Bioavailability topical delivery

Fine particle technology has broad applications in medicine for both therapeutics and diagnostics. The most common use of finely dispersed systems occurs in oral products that contain poorly water-soluble active agents. Fine (micro or nano) particles have increased surface area per unit dose relative to coarse active agent particles. As a result, the fine particles have much more favorable dissolution kinetics in-vivo. This can lead to increases in oral bioavailability, reductions in food-effect-associated variability, and more i id absorption and onset of therapeutic action. Topical delivery of active agent particles can also be enhanced when they are formulated as finely dispersed systems. 

Figure 8.6 Plasma concentration versus time profiles obtained following administration of different transdermal nitroglycerin systems for 24 hours (Modified from Transdermal Delivery Systems A Medical Rationale. Cleary, G.W. In Topical Drug Bioavailability, Bioequivalence, and Penetration. Shah, V.P. and Maibach, H.I. Eds. Plenum Press, New York, 1993, pp 17-68)...

Selection of the appropriate route of administration and delivery device is critical for the commercial success of a drug product. Although injections are the most efficient delivery method for proteins, they are not always the most suitable from the patient s perspective. Few routes of administration (IV, IM, SC, pulmonary, and topical for local delivery) have been successful to date with protein therapeutics because of the size and complexity of the protein structure. Consideration of the bioavailability via a given route must be made when determining the dose required. Use of a delivery device such as an implantable pump, needle-free injector, or dry-powder inhaler may yield a product with a commercial advantage over a competitor s product. 

Technological advances in both biotechnology and molecular biology have yielded a surge in the number of new chemical entities that are produced to treat specific diseases or ailments. However, a growing portion of these new chemical entities display poor aqueous solubility, leading to poor oral bioavailability and an inability to form intravenous formulations. Nanoparticle formation has been proposed and utilized as a method to improve oral bioavailability of poorly soluble drugs and as a method for delivery of particles via parenteral, pulmonary, and topical administration. 

Pilocarpine (139) is used as a topical miotic for controlling elevated intraocular pressure associated with glaucoma. The drug presents significant delivery problems due to its low ocular bioavailability (1-3% or less) and its short duration of action. The poor bioavailability was partly attributed to its poor permeability across the corneal membrane due to its low lipophilicity. Because of the low bioavailability,... 

Shah VP, Ludden TM, Dighe SV, et al. Bioavailability and bioequivalence of transdermal drag delivery systems. Regulatory considerations. In Shah VP, Maibach HI, eds. Topical Drag Bioavailabihty, Bioequivalence, and Penetration. New York Plenum Press, 1993 415-424. 

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