Drug application dermal

The generally low lipid content and the poor viscosity of lipid nanodispersions make these preparations, as they are, less suitable for dermal drug application. The handling of the preparation by the patient is improved by SLN incorporation into ointments, creams, and gels. Alternatively, ready-to-use preparations may be obtained by one-step production, increasing the lipid phase to at least 30%. However, increasing the lipid frequently results in an unwanted increase in particle size. Surprisingly, it has been found that very concentrated (30 to 40%) semisolid cetyl palmitate formulations preserve the colloidal particle size [10]. 

Because of the low permeability of the skin to many drugs, trans-dermal delivery has limited applications. The low permeability is attributed primarily to the stratum comeum, the outermost skin layer which consists of flat, dead cells filled with keratin fibers surrounded by lipid bilayers. One common method of increasing the passive transdermal diffusional drug flux involves pretreating the skin with a skin permeation enhancer. 

Obviously, if you wish to treat a skin condition or infection, a preparation that can be applied topically would be the preferred option. Similarly, inhalation would be the first choice if trying to treat a pulmonary or bronchial condition, such as asthma. Dermal application would also be the first choice for localized tissue treatments (e.g. muscle injury), provided that the drug can be absorbed through the skin. However, in most other situations it is necessary for drugs to enter the bloodstream in order for them to be transported to their site of action. This is most commonly achieved by ingestion, or by intravenous (i.v.), intramuscular (i.m.) or subcutaneous (s.c.) injection when the oral route is not suitable. 

In the pharmaceutical industry, the two most common routes of administration are via diet and gavage (PMA, 1988). Some compounds are given by drinking water, topical (dermal) application, or injection, depending on the expected clinical exposure route, which is the primary criterion for determining the route of administration in carcinogenicity studies. When more than one clinical route is anticipated for a drug, the dietary route is often chosen for practical reasons. 

After oral administration, drug and metabolite concentrations in blood, urine, and feces can easily be monitored. In contrast, topical application to the skin usually aims at a local treatment. Therefore, the main interest lies in determining the drug level within the skin, in order to evaluate the dermal bioavailability of compounds or assess the bioequivalence between different formulations. In the following sections, appropriate analytical techniques will be presented. 

In developing protein and peptide trans-dermal delivery systems, one must be mindful of the high interindividual variation in drug absorption across the skin. Large variations in bioavailability have been demonstrated with fentanyl patches, initially intended for postoperative pain relief but later abandoned due to unacceptable variability among individuals receiving the same dose [9]. Response in postoperative patients to the application of a fentanyl patch ranged from ineffective pain relief to severe respiratory depression, and effects were correlated with variations in plasma fentanyl levels [9]. 

In this section, we outline the applications of IR microscopic imaging to the molecular level determination of dermal and transdermal percutaneous absorption. The rationale for these experiments is that drugs often exhibit low penetration rates... 

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. 

Liposomes have widely reported an effective means of tran -dermal transport system. The use of liposomes has been reported in applications for topical and intravenous uses (35). Although the mechanism of this effect is not fully explained, it has been suggested that liposomes pass intact through the lipid-rich outer layer of the skin to the dermis, where they become localized. The suggestion has been made that the follicular pathway contributes to the liposomal delivery of drugs into the deeper skin strata (36). 

Liposomal systems also can form an effective drug reservoir in the upper layers of the skin. This is particularly useful for local skin therapy. Ethosomal carriers composed of phospholipid vesicular systems with alcohols are also effective at enhancing tran -dermal delivery of both lipophilic and hydrophilic compounds. The use of these ethosomes has been used in the delivery of minoxidil to the pilo-sebaceous section of the skin with better results than conventional liposomes. Similar results are reported in clinical studies with acyclovir in a topical therapy treatment of recurrent herpes labialis. Other application reports with ethosomes are patches containing testosterone (37). 

Topical applications in the form of spray also have been reported as vehicles for enhanced frawi-dermal delivery of drugs such as testosterone, estradiol, progesterone, and norethindrone acetate. More effective drug penetration was reported with enhancers padimate and octyl salicylate and compared with laurocapram and oleic acid (38). Other methods reported for enhanced percutaneous drug absorption include iontophoresis (39), ultrasound or sonophoresis (40), and electroporation (41). 

The encapsulation of hepatocytes for a bioartificial liver, and cell therapy for the treatment of other hormone deficiencies or neurodegenerative diseases, such as Alzheimer s and Parkinson s, are also under investigation. Additional examples of cell encapsulation in polymer-polymer coacervates include non-autologous gene therapy,blood substitutes as well as the treatment of prostate cancer. Pharmaceutical applications of microcapsules encompass, in addition, trans-dermal drug delivery and protein delivery such as is required in anti-inflammatory therapy for arthritis. 

Other cosolvents, such as DMSO, demonstrate skin penetration enhancement properties for a number of compounds. Although this could be a highly desirable property for many drugs, the use of DMSO as a solvent for dermal application has not been approved. 

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