The aim of this study was to investigate the corneal penetration of brinzolamide nanoemulsions and evaluate their in vitro and ex vivo irritancy potential. Twelve brinzolamide nanoemulsions were prepared by the spontaneous emulsification method and ex vivo permeability studies were conducted using excised bovine corneas fixed onto Franz diffusion cells. To confirm the safety of the formulations for ophthalmic use, preparations were examined for potential ocular irritancy using a cell viability assay on retinal cells, the hen's egg test-chorioallantoic membrane (HET-CAM) and the bovine corneal opacity-permeability (BCOP) test. Seven brinzolamide nanoemulsions exhibited superior penetration across isolated bovine cornea compared to the marketed brinzolamide suspension. The half maximal inhibitory concentration (IC50) values of various surfactants and oils determined using the sulforhodamine B cell viability assay on retinal cells showed that Transcutol P, Cremophor RH40 and Triacetin were the least toxic excipients and may be safely used in the eye at various concentrations. HET-CAM and BCOP tests revealed that NE6B and NE4C did not results in any irritation and were thus considered safe for ocular use. Our finding suggest that optimized nanoemulsions can be a safe and effective vehicle for ocular delivery of brinzolamide.

The aim of this study is to investigate the potential of D-alpha-tocopheryl poly (ethylene glycol 1000) succinate (TPGS) modified nanoliposomes as an ophthalmic delivery system of brinzolamide (Brz) for glaucoma treatment. The Brz loaded nanoliposomes containing TPGS (T-LPs/Brz) were firstly developed by a thin-film dispersion method. The average particle size was 96.87 ± 4.43 nm. The entrapment efficiency of the Brz was 95.41 ± 3.03% and the drug loading was 4.00 ± 0.13%. T-LPs/Brz exhibited obvious sustained release of Brz; in stark contrast to the normal liposomes of Brz (LPs/Brz) and the commercial formulation AZOPT® (Brz ophthalmic suspension, Brz-Sus). Enhanced trans-corneal transport of Brz was achieved with T-LPs/Brz. Compared with both Brz-Sus and LPs/Brz, the apparent permeability coefficient (Papp) of T-LPs/Brz was 10.2 folds and 1.38 folds higher, respectively. Moreover, T-LPs/Brz extended the cornea residence of Brz. White New Zealand rabbits treated with T-LPs/Brz had 3.18 folds and 1.57 folds Brz concentration 2 h after treatment than Brz-Sus and LPs/Brz, respectively. Further pharmacodynamic studies showed that T-LPs/Brz maintained an effective intraocular pressure (IOP) reduction from 3 h to 11 h after administration, while Brz-Sus and LPs/Brz presented effective IOP decreases from 3 h to 6 h and 3 h to 8 h respectively. The preliminary safety evaluation demonstrated that T-LPs/Brz had no significant side effects; specifically, no cornea damage and eye irritation. All the results indicated that TPGS modified nanoliposomes were a promising ocular delivery carriers for Brz to treat glaucoma. As such, T-LPs/Brz might be worthy of further translational study.

We report a case of a patient who developed a severe case of follicular conjunctivitis from brinzolamide after 1.5 years of consistent use. This patient was rechallenged again after resolution of the follicles and subsequently redeveloped similar conjunctivitis. This is the first confirmed reported case of follicular conjunctivitis from brinzolamide use.

Because no information is available on the use of brinzolamide during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.

Our purpose is to present an evidence-based approach, directed primarily towards eye-care specialists, clarifying whether certain drugs should or should not be used in patients with sulfonamide allergy. We conducted a literature search using PubMed to identify the risk of ophthalmic-specific drugs in patients with a self-reported sulfonamide allergy. MeSH key words included "sulfonamide" and "hypersensitivity". Articles specifically geared towards ophthalmic diseases were sought. The evidence illustrates that individuals with sulfonamide allergy are intrinsically predisposed to higher rates of allergic reaction that is not specific towards sulfonamide non-antimicrobials or sulfur-based medications. We provide a simplified algorithm using the 2017 Clinical Guide to Ophthalmic Drugs to help busy eye care clinicians determine whether a certain common ophthalmic medication is safe or unsafe to prescribe in a patient with a "sulfa allergy".