Development and in vitro Characterization of Self-nanoemulsifying Drug Delivery Systems of Valsartan

Authors: P. S. Rajinikanth, Yeoh Suyu, Sanjay Garg

Abstract:

The present study is aim to prepare and evaluate the selfnanoemulsifying drug delivery (SNEDDS) system of a poorly water soluble drug valsartan in order to achieve a better dissolution rate which would further help in enhancing oral bioavailability. The present research work describes a SNEDDS of valsartan using labrafil M 1944 CS, Tween 80 and Transcutol HP. The pseudoternary phase diagrams with presence and absence of drug were plotted to check for the emulsification range and also to evaluate the effect of valsartan on the emulsification behavior of the phases. The mixtures consisting of oil (labrafil M 1944 CS) with surfactant (tween 80), co-surfactant (Transcutol HP) were found to be optimum formulations. Prepared formulations were evaluated for its particle size distribution, nanoemulsifying properties, robustness to dilution, self emulsication time, turbidity measurement, drug content and invitro dissolution. The optimized formulations are further evaluated for heating cooling cycle, centrifugation studies, freeze thaw cycling, particle size distribution and zeta potential were carried out to confirm the stability of the formed SNEDDS formulations. The prepared formulation revealed t a significant improvement in terms of the drug solubility as compared with marketed tablet and pure drug.

Keywords: Self Emulsifying Drug Delivery System, Valsartan, Bioavailability, poorly soluble drug.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1332196

References:

[1] Lipinski C: Poor aqueous solubility - an industry wide problem in drug discovery. (http://americanpharmaceuticalreview.com/ViewArticle.aspx?ContentID =142)
[2] Di L, Kerns EH: Optimizing the physicochemical properties of clinical candidates during drug discovery. (http://mediaserver.aaps.org/meetings/webinars/ppb-9/ppb-9.pdf)
[3] Stegemann S, Leveiller F, Franchi D, Jong HD, Linden H: When poor solubility becomes an issue: From early stage to proof of concept. (http://capsugel.com/media/library/when-poor-solubility-becomes-anissue- from-early-stage-to-proof-of-concept.pdf)
[4] Product Leaftlet of Diovan. New Jersey: Norvartis; 2011 Apr
[5] Siddiqui N et al: Pharmacacological and Pharmaceutical Profile of Valsartan: A Review. Journal of Applied Pharmaceutical Science 2011; 01(04): 12-9
[6] Saydam M, Takka S: Bioavailability File: Valsartan. FABAD J. Pharm. Sci. 2007; 32: 185 - 196.
[7] Venkates KK, Arunkumar N, Verma PRP, Rani C: Preparation and in vitro characterization of valsartan solid dispersion using skimmed milk powder as carrier. IJPRIF. 2009, 1(3):431-7.
[8] Mahapatra AK, Murthy PN, Biswal S, Mahapatra APK, Pradhan SP: Dissolution enhancement and physicochemical characterization of valsartan in solid dispersions with ¶Çöü-CD, HP ¶Çöü-CD and PVP K-30. Dissolution Technologies 2011, 39-35.
[9] Dixit AR, Rajput SJ, Patel SG: Preparation and bioavailability assessment of SMEDDS containing valsartan. AAPS 2010, 11(1):314-21
[10] Jain CP, Naruka PS: Formulation and evaluation of fast dissolving tablets of valsartan. IJPS 2009, 219-26.
[11] Nielsen FS, Petersen KB, M├╝llertz A: Bioavailability of probucol from lipid and surfactant based formulations in minipigs: influence of droplet size and dietary state. Eur J Pharm Biopharm 2008, 69:553-62.
[12] Kumar GP, Rambhau D, Aapte SS: Oral bioavailability enhancement of carbamazepine in healthy human volunteers. J Pharm Research 2011, 4(2): 361-5.
[13] Taha EI, Al-Saidan S, Samy AM, Khan MA: Preparation and in vitro characterization of self-nanoemulsified drug delivery system (SNEDDS) of all-trans-retinol acetate. I J Pharm. 2004, 285(2004):109-19.
[14] Patel AR, Vavia PR: Preparation and in vivo evaluation of SMEDDS (Self-Microemulsifying Drug Delivery System) containing fenofibrate. AAPS 2007, 9(3):344-52
[15] Shafiq-un-Nabi S et al: Formulation Development and Optimization Using Nanoemulsion Technique: A Technical Note. AAPS Pharm. Sci. Tech. 2007, 8(2):28
[16] Mahmood EA, Bendas ER, Mohamed MI: Preparation and evaluation of self-nanoemulsifying tablets of carvedilol. AAPS 2009, 10(1):9192-7.
[17] Kassem AA, Marzouk MA, Ammar AA, Elosaily GH: Preparation and in vitro evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) containing clotrimazole. Drug Discovery and Therapeutics 2010, 4(5):373-9.
[18] Jeevana JB, Sreelakshmi K: Design and evaluation of selfnanoemulsifying drug delivery system of flutamide. J Young Pharm. 2011, 3(1):4-8.
[19] Gupta AK et al: Preparation and in-vitro evaluation of self-emulsifying drug delivery system of antihypertensive drug valsartan. International Journal of Pharmaceutics and Live Sciences March 2011, 2(3): 633 - 639.
[20] Patel J, Kevin G, Patel A, Raval M, Sheth N: Design and development of a self-nanoemulsifying drug delivery system for telmisartan for oral delivery. IJPI 2011, 1(2):112-8.
[21] Date AA, Desai N, Dixit R, Nagarsenker M: Self-nanoemulsifying Drug Delivery Systems: Formulation Insights, Applications and Advances. Nanomedicine 2010, 5(10).
[22] Pouton CW: Formulation of poorly water-soluble drugs for oral administration: Physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci. 2006, 29:278-87
[23] Mason TG, Wilking JN, Meleson K, Chang CB, Graves SM: Nanoemulsions: Formation, structure and physical properties. J. Phys. 2006, 18(2006): R635-666.
[24] Zetasizer Nano series technical notes. (http://www.nbtc.cornell.edu/facilities/downloads/Zeta%20potential%20 -%20An%20introduction%20in%2030%20minutes.pdf)
[25] Selection of emulsifiers. In Emulsion Science and Technology: A General Introduction. Edited by Tadros TF. UK: Wiley-VCH; 2009:25.
[26] Parambi DGT, Mathew M, Ganesan V: A validated stability indicating HPLC method for the determination of valsartan in tablet dosage forms. Journal of Applied Pharmaceutical Science 2011, 01(04): 97-9.