Preservatives ophthalmic solutions

Solutions for external or oral use do not require sterilization but generally contain antimicrobial preservatives. Ophthalmic solutions and parenteral solutions require sterilization (qv). 

Non preserved ophthalmic solutions are preferably delivered in single-dose packaging such as Redipac plastic tubes. In pharmacy preparation alternatives may be ... 

Other quaternary ammonium germicides, ben-zethonium chloride and benzalkonium bromide, have been used in several ophthalmic solutions. While these have the advantage of not being a chemical mixture, they do not possess the bactericidal effectiveness of benzalkonium chloride and are subject to the same incompatibility limitations. In addition, the maximum concentration for benzethonium chloride is 0.01%. Several new products that form gels in the eye, like Timolol Gel Forming Solution and Timoptic-XE, employ another quaternary preservative, BDAB, in the formulation. 

Since the organic mercurials offer an alternative to quaternary ammonium preservatives, and since preservative efficacy of ophthalmic solutions is essential, the choice among these alternatives should be based on a benefit-to-risk analysis as long as a ban is not imposed on the use of these organometallic preservatives. 

In general, aqueous ophthalmic solutions are manufactured by methods that call for the dissolution of the active ingredient and all or a portion of the excipients into all or a portion of the water and the sterilization of this solution by heat or by sterilizing filtration through sterile depth or membrane filter media into a sterile receptacle. If incomplete at this point, this sterile solution is then mixed with the additional required sterile components, such as previously sterilized solutions of viscosity-imparting agents, preservatives, and so on, and the batch is brought to final volume with additional sterile water. 

Surfactants. The use of surfactants is greatly restricted in formulating ophthalmic solutions. The order of surfactant toxicity is anionic > cationic >> nonionic. Several nonionic surfactants are used in relatively low concentrations to aid in dispersing steroids in suspensions and to achieve or to improve solution clarity. Those principally used are the sorbitan ether esters of oleic acid (Polysorbate or Tween 20 and 80), polymers of oxyethylated octyl phenol (Tyloxapol), and polyoxyl 40 stearate. The lowest concentration possible is used to perform the desired function. Their effect on preservative efficacy and their possible binding by macromolecules must be taken into account, as well as their effect on ocular irritation. The use of surfactants as cosolvents for an ophthalmic solution of chloramphenicol has been described [271]. This com-... 

Ophthalmic Solution 0.15% (Alphagan P) (contains Purite 0.005% as preservative]. Indications and Dosages ... 

Contraindications Ophthalmic solutions (both strengths) of phenylephrine HCl are contraindicated in patients with anatomically narrow angles or narrow-angle glaucoma, severe arteriosclerotic cardiovascular or cerebrovascular disease, use during intraocular operative procedures when the corneal epithelial barrier has been disturbed, and in persons with a known sensitivity to phenylephrine, sulfites, or any of its components including preservatives. The 10% solution is contraindicated in patients with aneurysms. 

Recognizing that long-term therapy with frequently applied preserved solutions can be toxic to the ocular surfece, manufecturers have formulated some ophthalmic solutions in imit-dose dispensers without preservatives (Figure 3-7). 

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). 

Metipranolol is available in the United States as OptiPranolol, a sterile ophthalmic solution of 0.3% racemic metipranolol HCl preserved with 0.004% BAG and approved for twice-daily use. 

Preservatives have been a differentiating point for the ophthalmic fourth-generation fluoroquinolones. In the United States gatifloxacin ophthalmic solution is preserved with benzalkonium chloride 0.005%, whereas moxifloxacin drops contain no preservative. Although several studies have attributed advantages or disadvantages related to the preservatives (or lack thereof), clinically no differences have been found. 

Blackburn HD, Polack AE, Roberts MS. Preservation of ophthalmic solutions some observations on the use of chlorbutol in plastic containers [letter]. ] Pharm Pharmacol 1978 30 666. 

Richards RME, McBride RJ. The preservation of ophthalmic solutions with antibacterial combinations. / Pharm Pharmacol 1972 24 145-148. 

Naido NT, Price CH, McCarthy TJ. Preservative loss from ophthalmic solutions during filtration sterilization. Aust Pharm Sci 1972 1(1) 16-18. 

Thiomerosal is used as a preservative in vaccines and ophthalmic solutions. 

Phenyl mercury borate Antiseptic, treatment of periapical periodontitis and preservative in ophthalmic solutions... 

Sterile Epinephrine Ophthalmic Solution USP takes us out of the realm of sterile parenteral products into ophthalmics. The manner of presentation of ophthalmics (i.e., as drops or ointments) is likely to be quite familiar. For the most part (but not exclusively) they are in multidose presentations. As such, most formulations include some form of preservative to control proliferation of any microorganisms that may by chance contaminate the product on one or other of the occasions when it is open, or during the time when it is left standing on the bathroom shelf. The inclusion of preservatives in a multidose formulation of an ophthalmic (or parenteral) is not a primary part of the process of achieving sterility. It has quite a separate purpose. 

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