Posaconazole double-layer osmotic pump controlled release tablet and preparation method thereof

Abstract

The invention belongs to the field of medicinal preparation and specifically provides a posaconazole double-layer osmotic pump controlled release tablet and a preparation method thereof. The tablet comprises a tablet core and a semipermeable controlled release film. The tablet core comprises a drug containing layer and a boosting layer. The drug containing layer is located inside the controlled release film which is provided with a drug releasing hole. The boosting layer is located inside the controlled release film at a place far away from the drug releasing hole. One end of the water-permeable controlled release film is provided with one or more drug releasing holes. The release curve of the preparation drug shows a zero-order release pattern, and thus the problem of drug resistance caused by long-term use of posaconazole dosage forms on the market is solved. Besides, the problems that the preparation technology is complex, the preparation cost is high, and the drug is unsuitable for industrialized mass production due to the adoption of a hot-melt extrusion technology are solved. Simultaneously, the in vivo-in vitro correlation of the drug is better ensured and the clinical monitoring of plasma concentration is better facilitated.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a posaconazole double-layer osmotic pump controlled-release tablet and a preparation method thereof. Background technique [0002] Schering-Plough's triazole antifungal drug posaconazole (trade name Noxafil) for the prevention of invasive Aspergillus (Aspergillus) and Candida (Candida) infections has been approved for marketing. The US FDA approved the drug for immunocompromised patients over 13 years old, especially hematopoietic stem cell transplant recipients with graft versus host disease (GVHD), blood cancer patients, and long-term leukopenia due to chemotherapy of patients. Posaconazole is the first antifungal drug approved for the prevention of invasive Aspergillus infections. The research results show that the effect of the drug on preventing Aspergillus infection is stronger than that of fluconazole (fluconazole), and its molecular structure is as follows: ...

AI Technical Summary

Problems solved by technology

The currently marketed products are posaconazole suspension and posaconazole sustained-release tablets, but posaconazole suspension has the disadvantages of poor stability, large oral dose and low bioavailability. Bioavailability (8-47%), further improvement depends on whether it is taken together with high-fat food; from the patent PCT / US2009 / 040652 and the instruction document of posaconazole sustained-release tablets, it can be known that posaconazole sustained-release tablets are prepared by heating Solvent extrusion technology pre-forms posaconazole and hydroxypropyl methylcellulose acetate succinate polymer into solid dispersion form, and then makes sustained-release tablets, which requires special and expensive hot-melt extrusion equipment, The preparation process is complicated, the production cost is high, and it is not suitable for industrialized large-scale production

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