Topical therapeutic systems bioavailability

Modification of the pharmacokinetics through structural alterations has provided several new steroids with a better GR affinity and therapeutic index and a lower bioavailability than the older drugs (Fig. 33.14). The new inhaled/intranasal glucocorticosteroids like mometasone furoate, budesonide and fluticasone propionate are more lipophilic than those used in oral and systemic therapy and have greater affinity for the GR than does dexamethasone as a consequence of their greater lipophilicity (43). Several of the topical corticosteroids, such as mometasone furoate, BDP, triamcinolone acetonide, and flunisolide, were reintroduced as inhalation and intranasal dosage forms for treatment of respiratory diseases (e.g., asthma or rhinitis). Inhaled budesonide and flunisolide are readily absorbed from the airway mucosa into the blood and are rapidly biotransformed in the liver into inactive metabolites. Mometasone furoate and fluticasone propionate are very potent anti-inflammatory steroids with an oral bioavailability of less than 1%. Obviously, the risk of systemic side effects for these newer corticosteroids is greatly reduced when compared with ... 

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. 

Although satisfactory therapeutic results are obtained with usual topical ophthalmic drug (topical ocular solutions and ointments) they present some inconveniences pt. Bioavailability is poor, requiring high doses and repeated applications. 2 . Diffusion of the drug into the bloodstream across de nasal mucosa which is continuous with the conjuntival sac, represents an additional risk of systemic toxicity. (Chang and Lee, 1987, Salminen,1990). 

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