Solutions ophthalmic

The lubricating properties of tears are an important feature in normal blinking. Kalachandra and Shah measured the coefficient of friction of ophthalmic solutions (artificial tears) on polymer surfaces and found no correlation with viscosity, surface tension or contact angle [58]. The coefficient of friction appears to depend on the structure of the polymer surfaces and decreases with increasing load and sliding speed. 

The principal OTC pharmaceutical products include cold remedies, vitamins and mineral preparations, antacids, analgesics, topical antibiotics, antiftingals and antiseptics, and laxatives. Others include suntan products, ophthalmic solutions, hemorrhoidal products, sleep aids, and dermatological products for treatment of acne, dandmff, insect parasites, bums, dry skin, warts, and foot care products (11). More recent prescription-to-OTC switches have included hydrocortisone, antihistamine and decongestant products, antiftingal agents, and, as of 1995, several histamine H2-receptor antagonists. 

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

Although tyrothricia is too toxic for parenteral therapy, it was formerly sold in the United States as oral lo2enges. Modem tyrothricin formulations are composed of 70—80% tyrocidines and 30—20% linear gramicidins. Tyrocidines are not as active as linear gramicidins and are too toxic for any therapeutic use by themselves. The bactericidal linear gramicidins are used in the United States solely as an ophthalmic solution in combination with polymyxin B sulfate and neomycin sulfate. The linear gramicidin is used in this aqueous product as a substitute for bacitracin, which lacks stabiUty under such conditions. 

The NF and reagent grades are employed in the pharmaceutical industry which makes use of benzyl alcohol s local anesthetic, antiseptic, and solvent properties (17—20). It also finds use in cough symps and drops ophthalmic solutions bum, dental (21), and insect repeUant solutions and ointments and dermatological aerosol sprays. It is used in nail lacquers and as a color developer in hair dyes by the cosmetics industry (22), and in acne treatment preparations (23). 

Figures 2 and 3 illustrate the constant release of pilocarpiae over the seven day treatment period. An initial burst of dmg iato the eye is seen ia the first few hours. This is temporary and the system drops to the rated value ia approximately six hours. The total amount of dmg released ia this transitory period is less than that normally given ia pilocarpiae ophthalmic solutions. The ocular hypotensive effect of these devices is hiUy developed within 2 hours of placement ia the conjunctival sac, and the hypotensive response is maintained throughout the therapy. This system replaces the need for eyedrops apphed four times per day to control iatraocular pressure.

Fblytrim Ophthalmic Solution—polymyxin B sulfate, trimethoprim sulfate... 

The USP has numerous requirements, e.g., ophthalmic solutions [need be] essentially free from foreign particles, suitably compounded and packaged for instillation into the eye, or ophthalmic suspensions [need contain] solid particles dispersed in liquid vehicle intended for application to the eye [1]. Ophthalmic suspensions are required to be made with the insoluble drug in a micronized form to prevent irritation or scratching of the cornea. A finished ophthalmic ointment must be free from large particles and must meet the requirements for leakage and for metal particles under ophthalmic ointments . These and other requirements will be discussed further in subsequent sections. 

Behind the relatively straightforward compositional nature of ophthalmic solutions, suspensions, and ointments, however, lie many of the same physicochemical parameters that affect drug stability, safety, and efficacy, as they do for most other drug products. But additionally, specialized dosage forms present the ophthalmic product designer with some extraordinary compositional and manufacturing challenges. These... 

Several guidelines are available in the literature for the pharmacist who must extemporaneously prepare an ophthalmic solution. The USP contains a section on ophthalmic solutions, as do other compendia and several standard textbooks. Since the pharmacist does not have the facilities to test the product, he or she should dispense only small quantities, with an expiration date of no more than 30 days. Refrigeration of the product should also be required as a precautionary measure. To reduce the largest potential source of microbial contamination, only sterile purified water should be used in compounding ophthalmic solutions. Sterile water for injection, USP, from unopened IV bottles or vials is the highest-quality water available to the pharmacist. Prepackaged sterile water with bacteriostatic agents should not be used. 

Richards [117], Mullen et al. [118], and the American College of Toxicology [119] have summarized the literature of benzalkonium chloride. The conclusion drawn was that benzalkonium chloride, up to 0.02%, has been well substantiated as being suitable for use in topical ophthalmic solutions when the conditions of its use are properly controlled. McDonald [121] found up to 0.02% to be permissible in ophthalmic solutions following extensive testing in rabbits. 

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. 

Because of these product sensitivities, most ophthalmic pharmaceutical products are aseptically manufactured and filled into previously sterilized containers in aseptic environments using aseptic filling-and-capping techniques. This is the case for ophthalmic solutions, suspensions, and ointments, and specialized technology is involved in their manufacture. 

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. 

The therapeutically inactive ingredients in ophthalmic solution and suspension dosage forms are necessary to perform one or more of the following functions adjust concentration and tonicity, buffer and adjust pH, stabilize the active ingredients against decomposition, increase solubility, impart viscosity, and act as solvent. The use of unnecessary ingredients is to be avoided, and the use of ingredients solely to impart a color, odor, or flavor is prohibited. 

The pH value is not the sole contributing factor to discomfort with use of some ophthalmic solutions. It is... 

Stablizers. Stabilizers are ingredients added to a formula to decrease the rate of decomposition of the active ingredients. Antioxidants are the principal stabilizers added to some ophthalmic solutions, primarily those containing epinephrine and other oxidizable drugs. Sodium bisulfite or metabisulfite are used in concentration up to 0.3% in epinephrine hydrochloride and bitartrate solutions. Epinephrine borate solutions have a pH range of 5.5 7.5 and offer a more difficult challenge to formulators who seek to prevent oxidation. Several patented antioxidant systems have been developed specifically for this compound. These consist of ascorbic acid and acetylcysteine, and sodium bisulfite and 8-hydroxyquinoline. Isoascorbic acid is also an effective antioxidant for this drug. Sodium thiosulfate is used with sodium sulfacetamide solutions. 

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-... 

High Ophthalmic solutions Transdermal patches Nasal aerosols Topical solutions Topical powders Oral tablets... 

WL Nelson, FT Fraunfelder, JM Sills, JB Arrowsmith, JN Kuritsky. (1986). Adverse respiratory and cardiovascular events attributed to timolol ophthalmic solution. Am J Ophthalmol 102 606-611. 

AK Mitra, TJ Mikkelson. (1982). Ophthalmic solution buffer systems. I. The effect of buffer concentration on the ocular absorption of pilocarpine. Int J Pharm 10 219-229. 

Impairment in visual accommodation results from paresis of ciliary muscles. Photophobia may also result. If severe, pilocarpine ophthalmic solution may be necessary. 

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