Topically applied drugs

Scheme 1 Ocular penetration routes for topically applied drugs. l,Transcornealpathway 2, noncorneal pathway 3, systemic return pathway 4, lateral diffusion. (From Ref. 1.)... 

Figure 6 Epithelial penetration routes for topically applied drugs. The transcellular route (1) is preferred by lipophilic drugs, while the paracellular route (2) is preferred by hydrophilic drugs.

Age Systemic toxicity from topically applied drugs is most likely in infants and small children because of their high ratio of surface area to body weight... 

Typically less than 3% of topically applied drugs in ocular dosage forms—solutions. 

Type IV Cell-mediated allergy is the mechanism involved in allergic contact dermatitis from topically applied drugs or induration of the skin at the site of an antigen injected intradermally. 

Mori K, et al. Design and feasibility assessment of topically applied drug formulations for electroporation. Chem Pharm Bull 2003 51 617-619. 

Fig. 6.14. Label-free chemical imaging of the penetration pathways for the topically applied drug diffusion enhancer dimethyl sulfoxide (DMSO) into mouse skin tissue Dual-frequency SRS imaging tuned into the characteristic vibration of DMSO at 670 cm-1 (bright gray regions) and the CH2 vibration of lipid-rich adipocytes at 2845 cm-1 (dark gray regions) at a depth of 65pm into the tissue. DMSO is hydrophilic and hence avoids lipid structures such as adipocytes (Image courtesy of Brian Saar, Chris Freudiger, and Wei Min [12])...

At the inner border of ONH, the ILM becomes continuous with the basement membrane of fibrous astrocytes lining the internal surface of the ONH [21]. However, the lateral borders between the ONH and the adjacent choroid and retina are not well defined. Furthermore, it was reported [49] that micro vessels in the prelaminar region of the ONH lack classical blood-brain barrier characteristics and display nonspecific permeability, possibly mediated by vesicular transport. Thus, there is a theoretical possibility that topically applied drugs can penetrate indirectly through the retrobulbar space and then, through the ONH, reach the posterior choroid and retina. It was reported that following retrobulbar administration of fluorescein, the dye rapidly accumulated in the ONH and penetrated later to the vitreous [50],... 

Steinstrasser, I., and Merkle, H. P Dermal metabolism of topically applied drugs Pathways and models reconsidered. Pharm. Acta Helv. 70(l) 3-24, 1995. 

Moisturizers are commonly used to treat both healthy and diseased skin, and therefore bridge the gap between medication and consumer good. Dermatologists routinely recommend them. They are used as prevention of irritant dermatitis, to treat minor skin complaints and as adjuvant therapy in combination with topically applied drugs. This suggests that they are useful in a medical/biological... 

Describe the two pathways for ocular adsorption of topically applied drugs. 

Precorneal Tear Film Corneal transparency and good visual function require a uniform eye surface. This is achieved by the tear film, which covers and lubricates the cornea and the external globe. It is about 7-8 pm thick and is the first structure encountered by topically applied drugs. The trilaminar structure of the tear film is shown in Figure 2. 

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],... 

Aluminum tubes are often used as the immediate package for dermal preparations. One important point to remember is that after the application of creams, ointments, or gels to the skin, all of the photo protection provided by the packaging is lost and photodegradation can occur. Topically applied drug substances with proven photoinstability, e.g., corticosteroids (36), retinoic acid (37), dithranol (38), and anti-mycotics (natamycine and nystatine) (39) fall into this category. 

It is generally accepted that the bioavailability of most topically applied drugs remains low. Various methods to increase this bioavailability have been used. One of the approaches is the use of absorption enhancers, and over the years, there has been a great interest in new chemical absorption enhancers. An absorption enhancer should be pharmacologically inert, non-toxic, have a rapid and reversible onset of action, be chemically and physically compatible with other formulation compounds, and be cosmetically acceptable. Of course not all absorption enhancers possess all of these characteristics, and a benefit-to-risk evaluation will determine the choice of a molecule as an absorption enhancer. The range of absorption enhancers that has been researched is large. Thus, overview of the most researched compounds is presented. 

The absorption process for a topically applied drug essentially involves the following stages dissolution of the drug in and release from the vehicle, drug... 

The absolute bioavailability of a topically applied drug can be determined only by measurement of plasma concentrations and comparing total areas... 

Burstein NL. Corneal cytotoxicity of topically applied drugs, vehicles and preservatives. Surv Ophthalmol 1980 25(l) 15-30. 

Topically applied drugs 221 Subconjunctival injections 223 Parenteral administration 224... 

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