Effect of Surfactants and Co-surfactants on Phase Behaviour and Physicochemical Properties of Self-nanoemulsifying Drug Delivery System Loaded with Plumbagin

Purpose: Plumbagin has wide pharmacological actions but limited solubility and low oral bioavailability. Self-nanoemulsifying drug delivery system (SNEDDS) has potential to improve solubility and dissolution rate. Selection of surfactant and co-surfactant is critical for a successful SNEDDS. Aim of present work was to investigate effect of different surfactants and co-surfactants on phase behaviour and physicochemical properties of SNEDDS loaded with plumbagin. Methods: Solubility of plumbagin in various oils, surfactants and co-surfactants was estimated. Out of those, CapmulMCM (oil), Tween20 and Tween 80 (surfactants), polyethylene glycol 400 and propylene glycol (co-surfactants) in varying concentrations and combinations of surfactant: co-surfactant (Smix) were employed to construct pseudo-ternary phase diagrams. Thermodynamic stability, dispersibility, robustness to dilution, self-emulsification time, % transmittance and globule size tested. Results: CapmulMCM, Tween20, Tween 80, polyethylene glycol (PEG) 400 and propylene glycol (PG) demonstrated the highest solubilisation and emulsification ability and studied further using ternary phase diagrams. Tween20 showed larger self-emulsification region compared to Tween 80 in combination with all co-surfactants studied. Tween 80 could not form any nano-emulsion with PEG 400. Propylene glycol gave clear isotropic regions with 30% of oil. With Tween 20, it could emulsify up to 40% of oil. SNEDDSs prepared using Tween20 with each of the co-surfactants passed dispersibility test. SNEDDSs containing Tween20 and propylene glycol displayed smaller globule size, less self-emulsification time, high transmittance and than those prepared with Tween20 and PEG 400. Conclusion: Tween20 and propylene glycol are suitable surfactant and co-surfactant for plumbagin loaded SNEDDS. © 2019 iGlobal Research and Publishing Foundation. All rights reserved. Cite this article as: Kamble, P.R. ; Shaikh, K.S. Effect of surfactants and co-surfactants on phase behaviour and physicochemical properties of self-nanoemulsifying drug delivery system loaded with plumbagin. Indo Global J. Pharm. Sci., 2020; 10(1): 1-11. DOI: http://doi.org/10.35652/IGJPS.2020. 10101 . Indo Global Journal of Pharmaceutical Sciences, 2020; 10(1): 1-11 2 have a novel property of forming fine oil-in-water (o/w) nanoemulsion in the nanometric range (10-100 nm) when introduced into the aqueous phase under gentle agitation [4]. Upon administration, the isotropic mixture will come in contact with the aqueous phase of gastrointestinal tracts and form an oil-in-water nanoemulsion with the aid of gastrointestinal motility. This spontaneous formation of nanoemulsion in the gastrointestinal tract presents the drug in a solubilized form, in small droplets of oil, all over its transit through the GIT [5]. The nano-sized droplets provide a large interfacial surface area for drug release and absorption. Apart from solubilization, the presence of oily phase in the formulation helps improve bioavailability by affecting the drug absorption [6]. Selection of a suitable selfnanoemulsifying formulation depends mainly upon the assessment of drug solubility in various components, the area of the self-nanoemulsifying region obtained in the phase diagram, and the droplet size of the resultant emulsion following self-emulsification [7]. Finally, SNEDDS offer the opportunity to deliver poorly water soluble drugs to the gastrointestinal tract in a dissolved state which leads to avoiding the dissolution step (which can limit the absorption rate of lipophilic drugs), reduction in inter-and intra-subject variability, reduction of food effect and ease of manufacturing and scale-up [8]. Plumbago zeylanica Linn (family Plumbaginaceae), is an erect semi-climbing shrub and grows throughout Asia, Africa and Australia. Traditionally, the aerial part of plant has long been used as medicine to treat rheumatic pain, scabies, skin diseases, dysmenorrhea, injury by bumping, wounds and even cancer. The roots of the plant and its constituents have been reported to possess potential antiatherogenic, cardiotonic, hepatoprotective, neuroprotective, antimicrobial and anti-ulcer activity. Plumbagin (5-hydroxy-2-methylnaphthalene 1, 4-dione) is a yellow crystalline naphthoquinone abundantly present in the roots of P. zeylanica. Plumbagin (PLB) has been explored for its anti-cancer, anti-inflammatory, anti-bacterial, anti-fungal, CNS stimulant and anti-ulcer activity [9]. Despite the great therapeutic interest, PLB showed low oral bioavailability (39%) due to its high lipophilicity (log P = 3.04) and poor aqueous solubility (79.3 ± 1.7 μg/ml); factors considered as major challenges in developing formulations for clinical efficacy [10]. Besides, the higher and frequent dose often causes severe side effects including diarrhea, skin rashes, increase in white blood cells and neutrophil count [9]. To overcome this problem a number of attempts have been made to enhance the solubility and, therefore, bioavailability of PLB. Singh and Udupa [11] prepared inclusion complex of PLB with beta-cyclodextrin employing neutralization method. Sheik et al. [12] developed nanoplumbagin encapsulated with cetyl trimethylammonium bromide or beta-cyclodextrin using ultrasonication. Chellampillai et al. [10] prepared surface modified PLB crystals by cold recrystallization technique. Rajalakshmi et al. [13] prepared different PLB crystals using anti-solvent precipitation, melt solidification, melt quenching, sonocrystallization and melt sonocrystallization processes. Sunil Kumar et al. [14] prepared PLB loaded long circulating PEGylated liposomes. Mandala et al. [15] prepared chitosan based PLB microsphere. Poor water solubility and consequent restricted absorption is a major limitation with many drugs despite their good efficacy. SNEDDS provides an opportunity for the improvement of the in vitro and in vivo performance of poorly water soluble drugs and thus serves as an ideal carrier for the delivery of drugs belonging to Biopharmaceutics Classification System (BCS) classes II and IV [32]. Thus, SNEDDS is an important viable option for PLB oral delivery. The performance of a SNEDDS depend sound selection of its component system, most importantly, the surfactant and co-surfactant system. The present study reports the effect of different surfactants and co-surfactants on the phase behaviour and properties of SNEDDS by use of ternary phase diagrams. This study helped in selection of product variables for optimization of PLB SNEDDS. MATERIALS AND METHODS