Original Article DEVELOPMENT AND IN VITRO EVALUATION OF NANOLIPID CARRIERS OF CLOBETASOL PROPIONATE AND PRAMOXINE HYDROCHLORIDE FOR TOPICAL DELIVERY DIXIT C. MOHAN 1 , AKHIL SURESH 1 , SHILPA MUKUNDAN 2 , SWATI GUPTA, VIDYA VISWANAD * Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, India Email: vidyaviswanad@aims.amrita.edu Received: 07 Dec 2017, Revised and Accepted: 10 Mar 2018 ABSTRACT Objective: Formulation and characterization of clobetasol propionate (CP) and pramoxine hydrochloride (PH) loaded nanostructured lipid carriers (NLC) offering improved performance in terms of drug loading and long-term stability for topical drug delivery. Methods: Drug-loaded NLC formulation was designed by melt-emulsification ultrasonication technique, by fluctuating the concentration of stearic acid and oleic acid. Poloxamer F68 and tween 80 were used as surfactants in the formulation and soya lecithin was used as stabilizer and co- surfactant. Differential scanning calorimetry (DLS), scanning electron microscopic studies (SEM), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), x-ray diffraction (XRD), are the techniques used to characterize the preparations. Optimized drug-loaded formulations were evaluated for particle size, zeta potential, entrapment efficiency, in vitro drug release, hemocompatibility assay and cytotoxicity screening. Results: For drug loaded formulation the particle size was found in nanometric range. In vitro drug release was carried out using dialysis membrane and drug release after 24h was found to be 90.98 %±1.89 for CP and 79.81 %±4.20 for PH. Conclusion: The formulated NLC is a potential approach for sustained release of drug which may reduce systemic side effects, increase skin retention time and duration of action. Further in vivo studies will confirm the effect of NLC to increase skin retention time, decreases systemic absorption of the corticosteroid thereby avoiding side effects. Keywords: Clobetasol propionate, Pramoxine hydrochloride, NLC, Melt-emulsification ultrasonication method, Atopic dermatitis © 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) DOI: http://dx.doi.org/10.22159/ijap.2018v10i3.24171 INTRODUCTION Atopic dermatitis (AD) is a highly pruritic chronic inflammatory skin disease that commonly presents during early childhood [1] and is often thought as synonymous with eczema. In several cases, atopic dermatitis is the first manifestation of atopy and is frequently associated with personal and family history of respiratory allergy and have profound effects on patient’s lives, career, choices and social interactions [2]. The prevalence of AD has increased exponentially over the past few decades in industrialized nations affecting 15% to 30% and 2% to 10% of children and adults, respectively [3]. Among individuals infected with AD, up to 60% of males and 55% of females are diagnosed under the age of 1 and less than 2% of new cases occur after the age of 20 [4]. Nanostructured lipid carriers (NLC) are the second generation SLN composed of solid lipid matrix which are incorporated with liquid lipids [5]. The small size of the lipid particles ensures close contact to stratum corneum (SC) and can increase the amount of drug penetrating into mucosa or skin. Due to their solid lipid matrix, a controlled release from these carriers is possible. This becomes an important tool when it is necessary to supply the drug over a prolonged period of time, to reduce systemic absorption, and when drug produces irritation in high concentrations [6]. NLCs have a higher loading capacity for a number of active compounds, and the potential expulsion of active compounds during storage is minimized [7]. Because of the small size of NLCs, close contact with the SC is guaranteed and the amount of the drug penetrated into the skin can be increased [8]. Corticosteroids have been successfully employed for the treatment of several inflammatory skin conditions. Their clinical efficacy is associated with drug skin retention; however, they can permeate the SC, reaching deeper skin layers, which may cause local and systemic side effects. CP is a super-potent topical corticosteroid. Skin atrophy, skin infections and hypothalamic-pituitary-adrenal (HPA) axis suppression are some of the possible side effects of topical corticosteroids. Improvements in the safety of topical corticosteroid therapy may be achieved by drug nanoencapsulation, which can increase the drug’s accumulation in the skin while minimizing deep drug permeation and adverse systemic effects [9]. In the present work, CP and PH were encapsulated in NLCs to increase drug retention in the outer skin layers and avoid systemic absorption. PH is a local anaesthetic that will help to reduce the itching sensation, currently, there are no combinational dosage form of these two drugs available in the market. MATERIALS AND METHODS Materials CP was gifted by mahima life sciences, haryana, India. PH was purchased from sigma-aldrich Co. LLC. Stearic acid was obtained from nice chemicals; kochi. Oleic acid is obtained from loba chem. Pvt. Ltd, mumbai. Poloxamer F68 was shipped from research-lab fine chem industries mumbai, India and Tween 80 was procured from nice chemicals, kochi. Soya lecithin is obtained from hi media laboratories Pvt. Ltd. mumbai, India. Millipore water was used during the course of the study. Preformulation studies The melting point of CP and PH (both are API) were determined by open capillary tube method. Methanol, dimethyl sulphoxide (DMSO), diethyl ether and ethanol are the organic solvents used to determine the solubility of pure drugs by the shake flask method reported as [10]. Solution of both drugs ranging from 2-10 µg/ml were scanned from 200-400 nm using a UV-visible spectrophotometer, support to define the absorption maxima (λ max). Partition coefficient was done by equal millilitre of N-octanol and water in separating funnel. 100 mg of the drug was added to it, which is then equilibrated for 2h at a constant temperature with intermittent shaking at regular intervals and separate the aqueous layer and organic layer. Collect 1 ml of the aqueous layer and the concentration of drug in it were determined at 240 nm by UV spectrophotometer. The same procedure was repeated for PH and the concentration of drug in it was determined at 224 nm by UV Spectrophotometer [10]. International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 10, Issue 3, 2018