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

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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.

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Funding

The authors would like to thank Lupin Ltd. (Research Park) Pune, for providing financial support for this research.

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Authors and Affiliations

  1. Advanced Drug Delivery Systems, Pharma Research, Lupin Limited, 46/47A, Nande Village, Mulshi Taluka, Pune, 412115, India

    Hemant Bhalerao & Sajeev Chandran

  2. Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India

    K. B. Koteshwara

Authors
  1. Hemant Bhalerao
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  2. K. B. Koteshwara
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  3. Sajeev Chandran
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Corresponding author

Correspondence to Sajeev Chandran.

Ethics declarations

Animal handling and studies were conducted in accordance with the Principles of Laboratory Animal Care (National Institutes of Health publication no 92–93, revised in 1985) and in conformation with guidelines of The Association for Research in Vision and Ophthalmology. The Institutional Animal Ethics Committee of Poona College of Pharmacy, Pune, India, approved the study (Protocol no: CPCSEA/PCP/PCL01/2018 and CPCSEA/PCP/PCL27/2018).

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Bhalerao, H., Koteshwara, K.B. & Chandran, S. Levofloxacin Hemihydrate In Situ Gelling Ophthalmic Solution: Formulation Optimization and In Vitro and In Vivo Evaluation. AAPS PharmSciTech 20, 272 (2019). https://doi.org/10.1208/s12249-019-1489-6

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  • DOI: https://doi.org/10.1208/s12249-019-1489-6

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