Sanap Sachin Nashik, Bisen Amol Chhatrapati, Kedar Ashwini, Yadav Karan Singh, Krishna Atul, Akhir Abdul, Chopra Sidharth, Mugale Madhav Nilakanth, Bhatta Rabi Sankar
Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Int J Biol Macromol. 2022 Dec 1;222(Pt B):2785-2795. doi: 10.1016/j.ijbiomac.2022.10.058. Epub 2022 Oct 11.
Bacterial and fungal co-infection leads to polymicrobial keratitis (PMK). The current study produced swellable mucoadhesive biopolymeric films composed of chitosan, HPMC, and glycerol using cast drying method. The film was dual-loaded with fluconazole (FCZ) and ofloxacin (OFX) to treat PMK. The prepared film exhibited excellent thickness, folding endurance, surface pH, tensile strength, and stability characteristics. In addition, it also exhibited good in vitro antimicrobial activity, ex-vivo mucoadhesion, and corneal permeation. AUC and MRT were 6.5 and 5.2-fold higher for a film containing FCZ and 22.5 and 2.5-fold higher for a film containing OFX than their marketed formulations. PK-PD simulation study supports desired efficacy of the proposed dosage form. Thus, the film exhibits longer pre-corneal drug residence time and enhanced ocular bioavailability, most likely resulting in high patient compliance. The proposed film could be a prominent replacement for the existing dosage form and may present a viable alternative for the treatment of PMK.
细菌和真菌的合并感染会导致微生物性角膜炎（PMK）。当前的研究采用流延干燥法制备了由壳聚糖、羟丙基甲基纤维素（HPMC）和甘油组成的可膨胀粘膜粘附生物聚合物薄膜。该薄膜双重负载氟康唑（FCZ）和氧氟沙星（OFX）以治疗PMK。所制备的薄膜表现出优异的厚度、耐折性、表面pH值、拉伸强度和稳定性特征。此外，它还表现出良好的体外抗菌活性、离体粘膜粘附性和角膜渗透性。含有FCZ的薄膜的AUC和MRT分别比其市售制剂高6.5倍和5.2倍，含有OFX的薄膜的AUC和MRT分别比其市售制剂高22.5倍和2.5倍。PK-PD模拟研究支持了所提出剂型的预期疗效。因此，该薄膜表现出更长的角膜前药物滞留时间和增强的眼部生物利用度，极有可能提高患者的依从性。所提出的薄膜可能成为现有剂型的重要替代品，并可能为PMK的治疗提供可行的选择。
