Khan Ikram Ullah, Shoukat Mehwish, Asif Muhammad, Khalid Syed Haroon, Asghar Sajid, Munir Muhammad Usman, Irfan Muhammad, Rasul Akhtar, Qari Sameer H, Qumsani Alaa T, Hassan Mohamed M, Alahdal Maryam A, Usman Muhammad, Khan Zulqurnain
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan.
Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
Microorganisms. 2022 Jun 7;10(6):1171. doi: 10.3390/microorganisms10061171.
We developed alginate-based floating microbeads of clarithromycin with therapeutic oils for the possible eradication of () infections by enhancing the residence time of the carrier at the site of infection. In pursuit of this endeavor, the alginate was blended with hydroxy propyl methyl cellulose (HPMC) as an interpenetrating polymer to develop beads by ionotropic gelation using calcium carbonate as a gas generating agent. The developed microbeads remained buoyant under gastric conditions for 24 h. These microbeads initially swelled and afterwards decreased in size, possibly due to the erosion of the polymer. Furthermore, swelling was also affected by the type of encapsulated oil, i.e., swelling decreased with increasing concentrations of eucalyptus oil and increased with increasing concentrations of oleic acid. Antibacterial assays of the formulations showed significant antibacterial activity against () and (); these assays also showed synergistic activity between clarithromycin and therapeutic oils as evident from the higher zone of inhibition of the microbeads as compared to the pure drug and oils. Scanning electron microscopy (SEM) images revealed a smoother surface for oleic acid containing the formulation as compared to eucalyptus oil containing the formulation. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) revealed the development of a stable formulation, while Fourier transform infrared spectrophotometry (FTIR) studies did not reveal any interaction between the polymers and the active ingredients. Optimized formulations (CLM3 and CLM6) were designed to release the drug in a controlled manner in gastric media by Fickian diffusion. Conclusively, the developed microbeads are a promising carrier to overcome the narrow therapeutic index and low bioavailability of clarithromycin, while the presence of therapeutic oils will produce synergistic effects with the drug to eradicate infection effectively.
我们研发了含克拉霉素的藻酸盐基漂浮微珠，并添加了治疗性油剂，旨在通过延长载体在感染部位的停留时间来根除（）感染。为实现这一目标，将藻酸盐与羟丙基甲基纤维素（HPMC）混合作为互穿聚合物，以碳酸钙作为气体发生剂通过离子凝胶法制备微珠。所制备的微珠在胃部条件下可保持漂浮24小时。这些微珠最初会膨胀，随后尺寸减小，这可能是由于聚合物的侵蚀所致。此外，膨胀还受包封油类型的影响，即随着桉叶油浓度的增加膨胀减小，而随着油酸浓度的增加膨胀增大。制剂的抗菌试验显示对（）和（）具有显著的抗菌活性；这些试验还表明克拉霉素与治疗性油剂之间具有协同活性，从微珠的抑菌圈比纯药物和油剂更大即可明显看出。扫描电子显微镜（SEM）图像显示，含油酸制剂的表面比含桉叶油制剂的表面更光滑。差示扫描量热法（DSC）和热重分析（TGA）表明所制备的制剂稳定，而傅里叶变换红外光谱（FTIR）研究未显示聚合物与活性成分之间存在任何相互作用。优化后的制剂（CLM3和CLM6）经设计可通过菲克扩散在胃部介质中以可控方式释放药物。总之，所研发的微珠是一种有前景的载体，可克服克拉霉素治疗指数窄和生物利用度低的问题，而治疗性油剂的存在将与药物产生协同作用，有效根除感染。
