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Coupling hot-melt extrusion (HME) with fused deposition modeling three-dimensional printing (FDM-3DP) can facilitate the fabrication of tailored, patient-centered, and complex-shaped ocular dosage forms. We fabricated ciprofloxacin HCl ocular inserts by coupling high-throughput, solvent-free, and continuous HME with FDM-3DP. Insert fabrication utilized biocompatible, biodegradable, bioadhesive Klucel™ hydroxypropyl cellulose polymer, subjected to distinct FDM-3DP processing parameters, utilizing a design of experiment approach to achieve a tailored release profile. We determined the drug content, thermal properties, drug-excipient compatibility, surface morphology, in vitro release, antibacterial activity, ex-vivo transcorneal permeation, and stability of inserts. An inverse relationship was noted between insert thickness, infill density, and drug release rate. The optimized design demonstrated an amorphous solid dispersion with an extended-release profile over 24 h, no physical or chemical incompatibility, excellent mucoadhesive strength, smooth surface, lack of bacterial growth (Pseudomonas aeruginosa) in all release samples, and prolonged transcorneal drug flux compared with commercial eye drops and immediate-release inserts. The designed inserts were stable at room temperature considering drug content, thermal behavior, and release profile over three months. Overall, the fabricated insert could reduce administration frequency to once-daily dosing, affording a promising topical delivery platform with prolonged antibacterial activity and superior therapeutic outcomes for managing ocular bacterial infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Amorphous solid dispersions (ASDs) have gained attention as a formulation strategy in recent years, with the potential to improve the apparent solubility and, hence, the oral bioavailability of poorly soluble drugs. The process of formulating ASDs is commonly faced with challenges owing to the intrinsic physical and chemical instability of the initial amorphous form and the long-term physical stability of drug formulations. Numerous research publications on hot-melt extrusion (HME) technology have demonstrated that it is the most efficient approach for manufacturing reasonably stable ASDs. The HME technique has been established as a faster scale-up production strategy for formulation evaluation and has the potential to minimize the time to market. Thermodynamic evaluation and theoretical predictions of drug-polymer solubility and miscibility may assist to reduce the product development cost by HME. This review article highlights robust and established prediction theories and experimental approaches for the selection of polymeric carriers for the development of hot melt extrusion based stable amorphous solid dispersions (ASDs). In addition, this review makes a significant contribution to the literature as a pilot guide for ASD assessment, as well as to confirm the drug-polymer compatibility and physical stability of HME-based formulations., (Copyright © 2022 Elsevier B.V. All rights reserved.)