Ocular bioavailability

Drug delivery problems associated with pilocarpine, most notably low ocular bioavailability and short duration of action, continue to be significant (44). In an effort to prolong delivery and to avoid undesirable effects, an investigation was carried out on the incorporation and in vitro release of pilocarpine from a soluble film... 

Use of nasolacrimal occlusion decreases systemic absorption up to 60% and may increase ocular bioavailability of the drug. After instillation of the eye drop, the patient should close the eye and press a finger gently against the nasolacrimal duct (tear duct) for 2 to 3 minutes. 

GM Grass, JR Robinson. (1984). Relationship of chemical structure to corneal penetration and influence of low viscosity solution on ocular bioavailability. J Pharm Sci 73 1021-1027. 

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]. 

Calvo et al. [63] studied ehitosan (CS)- and poly-L-lysine (PLL)-eoated poly-e-caprolactone (PECL) nanocapsules for oeular application. In comparison with commercial eye drops, the systems investigated (uncoated, PLL-coated, and CS-coated nanocapsules) significantly increased the eoneentrations of indomethacin in the cornea and aqueous humor of rabbit eyes. The ehitosan-eoated formulation doubled the ocular bioavailability of indomethacin over the uncoated partieles, whereas the PLL coating was ineffective. The authors eoneluded that the speeifie nature of CS was responsible for the enhaneed indomethaein uptake and not the positive surfaee eharge. Both the PLL- and CS-eoated nanoeapsules displayed good oeular toleranee [63]. 

Bary, A. R., Tucker, I. G., and Davies, N. M. 2001. An insight into how cyclodextrins increase the ocular bioavailability of poorly water-soluble compound3roceedings-28th International Symposium on Controlled Release of Bioactive Materials and 4th Consumer and Diversi ed Products Conference San Diego, CA, United States, June 23-27, 2001. 

In conclusion, the approval of Restasis by the FDA is an important milestone in lipid emulsion research for ophthalmic application. This approval reflects the achievements of the last decade in terms of the availability of better ingredients, improved manufacturing processes, feasibility of sterilization, and better understanding of the optimization process. In all of the comparative studies done so far, positively charged SME achieved better ocular bioavailability regardless of the studied drug. Research efforts are underway to further explore the mechanism of interaction of positively charged SMEs with ocular tissues and to translate the results of this research into enhanced clinical performance. 

Until recently, the topical ophthalmic use of some interesting and promising either lipophilic or macromolecular therapeutic substances has been limited clinically because of their restrictive physicochemical properties, which has exhibited poor ocular bioavailability. It is possible... 

Burstein, N.L., and J.A. Anderson. 1985. Corneal penetration and ocular bioavailability of drugs. 

Calvo, P., et al. 1996. Improved ocular bioavailability of indomethacin by novel ocular drug carriers. J Pharm Pharmacol 48 1147. 

Sznitowska, M., et al. 2000. Increased partitioning of pilocarpine to the oily phase of submicron emulsion does not result in improved ocular bioavailability. Int J Pharm 202 161. 

Tear film factors [4] that can influence the ocular bioavailability of a drug are as follows ... 

A major challenge in ocular therapeutics is to improve ocular bioavailability from less than l%-3% to at least 15%—20%. The last three decades have witnessed continued efforts in this direction, and current investigations are being pursued along the following lines ... 

Furthermore, addition of a penetration enhancer to the vehicle of an ophthalmic solution has been used to reduce the size of the drop instilled. Since this reduction in drop size results in a decreased washout and systemic drug loss, this would result in a decreased potential for systemic toxicity, at the same time improving the ocular absorption of poorly absorbed drugs [109], Therefore, improved ocular bioavailability and therapeutic response could be obtained. 

Formulation factors affecting ocular bioavailability on topical application... 

Emulsions have been used for centuries for the oral administration of medical oils and vitamins and as dermatological vehicles. Recently, their application has been extended as drug carriers in the delivery and targeting of ophthalmic drags. An indomethacin emulsion has been reported to increase ocular bioavailability and efficacy compared to commercially available formulation in rabbits. 0.4% indomethacin emulsion showed 2.2 fold increase in the area under the anterior aqueous drag concentration/time curve compared to a 1% indomethacin suspension. The emulsion formulation also reduced ocular surface irritation caused by indomethacin Similar advantages have been shown for a pilocarpine emulsion which produced a prolonged therapeutic effect in comparison with pilocarpine hydrochloride eyedrops in man. It can be administered only twice a day, rather than four times daily for conventional formulation. 

Formulation Approaches to Improve Ocular Bioavailability 5.9.3.1 Conventional Dosage Forms... 

As a consequence, the typical corneal contact time is limited to 1-2 min and the ocular bioavailability is usually less than 10% [2], Furthermore, there is an initial peak dose of the drug, which is usually higher than that needed for a therapeutic effect, followed by a sharp drop-off in concentration to subtherapeutic levels. 

The cul-de-sac normally holds 7-9 pL of tear fluid, with the normal tear flow rate being 1.2-1.5pL/min [4], The loss from the precorneal area by drainage, tear fluid turnover, and noncorneal absorption plays an important role in determining the ocular bioavailability of a drug. As the drainage rate is much faster than the ocular absorption rate, most of the topically applied drug is eliminated from the precorneal area within the first minute [4],... 

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