Brinzolamide Dimethyl Sulfoxide In Situ Gelling Ophthalmic Solution: Formulation Optimisation and In Vitro and In Vivo Evaluation

Hemant Bhalerao, K. B. Koteshwara, Sajeev Chandran

Research output: Contribution to journalArticle

Abstract

In the present work, a cost-effective, stable and sustained release ophthalmic solution formulation of brinzolamide (BRZ) was developed for the treatment of glaucoma. The prototype formulation undergoes 'in situ gelling' when administered in the eye, thereby providing longer residence (16-24 h). As a result, the same therapeutic endpoint is achieved with once daily dosing vis-à-vis the commercially available product Azopt® (brinzolamide 1.0% w/v, Alcon Laboratories, USA) that requires 3-4 times instillations per day. The prototype formulations were prepared using dimethyl sulfoxide, polyoxyl 35 castor oil and polysorbate 80. Gellan gum was used as the in situ gelling agent. Formulation variables like (i) concentration of the drug, dimethyl sulfoxide and in situ gelling agent and (ii) type and concentration of solubiliser showed a significant effect on the solubility of brinzolamide, in vitro gelling time, in vitro drug release and in situ gel stability. Prototype formulations were evaluated in New Zealand white rabbits for ocular toxicity and efficacy study. The tested formulations were well tolerated and reduced intraocular pressure (IOP) from 25-28 to 12-14 mmHg compared to saline and placebo control samples. Additionally, a significant increase in the area under change in IOP from baseline (ΔIOP) vs. time curve and a longer mean residence time (MRT) were also observed for the test formulations (7.4 to 17.7 h) compared to the commercially available suspension of Azopt® (4.9 h) (p < 0.0001). Thus, 'in situ gelling' formulation strategy described in this work can work as a viable option for ocular delivery of brinzolamide for the treatment of glaucoma.

Original languageEnglish
Number of pages1
JournalAAPS PharmSciTech
Volume21
Issue number2
DOIs
Publication statusPublished - 16-01-2020

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Ophthalmic Solutions
Dimethyl Sulfoxide
Intraocular Pressure
Glaucoma
Polysorbates
Solubility
In Vitro Techniques
brinzolamide
Suspensions
Therapeutics
Gels
Placebos
Rabbits
Costs and Cost Analysis
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

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Brinzolamide Dimethyl Sulfoxide In Situ Gelling Ophthalmic Solution : Formulation Optimisation and In Vitro and In Vivo Evaluation. / Bhalerao, Hemant; Koteshwara, K. B.; Chandran, Sajeev.

In: AAPS PharmSciTech, Vol. 21, No. 2, 16.01.2020.

Research output: Contribution to journalArticle

TY - JOUR

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