The Preparation Of Gllipizide Tablet And Its Study In Vivo

Diabetes become after the heart cerebrovascular disease and the tumor. At present in the market the anti-diabetic preparation is numerous, because the high cost of imported peparations and diabetes are chronic diseases which need for long-term adherence rule medication to control blood glucose levels. Thus for ordinary diabetic patients, the choice of an effective, safe and cheap products are the most important. Glipizide belongs to the second-generation sulfonylurea hypoglycemic agent. Its mechanism is related to B cell membrane on the sulfonylurea receptor specific binding, so that K+ channels closed, causing changes in membrane potential, Ca2+ channel to open, within cytosolic Ca2+ rise, to insulin secretion. Compared to the first-generation sulfonylurea drugs, glipizide is more selective B cell binding capacity. The use of smaller doses could reduce hypoglycemia, neutropenia and the risk of cardiovascular adverse reactions. Glipizide was chosen as research object in this paper which is insoluble drugs, but good absorption in vivo. So the dissolution of drugs in vivo became a major factor to durg absorption. At present many similar formulations in the market, excipients and manufacturing process and other factors could be directly change drug release in human body. Drug released too fast can lead to low blood glucose, the contrary, the release too slow while the hypoglycemic effect is not significant. Thus through bioequivalence test, compare the inherent quality of self-made and of market formulation.This paper studies glipizide various physical and chemical properties, the establishment of shake flask-UV spectrophotometric determination of glipizide of oil-water distribution coefficient, high performance liquid chromatography glipizide equilibrium solubility, UV determination of glipizide ionization constant. Methodological study demonstrated that the method is accurate and reliable, and convenient. Determination of the drug’s physical and chemical property provides a theoretical basis for the prescription research.Using everted intestinal sac method study glipizide in the rat intestine in the absorption characteristics. Intestinal absorption in vitro experimental results show that glipizide in the rat duodenum, jejunum, ileum and colon has a higher apparent permeability coefficient. And glipizide is completely absorbed drug. But there is significant difference in the permeability coefficient of different site of intestinal; the permeability of jejunum is strongest. To some extent the addition of surfactant can increase absorption of glipizide. The pH value of intestinal nutrient solution is lower than the pKa of glipizide, absorption of glipizide in the small intestine is better for drug existed mainly in molecular form. Through single-factor study was carried out to optimize the description of glipizide tablets and the preparation process. Compare the dissolution curve of self-made and market tablets, the results show that the self-made and the market is similar in vitro dissolution. The results of stress testing and accelerated testing showed that self-made glipizide tablets were stable under all conditions.With two-crossover design, the pharmacokinetics of self-made glipizide tablets in human was studied compared to the reference tablets. The main pharmacokinetic parameters of the test and reference formulations were as follows:Cmax were 381.14±111.76 ng·mL-1 and 362.07±101.55 ng·mL-1, Tmax were 2.5±1.36 h and 3.69±1.94 h, T1/2 were 4.21±2.02 h and 5.08±2.60 h, AUC0-24 were 2118.17±635.21 ng·h·mL-1 and 2216.13±766.44 ng·h·mL-1, AUC0-∞were 2363.84±651.60 ng·h·mL-1 and 2368.10±913.72 ng·h·mL-1 respectively. The relative bioavailability of glipizide was 106.77±27.10%. The results of analysis of variance and two one-sided t-test demonstrated that the two dosage forms were bioequivalent.