators,the preparation process of microporous capsule shell was determined.Through the single factor,the accumulative releasing degree of the drug in vitro and the fitting degree with the zero order equation were used as evaluation indicators to determine the optimal capsule shell and content formulation of Sal B microporous osmotic pump capsules.In the formulation of the capsule shell,cellulose acetate(CA)was used as the material of the capsule shell,polyethylene glycol 2000(PEG2000)was used as the porogen,and triethyl citrate(TEC)was used as the plasticizer;In the formulation of the capsule contents,Sal B was the main drug,sodium chloride(Na Cl)was the osmotic active substance,carboxymethyl cellulose sodium(CMC-Na)was the blocker,and microcrystalline cellulose(MCC)was thinner.According to the fitting situation,it was determined that the CA concentration,the amount of porogen and the amount of osmotic active substance were the main factors affecting the drug release.The star-point design-response surface method was used to fit the best formulation,the final CA concentration was 6.9%,the amount of porogen(PEG2000)was 8.52 mg,and the amount of osmotic active substance(Na Cl)was 34.15 mg.The test results show that the formulation and process of Sal B microporous osmotic pump capsules are feasible.In the investigation of the release mechanism,the effects of release pathways,diffusion mechanisms,different osmotic media,medium hydrodynamics,and p H value on the accumulative releasing degree were examined separately.The results show that the release route and the osmotic pressure difference have an effect on the drug release in the microporous osmotic pump capsule,and the drug release is not affected by the medium hydrodynamics and p H value.The stability test and quality evaluation of the prepared Sal B microporous osmotic pump capsules were conducted,and the changes of the pharmaceutical preparations under the influence of temperature,humidity,and light were investigated.The results show that the quality of the capsule shell meets the requirements of the Pharmacopoeia,and the pharmaceutical preparations are relatively stable under the light and heat factors,but have a certain hygroscopic effect,and should be stored sealed in a dry condition.In this experiment,the Sal B microporous osmotic pump capsules were successfully prepared.The degree of drug release in the preparation was relatively complete within 12 hours(accumulative release degree > 90%)and was close to the zero-order release rule,which achieved a good controlled release effect,which was in line with expectations.