Preparation of Venlafaxine Hydrochloride Osmotic Pump Release Tablets
|School||Hebei Medical University|
|Keywords||Venlafaxine Hydrochloride Osmotic pump tablet Controlled Release Tablets Orthogonal design Beagle dogs|
Objective: Venlafaxine hydrochloride is a new class of phenylethylamine derivatives, is a new antidepressant with a unique chemical structure and role of neuropharmacology. By blocking the 5 - hydroxytryptamine (5-HT) and norepinephrine (NE) reuptake of two neurotransmitters play an antidepressant effect, venlafaxine applicable to all types of depression associated with anxiety and depression and generalized anxiety disorder, depression both psychomotor retardation have agitated behavior also has a good effect. Existing ordinary preparations often take a day administered 2 or 3 times, plasma concentrations have fluctuated considerably, significant side effects. Therefore, there is an urgent need to slow controlled preparation and infiltration pump tablets is a typical representative of the controlled release formulations made of venlafaxine osmotic pump tablets constant release rate within a certain time frame. release a certain amount of drugs, drug release characteristics of a zero-order release kinetics, and reduce the number of to want to improve patient compliance, reduce side effects, and to ensure the safety and efficacy of the drug, and the drug release rate from the gastrointestinal Road pH, peristalsis speed and gastric emptying in vivo correlation. Methods: Preparation of tablet core with a single punch tableting mechanism, cellulose acetate coating materials, PEG400 as porogen, diethyl phthalate as plasticizer, acetone as solvent in the preparation of a coating liquid, a pan coating method Preparation of venlafaxine hydrochloride osmotic pump tablets. Preliminary literature and on the basis of preliminary experiments to determine the speed of the coating process, the coating temperature, coating pan and spray pressure. The hardness of the tablet core, the diameter of the tablet cores, osmolality promoting agent types, the osmolality promoting agent in an amount, the amount of porogen and weight of the coating film to inspect and evaluate their similarity factor method, the in vitro release curve similar sex. In the above experiments based on the amount of osmotic pressure accelerator porogen amount and weight of the coating film as the three factors, respectively, select the level of 3, L9 (34) orthogonal experiment, using a weighted scoring method to 2,6,10 hours of the release of three ratings points determining the optimal prescription. Optimize prescription preparation venlafaxine hydrochloride osmotic pump tablets in vitro release experiments, the cumulative release curve. Release experimental device in accordance with the first method of the People's Republic of China Pharmacopoeia 2005 edition two Appendix XC dissolution assay, 900 ml of water release medium speed of 75 rpm, medium temperature (37.5 ± 0.5) ° C, respectively, in 1 2, 4, 6, 8, 10, 12 hours to take liquid, adding 5 ml volume with temperature release media over 0.8μm microporous membrane, the filtrate as the test solution. Constant volume after shaking precision another sophisticated take Venlafaxine Hydrochloride 13 mg is set to 100 ml volumetric flask, 25 ml of a constant volume in a 50 ml volumetric flask, as a control solution. In the following chromatographic conditions, the control solution and the test solution was measured to calculate the cumulative release of the peak area. Literature and preliminary experiments on the basis of established HPLC analysis method for determination of venlafaxine hydrochloride. Chromatographic conditions: column was a Kromasil C8 (250mm × 4.6mm, 5μm); mobile phase was 0.1 mol / ml ammonium dihydrogen phosphate: acetonitrile (60:40); flow rate of 1.0 ml / min; column temperature was 25 ° C; detection wavelength of 230 nm. Preliminary investigation of stability osmotic pump tablets of venlafaxine hydrochloride, impact factor experiments including high temperature, high humidity, and bright light three influencing factors experiment, sampling at 0, 5, 10 days of its appearance, content release visit. The acceleration test at 40 ℃, relative humidity of 75% under the conditions of its appearance, content, and release respectively in 0,6 months sampling investigated. Pharmacokinetic experiments: Beagle dogs for experimental animals, randomized Beagle dogs were divided into two groups, were orally given to the production of Chengdu Great Southwest Pharmaceutical Co., Ltd. of venlafaxine capsules and homemade hydrochloric text venlafaxine osmotic pump tablets, blood was collected at predetermined time points and analyzed for plasma treatment, crossover study week later cleaning. At different time points after administration plasma concentration was determined by high performance liquid chromatography, using non-compartment model to calculate various pharmacokinetic parameters. Results: through single factor and orthogonal experiment screened tablet technology for tablet core diameter of 11 mm, hardness of 8 kg, tablet weight of 400 mg. The coating process: the coating temperature 40 ° C, the coating the pot speed of 60 rpm, spray pressure kg/cm2. Best prescription: osmolality promoting agent is mannitol and lactose (1:1), and the osmolality promoting agent, with the primary drug ratio of 4:1, the coating liquid is of cellulose acetate and 10% (g / g) PEG400 The weight of the coating film is 3% of the tablet core and the cellulose acetate concentration of 4% (w / v). Determination of in vitro content Venlafaxine Hydrochloride by HPLC retention time of 4.5 min, excipients on the determination of non-interference, the linear range of 5 ~~ 100μg/ml linear regression equation was C = 21743A 5877.1 (r = 0.9999 ), day precision (RSD) of 1.04 to 1.85% day precision (RSD) of 0.25 to 0.43%, the recovery rate of 98.96 to 100.12 percent. Experiment of the influence factors, the sample at 5 days and 10 days at 92.5% relative humidity weight gain is large, the sample does not gain weight at 5 days and 10 days and at 75% relative humidity, 10 days after the appearance, the content and release unchanged; under 60 ° C and 4500 ± 500 lx glare conditions, 10 days after the sample appearance, the content and release are unchanged. Addition of experiments, in 6 months after sample appearance, the content and release are constant. Pharmacokinetic studies, experiments, according to the selected liquid conditions, the main pharmacokinetic parameters were: osmotic pump tablets and capsules, Tmax (h) were 6.333 ± 0.816 and 3.833 ± 0.408; Cmax (μg / ml were 17.09 ± 2.284 and 7.697 ± 0.738, 0.415 ± 0.106 and 0.981 ± 0.29), respectively; MRT (h). Visible osmotic pump tablet compared with the commercially available capsules drug peak concentration time and MRT were prolonged, and peak concentration decreased. Conclusion: Venlafaxine hydrochloride osmotic pump tablets have significant drug release characteristics of controlled release formulations, in line with the zero-order release kinetics model, capable of constant rate of release 12 hours, good reproducibility, and temperature, humidity, light not affect the quality of the preparation. At the same time to establish the content determination, release determination method provides a reliable method to examine quality. In vivo experiments to prove the drug peak time and MRT than those commercially available capsules long, and reduce peak concentration.