Development and optimization of hot-melt extruded moxifloxacin hydrochloride inserts, for ocular applications, using the design of experiments

Ruchi Thakkar; Neeraja Komanduri; Narendar Dudhipala; Siddharth Tripathi; Michael A Repka; Soumyajit Majumdar

doi:10.1016/j.ijpharm.2021.120676

Development and optimization of hot-melt extruded moxifloxacin hydrochloride inserts, for ocular applications, using the design of experiments

Int J Pharm. 2021 Jun 15:603:120676. doi: 10.1016/j.ijpharm.2021.120676. Epub 2021 May 5.

Authors

Ruchi Thakkar¹, Neeraja Komanduri¹, Narendar Dudhipala¹, Siddharth Tripathi², Michael A Repka³, Soumyajit Majumdar⁴

Affiliations

¹ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, University, MS 38677, USA; Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA.
² Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA; National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS, USA.
³ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, University, MS 38677, USA; Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA; Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS 38677, USA.
⁴ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, University, MS 38677, USA; Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA. Electronic address: majumso@olemiss.edu.

PMID: 33961956
DOI: 10.1016/j.ijpharm.2021.120676

Abstract

The current study sought to formulate sustained-release hot-melt extruded (HME) ocular inserts of moxifloxacin hydrochloride (MOX; MOX-HME) for the treatment of bacterial keratitis. The concentration of Eudragit™ FS-100 (FS) and propylene glycol (PG) used as polymer and plasticizer, respectively, in the inserts were optimized using the central composite design (CCD) to achieve sustained release. The inserts were characterized for weight, thickness, surface characteristics, pH, and in vitro release profile. The crystalline characteristics of MOX and surface morphology of the inserts were evaluated using differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Furthermore, ex vivo permeation through rabbit cornea and stability of the optimized MOX-HME insert was investigated. The results demonstrate an inverse correlation between FS concentration and MOX release from the MOX-HME inserts, and a potential 24 h release. The optimized MOX-HME inserts were found to be stable at room temperature for four months, showing no significant change in drug content, pH and release profile. MOX converted into an amorphous form in the MOX-HME inserts and did not recrystallize during the study period. SEM analysis confirmed the smooth surface of the MOX-HME insert. The ex vivo studies revealed that the MOX-HME inserts provided a much prolonged transcorneal MOX flux as compared to the commercial ophthalmic solution and the immediate-release MOX-HME insert. The results indicate that MOX-HME inserts could potentially provide a once-a-day application, consequently reducing the dosing frequency and acting as an alternative delivery system in the management of bacterial infections.

Keywords: Design of experiments; Eudragit™ FS-100; Hot-melt extrusion; Moxifloxacin; Ocular bacterial infections; Ocular inserts; Sustained release.

MeSH terms

Animals
Calorimetry, Differential Scanning
Drug Compounding
Hot Temperature*
Moxifloxacin
Polymers*
Rabbits
Solubility

Substances

Polymers
Moxifloxacin