黄芩素-盐酸小檗碱双药共晶的制备与评价

Preparation and evaluation of baicalein-berberine hydrochloride dual-drug cocrystal

关键词:  黄芩素  盐酸小檗碱  药物共晶  分子间相互作用  难溶性药物  口服生物利用度

Key words:  baicalein,berberine  Hydrochloride,pharmaceutical  cocrystals,intermolecular  interactions, poorly  soluble drugs, oral  bioavailability

摘要:

目的 制备黄芩素-盐酸小檗碱共晶以改善其溶解度和生物利用度。方法 采用溶剂挥发法制备共蒸发物,表征其形态、结晶及热力学等特性,测定其平衡溶解度、体外溶出度及大鼠口服药动学行为,并与原料药进行比较。结果 两药的甲醇共蒸发物呈黄色粉末、由大量长柱状结晶聚集而成,其熔点和衍射峰的变化证实了共晶形成,红外光谱提示存在氢键和π堆叠；所得共晶在水中的溶解度均高于原料药,其中黄芩素为3.19倍、盐酸小檗碱约1.14倍,体外溶出亦显著加快,大鼠口服后Cmax、AUC相较于物理混合物提高了1.31-1.63倍。结论 本研究成功制备了黄芩素-盐酸小檗碱共晶,不仅为解决难溶性药物的临床应用问题提供了新策略,也为中药活性成分的制剂创新和药效提升开辟了新途径。

Abstract:

Objective To prepare a Cocrystal of Baicalein and Berberine Hydrochloride to improve their solubility and bioavailability. Methods The co-evaporates were prepared by solvent volatilization method. The morphology, crystalline structure, and thermodynamic characteristics were characterized. The equilibrium solubility, in vitro dissolution rate, and the pharmacokinetic behavior after oral administration in rats were measured and compared with the original drugs. Results The coevaporates of the two drugs from methanol are yellow powder composed of numerous rod-like crystals, showed changes in melting points and diffraction peaks, confirming the formation of the cocrystal. Infrared spectroscopy indicated the presence of hydrogen bonds and π-stacking interactions. The cocrystal demonstrated higher solubility in water than the original drugs, with baicalein"s solubility increasing by 3.19 times and berberine hydrochloride"s by approximately 1.14 times. The in vitro dissolution rate was significantly enhanced, and after oral administration in rats, both the maximum concentration Cmax and the area under the curve AUC were 1.31 to 1.63 times higher compared to the physical mixture. Conclusion The successful preparation of the baicalein-berberine hydrochloride cocrystal offers a novel strategy for addressing the clinical application challenges of poorly soluble drugs. It also paves the way for innovation in the formulation of traditional Chinese medicine active components and the enhancement of their therapeutic effects.