Venlafaxine hydrochloride long-acting controlled-release pellets and preparation method thereof

Abstract

The invention provides venlafaxine hydrochloride long-acting controlled-release pellets. The pellets comprise (1) first controlled-release pellets each of which comprises a first pill and a first controlled-release layer coating the surface of the first pill; (2) second controlled-release pellets each of which comprises a second pill and a second controlled-release layer coating the surface of the second pill, wherein the first controlled-release pellets and the second controlled-release pellets are mixed in the proportion being 1:1 and are wrapped by capsules, and the whole controlled-release pellets are formed. According to the venlafaxine hydrochloride long-acting controlled-release pellet, a pellet core adopts single microcrystalline cellulose, ethyl cellulose with proper viscosity and the appropriate quantity of coatings are selected for preparation of the first controlled-release pellet body and the second controlled-release pellet body, and the drug release quantity of active ingredients can be controlled perfectly, sustainably and stably in 2h, 4h, 8h, 12h, 24h or other time after the pellet is taken by adopting the process that the pellet and the control-release pellet bodies are prepared once on a fluidized bed.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, and belongs to the technology of sustained-release preparations, in particular to venlafaxine hydrochloride long-acting sustained-release pellets and a preparation method thereof. Background technique [0002] Venlafaxine Hydrochloride (VenlafaxineHydrochloride), chemical name (R / S)-1-[2-(dimethylamine)-1-(4-methoxyphenyl)ethyl]cyclohexane hydrochloride, molecular formula for C 17 h 27 NO 2 ·HCl, the structural formula is shown in Formula 1, the appearance is white or off-white powder, easily soluble in water, and belongs to three biogenic amine reuptake inhibitors including serotonin, norepinephrine and dopamine, and is mostly used in pharmaceuticals It exists in the form of hydrochloride and is clinically used to treat various types of depression, including depression with anxiety and generalized anxiety disorder. [0003] [0004] The structural formula of formula 1 ...

AI Technical Summary

Problems solved by technology

The weak point of this technical scheme is: 1. ball core contains active ingredient (main drug), sodium chloride / or potassium chloride, microcrystalline cellulose and excipient, and raw material cost is high, and preparation process is complicated; 2. main drug , sodium chloride, and potassium chloride have high water solubility, so the active ingredients are easy to migrate during the coating process, and the water content of the pills must be strictly controlled. The process quality control is difficult and affects large-scale production; The pills are prepared by mass granulation, and the roundness of the obtained pills is poor, which affects the coating quality, and the preparation of pills and sustained-release pills requires switching between two sets of equipment, which is inconvenient to operate and consumes time and energy.

The disadvantages of this technical solution are: 1. the preparation first uses the extrusion spheronization method to prepare the pills containing the skeleton material, and then transfers to the inner coating of the fluidized bed. The production equipment involved includes an extrusion spheronizer and a fluidized bed, which makes the labor force Increased cost (intensive labor), low efficiency of working hours, and does not comply with the provisions of "to minimize the transfer of intermediate processes" in GMP; The polyacrylic resin NE30D will cause the migration of venlafaxine hydrochloride during the coating process. If the thickness of the coating film is inconsistent, it will lead to unstable drug release and low bioavailability

The disadvantages of this technical solution are: ① the sustained-release film contains plasticizers and pore-forming formulations, and the plasticizer is a toxic chemical substance that is easy to cause cancer, and the pore-former will accelerate the release of the drug; ② the sustained-release film only uses A coating of sustained-release material, which is not conducive to the perfect release of the drug at each release control point of 2h, 4h, 8h, 12h, and 24h, especially in the late stage of drug release, which may affect its effective maintenance due to the rapid release rate blood concentration

The disadvantages of this technical solution are: ① porogens and plasticizers are used in the slow-release film, and plasticizers are toxic chemicals. Long-term use will cause abnormalities in the reproductive system, and even cause the risk of teratogenicity and cancer, such as Taiwan After the "plasticizer diethyl phthalate incident", the country has begun to strictly control the use of plasticizers; There are multiple processes such as drug application, isolation layer coating, and sustained-release film coating, which are complex, time-consuming and energy-consuming

The disadvantages of this technical solution are: 1. when the pills are prepared by the powder layering method, the drying time of the pills is as long as 24 hours, which is quite time-consuming, and certain dust will be generated in the preparation, which will affect the yield of the product; 2. the process should be After the slow-release coating is completed, aging in the oven is required for 4 hours, the process cycle is long, time-consuming and energy-consuming

Images