Drug delivery systems ophthalmic vehicles

There is a tendency in ophthalmic drug delivery systems towards a combination of several drug delivery technologies to achieve not only prolonged contact time of the vehicle at the ocular surface, but also to slow down the elimination of the drug, so improving therapeutic response. 

W.D. Ma, H. Xu, C. Wang, S.E Nie, and W.S. Pan, Pluronic F127-g-poly(acrylic acid) copolymers as in situ gelling vehicle for ophthalmic drug delivery system, Int J Pharm, 350, 247-256, 2008. 

A host of bioadhesive controlled release systems have been proposed in recent years. Among the most commonly studied applications of bioadhesive materials is the area of buccal controlled delivery [408], The buccal delivery of small peptides from bioadhesive polymers was studied by Bodde and coworkers [409], and a wide range of compositions based on poly(butyl acrylate) and/or poly(acrylic acid) gave satisfactory performance. Bioadhesive poly(acrylic add)-based formulations have also been used for oral applications [402,410] for the sustained delivery of chlorothiazide [410] and for a thin bioadhesive patch for treatment of gingivitis and periodontal disease [411]. Other bioadhesive applications of polyelectrolytes include materials for ophthalmic vehicles [412,413], and systems for oral [410,414,415-419], rectal [420,421] vaginal [422] and nasal [423] drug delivery. 

Ointments are commonly used for topical application of drugs to the eye.These vehicles are primarily mixtures of white petrolatum and liquid mineral oil with or without a water-miscible agent, such as lanolin.The mineral oil is added to the petrolatum to allow the vehicle to melt at body temperature, and the lanolin is added to the nonemulsive ointment base to absorb water. This allows for water and water-soluble drugs to be retained in the delivery system. Commercial ophthalmic ointments are derivatives of a hydrocarbon mixture of 60% petrolatum USP and 40% mineral oil USP, forming a molecular complex that is semisolid but melts at body temperature. In general, ointments are well tolerated by the ocular tissues, and when antibiotics are incorporated they are usually more stable in ointment than in solution. 

Pilocarpine is commerciaUy available in a carbomer gel vehicle.The 4% pilocarpine gel is packaged in a 3-5-g tube similar to ophthalmic ointments. A practical advantage of this sustained delivery system is the once-daily dosage regimen, with the drug usuaUy administered at bedtime. Minor side effects include superficial corneal haze, which may occur after long-term use (>8 weeks), and superficial pimctate keratitis, which can affect almost one-half the treated patients but usually resolves spontaneously. 

The main challenge in ocular delivery is to increase the bioavailability of the drug and its residence time in the cornea, conjunctiva, and epithelia. Nanoscale polymers such as dendrimers can contribute to sustained release of encapsulated drugs at these sites. PAMAM dendrimers have been employed as ophthalmic vehicles in ocular delivery systems with pilocarpine nitrate and tropicamide (Vandamme and Brobeck 2005). 

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