5 and 6

Aceclofenac, an NSAID, has been recommended orally for the treatment of rheumatoid arthritis and osteoarthritis. It also has anti-inflammatory, antipyretic and analgesic activity. The oral administration of aceclofenac causes gastrointestinal ulcers and gastrointestinal bleeding in chronic use. Due to gastrointestinal bleeding it may cause anemia. Transdermal delivery of aceclofenac may avoid these side effects, may help in the better patient compliance and bypasses first pass metabolism.7, 8 and 9 Therefore, an improved aceclofenac formulation is desirable which gives high degree of permeation and is devoid of chemical penetration enhancers.10 In the study check details Compritol 888 ATO, PEG-8 Miglyol

812 were selected as a solid and liquid lipids respectively. A nonionic surfactant Polysorbate 80 was used as stabilizer. The aceclofenac loaded NLC were optimized by using Box–Behnken Design. The selected formulations were evaluated for the Ex vivo animal skin study and pharmacodynamic study. Aceclofenac was provided by Ranbaxy FDA approval PARP inhibitor Laboratories, Gurgaon, Compritol 888 ATO by Gattefosse India Pvt. Ltd., PEG-8 Miglyol 812 by Subhash Chemicals, Polysorbate 80, ethyl acetate and other required chemicals are procured from Loba Chemie. The water used for all experiments was double distilled water. The NLC was prepared by a modified method of melt ultrasonication and high speed homogenization. Aceclofenac was dispersed in the about 10 g of mixed lipid phase (consisted of Compritol 888 ATO and PEG-8 Miglyol®812) maintained at around 10 °C above the melting temperature of mixed lipid. 2–5–10% (w/w) hot aqueous phase (Polysorbate 80) was heated to the same temperature then added drop by drop into the molten lipid phase under high speed homogenizer (ultra turrax) with 10000 rpm for 5 min. A hot pre-emulsion thus obtained was ultrasonicated using an ultrasonic

probe (PCI Instruments India) and again homogenized. The obtained dispersion cooled at room temperature was filtered through a millipore Linifanib (ABT-869) filter (0.45 μm). Aceclofenac loaded NLC gel was prepared by using Carbopol solution as a gelling vehicle for the NLC dispersion of aceclofenac. The gel consistency was obtained by adjusting the pH of the formulation. A three-factor, three-level Box–Behnken experimental design was used to optimize the procedure.11 and 12 (Table 1). The prepared NLCs were evaluated for the depression in melting point as compared with the pure lipid. The characterization was performed by using SEM and Master sizer (Malvern UK) for surface properties and size of the particles in the NLC dispersion. The lipid compatibility with the drug was studied by using FT IR and DSC graphs. The NLCs were evaluated for the rheological behavior by using Brookfield Viscometer (RVDV Pro II).