Levofloxacin Hemihydrate In Situ Gelling Ophthalmic Solution: Formulation Optimization and In Vitro and In Vivo Evaluation

Hemant Bhalerao, K. B. Koteshwara, Sajeev Chandran

Research output: Contribution to journalArticle

Abstract

Bacterial conjunctivitis is a leading cause of ocular infections requiring short-term therapeutic treatment with frequent administration of drugs on daily basis. Topical dosage forms available in the market for the treatment of bacterial conjunctivitis such as simple drug solutions and suspensions are rapidly eliminated from the precorneal space upon instillation due to tear turn over and nasolacrimal drainage, limiting intraocular bioavailability of drug to less than 10% of the administered dose. To overcome issues related to conventional drop, an effort was made to design and evaluate prolong release ophthalmic solution of levofloxacin hemihydrate (LFH) using ion-sensitive in situ gelling polymer. Gellan gum was used as the in situ gelling agent. Formulations were screened based on in vitro gelation time, in vitro drug release, and stability towards sol to gel conversion upon storage. The prototype formulations exhibiting quick in vitro gelling time (< 15 s), prolonged in vitro drug release (18–24 h), and stability for at least 6 months at 25°C/40% relative humidity (RH) and 40°C/25% RH were evaluated for pharmacokinetic studies using healthy New Zealand white rabbits. Tested formulations were found to be well-tolerated and showed significant increase in AUC0–24 (22,660.39 h ng/mL) and mean residence time (MRT 12 h) as compared with commercially available solution Levotop PF® (Ajanta Pharma Ltd., India)(AUC0–24 6414.63 h ng/mL and MRT 4 h). Thus, solution formulations containing in situ gelling polymer may serve as improved drug delivery system providing superior therapeutic efficacy and better patient compliance for the treatment of bacterial conjunctivitis.

Original languageEnglish
Article number272
JournalAAPS PharmSciTech
Volume20
Issue number7
DOIs
Publication statusPublished - 01-10-2019

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Levofloxacin
Ophthalmic Solutions
Bacterial Conjunctivitis
Drug Stability
Humidity
Polymers
Pharmaceutical Preparations
Therapeutics
Eye Infections
Dosage Forms
Polymethyl Methacrylate
Drug Delivery Systems
Patient Compliance
Tears
Biological Availability
Drainage
India
Suspensions
Pharmacokinetics
Gels

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

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title = "Levofloxacin Hemihydrate In Situ Gelling Ophthalmic Solution: Formulation Optimization and In Vitro and In Vivo Evaluation",
abstract = "Bacterial conjunctivitis is a leading cause of ocular infections requiring short-term therapeutic treatment with frequent administration of drugs on daily basis. Topical dosage forms available in the market for the treatment of bacterial conjunctivitis such as simple drug solutions and suspensions are rapidly eliminated from the precorneal space upon instillation due to tear turn over and nasolacrimal drainage, limiting intraocular bioavailability of drug to less than 10{\%} of the administered dose. To overcome issues related to conventional drop, an effort was made to design and evaluate prolong release ophthalmic solution of levofloxacin hemihydrate (LFH) using ion-sensitive in situ gelling polymer. Gellan gum was used as the in situ gelling agent. Formulations were screened based on in vitro gelation time, in vitro drug release, and stability towards sol to gel conversion upon storage. The prototype formulations exhibiting quick in vitro gelling time (< 15 s), prolonged in vitro drug release (18–24 h), and stability for at least 6 months at 25°C/40{\%} relative humidity (RH) and 40°C/25{\%} RH were evaluated for pharmacokinetic studies using healthy New Zealand white rabbits. Tested formulations were found to be well-tolerated and showed significant increase in AUC0–24 (22,660.39 h ng/mL) and mean residence time (MRT 12 h) as compared with commercially available solution Levotop PF{\circledR} (Ajanta Pharma Ltd., India)(AUC0–24 6414.63 h ng/mL and MRT 4 h). Thus, solution formulations containing in situ gelling polymer may serve as improved drug delivery system providing superior therapeutic efficacy and better patient compliance for the treatment of bacterial conjunctivitis.",
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Levofloxacin Hemihydrate In Situ Gelling Ophthalmic Solution : Formulation Optimization and In Vitro and In Vivo Evaluation. / Bhalerao, Hemant; Koteshwara, K. B.; Chandran, Sajeev.

In: AAPS PharmSciTech, Vol. 20, No. 7, 272, 01.10.2019.

Research output: Contribution to journalArticle

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