Comparative efficacy of fixed dose combination of brinzolamide 1% and timolol 0.5% without versus with benzalkonium chloride following single ocular instillation in New Zealand white rabbits

Monali Vakharia; Bharat Pateliya; Sukhendu Bikash Ghose; Vinod Burade; Poonam Rohira

doi:10.18203/2319-2003.ijbcp20232561

Authors

Monali Vakharia Department of India Medical Affairs, Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India
Bharat Pateliya Department of Pharmacology, Sun Pharmaceutical Industries Limited, Tandalja, Gujarat, India
Sukhendu Bikash Ghose Department of Formulation Development, Sun Pharmaceutical Industries limited, Tandalja, India
Vinod Burade Department of Pharmacology, Sun Pharmaceutical Industries Limited, Tandalja, Gujarat, India
Poonam Rohira Department of India Medical Affairs, Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20232561

Keywords:

Potassium sorbate, BAK, Ophthalmic suspension, IOP, Brinzolamide, Timolol

Abstract

Background: Benzalkonium chloride (BAK) is the most used preservative in topical ophthalmic formulations. BAK causes dry eye and trabecular meshwork degeneration. Hence, BAK-free formulations are desirable for chronic conditions like glaucoma. The objective of this study was to compare the efficacy of BAK-free versus BAK-containing ophthalmic suspension of fixed dose combination (FDC) of brinzolamide and timolol on their intraocular pressure (IOP) lowering effect following a single ocular instillation in New Zealand White (NZW) rabbits.

Methods: Twelve normotensive NZW rabbits (male) between 9-12 months of age (3.4-4.4 kg) received a single ocular instillation (35 ml) in left eye of either ophthalmic suspension containing FDC of brinzolamide (1% w/v)/timolol (0.5% w/v) without BAK (n=6, test) or with BAK 0.01% w/v (n=6, reference). IOP was measured before ocular instillation (baseline) and at 2, 4, 6, 8 and 24 hours after instillation using a pneumatonometer. Change in IOP from baseline were calculated and analysed using repeated measures analysis of variance (ANOVA) followed by Bonferroni post-test for pairwise comparisons.

Results: Significant IOP reduction (p<0.05) from baseline was seen in both test and reference groups, up to 6 hours after instillation. Maximum IOP reduction was 25.5% and 22.6% at 2 hours in the test and reference group respectively. No significant differences (p>0.05) were observed between the test and reference group for the change in IOP at all time points.

Conclusions: BAK-free and BAK-containing ophthalmic suspension of FDC of brinzolamide 1% and timolol 0.5% after a single ocular instillation in normotensive NZW rabbits produces similar reductions in IOP.

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