Studies On Venlafaxine Hydrochloride Oral Sustained Release Preparations

Venlafaxine hydrochloride is a new therapeutic agent for anti-depression, which has strong therapeutic effect, high safety and preferable tolerance compared with TCA, MAOI and SNRIs. Two kinds Venlafaxine hydrochloride sustained release preparations （sustained release capsules and sustained release tablets） were prepared based on the commercially available Venlafaxine hydrochloride sustained release capsules.In vitro analytical method for two preparations have been established and tested.Venlafaxine hydrochloride pellets were prepared by means of powder layering with the centrifugal granulation equipment. Through the formulation screening and procedure optimizing, it was discovered that the yield of the objective pellets （18-24 mesh cut） was about 80%. The results suggested the preparation procedure and formulation of Venlafaxine hydrochloride pellets could reach the expected goals.A fluid-bed spray processor was adopted for the coating of the pellets. The influence of coating solution’s formulation and coating procedure on the release of sustained release pellets was observed. The optimal preparation was coated by the ethylcellulose （20 cps）. The results of the quality studies on Venlafaxine hydrochloride sustained release capsules showed that the release homogeneity of one batch and the release repeatability of three batches were good. The release wasn’t influenced by pH value of the release media. The stability test showed that Venlafaxine hydrochloride sustained release capsules were stable.Based on the direct press procedure, single-factor tests on the influence factors of formulation and procedure on the release of sustained release tablets were carried out to obtain the optimal formulation and procedure. Kollidon（?） SR was selected as the matix materials to prepare the tablets and Kollicoat（?） SR aqueous dispersions was selected to coat the tablets. The results of quality studies on Venlafaxine hydrochloride sustained release tablets showed that the release homogeneity of one batch and the release repeatability of three batches were good. The release wasn’t influenced by pH value of release media. The stability test showed that Venlafaxine hydrochloride sustained release tablets were stable.The HPLC method for determination of Venlafaxine hydrochloride in dog plasma was developed. According to three-crossover design, the time-concentration curve of the test and reference preparations was plotted. AUC_0-36, T_max and C_max of the reference capasule, sustained release capsules and sustained release tablets were （1172.54±276.05）, （1202.02±260.75） and （1107.25±202.85） ng·h·mL^-1; （6.7±0.8）, （7.2±0.4） and （7.2±0.8） h; （102.00±34.00）, （92.41±27.18） and （106.57±19.40） ng·mL^-1 respectively. The relative bioavailability of sustained release capsules and sustained release tablets were （102.92±6.35） % and （96.04±13.20） % respectively.