Studies On Compound Nicotinic Acid Sustained-Release Tablets

Nicotinic acid, one of the blood lipid-requlating drags earliest used to reduce the case fatality rate, has been holding important position in the therapy of high blood-lipid. Nicotinic acid has exact curative effect but show great adverse effects, so it should be made into sustained-release dosage form and co-administered with other drags to lighten them. In this study, nicotinic acid and lovastatin were made into compound preparation which can be administered once daily, with nicotinic acid as the part of sustained-release layer and lovastatin as the part of immediate-release layer.According to the results of pre-formulation and preliminary experiments, in vitro release of drag was chosen as the response of screening, and mixture design was applied to select HPMC as the primary excipient and lactose as the filler of compound nicotinic acid sustained-release tablets. The optimal formulation was obtained through optimizing the amounts of excipients by central composite design. Mixture design and central composite design were employed to analyze the factors influencing the release percentage of compound nicotinic acid sustained-release tablets. It showed that the matrix material retarded the drug release evidently. The retardation ability of HPMC was better than Compritol 888 ATO when they were used at the same amount. The higher the amount of matrix material, the slower the rate of drag release. Different lands and amounts of fillers had no obvious effect on drag release.Preparation technology studies demonstrated that different preparation technologies had effects on drug release to some degree and the influence of tablet-compressing strength was minor.The results of different methods measuring release percentage had no obvious difference. Different rotation speed had no obvious influence on drug release. Release media with different pH value influenced drug release markedly.The result of study on the mechanism of drug release showed that in vitro drug release was fitted to first-order kinetics and mechanism of release was irregular diffusion. The result of preliminary test on stability indicated that this preparation should be stored in a well-closed , light-resistant and cool place.The study of in vivo pharmacokinetics on dogs showed that the relative bioavailabilities of nicotinic acid and lovastatin in tablets self-made were 105.9% and 105.6%, respectively. For nicotinic acid,Tmax of the test and the reference preparations were 4.0h and 1.0h; Cmax of them were 111.8g/mL and 107.2g/mL, respectively. For lovastatin, both Tmax of the two preparations were 3.2 h; Cmax of them were 208.7ng/mL and 196.2 ng/mL. Nicotinic acid, the sustained-release part, showed good IVTVC.