This review is focused on the two avenues of development that promise a major impact on future ocular drug therapeutics: bioadhesives, including hydrogels and other agents like carbopols, polyacrylic acids, chitosan, etc., and penetration enhancers, including different surfactants, calcium chelators, etc. The capacity of some polymers to adhere to the mucin coat covering the conjunctiva and the corneal surface of the eye forms the basis for ocular mucoadhesion. These systems markedly prolong the residence time of a drug in the conjunctival sac, since clearence is now controlled by the much slower rate of mucus turnover rather than the tear turnover rate. But improving the corneal drug retention alone is inadequate in bringing about a significant improvement of drug bioavailability. Another approach consists of transiently increasing the pentration characteristics of the cornea with appropriate substances, known as penetration enhancers or absorption promoters. The main aim of this article is to give an insight into the potential application of mucoadhesives and corneal penetration enhancers for the conception of innovative opthalmic delivery appraoches, to decrease the systemic side effects, and create a more focused effect, which may be achieved with lower doses of the drug. Ophthalmic formulations based on these mucoadhesives and penetration enhancers are simple to manufacture and exhibit an excellent tolerance when administered into the cornea. The use of the former considerably prolongs the corneal contact time and the use of the latter increases the rate and amount of drug transport. The various corneal epithelial barriers along with the major routes of transport of drugs are discussed. The article includes a list of the various substances in use or under investigation for the aforementioned properties, along with their mechanisms of action. A fair appraisal of the subject with regard to these two therapeutic approaches and any expected ill effects has been made.

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The myriad of side effects induced by acetazolamide (oral use), the introduction of newer topical carbonic anhydrase inhibitors (CAI's) and the advent of other antiglaucoma medications has led to a decreased interest in acetazolamide. The use of cyclodextrins to improve the solubility and bioavailability of poorly soluble drugs has however, rekindled an interest in acetazolamide (ACZ), because its poor solubility is one of the major factor responsible for its failure to show topical effectiveness. Since water soluble polymers have been reported to improve the complexing capabilities of beta-cyclodextrins, in the present study water soluble polymers like polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), hydroxypropymethylcellulose (HPMC) and the mucoadhesive polymer Carbopol 934P were incorporated into aqueous 10% w/v 2HP-beta-CD solution to improve the solubility of ACZ. The effect of these polymers on the corneal transport of 5 mg/ml (0.5% w/v) solution of ACZ in aqueous 10% 2HP-beta-CD was evaluated. The inclusion of these polymers significantly increased the solubility of ACZ from 3.43 mg/ml in aqueous 10% 2HP-beta-CD to 5.1 mg/ml (48.6%) in 0.05% PVP; 6.80 mg/ml (98.3%) in 0.05% PVA; and 6.74 mg/ml (96.5%) in 0.2% Carbopol 934P. From amongst the various polymers assessed in the study, PVA was deemed the best, based on the premise of better apparent permeability coefficient (P(app)) upon in vitro corneal permeation studies. Inspite of a large enhancement in solubility produced by Carbopol 934P, surprisingly, it could not efficiently increase the Papp.