**1. Introduction**

24 Rheumatoid Arthritis – Treatment

Weusten, Bas L.A.M., Johannes W.G. Jacobs, and Johannes W.J. Bijlsma. 1993. Corticosteroid

Xystrakis, E. 2005. Reversing the defective induction of IL-10-secreting regulatory T cells in

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pulse therapy in active rheumatoid arthritis. *Seminars in Arthritis and Rheumatism*

glucocorticoid-resistant asthma patients. *Journal of Clinical Investigation* 116, no. 1

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed drug groups. These drugs are used dermally or systemically in treatment of various rheumatic diseases, including rheumatoid arthritis (RA), as well as for osteoarthritis, low back pain and some joint diseases. The mechanism of action of NSAIDs is reversible inhibition of the cyclooxygenase enzyme (COX) and decreasing the synthesis of prostaglandins (Lionberger 2010; Massey 2010). However, these drugs lead to unfavorable effects specifically on the stomach as a result of inhibition of prostaglandins (PGs), which play a role in protection of the gastric mucosa, in systemic administration. The severity of these unfavorable side effects may range from a simple ailment like dyspepsia to peptic ulcer and gastrointestinal hemorrhage. Furthermore, the acidic character of NSAIDs may lead to local irritation and lesions on the gastrointestinal mucosa. Therefore, some NSAIDs are administered percutaneously and transdermally to achieve local or systemic effect as an alternative to oral and parenteral administration (Heyneman et al., 2000; Hooper et al., 2004). In dermal administration, the drug substances have to pass the *stratum corneum (SC)*  layer to reach lower layers of the skin and/or to enter systemic circulation. In this context, formulation of the product may play a key role for penetration and absorption of the active ingredient (Lee & Maibach, 2006). Several formulation approaches for cutaneous administration of NSAIDs have been employed. The conventional pharmaceutical forms particularly used for dermal administration to achieve local effect are gels, creams and ointments (Williams, 2003). Furthermore, studies on novel drug delivery systems are available for transdermal administration of NSAIDs. These new approaches include liquid crystals, nano/micro emulsions, liposomes, solid lipid particles and patches. These systems are used to enhance cutaneous passage of drugs into systemic circulation and to target different layers of the skin (Guy, 2010; Santos et al., 2008; El Maghraby et al., 2008; Ceve, 2004). Different approaches have been performed to enhance cutaneous passage of drugs with the objective of overcoming the low skin permeability (Guy, 2010; Tromer & Neubert,

Novel Formulation Approaches for Dermal and

Transdermal Delivery of Non-Steroidal Anti-Inflammatory Drugs 27

Table 1. Classification of NSAIDs according to chemical structure (Heynemann et al., 2000; Hadgraft et al., 2000; Marnett, 2009).

2006). The most frequently used approach is to include penetration enhancers in formulations. In addition to penetration enhancers, there are studies available in which physical methods such as iontophoresis is used in improving of skin delivery of drugs (Guy, 1996; Benson, 2005; Williams, 2003).

The chapter deals with the classification and mechanisms of action of NSAIDs used in treatment of various rheumatic diseases as well as for osteoarthritis, low back pain and some joint diseases. The advantages of skin delivery of NSAIDs to target affected tissues and/or to achieve systemic effect are also emphasized. In particular, recent studies in which novel drug delivery systems were developed for dermal and transdermal administration of NSAIDs are summarized.
