Lenalidomide pharmaceutical composition and preparation method therefor

Abstract

The invention relates to a lenalidomide pharmaceutical composition and a preparation method therefor. A lenalidomide solid dispersion comprises 2%-40% of lenalidomide and 60%-98% of water-soluble support, wherein the water-soluble support is povidone. According to the lenalidomide pharmaceutical composition provided by the invention, the drug loading capacity is large, and prepared solid preparations are high in bioavailability, good in solubility and stable and controllable in quality; and the preparation method for the lenalidomide pharmaceutical composition is simple in process, good in reproducibility and high in operability and is applicable to large-scale production.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a lenalidomide pharmaceutical composition and a preparation method thereof. Background technique [0002] Lenalidomide is an antineoplastic drug developed by Celgene Biopharmaceutical Company of the United States. It is an analogue of thalidomide, but it has fewer side effects than thalidomide and does not cause neonatal deformities. Clinically, it is mainly used for the treatment of myelodysplastic syndrome (MDS), multiple myeloma (MM), leukemia and mantle cell lymphoma, and was approved by the FDA in 2005. Lenalidomide is a new generation immunomodulator with anti-angiogenic and anti-tumor properties and has a dual mechanism of action. [0003] Lenalidomide (Lenalidomide), the chemical name is 3-(7-amino-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione, and its structural formula is as shown in formula I below, Molecular formula C 13 h 13 N 3 o ...

AI Technical Summary

Problems solved by technology

However, the upper limit of the drug loading of lenalidomide solid dispersions on the market is usually 20%. The higher the drug loading, the more prone to "coarsening" of the crystal form, which affects the dissolution of the drug. Therefore, it is necessary to choose a suitable carrier. The solubility and stability of the prepared solid dispersion with high drug loading (20-40%) are good

[0007] The patent of Publication No. CN101537184A provides a pharmaceutical composition of poorly water-soluble drugs and its preparation method. Example 6 in the description discloses a capsule or tablet with lenalidomide as the active ingredient. The specific preparation method: in the future Nalidomide, Povidone and Eudragit resin are dissolved in ethanol and sprayed on the surface of lactose granules / pills, and then mixed with other auxiliary materials such as magnesium stearate to fill capsules or be compressed into tablets, but there are following defects in this technical scheme: (1 ) uses the mixture of povidone and Eudragit resin as the carrier, releases the drug slowly, and cannot reach the required blood concentration in a short time; (2) There are amino groups in the molecular structure of lenalidomide, and lactose excipients may occur The "Maillard reaction" makes solid oral preparations increase in impurities and is prone to change in appearance and color; (3) The process in this technical solution is complicated, and crystal form changes may occur during the preparation process or the reproducibility of the granulation process is poor. Drug dissolution has a greater impact on

But this technical scheme has the following defects: (1) the prescription uses poloxamer as a carrier, when increasing the proportion of lenalidomide in the solid dispersion, especially when the proportion of the dosage is 20-40%, It is uncertain whether it can separate out crystals; (2) povidone is only used as a solubilizer or binder in this technical scheme

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