|
Floating Drug balance principle, which is based on fluid dynamics (hydrodynamically balanced With system, HBS) made of a special kind of sustained release dosage forms, the advantage of such a sustained-release formulations than other sustained-release formulations is that the dosage form can be a long time floating in the gastric juice on influenced by the gastric emptying, a long residence time in the stomach. The maleate Trimebutine, (trimebutine maleate, TMB) is a direct role in gastric function modifier of the gastrointestinal smooth muscle, but the half-life of only 2.7 h dosing interval is short plasma concentration fluctuations prone side effects. In this study, the original basis for the work of the laboratory, under according to Malay Trimebutine acidic with good solubility characteristics, prepared floating tablets and pharmacokinetic study of preparation of the the Malay Trimebutine stomach evaluated between the characteristics in vitro indicators and pharmacokinetics. One of Floating floating performance this experiment hydroxypropyl methyl cellulose (HPMC) K4M, K15M, K20M three models as a gel matrix material floating tablets, lactose, starch, cetyl alcohol, carbonated sodium hydrogen additive powder direct compression from the water uptake kinetics expansion dynamics dissolution kinetics of three aspects of the the tablet floating and integrity were investigated. HPMCK20M direct compression tablets rapidly disintegrating, does not have the characteristics of the floating sustained release, HPMC K4M, HPMC K15M direct compression tablets sustainable floating additives, lactose, starch, cetyl alcohol tablets considerable added bicarbonate sodium tablet disintegrating accelerated. By Higuchi kinetic equation fitting, to clarify the different excipients on floating investigated tablet floating mechanism. , The Malay Trimebutine stomach floating tablets on the basis of the original laboratory work, floating in vitro and release as a screening indicator, prescription and process factors influencing prescriptions. Using the 4 factors (HPMC K15M, cetyl alcohol, sodium bicarbonate, magnesium stearate) and 3 levels of the orthogonal design to carry out the investigation of the excipients performance, and chooses the optimal prescription. The results showed that the impact of sodium bicarbonate tablets, followed by the gel matrix materials (HPMC K15m), magnesium stearate, and the fourth is to help bleaching agent (cetyl alcohol). According to the standards of the Chinese Pharmacopoeia (2005 edition), preliminary stability of the maleate Trimebutine of Floating including impact factor test, accelerated experiments focus on appearance, content, release check project investigated the high temperature , humidity, light on the maleate Trimebutine of Floating nature. Stability investigation showed that the preparation is more sensitive to humidity, and therefore should be stored in a dry environment. Third, the floating the Malay Trimebutine stomach tablets dogs in vivo pharmacokinetic studies established a reverse phase - high performance liquid chromatography (RP-HPLC) determination of total plasma the Malay Trimebutine concentration analysis method, by confirmatory analysis method, the results comply with the requirements of \Healthy dogs, two-cycle crossover controlled trial method, a single dose (300 mg / only) were given stomach maleate Trimebutine, floating tablets (test formulation) and ordinary tablets (reference formulation) with WinNonlin software calculating pharmacokinetic parameters, and the experimental data for statistical analysis. Using non-compartment model, the test formulation C max (ng · mL -1 ) (h) the T max, t 1/2 (h), k a (h -1 ), AUC 0-t (ng · h · mL of -1 ) the AUC 0 - ∞ (ng · h · mL -1 ) were 167.85 ± 57.82,3.67 ± 0.58,2.57 ± 0.41,0.27 ± 0.08,468.23 ± 154.6,545.69 ± 178.35; reference formulations C max (ng · mL -1 max (h), t 1/2 (h), k a (h -1 ), AUC 0-t (ng · h · mL -1 ), AUC 0 - ∞ (ng · h · mL -1 ) 475.41 ± 186.80,0.75 ± 0.25,2.43 ± 0.18,0.29 ± 0.03,650.64 ± 173.2,740.48 ± 185.62; relative bioavailability of 90.05 ± 26.99%. The results showed that the absorption process in vivo gastric floating formulations with sustained release characteristics in vitro release of a good correlation between the percentage of percentage and in vivo absorption (r = 0.951).
|