In ophthalmic formulations

Co-administration of ofloxacin and chitosan in eyedrops increased the bioavailabUity of the antibiotic [290]. Trimethyl chitosan was more effective because of its solubility (plain chitosan precipitates at the pH of the tear fluid). On the other hand, N-carboxymethyl chitosan did not enhance the corneal permeability nevertheless it mediated zero-order ofloxacin absorption, leading to a time-constant effective antibiotic concentration [291]. Also W,0-carboxymethyl chitosan is suitable as an excipient in ophthalmic formulations to improve the retention and the bioavailability of drugs such as pilocarpine, timolol maleate, neomycin sulfate, and ephedrine. Most of the drugs are sensitive to pH, and the composition should have an acidic pH, to enhance stability of the drug. The delivery should be made through an anion exchange resin that adjusts the pH at around 7 [292]. Chitosan solutions do not lend themselves to thermal sterilization. A chitosan suspension, however. 

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. 

Presoaked lenses are considered a more efficient and reliable delivery system. However, the soaking of lenses in ophthalmic formulations to incorporate the drag into the lens may cause toxicity to corneal epithelium because preservatives, such as benzalkonium chloride, have a great affinity for the hydrophilic contact lens material and are concentrated in the contact lens. Contact lens for sensitive wearers may also cause foreign-body sensation, blurring and decreased oxygen tension on the corneal surface resulting from occlusion by contact lens. 

Phenylephrine and the imidazole derivatives are chemically compatible with a variety of compounds. They can be combined in ophthalmic formulations with antihistamines, corticosteroids, and antimicrobial agents. 

Chlorhexidine and its salts are widely used, primarily as topical disinfectants. As excipients, chlorhexidine salts are mainly used as antimicrobial preservatives in ophthalmic formulations. 

Therapeutically, mineral oil has been used as a laxative, see Section 14. It is indigestible and thus has limited absorption. Mineral oil is used in ophthalmic formulations for its lubricant properties. It is also used in cosmetics and some food products. ... 

Light mineral oil is used in applications similar to those of mineral oil. It is used primarily as an excipient in topical pharmaceutical formulations where its emollient properties are exploited in ointment bases see Table I. It is also used in ophthalmic formulations. Light mineral oil is additionally used in oil-in-water and polyethlylene glycol/gylcerol emulsions as a solvent and lubricant in capsules and tablets as a solvent and penetration enhancer in transdermal preparations and as the oily medium used in the microencapsulation of many drugs. ... 

Jarho P, Jarvinen K, Urtti A, Stella V, Jarvinen T. The use of cyclodextrins in ophthalmic formulations of dipivefrin. Int ]... 

Reader MJ. Influence of isotonic agents on the stability of thimerosal in ophthalmic formulations. ] Pharm Sci 1984 73(6) 840-841. 

Hydrophilic polymeric vehicles, such as poly (vinyl alcohol) (PVA) and hydroxypropyl-methylcellulose (HPMC), are used in ophthalmic formulations. PVA increases the effectiveness of the dmg substance. HPMC has likewise been found to reduce the effective dose of neomycin sulfate required to prevent infection of corneas of experimental animals (Table 9.11). 

Neomycin is not usually administered parenter-ally to animals because of nephrotoxicity and ototoxicity. Only 3% of a dose of neomycin is absorbed following p.o. administration it is, therefore, used in the therapy of coliform enteritis in small and large animals. It is available as tablets, boluses and water additives, in many different combinations with antibiotics, corticosteroids and anticholinergic agents. It can also be used to decrease nitrogenous waste production by the normal gastrointestinal flora in animals with hepatic encephalopathy. Neomycin is not absorbed through the skin, so it is frequently utilized as the antibacterial constituent in ophthalmic formulations (especially in combination with bacitracin and polymyxin B) and in preparations for the treatment of otitis externa in small animals. 

A list of regulatory approved antimicrobial preservatives used in ophthalmic formulations with recommended concentration ranges is shown in Table 12.7. The use of methyl- and propylparabens, thimerosal and other mercurial preservatives has decreased in recent years due to adverse reactions associated with their use (Wade and Weller 1994). 

By far, the most widely used antimicrobial preservative used in ophthalmics is BKC (70 percent of all commercial products). It is often used in combination with disodium ede-tate because of the synergistic effects, allowing lower concentrations of BKC to be used. Even the use of BKC has been questioned because of some evidence of eye toxicity in rabbits (Dormans and van Logten 1982), and some people have developed hypersensitivity to this preservative. However, BKC does possess good pharmaceutical properties, being stable in solution, stable to autoclaving, and at the usual concentration of 0.01 percent, is an effective preservative over the range of pH values typically used in ophthalmic formulations. 

Kumar, T.R.S Shedbalkar, V.P. Bhalla, H.L. High-performance liquid-chromatographic determination of ketorolac tromethamine in ophthalmic formulations. Indian Drugs 1997, 34 (9), 532-535. 

Poly(acrylic acid) (PAA) (Figure 16.5) is an anionic mucoadhesive polymer produced by the radical polymerization of acrylic add. PAA and its derivatives—weakly crosslinked PAAs, also known as Carbomers or Carbopol—are widely used in ophthalmic formulation, such as the ones used for the management of the dry eye condition. Generally, PAA and its derivatives are used in the preparation of mucoadhesive ocular drug delivery formulations [25], either in the form of viscous gels [26], nanoparticles... 

CiT-Cie alkyldimethylbenzylammo-nium chlorides determination in ophthalmic formulations Spherisorb CN 60 40 H2O/CH3CN, 0.1% triethyl-amine, pH 2.5 UV,215nm 291... 

C 2-Ci(i alkyldimethylbenzylammo-nium chlorides determination in ophthalmic formulations DuPont Zorbax Stablebond CN, 4.6 X 150 mm, 4(PC 250 150 2 H20/THF/triethylamine, adju.sted to pH 3.0 with H3PO4 UV,2l5nm 292... 

C12-C14 alkyldimethylbenzylammo-nium chlorides determination in ophthalmic formulations Keystone Scientific CPS Hypersil-1 cyano, 4.6 x 150 mm 65 35 CH3CN/(aqueous 0.05 M sodium propionate adjusted to pH 5.3 with H2SO4) UV,214nm 293... 

C 2-Ci5 alkyldimethylbenzylammo-nium chlorides determination in ophthalmic formulations Waters pBondapak Phenyl, 3.9 X 300 mm 65 35 CHjCN/pH 6.3 buffer (0.05 M KH2PO4,0.057 M sodium hexanesulfonate, pH adjusted with NaOH) UV, 215 nm 294,295... 

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