Eye drops containers

Preservative availability may be appreciably reduced by interaction with packaging materials. Examples include the permeation of phenolic preservatives into the rubber wads and teats of multi-dose injection or eye-drop containers and by their interaction with flexible nylon tubes for creams. Quaternary ammonium preservative levels in formulations have been significantly reduced by adsorption onto the surfaces of plastic and glass containers. Volatile preservatives such as chloroform are so readily lost by the routine opening and closing of containers that their usefulness is somewhat restricted to preservation of medicines in sealed, impervious containers during storage, with quite short use lives once opened. 

Examples of preservatives are phenylmercuric nitrate or acetate (0.002% w/v), chlorhexidine acetate (0.01 % w/v), thiomersal (0.01 % w/v) and benzalkorrium chloride (0.01 % w/v). Chlorocresol is too toxic to the comeal epithehum, but 8-hydroxyquinoline and thiomersal may be used in specific instances. The principal considerahon in relation to antimicrobial properties is the activity of the bactericide against Pseudomonas aeruginosa, a major source of serious nosocomial eye infections. Although benzal-konium chloride is probably the most active of the recommended preservatives, it cannot always be used because of its incompatibility with many compounds commonly used to treat eye diseases, nor should it be used to preserve eye-drops containing anaesthetics. Since benzalkonium chloride reacts with natural mbber, silicone or butyl rabber teats should be substituted. Since silicone mbber is permeable to water vapour, products should not be stored for more than 3 months after manufacture. As with all mbber components, the mbber teat should be pre-equilibrated with the preservative prior to... 

All eye drops, including chloramphenicol, are sterile before opening and must be d iscarded within 4 weeks of opening. Eye drops contain a preservative and are available in small-volume containers (10 ml). 

In vitro studies have shown that precipitation occurs when eye drops containing thimerosal are mixed with latanoprost. If such drugs are used, administer with an interval of at least 5 minutes between applications. 

Kompa, S., Redbrake, C., Dunkel, B., Weber, A., Schrage, N. Corneal calcification after chemical eye bums caused by eye drops containing phosphate buffer. Burns 32(6), 744-747 (2006)... 

Systemic absorption may occur when eye drops containing beta-blockers are administered. Beta-receptors are found in heart muscle (predominantly beta-1) and the smooth muscle of the blood vessels and bronchioles (mainly beta-2). Selective beta-blockers (atenolol, bisoprolol, metoprolol, nebivolol, acebutolol) primarily (but not exclusively) antagonize beta-1 receptors, while the non-selective drugs (carvedilol, celiprolol, esmolol, labetalol, nadolol, oxprenolol, pindolol, propanolol, sotalol, timolol) block both beta-1 and beta-2 receptors,... 

Bianchi U, Mezzanotte R, Vanni R, Ferrucci L. Do eye drops containing photosensitizers represent therapeutic absurdity Riv Farmacol 1982 13(3) 233-236. 

Since the introduction of propranolol, it has been recognized that patients with bronchial asthma treated with beta-adrenoceptor antagonists can develop severe airways obstruction (84), which can be fatal (85) or near fatal (86,87) this has even followed the use of eye-drops containing timolol (88). Beta-blockers upset the balance of bronchial smooth muscle tone by blocking the bronchial beta2-adrenoceptors responsible for bronchodilata-tion. They also promote degranulation of mast cells and depress central responsiveness to carbon dioxide (89,90). 

Contact dermatitis on the eyelids developed in a 70-year-old-woman after she had used eye-drops containing diclofenac. Patch tests were positive to both diclofenac and indometacin, suggesting possible crossreactivity between the two compounds (32). 

Gesztes T. Prolonged apnoea after suxamethonium injection associated with eye drops containing an anticholinesterase agent. Br J Anaesth 1966 38(5) 408-9. 

Kodym A, Marcinkowski A, Kukula H. Technology of eye drops containing aloe (Aloe arborescens M-Liliaceae) and eye drops containing both aloe and neomycin sulphate. Acta Pol Pharm 2003 60(1) 31-39. 

Eye drops containing phenylmercuric nitrate as a preservative should not be used continuously for prolonged periods as mercurialentis, a brown pigmentation of the anterior capsule of the lens may occur. Incidence is 6% in patients using eye drops for greater than 6 years however the condition is not associated with visual impairment. Cases of atypical band keratopathy have also been attributed to phenylmercuric nitrate preservative in eye drops. " ... 

Therapeutically, sodium propionate has been used topically in concentrations up to 10% w/w alone or in combination with other propionates, caprylates, or other antifungal agents, in the form of ointments or solutions for the treatment of dermatophyte infections. Eye drops containing 5% w/v sodium propionate have also been used. See Section 18. 

Antistin" and many others) is an imidazoline, one of the ethylenediamine series of HISTAMINE Hi-receptor ANTAGONISTS. It is used topically for inflammation and allergic conjunctivitis, as eye-drops containing antazoline sulphate (together with the vasoconstrictor xylometazolinc hydrochloride as Otrivine-Antistin ). antazoline phosphate antazoline. antazoline sulphate antazoline. 

A differential spectrophotometric method for the determination of sulfacetamide in the presence of sulfanilamide has been reported (45). Sulfacetamide in eye drops containing ethyl p-hydroxybenzoate may be determined in pH 5.8 phosphate buffer at 257 and 223 nm. The UV absorption of ethyl p-hydroxybenzoate does not change within pH 1-6. The method is simple and rapid, with the coefficient of variation and recovery of 0.63 and 99.58% respectively (46). 

The BP monograph for Chloramphenicol Eye Drops contains a limit test for 2-amino-l-(4-nitrophenyl)propane-1,3-diol (Figure 8.26). 

An isolated report describes an 83-year-old woman stabilised on warfarin who showed a rise in her INR to about 8.9 from her normal range of 1.9 to 2.8 within 2 weeks of starting to use eye drops containing chloramphenicol 5 mg/mL, dexamethasone sodium phosphate 1 mg/mL and tet-rahydrozoline hydrochloride 0.25 mg/mL. She used one drop in each eye... 

The cytotoxicity of MPC-based eye drops containing 0.1% Lipidure-PMB (a copolymer of MPC and butyl methacrylate NOF Corp.) was examined and it was found to have similar nontoxicity to other clinically approved artificial tear products. " From these literature reports it appears that the unique properties and nontoxicity of MPC are ideal for ophthalmological applications. 

Boer Y (1981) Irritation by eye drops containing 2-phenylethanol. Pharm Weekbl Sci Ed 3 122-3... 

In this section the general requirements for eye drop containers is discussed. Various multidose containers and some single use containers are described. 

There is currently no eye drop container available for pharmaceutical preparations that meets all these requirements. Table 24.7 shows which requirements are met by some containers. 

Most eye drop containers deliver drops that are too large for the absorbing capacity of the eye [27]. The drop size varies from 25 to 75 microlitres. The drop size not only depends on the type of dropper used, but also on the formulation of the preparation. A smaller eye drop volume, from 5 to 15 microlitres, provides a sufficient effect. Devices to administer eye drops are discussed in Sect. 24.4.19. Physical factors that determine the drop size are also described in that section. 

Table 24.7 Data about several eye drop containers commercially available...

Due to the vulnerability of the eye some specific requirements apply to the dropper system used for the administration of eye drops. The combination bottle/dropper is discussed in the paragraph on eye drop containers (Sect. 24.4.2). The handling of an eye drop bottle can present problems, for example for people with trembling hands. A supporting device can help to drop successfully. The choice of device depends on the type of dropping bottle the patient uses. 

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