Eyedrops

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.

For example, PGF201 agonists such as latanaprost have been developed as eyedrops to reduce intraocular pressure for the treatment of glaucoma. Topical instillation of these agonists is effective in lowering intraocular pressure and may be used as a first-line therapy for the treatment of glaucoma. 

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. 

Chlorbutol (trichlorobutanol trichloro-r-butanol trichlorobutanol). Typical in-use concentration 0.5%. It has been used as a preservative in injections and eyedrops. It is... 

Eyes Eyedrops avoid contact lenses if possible during treatment course... 

The conventional concentration of benzalkonium chloride in eyedrops is 0.01%, with a range of 0.004-0.02% [111]. While uptake of benzalkonium chloride itself into ocular tissues is limited [113], even lower concentrations of benzalkonium chloride have been reported to enhance corneal penetration of other compounds including therapeutic agents [93,112,114]. The differential effect of this preservative on the cornea compared to the conjunctiva can be exploited to target a drug for corneal absorption and delivery to the posterior segment of the eye [115]. Its use has been proposed as a means of delivering systemic doses by an ocular route of administration [116]. 

Gel-Forming Solutions. One disadvantage of solutions is their relatively short residence time in the eye. This has been overcome to some degree by the development of solutions that are liquid in the container and thus can be instilled as eyedrops but gel on contact with the tear fluid and provide increased contact time with the possibility of improved drug absorption and increased duration of therapeutic effect. 

Pharmaceutical scientists have developed improved suspension dosage forms to overcome problems of poor physical stability and patient-perceived discomfort attributed to some active ingredients. An important development aspect of any suspension is the ability to resuspend easily any settled particles prior to instillation in the eye and ensure that a uniform dose is delivered. It would be ideal to formulate a suspension that does not settle since the patient may not always follow the labeled instructions to shake well before using. However, this is usually not feasible or desirable since the viscosity required to retard settling of the insoluble particles completely would likely be excessive for a liquid eyedrop. The opposite extreme, of allowing complete settling between doses, usually leads to a dense layer of agglomerated particles that are difficult to resuspend. 

Oils have been used as vehicles for several topical eyedrop products that are extremely sensitive to moisture. Tetracycline HC1 is an antibiotic that is stable for only a few days in aqueous solution. It is supplied as a 1% sterile suspension with Plastibase 50W and light liquid petrolatum. White petrolatum and its combination with liquid petrolatum to obtain a proper consistency is routinely used as the vehicle for ophthalmic ointments. 

Eyedrops have been packaged almost entirely in plastic dropper bottles since the introduction of the Drop-Tainer plastic dispenser in the 1950s. A few products... 

The chief disadvantages of the use of ophthalmic ointments are their greasy nature and the blurring of vision produced. They are most often used as adjunctive nighttime therapy, with eyedrops administered during the day. The nighttime use obviates the difficulties produced by blurring of vision and is stated... 

The carbomer polymeric gel base itself has been used successfully to treat moderate to severe cases of dry eye (keratoconjunctivitis sicca) [282]. The dry eye syndrome is usually characterized by deficiency of tear production and, therefore, requires frequent instillation of aqueous artificial tear eyedrops to keep the corneal epithelium moist. The gel base applied in a small amount provides a prolonged lubrication to the external ocular tissues, and some patients have reduced the frequency of dosing to control their symptoms to three times a day or fewer. 

There are two EPARs for eyedrops. Specific issues considered for these include container composition and tamper evidence, the optimization of the formulation and manufacture, preservative and preservation issues, and justification for the use of nonterminal sterilization processes. Many of the points concerning active ingredients and excipients are similar to those discussed above. Changes in formulation during the development process (e.g., for carbomers or surfactants) are mentioned. Particle size controls for suspension products are discussed. 

The ocular route is used mainly for the local treatment of eye pathologies. Absorption of drugs administered by conventional eyedrops can result in poor ocular bioavailabilities (2-10%). This is due to the limited area of absorption, the lipophilic character of the corneal epithelium, and a series of elimination factors that reduce the contact time of the medication with the comeal surface, such as drainage of instilled solutions, lacrimation, and tear turnover and tear evaporation [56]. 

When methyl 2-cyanoacrylate was applied as an adhesive to rabbit or human eyes, some reports described corneal haze and inflammation other reports with highly purified material indicated less toxicity. Mistaken use in the eyes as eyedrops has caused immediate brief smarting and firm gluing of the eyelids together. Acetone on a swab can be used to unglue the lids and remove the glue from the cornea with minimal, if any, injury to the corneal epithelium. ... 

The formation of liquid drops when flow occurs through thin tubes is a common daily phenomenon. In some cases, such as eyedrops, the size of the drop plays a significant role in the application and dosage of the medicine. The drop formed when liquid flows through a circular tube is shown in Figure 2.10. 

In the calculation using the results of this experiment it is better to use amount rather than concentration as a standard measure since after the initial accurate volume measurement used for the addition of the standard and internal standard to the calibration solution (Solution 1) and for the addition of the internal standard to a fixed volume of eyedrops the volumes need only be measured approximately this is the advantage of using an internal standard (Fig. 11.18). The following formula is used ... 

Solution 1 is prepared from exactly 5 ml of 0.4092% w/v atropine sulphate solution and exactly 1 ml of 2.134% w/v homatropine hydrobromide solution. The solution is basified and extracted, the solvent is removed and the residue is treated with 2 ml of BSA and then diluted to 50 ml with ethyl acetate. Solution 3 is prepared from exactly 2 ml of eyedrops and exactly 1 ml of 2.134% w/v homatropine hydrobromide solution. The solution is basified and extracted, the solvent is removed and the residue is treated with 2 ml of BSA and then diluted to 50 ml with ethyl acetate. 

This was the amount originally present in 2 ml of eyedrops therefore percentage of w/v of atropine sulphate in eyedrops... 

The amount determined in the eyedrops is well below the stated amount of 1 % w/v and this is because this sample of eyedrops was ca 10 years old and had probably suffered extensive degradation. 

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