Formulation development and in Vitro-Ex vivo characterization of hot-melt extruded ciprofloxacin hydrochloride inserts for ocular applications: Part I

Abdullah Alzahrani; Ahmed Adel Ali Youssef; Samir Senapati; Siddharth Tripathi; Suresh Bandari; Soumyajit Majumdar; Michael A Repka

doi:10.1016/j.ijpharm.2022.122423

Formulation development and in Vitro-Ex vivo characterization of hot-melt extruded ciprofloxacin hydrochloride inserts for ocular applications: Part I

Int J Pharm. 2023 Jan 5:630:122423. doi: 10.1016/j.ijpharm.2022.122423. Epub 2022 Nov 24.

Authors

Abdullah Alzahrani¹, Ahmed Adel Ali Youssef², Samir Senapati³, Siddharth Tripathi⁴, Suresh Bandari³, Soumyajit Majumdar⁵, Michael A Repka⁶

Affiliations

¹ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Department of Pharmacy, East Jeddah Hospital, Ministry of Health, Jeddah 22253, Saudi Arabia.
² Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Department of Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
³ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
⁴ National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS, USA; Research Institute of Pharmaceutical Sciences, University of Mississippi, Oxford, MS 38677, USA.
⁵ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Research Institute of Pharmaceutical Sciences, University of Mississippi, Oxford, MS 38677, USA.
⁶ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Research Institute of Pharmaceutical Sciences, University of Mississippi, Oxford, MS 38677, USA; Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS 38677, USA. Electronic address: marepka@olemiss.edu.

Abstract

This study developed, optimized, characterized, and evaluated bioadhesive, hot-melt extruded (HME), extended-release ocular inserts containing ciprofloxacin hydrochloride (CIP-HCL) to improve the therapeutic outcomes of ocular bacterial infections. The inserts were fabricated with FDA-approved biocompatible, biodegradable, and bioadhesive polymers that were tuned in different ratios to achieve a sustained release profile. The results revealed an inverse relationship between the Klucel™ hydroxypropyl cellulose (HPC, 140,000 Da) concentration and drug release and extended-release profile over 24 h. The CIP-HCL-HME inserts presented stable drug content, thermal behavior, surface pH, and release profiles over three months of room-temperature storage and demonstrated adequate mucoadhesive strength. SEM micrographs revealed a smooth surface. Bacterial growth was not observed on the samples during the in vitro release experiment (0.5-24 h), indicating that a minimum inhibitory concentration (MIC) of 90 against Pseudomonas aeruginosa was achieved. Ex vivo transcorneal permeation studies using excised rabbit corneas revealed that the prepared ocular inserts prolonged the transcorneal flux of the drug compared to commercial eye drops and immediate-release inserts and could reduce the administration frequency to once daily. Therefore, the inserts could increase patient compliance and exhibited prolonged antibacterial activity and thus could provide better therapeutic outcomes against ocular bacterial infections.

Keywords: Ciprofloxacin; Experimental design; Hot-melt extrusion; Klucel™ JXF; Ocular bacterial infection; Ocular insert; Sustained release.

MeSH terms

Animals
Bacterial Infections*
Ciprofloxacin*
Delayed-Action Preparations
Drug Delivery Systems / methods
Eye
Rabbits

Substances

Ciprofloxacin
Delayed-Action Preparations

Grants and funding

P30 GM122733/GM/NIGMS NIH HHS/United States