Health Sciences Research Centre, Princess Nourah bint Abdulrahman University, Riyadh 84428, Saudi Arabia.
Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, The University of Jordan, Amman, Jordan.
Eur J Pharm Biopharm. 2023 Oct;191:78-89. doi: 10.1016/j.ejpb.2023.08.012. Epub 2023 Aug 22.
The goal of the study was to look into drug-polyelectrolyte complexation between ciprofloxacin (Cipro) and λ-carrageenan (CRG), and to employ the complex as a sustained-release matrix. The maximum binding capacity of the complexation was determined using the dialysis bag method and employed to prepare the complex. In comparison to Cipro, CRG, and their physical mixing, the complex was examined using differential scanning calorimetry, Fourier infrared spectroscopy, powder X-ray diffraction, and scanning electron microscopy. Cipro-CRG matrices, manufactured as direct compression tablets based on the greatest binding capacity, were assessed for swelling, erosion and drug release in 0.1 M HCl, in comparison with those of CRG, Hydroxypropyl methylcellulose (HPMC) and Cipro-HPMC matrices. In vivo absorption study comparing the Cipro-CRG matrix to Cipro immediate-release tablet was also carried out. The greatest binding capacity of Cipro to CRG was 55% (w/w). Multiple interactions, including electrostatic interaction, Vander wall forces, and hydrogen bonding, have been proposed to be involved in complexation with drug amorphization. As a result of the complexation, the swelling and erosion properties of CRG changed, with Cipro-CRG matrix showing substantially less swelling and erosion than Cipro-free CRG matrix. Cipro-CRG matrix exhibited swelling and erosion similar to Cipro-HPMC matrix. However, the former matrix demonstrated Cipro release with significantly less burst impact and a significantly slower release rate. Furthermore, Cipro-CRG matrices in vivo demonstrated slow-prolonged oral drug absorption with consequent significant changes in pharmacokinetic parameters in comparison to those obtained for immediate-release tablets.
本研究旨在探讨环丙沙星(Cipro)与 λ-卡拉胶(CRG)之间的药物-聚电解质络合作用,并将该复合物用作缓释基质。采用透析袋法确定络合的最大结合能力,并用于制备复合物。与 Cipro、CRG 及其物理混合物相比,通过差示扫描量热法、傅里叶红外光谱法、粉末 X 射线衍射法和扫描电子显微镜法对复合物进行了研究。根据最大结合能力,将 Cipro-CRG 基质制成直接压片,评估其在 0.1 M HCl 中的溶胀、侵蚀和药物释放情况,并与 CRG、羟丙基甲基纤维素(HPMC)和 Cipro-HPMC 基质进行比较。还进行了 Cipro-CRG 基质与 Cipro 速释片的体内吸收比较研究。Cipro 与 CRG 的最大结合能力为 55%(w/w)。提出了多种相互作用,包括静电相互作用、范德华力和氢键,参与药物非晶化的络合作用。由于络合作用,CRG 的溶胀和侵蚀性质发生了变化,Cipro-CRG 基质的溶胀和侵蚀明显小于无 Cipro 的 CRG 基质。Cipro-CRG 基质的溶胀和侵蚀与 Cipro-HPMC 基质相似。然而,前者的基质表现出 Cipro 释放,具有明显较小的突释影响和较慢的释放速率。此外,与速释片相比,Cipro-CRG 基质在体内表现出缓慢延长的口服药物吸收,导致药代动力学参数发生显著变化。