Nifedipine solid dispersion and preparation method thereof

Abstract

The invention discloses a nifedipine solid dispersion and a preparation method thereof. The nifedipine solid dispersion comprises nifedipine and at least one carrier, and the mass fraction of the nifedipine is 10%-50%; the method comprises the steps that after the nifedipine and the carriers are respectively smashed, sieved and mixed proportionally, the mixture is extruded out through a differential asymmetric double-screw extruder, and the nifedipine solid dispersion is prepared. By optimizing the formula design and the preparation technology of extrusion of a hot melted body, the nifedipineis combined with povidone through chemical bonds, after being converted into an amorphous state from an original crystalline state, a large amount of nifedipine can be dissolved in water, the dissolution rate is greatly increased, and the bioavailability of the nifedipine is greatly improved; in addition, the solid dispersion is stable in performance, it is avoided that the solid dispersion goes bad due to long-time placement, and the nifedipine solid dispersion and the preparation method thereof have the technical advantages that the hot melting extrusion technology is simple in preparation,and the consumed time is shorter, and are beneficial for achieving industrialization.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations. More specifically, it relates to a nifedipine solid dispersion and a preparation method thereof. Background technique [0002] Cardiovascular and cerebrovascular diseases are collectively referred to as cardiovascular and cerebrovascular diseases, and generally refer to ischemic or hemorrhagic diseases of the heart, brain and systemic tissues caused by hyperlipidemia, blood viscosity, atherosclerosis, and high blood pressure. Cardiovascular and cerebrovascular diseases are a serious threat to human beings with high morbidity and mortality. Even if the most advanced and perfect treatment methods are applied, more than 50% of cerebrovascular accident survivors cannot fully take care of themselves. The number of patients with cardiovascular and cerebrovascular diseases is large, ranking first among various causes of death. [0003] Nifedipine is a 1,4-dihydropyridine calcium io...

AI Technical Summary

Problems solved by technology

This patent meets technical requirements through the synergistic effect of solid dispersion and disintegrant, and uses solid dispersion technology to improve drug solubility and drug absorption effect, but there are still the following defects: 1) A large amount of polyethylene glycol and mannitol are used in the preparation process and other pharmaceutical excipients, its drug loading is on the low side; 2) Since nifedipine has light instability, it must be considered to avoid light in the wet granulation preparation process; 3) Nifedipine after pre-crushing and powdering Dipine still exists in the adjuvant with tiny crystalline state, can gather during tabletting and placing process, causes solubility to decline (A Jiye, Liu Yun, Feng Lin, the influence of solid preparation process on drug crystal form, Chinese Journal of Pharmaceutical Industry, 2000 Year 11 issue), the preparation 30min in 37 ℃ 1% sodium dodecylsulfonate solution dissolution rate is 34.2% ~ 97.87%, but nifedipine is almost insoluble in water, its poor solubility and dissolution rate in water are Main reasons for its low oral bioavailability

This patent has the following defects: 1) To obtain a molecularly dispersed solid dispersion requires the use of a large amount of carrier material, resulting in a low drug loading; 2) This patent does not characterize the state of nifedipine in the solid dispersion; 3 ) has an extrusion temperature of 100-120°C, while nifedipine has a higher melting point of 171-175°C, it is difficult to extrude in this temperature range, and a higher extrusion temperature exceeds the maximum tolerance of most carrier materials. Temperature, unable to solve the problem of drug and carrier stability

[0006] At present, there are still difficulties in the clinical application and preparation development of nifedipine: 1) Nifedipine is a short-acting antagonist with a short duration of action; Adverse reactions; 2) Nifedipine is insoluble in water, and a release blocker needs to be added during the preparation of sustained-release preparations, which may lead to slow release of the drug in the early stage and cannot quickly exert its drug effect; 3) Existing nifedipine solid dispersion There are also complex processes in body preparation, such as the solvent-cultivation method is only suitable for the preparation of small doses of drugs (generally less than 50 mg), the spray drying method is time-consuming, and the cost is high, and the solvent method is likely to cause organic solvent residues. The manufacturing cost is high and the efficiency is low. Disadvantages; 4) Continuous processing requires excellent self-cleaning function to ensure narrow and consistent residence time distribution

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