Preparation Of Two AngiotensinⅡtablets And Osmotic Pump Controlled-release Tablet Of ST1213

This topic mainly studies two Ang Ⅱ antagonism tablets which including prescription and preparation techniques of ST0723 and ST0903 tablet, the preparation of osmotic pump controlled-release tablet of ST1213 and the optimization of formulation by central composite design. The ST0723 was made of wet granulation which select adhesive one.However, the ST0903 was made of dry granulation, which no adhesive added. The preparation of osmotic pump controlled-release tablet of ST1213 was use excipients V and excipients VII as the tablet core. The coating materials consisted of excipients VIII, excipients IX and excipients X, meanwhile, acetone-isopropylalcohol(vandv, 4:1) co-solvent was employed as the coating medium.This study includes the following four parts:1. Preparation of ST0723 tabletST0723 is a type of Angiotensin Ⅱ receptor inhibitor tablet, which belongs to the poorly soluble drugs. In order to improving its dissolution, we use excipients I, excipients V as a filling agent, excipients VI as disintegrating agent, excipients III as glidants,excipients IV as lubricant. Experiments respectively to investigate the choice of adhesive,the dosage of disintegrant, different pressure influence on dissolution, and so on, by fine-tuning the formulation to achieve the original drugdissolution.2. Preparation of ST0903 tabletIn this part, ST0903 is a type of Angiotensin Ⅱ receptor inhibitor tablet, which belongs to the poorly soluble drugs. However, duing to its hygroscopicity and polymorphy, ST0903 is not so stable like ST0723. So in consider of its instability, we use the technology of dry granulation. In the selection of excipients,we use excipients I as diluent, excipients II as disintegrating agent, excipients III as glidants,excipients IV as lubricant. Experiment respectively investigates the roll wheel speed, the roller pressure, the dose disintegrating agent,and so on,which all affect the dissolution.To improve the dissolution, changing parameters by fine-tuning the prescription process, comparing with the original curve, to achieve the original effect of dissolution.3. Preparation of ST1213 osmotic pump controlled-release tabletIn this part, release of the model drugs in vitro was determined by UV method. By preparation of solid dispersions of ST1213 to achive the solubilization level, Central Composite Design-Response Surface Method was used to optimize the coating formulation. Tablet core material was use excipients VII, excipients V as the diluent. The coating materials consisted of excipients VIII, excipients IX and excipients X, meanwhile, acetone-isopropylalcohol(vandv, 4:1) co-solvent was employed as the coating medium.In the formulation design, the effects of three independence variables, tablet weight gain, the amount of excipients IX, particle size, were evaluated. Response variables selected in the research were 12 h cumulative drug release in vitro and linearity of the release curve as dependent variables. Central composite design-response surface methodology was applied to optimize monolithic osmotic pump controlled-release tablets formulation. An optimal formulation was obtained based on the optimal experimental conditions. The optimization area was successfully found. The optimal formulation was as follows: the contene of excipients IX was 0.71%, weight gain in coating was 3.00%, number of the release orifice was 0.4mm. The dissolution profiles of the self-made osmotic pump tablets were similar tothat of the target profile. The self-made osmotic pump tablets had excellent zero-order release characteristics in the time period of 12 h and the reproducibility of releasing appeared good.