4.2.2.3 Transfersomes

Transfersomes are defined as elastic vesicles that can be highly deformed. They are the first generation of elastic vesicles that contain phospholipids and an edge activator. Classical liposomes have a diameter varying from 200 to 400 nm, which is too large to pass through SC. However, transfersomes reach deeper dermal tissues and even the systemic circulation with their elasticity and highly deformable structure (Benson, 2009). It has been demonstrated that as classical liposomes cannot be deformed in the same way, transfersomes ensure higher skin permeation than liposomes in an in vitro comparison of skin permeation of transfersomes and liposomes loaded with meloxicam (Duangjit et al.,

Novel Formulation Approaches for Dermal and

Flufenamic acid Poly(lactide-co-

Nimesulide Nanocapsule

Nimesulide Nanocapsule

permeability.

**5. Conclusions** 

/nanoemulsion / nanospheres

/nanoemulsion / nanospheres

glycolide) nanoparticles

Transdermal Delivery of Non-Steroidal Anti-Inflammatory Drugs 41

study, pharmacokinetic data obtained with dermally administered ketoprofen patch was compared to the data of gel formulation. The obtained plasma level of ketoprofen was

**NSAIDs Nano carrier Results Refs** 

inflammatory activity up to 24 h.

accumulation in the skin.

conventional solution.

exhibited fasted drug input and sustained anti-

Nanoencapsulation of flufenamic acid has significantly increased drug transport and

increase in drug permeation with respect to its

indomethacin was observed with NLC hydrogels compared to its aqueous solution and hydro-

prologed anti-inflammatory effect compared to

sustained drug release pattern due to form a drug reservoir into skin. \*\*requires rewriting\*\*

Nimesulide-loaded nanocarriers formulated in hydrophilic gels exhibited good physicochemical properties for its dermal

Following the application of gel formulations of nimesulide based on nanocarriers was detected viable epidermis compared to conventional gel

sustained drug release over 24 h period.

n-butylcyanoacrylate nanocapsules was improved with respect to conventional gel Joshi & Patravale, 2008

2006

Luengo et al.,

Gonzales-Mira et al., 2011

Jain et al., 2005

Ricci et al., 2005

Miyazaki et al.,

Puglia et al., 2008

Puglia et al., 2006

Alves et al., 2005

Alves et al., 2005

2003

demonstrated to be higher than the gel formulation (Mazieres, 2005).

Celecoxib NLC based gel Gel formulations of celecoxib prepared with NLC

Flurbiprofen NLC NLC formulation of flurbiprofen was led to the

Flurbiprofen SLN SLN dispersion and gel formulation showed a

Indomethacin NLC Prolonged in vivo anti-inflammatory activity of

alcoholic gel.

Indomethacin Nanocapsule Transdermal delivery of indomethacin with poly

formulation.

Ketoprofen SLN Ketoprofen loaded SLN formulations showed a

its solution.

administration.

formulations.

Table 5. Studies on the development of nanocarriers of NSAIDs to improve their skin

During the last two decades, skin has been shown to be a suitable delivery site for drugs that are formulated dermally. Researchers have been trying to overcome gastrointestinal side effects by dermal and transdermal delivery of NSAIDs. Dermal administration of

Ketorolac NLC NLC formulation of ketorolac exhibited a

2011). In the same study, the structure of the skip was studied after administration of transfersomes, and it has been found that the structure of lipids in SC was disrupted.

#### 4.2.2.4 Ethosomes

Ethosomes contain phospholipids like classical liposomes; however, they also contain high levels of alcohol. It has also been demonstrated that its components can reach deeper layers of the skin or enter into systemic circulation. Action mechanisms of these carriers in improving permeation is explained by their alcohol content as penetration enhancers as well as disruption of intercellular lipid structure of SC by the phospholipids in their content (Godin & Touitou, 2003; Williams, 2003). Barupal et al. (2010) prepared ethosomes to investigate dermal administration of aceclofenac. They demonstrated that ethosomes have a high drug loading capacity and a good stability.

#### **4.2.3 Nano carriers (Solid lipid nanoparticles-SLN, nanostructured lipid carriers-NLC, and nanocapsules)**

It is observed that SLN and NLC formulations have been developed in the last decade for their desirable properties in terms of transdermal administration. SLN are water-in-oil emulsions containing solids as oil phase, and are prepared from solid lipids or from blends of these lipids. NLCs are new generation lipid particles, which have been developed to overcome certain disadvantages of SLNs, such as limited drug loading capacity, gellification risk and drug leakage due to lipid polymorphism during storage. NLCs contain mixtures of different solid lipids blended with liquid oils. The most important advantage of these carriers is their low risk of toxicity. Small size of lipid particles ensures close contact with SC, and may enhance dermal penetration of drug.

Polymeric nanoparticles are also prepared from biologically degradable or non-degradable polymers. The ability of polymeric particles to improve penetration of drugs and their dermal/transdermal applications to target accumulation in different layers of the skin are studied. However, dermal/transdermal administration of polymeric particles have been less studied than lipidic particles. Table 5 summarizes the studies in the literature on nanocarriers of NSAIDs that are dermally and transdermally administered.

#### **4.2.4 Transdermal patches**

Transdermal patches are drug carriers that contain an adhesive layer and ensure access of drugs to systemic circulation with controlled release rate. Additionally, the adhesive layer provides a firm contact for the drug to the skin. In general, transdermal patches are classified into two main groups by their methods of formulation, which are membrane-type (reservoir type) and matrix-type. In the former formulation, drug is contained in the adhesive and the drug release rate is controlled by the membrane. In the latter, drug molecules are dispersed or dissolved in polymer matrix. In cases where the matrix is not self-adhesive, a special adhesive layer is added. In transdermal patches, formulation components should be compatible with the skin, and they should be chemically stable and appropriate for use in combination (Padula et al., 2007; Vasilev et al., 2001; Williams, 2003). Among NSAIDs, adhesive types of transdermal patch formulations of meloxicam have been developed and evaluated in vitro/in vivo (Ah et al., 2010). In vivo anti-inflammatory activity of the formulation was compared to the piroxicam patch using adjuvant arthritis model. In conclusion, the meloxicam patch had a better anti-inflammatory effect. In another

2011). In the same study, the structure of the skip was studied after administration of

Ethosomes contain phospholipids like classical liposomes; however, they also contain high levels of alcohol. It has also been demonstrated that its components can reach deeper layers of the skin or enter into systemic circulation. Action mechanisms of these carriers in improving permeation is explained by their alcohol content as penetration enhancers as well as disruption of intercellular lipid structure of SC by the phospholipids in their content (Godin & Touitou, 2003; Williams, 2003). Barupal et al. (2010) prepared ethosomes to investigate dermal administration of aceclofenac. They demonstrated that ethosomes have a

**4.2.3 Nano carriers (Solid lipid nanoparticles-SLN, nanostructured lipid carriers-NLC,** 

It is observed that SLN and NLC formulations have been developed in the last decade for their desirable properties in terms of transdermal administration. SLN are water-in-oil emulsions containing solids as oil phase, and are prepared from solid lipids or from blends of these lipids. NLCs are new generation lipid particles, which have been developed to overcome certain disadvantages of SLNs, such as limited drug loading capacity, gellification risk and drug leakage due to lipid polymorphism during storage. NLCs contain mixtures of different solid lipids blended with liquid oils. The most important advantage of these carriers is their low risk of toxicity. Small size of lipid particles ensures close contact with

Polymeric nanoparticles are also prepared from biologically degradable or non-degradable polymers. The ability of polymeric particles to improve penetration of drugs and their dermal/transdermal applications to target accumulation in different layers of the skin are studied. However, dermal/transdermal administration of polymeric particles have been less studied than lipidic particles. Table 5 summarizes the studies in the literature on nano-

Transdermal patches are drug carriers that contain an adhesive layer and ensure access of drugs to systemic circulation with controlled release rate. Additionally, the adhesive layer provides a firm contact for the drug to the skin. In general, transdermal patches are classified into two main groups by their methods of formulation, which are membrane-type (reservoir type) and matrix-type. In the former formulation, drug is contained in the adhesive and the drug release rate is controlled by the membrane. In the latter, drug molecules are dispersed or dissolved in polymer matrix. In cases where the matrix is not self-adhesive, a special adhesive layer is added. In transdermal patches, formulation components should be compatible with the skin, and they should be chemically stable and appropriate for use in combination (Padula et al., 2007; Vasilev et al., 2001; Williams, 2003). Among NSAIDs, adhesive types of transdermal patch formulations of meloxicam have been developed and evaluated in vitro/in vivo (Ah et al., 2010). In vivo anti-inflammatory activity of the formulation was compared to the piroxicam patch using adjuvant arthritis model. In conclusion, the meloxicam patch had a better anti-inflammatory effect. In another

transfersomes, and it has been found that the structure of lipids in SC was disrupted.

4.2.2.4 Ethosomes

**and nanocapsules)** 

**4.2.4 Transdermal patches** 

high drug loading capacity and a good stability.

SC, and may enhance dermal penetration of drug.

carriers of NSAIDs that are dermally and transdermally administered.

study, pharmacokinetic data obtained with dermally administered ketoprofen patch was compared to the data of gel formulation. The obtained plasma level of ketoprofen was demonstrated to be higher than the gel formulation (Mazieres, 2005).


Table 5. Studies on the development of nanocarriers of NSAIDs to improve their skin permeability.
