4.2.2.2 Niosomes

38 Rheumatoid Arthritis – Treatment

etofenamate, ibuprofen and salicylic acid that are commercially available. Lotion-type

Microemulsions are transparent liquid dispersions with a droplet size of 20-200 nm. Their formulations include four fundamental components, which are water, oil, surfactant and co-surfactant. The advantages of microemulsions include enhancing solubility of drugs, thermodynamic stability, ease of preparation and low costs (Neubert, 2011). Microemulsions have recently attracted attention in enhancing dermal permeation of lypophilic drugs as well as hydrophilic drugs. The oils and surfactants included in the composition of microemulsions also act as penetration enhancers. Besides, the composition of formulation and the internal structure of phases enhance diffusion of the drug inside the carrier and improve the partition of drug to SC (Kogan & Garti, 2006). The most important disadvantage of microemulsions is potential risk of skin irritation due to their high content of surfactants. Kantarc et al. (2007) prepared microemulsion formulations containing diclofenac sodium, and optimized it in with vitro tests. The irritant effect of formulations was investigated on healthy volunteers, and their safety was demonstrated. In another study, lecithin microemulsions of ketoprofen were developed (Paolino et al., 2002). Permeation of drug from microemulsion formulation was compared to the conventional dermal ketoprofen formulation. In this study performed with healthy volunteers, it was demonstrated that ketoprofen microemulsions enhanced the permeation of drug and has good skin tolerability (Amrish & Kumar, 2009). Dalmora et al. (2001) administered microemulsions loaded with piroxicam to rats in vivo, and demonstrated that dermal anti-inflammatory effect was extended, and inflammation inhibition lasted for nine days following single-dose administration. In vivo antiinflammatory activity study has also demonstrated that microemulsions containing flurbiprofen performed better than conventional gel formulation (Ambade et al., 2008). In another study, nano/submicron emulsions of flurbiprofen were suggested as dermal

Vesicular systems such as liposomes, niosomes and transfersomes have been developed for optimization of dermal penetration of drugs and particularly for dermal targeting. Vesicular systems have the advantages of controlling release rate of the active ingredient and to ensure localization of dermally administered drugs in dermal layers. Besides, transdermal administration of vesicular systems helps to carry drug molecules into systemic circulation

Liposomes are described as lipidic vesicles containing water. Cholesterol and phospholipids or amphiphilic ingredients of these compounds are typically used as lipids. Liposomes can capture hydrophilic molecules or contain lipophilic molecules in their membranes. Some liposomes can be adsorbed in the skin surface or may go into fusion. Fusion of liposomes may increase the drag force required for permeation of the molecule and facilitate dermal

preparations of bufexamac and salicylic acid are used in treatments (Table 4).

**4.2 Novel formulation approaches for improving skin delivery of NSAIDs** 

**4.2.1 Micromemulsions** 

carriers (Fang et al., 2004).

**4.2.2 Vesicular carriers** 

4.2.2.1 Liposomes

(El Sayed et al., 2007; Ceve, 2004).

Niosomes are liposomes prepared with non-ionic surfactants. Dermal penetration of niosomes depend on i) potential penetration-enhancing activity of surfactants in its content, ii) penetration of the vesicle to SC, iii) accumulation of vesicle on the skin surface and/or increasing thermodynamic activity of the drug on the skin surface. These mechanisms depend on the physicochemical properties of the drug, the vesicle and the lipids used (Choi & Maibach, 2005; Williams, 2003). Niosomes are the vesicular systems that are most studies in dermal and transdermal formulations of NSAIDs. This is because niosomes prevent transepidermal water loss, and they act on the lipid structure in the intracellular domain with the effect of high amount of surfactant in their content and overcome the barrier characteristic of the SC layer.

It has been observed that dermal retention and dermal penetration of the drug was enhanced with dermally administered noisome formulation of nimesulid. Besides, it has been determined that the noisome formulation has a faster anti-inflammatory activity than the commercial gel formulation (Shahiwala & Misra, 2002). Manosroi et al. (2008) obtained a higher flux of the drug in SC and deeper dermal tissues (live epidermis and dermis) with elastic noisome formulations loaded with diclophenac diethylammonium. Niosome-like vesicles consisting of hydrated mixtures of cholesterol and non-ionic surfactants are defined as "proniosomes" (Alsarra et al., 2005; Ammar et al., 2011). Alsarra et al. (2005) demonstrated that proniosomes of ketorolac improves permeation of the drug and shortens its lag time. In another study, formulations of proniosome were developed for transdermal delivery of tenoxicam. It has been stressed that proniosome formulation loaded with tenoxicam had higher anti-inflammatory and analgesic effect than the commercially available tenoxicam tablets (Ammar et al., 2011).
