使用各种亲水性聚合物的布洛芬共晶体的合成、表征及稳定性优化

Synthesis, Characterization, and Stability Optimization of Ibuprofen Cocrystals Employing Various Hydrophilic Polymers.

作者信息

Hassan Ayesha, Khan Jamshaid Ali, Nasir Fazli, Shabir Hira, Hannan Peer Abdul, Ullah Rahim, Jan Afnan, Khalid Asaad, Khan Ajmal, Al-Harrasi Ahmed

机构信息

Department of Pharmacy, University of Peshawar, Peshawar, KPK, Pakistan.

Department of Pharmacy, Faculty of Life Sciences, Sarhad University of Science and Information Technology, Peshawar, KPK, Pakistan.

出版信息

Curr Pharm Des. 2025;31(11):873-883. doi: 10.2174/0113816128305926240530051853.

DOI:10.2174/0113816128305926240530051853

PMID:38867533

Abstract

BACKGROUND

Cocrystals are an efficient way for the delivery of low soluble drugs but when dissolved they rapidly disproportionate. To formulate the cocrystals in tablets, cocrystals must be stabilized. In this study ibuprofen-nicotinamide (IBU-NIC) cocrystals were synthesized initially by slow solvent evaporation and for bulk production by fast solvent evaporation techniques.

METHODS

The cocrystals were characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectrophotometer (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and optical microscopy. The ibuprofen cocrystals showed greater solubility compared to the parent drug.

RESULTS

Intrinsic dissolution data was utilized for efficacious screening of tablet formulations. Using hydrophilic polymers at a ratio of 6:1 (polymer to IBU-NIC cocrystal ratio), hydroxypropyl methylcellulose (F), polyvinylpyrrolidone (PVP) K-30 (F) and PVP K-90 (F3), three tablet formulations were prepared that stabilized cocrystals during dissolution. The drug release profiles after 60 minutes from formulations F (92.30), F (98.54), F (99.88) were all higher compared to the marketed brand BRUFEN F, (79.61%) in a simulated intestinal media (p<0.001).

CONCLUSION

Significant increase in the dissolution rate of cocrystal was observed with no phase change in all formulations.

摘要

背景

共晶体是递送低溶性药物的有效方式，但溶解后它们会迅速发生歧化反应。为了将共晶体制成片剂，必须使其稳定。在本研究中，布洛芬 - 烟酰胺（IBU - NIC）共晶体最初通过缓慢溶剂蒸发法合成，然后通过快速溶剂蒸发技术进行批量生产。

方法

通过粉末X射线衍射（PXRD）、傅里叶变换红外光谱仪（FTIR）、差示扫描量热法（DSC）、热重分析（TGA）和光学显微镜对共晶体进行表征。与母体药物相比，布洛芬共晶体表现出更高的溶解度。

结果

利用固有溶出数据对片剂配方进行有效筛选。以6:1的比例（聚合物与IBU - NIC共晶体的比例）使用亲水性聚合物，即羟丙基甲基纤维素（F1）、聚乙烯吡咯烷酮（PVP）K - 30（F2）和PVP K - 90（F3），制备了三种片剂配方，它们在溶解过程中能使共晶体稳定。在模拟肠液介质中，60分钟后F1（92.30%）、F2（98.54%）、F3（99.88%）配方的药物释放曲线均高于市售品牌布洛芬（BRUFEN F，79.61%）（p < 0.001）。