Paliperidone release rate progressive increasing preparation and preparation method thereof

Abstract

The invention discloses a paliperidone release rate progressive increasing preparation and a preparation method thereof. The paliperidone release rate progressive increasing preparation provided by the invention, from outside to inside, comprises a non-essential damp-proof beautiful coating, a semipermeable rigid film shell which plays a vital role, and an osmotic pump tablet core provided with one or more holes. The osmotic pump tablet core, from top to bottom, is composed of a controlled-release layer, a drug-containing layer and a push promoting layer; and penetration enhancers in the push promoting layer, in accordance with different coating weight increasing degrees, include a coating penetration enhancer I, a coating penetration enhancer II and a coating penetration enhancer III. The various coating penetration enhancers, which are different in coating weight increasing degree, differ in osmotic pressure in water. With the application of the paliperidone release rate progressive increasing preparation disclosed by the invention, when water enters the tablet core along with an osmotic pressure difference, the push promoting layer absorbs water to be swelled so as to push the outward release of the drug-containing layer and the controlled-release layer, and as time varies, the isolating coating penetration enhancers are exposed in the water, so that the osmotic pressure is continuously increased, a water-absorbing rate is increased and a drug-release rate is increased as well, thus progressive increasing drug release is achieved; therefore, the drug-release rate is effectively controlled, a blood drug concentration curve is kept stable and the fluctuation of blood drug concentration is relieved.

Description

technical field [0001] The invention relates to a preparation with increasing release rate of paliperidone and a preparation method thereof, belonging to the technical field of pharmaceutical preparations. Background technique [0002] Schizophrenia and bipolar mania are the most common types of mental illnesses characterized by changes in basic personality, splits in thinking, emotion, and behavior, and incoordination between mental activities and the environment, and are one of the severe mental illnesses. Schizophrenia occurs mostly in young adults without organic changes, and is a functional psychosis. Patients are generally unconscious and have impairments in motor skills, but when they attack, they not only affect their ability to work, but also have a great impact on the patient's work, study, and life. Drug therapy is one of the most commonly used and effective treatment methods so far. It can not only effectively control the symptoms of mental illness patients, but...

AI Technical Summary

Problems solved by technology

In this patent, the three-layer sac-shaped osmotic pump tablet containing paliperidone is administered orally, and the drug is released incrementally through the ratio of the two drug-containing layers. The patent introduces the paliperidone three-layer capsule in detail However, we regret to find that based on the following reasons, this three-layer sac-shaped osmotic pump tablet still has the defects of special process and high production cost.

The preparation process of the three-layer sac-shaped osmotic pump tablet is relatively complicated. During the preparation process, it is necessary to prepare two kinds of drug-containing granules with different drug contents, and detect the contents of the granules separately, and then perform tablet compression, and finally need to use laser marking. The purpose of drug release can only be achieved by punching two drug release holes in the hole machine, which greatly reduces the production efficiency. At the same time, because its shape is a capsule, according to the pressure distribution of the tablet during the tablet compression process, the thicker the tablet, the smaller the pressure in the middle of the tablet. In this way, capsule-shaped tablets require greater pressure to form than ordinary-shaped tablets, but ordinary tablet presses cannot reach this pressure, so special tablet press equipment is required to achieve

[0008] Chinese patent 101711752A discloses a controlled-release preparation of benzisoxazole derivatives and its preparation method. This patent uses paliperidone as a model drug to invent a double-layer compressed tablet and triple-coated osmotic pump The preparation has an increasing effect in the early stage of drug release, and a process of constant drug release in the later stage. However, we regret to find that the patented process is complicated, and the production efficiency of the three-layer coating film is greatly lower, and it cannot be well developed. In vivo and in vitro fitting with the original research product Invega

However, we regret to find that this invention does not need to release the drug for the clinical treatment of paliperidone. For example, the initial blood concentration of the drug should not rise too fast, otherwise the adverse reactions will be prominent, and tachyphylaxis will appear after the increase , the absorption rate is low after the colon, if the release rate is maintained at the same level as the small intestine, it is difficult to achieve the required therapeutic concentration, etc. These problems are not well explained in the description of the invention

[0010] Dr. Li Wei's paper "Research and Evaluation of Innovative Preparation Technology in the Industrialization of Osmotic Pump Controlled Release Preparations" explained the significance of quasi-in-situ pore-forming technology to promote the industrialization of osmotic pump technology, but this paper only involves how in-situ pore-forming technology Improve the efficiency of industrialization, without involving in-situ pore-making to adjust the release profile, to obtain a drug release profile suitable for clinical needs

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