(T1130-02-11) Formulation Development and Characterization of Dual Drug Loaded Hot-Melt Extruded Inserts for Better Ocular Therapeutic Outcomes: Sulfacetamide/Prednisolone

Purpose: The objective of this investigation was to formulate, characterize, and evaluate a bioadhesive, hot-melt extruded (HME), immediate- and extended-release ophthalmic inserts containing a fixed-dose combination of Prednisolone Sodium Phosphate (PSP) and Sulfacetamide Sodium (SA) to improve the treatment outcomes of multiple ocular bacterial infections. This contemporary approach aims to curb the disadvantages of the conventional method of preparations of ophthalmic inserts. The adopted approach could prolong ocular residence time, improve bioavailability, and reduce the frequency of administration while maintaining a scalable process for insert manufacturing, which ultimately can be commercialized.

Methods: The ocular inserts were formulated using a HAAKE Minilab II extruder. These inserts were evaluated for Appearance, thickness, and weight drug content, surface pH, moisture uptake & loss, drug-excipient compatibility, chemical interactions, swelling index, thermal characteristics, ex vivo bioadhesion, in vitro drug release, ex vivo transcorneal permeation, ex vivo corneal deposition, and surface morphology. Moreover, the inserts’ stability was checked over 90 days.

Results: The HPC-HF and EC-containing inserts extended the release of both drugs ( >4 h) compared to PEO-N10-based inserts that showed the release of the loaded amount of both drugs immediately ( < 1 h). All fabricated inserts were stable over 90-day storage at room temperature (25ºC) and accelerated conditions (40ºC) for drug content and thermal behavior. The developed PSP-SA inserts exhibited optimum bioadhesive strength and smooth surface favorable for topical ocular application. Ex vivo transcorneal permeation studies using freshly isolated rabbit corneas demonstrated that the extended-release inserts slowed down the transcorneal flux of the drug in comparison to the immediate-release inserts and the commercial solution eyedrops.

Conclusion: Immediate and sustained-release ocular inserts were successfully prepared using hot-melt extrusion technology. The in-vitro characterization of the fabricated inserts revealed the sustained-release performance of the HPC-HF and EC-containing inserts. In addition, these inserts also showed retarded flux of the drugs through the corneal membrane when evaluated against marketed solution eyedrops and the immediate-release PEO insert. The inserts also showed stability at 25°C and 40°C by showing no change in the drug content, physical appearance, and thermal characteristics for 3 months. The fabricated inserts could decrease frequent application, prolong the therapeutic effect, and increase patient compliance compared to the conventional solution eyedrops.

References: Alzahrani, A.; Adel Ali Youssef, A.; Nyavanandi, D.; Tripathi, S.; Bandari, S.; Majumdar, S.; Repka, M.A. Design and Optimization of Ciprofloxacin Hydrochloride Biodegradable 3D Printed Ocular Inserts: Full Factorial Design and In-Vitro and Ex-Vivo Evaluations: Part II. Int. J. Pharm. 2022, 122533
Thakkar, R.; Komanduri, N.; Dudhipala, N.; Tripathi, S.; Repka, M.A.; Majumdar, S. Development and Optimization of Hot-Melt Extruded Moxifloxacin Hydrochloride Inserts, for Ocular Applications, Using the Design of Experiments. Int. J. Pharm. 2021, 603

Acknowledgements: Scanning Electron Microscopy images presented in this work were generated using the instruments and services at the Microscopy and Imaging Center, The University of Mississippi. This facility is supported in part by grant 1726880, National Science Foundation.

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