A method for preparing flaky ibuprofen crystals from aqueous solution by adding crystal form control agent

Abstract

A method for preparing flaky ibuprofen crystals from an aqueous solution by adding a crystal form control agent, belonging to the new technical field of pharmaceutical preparations, comprising the following steps: first preparing an aqueous solution containing ibuprofen, urea and polyvinyl alcohol, and raising the temperature to 100° C, keep warm for 12 to 24 hours and then cool to room temperature to prepare ibuprofen aqueous solution; then use hydrochloric acid and potassium chloride to prepare a buffered aqueous solution of pH=1 and add polyethylene glycol with a molecular weight of 400 grams per mole and a molecular weight of 1000 Polyethylene glycol in grams per mole, polyethylene glycol with a molecular weight of 2000 grams per mole, polyethylene glycol with a molecular weight of 10000 grams per mole, L-glutamic acid or polyacrylic acid as a crystal form control agent, Subsequently, the ibuprofen aqueous solution was added dropwise to the pH=1 buffer aqueous solution containing the crystal form control agent, stirred and reacted for 4 hours, filtered, washed twice with deionized water, and finally dried at 40°C for 12 hours to prepare the tablet ibuprofen crystals. The flaky ibuprofen crystals prepared by the method are adjustable in size and uniform in size, which is beneficial to the realization of subsequent tableting and wrapping processes, and the specific surface area of ​​the crystals is small, so that the effect of slowly releasing the ibuprofen can be realized.

Description

technical field [0001] The invention discloses a method for preparing flaky ibuprofen crystals from an aqueous solution by adding a crystal form control agent, which belongs to the new technical field of pharmaceutical preparations. Background technique [0002] Ibuprofen can be used to treat diseases such as fever and pain. Different forms of ibuprofen crystals will have different properties, such as solubility, melting point and therapeutic effect. At the same time, the crystal form will also affect the flow properties, tablet performance and Package performance. The crystallization of ibuprofen can be realized by melting method, solvent method and supercritical fluid method. The most commonly used solvent method is to dissolve ibuprofen in organic solvents, such as n-hexane, n-heptane and absolute ethanol etc., and then Ibuprofen crystals are prepared from anti-solvent by the method of anti-solvent crystallization, but a part of organic solvent will remain in the ibuprof...

AI Technical Summary

Problems solved by technology

In recent years, in order to avoid the use of organic solvents, a method of preparing ibuprofen crystals directly in aqueous solution after melting has been developed (A.O. Abioye et al. International Journal of Pharmaceuticals 509(2016)264-278), but this method requires precise temperature control and stirring speed, after all, the melting and recrystallization process of ibuprofen is greatly affected by temperature changes and stirring speed

So far, there are few studies on the preparation of ibuprofen crystals from aqueous solution instead of directly through the melting process, especially the preparation of ibuprofen with specific morphology (such as flakes, etc.) from aqueous solution is very rare.

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