Viscosity ophthalmic formulations

Although usually considered to be inactive ingredients in ophthalmic formulations added because they impart viscosity, many of these polymers function as ocular lubricants. They are marketed as the active ingredients in OTC ocular lubricants used to provide relief from dry eye conditions. The regulatory requirements for these OTC products are found in the FDA Code of Federal Regulations (21CFR349.12), and their formulations are presented in the Twelfth Edition of the APhA Handbook of Nonprescription Drugs. 

Hydroxyethylcellulose (HEC) (Nalrosol, Hercules) 135-140 °C T — 70S Ctccnposmoi Soluble in hot or cold water Insoluble in organic solvents Viscosity = 2-20,0(X) MPa for 2% aqueous solution. Ophthalmic formulations Topical formulations Thickener Stabiliser Water binder... 

Most ophthalmic products, however, cannot be heat sterilized. In general, the active principle is not particularly stable to heat, either physically or chemically. Moreover, to impart viscosity, aqueous products are generally formulated with the inclusion of high molecular weight polymers, which may, similarly, be affected adversely by heat. 

MF Saettone, D Monti, MT Torracca, P Chetoni. (1994). Mucoadhesive ophthalmic vesicles Evaluation of polymeric low-viscosity formulations. J Ocular Pharmacol 10 83-92. 

Coating formulations (lacquers) are clear, transparent, low-viscosity, solvent-free liquids that are stable with a shelf life of several months and are suitable for optical applications ranging from the ophthalmic to the optical fibre market. As an example of the former, Figure 4.15 shows a plate half coated with a layer of ABRASIL coating material only a few micrometres thick with the scratch traces from steel wool being observed on the uncoated half.18... 

Saettone, M.F., Monti, D., Torraeea, M.T., and Chetoni, P., Mucoadhesive ophthalmic vehicles evaluation of polymeric low-viscosity formulations, J. Ocul. Pharmacol., 10 83-92... 

Levobunolol is suppUed as a 0.25% and 0.5% sterile ophthalmic solution of the levo-isomer of the hydrochloride salt.The formulation contains a viscosity agent, 1.4% polyvinyl alcohol, and is preserved with BAG 0.004% (see Table 10-1). 

Substituted Cellulose Ethers. Since their introduction for ophthalmic use, MC and other substituted cellulose ethers such as hydroxyethylcellulose, hydroxypropylcel-lulose, hydroxypropyl methylcellulose (HPMC), and carboxymethylcellulose (CMC) have been used in artificial tear formulations.These colloids dissolve in water to produce colorless solutions of varying viscosity. They have the proper optical clarity, a refractive index similar to the cornea, and are nearly inert chemically. Their relative lack of toxicity, their viscous properties, and their beneficial effects on tear film stability have made cellulose ethers useful components of artificial tear preparations. Historically, the most frequently used representative of this group was MC. 

In ophthalmic preparations, a 0.5-1.0% w/v solution of a highly substituted, high-viscosity grade of methylcellulose has been used as a vehicle for eye drops. However, hypromellose-based formulations are now preferred for ophthalmic preparations. 

A second ophthalmic gel, for the delivery of pilocarpine, is poloxamer407. This vehicle was chosen because of its low viscosity, optical clarity, and mucomimetic properties, and for its previous acceptability in ophthalmic preparations. This formulation enhanced pilocarpine activity, as indicated by miosis measurements in rabbits, compared to a pilocarpine aqueous solution of equal drug concentration. 

When formulating aqueous ophthalmic preparations attention should be given to osmolality, pH, solubility, chemical interactions, stability of the active substance, together with viscosity and the choice of a preservative. Sterility is of critical importance and therefore the most appropriate sterilisation method must be chosen. 

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