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

Authors
  • Bhalerao, Hemant1
  • Koteshwara, K.B.2
  • Chandran, Sajeev1
  • 1 Lupin Limited, Lupin Research Park, 46/47A, Nande Village, Mulshi Taluka, Pune, 412115, India , Pune (India)
  • 2 Manipal Academy of Higher Education, Manipal, Karnataka, India , Manipal (India)
Type
Published Article
Journal
AAPS PharmSciTech
Publisher
American Association of Pharmaceutical Scientists
Publication Date
Jan 16, 2020
Volume
21
Issue
2
Identifiers
DOI: 10.1208/s12249-019-1555-0
Source
Springer Nature
Keywords
License
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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.

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