Self Nano-emulsifying Drug Delivery System to Enhance Solubility and Dissolution of Candesartan Cilexetil

Aim: Self nano-emulsifying drug delivery system (SNEDDS) of candesartan cilexetil was explored to enhance its oral bioavailability. SNEDDS has tremendous potential in enhancing oral bioavailability of poorly aqueous soluble therapeutic agents. SNEDDS are pre-concentrate mixture of oil, surfactant and co-surfactant produces nanoemulsion after oral administration due to mild agitation produced by gastro motility within the size range of 20-200nm. Methodology: The formulations were developed by selecting capmul MCM®, triacetin® and caprylic acid® under the oil phase based on solubility of drug; cremophore RH40®, brij35® under surfactants category and transcutol P under co-surfactant on basis of their emulsification property. Optimum concentrations were choosen from the Terinary phase diagrams and evaluated for their properties. Results: From the results of ternary diagrams 16 formulations were selected (A1, A2, A3, A4, B1, B2, C1, C2, C3, C4, D1, D2, E1, E2, F1, F2) and subjected to characterization studies. Best formulations were subjected to particle size analysis and in vitro release studies. Among selected formulations, A1 and C1 have shown high in vitro drug release profiles with less selfemulsification time having grade A dispersibility without any precipitation and phase separation. Discussion: Concentration of surfactant helps in reducing the size of the particle when compared to the co-surfactant concentration. Enhanced dissolution of candesartan cilexitil may be attributed to the spontaneous formation of nanoemulsion in vitro with a decreased particle size that leads to the increased surface area leaving the drug candesartan as finely dispersed particles in dissolution media. Conclusion: Formulation C1 consists of triacetin oil 30% w/w, cremophore RH 40 6%w/w and transcutol P 64%w/w showed best emulsification characteristics like 99% percent transmittance, with increased dissolution profile (98%) than pure drug (45%) with nano range goblet size (165.9nm).

[1]  G. Abdelbary,et al.  Bioavailability enhanced clopidogrel -loaded solid SNEDDS: Development and in-vitro/in-vivo characterization , 2019, Journal of Drug Delivery Science and Technology.

[2]  Ming-Hua Chen,et al.  Effect of liquid oils on the properties of multiple emulsions containing liquid crystals , 2017 .

[3]  P. Verma,et al.  SOLID DISPERSION OF ORAL CANDESARTAN CILEXETIL TABLETS FOR HYPERTENSION: DEVELOPMENT AND CHARACTERISATION , 2017 .

[4]  J. Esquena Current Opinion in Colloid and Interface Science , 2016 .

[5]  Y. Pore,et al.  FORMULATION AND EVALUATION OF NEUSILIN US2 ADSORBED AMORPHOUS SOLID SELF-MICROEMULSIFYING DELIVERY SYSTEM OF ATORVASTATIN CALCIUM ® , 2016 .

[6]  S. Sahoo,et al.  Mixed surfactant based (SNEDDS) self-nanoemulsifying drug delivery system presenting efavirenz for enhancement of oral bioavailability. , 2016, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[7]  S. Arora,et al.  Development of surface stabilized candesartan cilexetil nanocrystals with enhanced dissolution rate, permeation rate across CaCo-2, and oral bioavailability , 2016, Drug Delivery and Translational Research.

[8]  J. Patel,et al.  Self nano-emulsifying drug delivery system for Embelin: Design, characterization and in-vitro studies , 2015 .

[9]  J. Ali,et al.  Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design, characterization, in vitro and in vivo evaluation , 2015, Drug delivery.

[10]  R. N. Dash,et al.  Design, optimization and evaluation of glipizide solid self-nanoemulsifying drug delivery for enhanced solubility and dissolution , 2015, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[11]  O. Ahmed,et al.  Design and optimization of self-nanoemulsifying delivery system to enhance quercetin hepatoprotective activity in paracetamol-induced hepatotoxicity. , 2014, Journal of pharmaceutical sciences.

[12]  K. Gujar,et al.  Design and evaluation of self‑nanoemulsifying drug delivery systems for nebivolol hydrochloride , 2014 .

[13]  R. Deveswaran,et al.  Development of Orodispersible Tablets of Candesartan Cilexetil-β-cyclodextrin Complex , 2013, Journal of pharmaceutics.

[14]  Bhupinder Singh,et al.  Optimized self nano-emulsifying systems of ezetimibe with enhanced bioavailability potential using long chain and medium chain triglycerides. , 2012, Colloids and surfaces. B, Biointerfaces.

[15]  D. Bhagwat,et al.  Formulation and evaluation of solid self micro emulsifying drug delivery system using aerosil 200 as solid carrier , 2012 .

[16]  C. Solans,et al.  Nano-emulsions: Formation by low-energy methods , 2012 .

[17]  Neha Joshi,et al.  ENHANCED ORAL BIOAVAILABILITY OF OLMESARTAN BY USING NOVEL SOLID SELF EMULSIFYING DRUG DELIVERY SYSTEM , 2012 .

[18]  Bhupinder Singh,et al.  Development of optimized self-nano-emulsifying drug delivery systems (SNEDDS) of carvedilol with enhanced bioavailability potential , 2011, Drug delivery.

[19]  K. Ofokansi,et al.  Self-Nanoemulsifying Drug Delivery Systems Based on Melon Oil and its Admixture with a Homolipid from Bos indicus for the Delivery of Indomethacin , 2011 .

[20]  K. Sreelakshmi,et al.  Design and Evaluation of Self-Nanoemulsifying Drug Delivery System of Flutamide , 2011, Journal of young pharmacists : JYP.

[21]  Anjali U. Patel,et al.  Formulation and development of a self-nanoemulsifying drug delivery system of irbesartan , 2011, Journal of advanced pharmaceutical technology & research.

[22]  Mushir M. Ali,et al.  Study of surfactant combinations and development of a novel nanoemulsion for minimising variations in bioavailability of ezetimibe. , 2010, Colloids and surfaces. B, Biointerfaces.

[23]  O. Abdallah,et al.  Self-nanoemulsifying drug delivery systems of tamoxifen citrate: design and optimization. , 2009, International journal of pharmaceutics.

[24]  Han‐Gon Choi,et al.  Enhanced oral bioavailability of dexibuprofen by a novel solid self-emulsifying drug delivery system (SEDDS). , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[25]  Rajeev Gupta,et al.  Hypertension epidemiology in India: lessons from Jaipur Heart Watch , 2009 .

[26]  Y. Liu,et al.  Preparation and evaluation of self-microemulsifying drug delivery system of oridonin. , 2008, International journal of pharmaceutics.

[27]  Sushma Talegaonkar,et al.  Development and bioavailability assessment of ramipril nanoemulsion formulation. , 2007, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[28]  J. Leroux,et al.  pH-responsive polymeric micelles of poly(ethylene glycol)-b-poly(alkyl(meth)acrylate-co-methacrylic acid): influence of the copolymer composition on self-assembling properties and release of candesartan cilexetil. , 2007, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[29]  A. Date,et al.  Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil. , 2007, International journal of pharmaceutics.

[30]  Chong-K. Kim,et al.  A new self-emulsifying formulation of itraconazole with improved dissolution and oral absorption. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[31]  C. Solans,et al.  Formation of Nano-emulsions by Low-Energy Emulsification Methods at Constant Temperature , 2001 .