FORMULATION AND IN VITRO EVALUATION OF AZILSARTAN MEDOXOMIL NANOSUSPENSION


Nizar Awish Jassem, Nawal Ayash Rajab

Abstract


Objective: The objective of this study was to formulate and evaluate of the poorly soluble drug, azilsartan medoxomil into nanosuspension to increase the solubility and enhance the dissolution rate and then improve its bioavailability.

Methods: Nanosuspension of azilsartan medoxomil was prepared using solvent-antisolvent precipitation method using PVP-K30 as a stabilizer. Eight formulations were prepared to show the effect of different parameters in which four formulations show the effect of stabilizer concentration, three formulations show the effect of stirring speed and two formulations prepare to show the effect of the addition of co-stabilizer such as sodium lauryl sulphate (SLS) and tween 80. All these formulation are evaluated for their particle size and entrapment efficiency. The selected one was evaluated for zeta potential, scanning electron microscope (SEM), saturation solubility, and in vitro drug release.

Results: All the prepared formulations were in the nano size. The optimum concentration of the stabilizer was in the formulation when the drug: stabilizer ratio 1:1 and optimum stirring speed was 300 rpm. Dramatic effect on the particle size reduction was found by the addition of co-stabilizer (SLS) in formulation F3 that has P. S 157±0.0 nm. The selected formula F3 showed an enhanced dissolution profile compared to the pure drug at all-time intervals.

Conclusion: The results show that the formulation that contain drug: PVP-K30: SLS in ratio 1:0.75:0.25 is the best one and can be utilized to formulate azilsartan medoxomil nanosuspension.


Keywords


Azilsartan medoxomil, Solubility, Bioavailabilit

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References


Limbachiya MI. Solubility enhancement techniques for poorly soluble drugs: a review. Int J Periodontics Restorative Dentistry 2011;4:71-86.

Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW, et al. Strategies to address low drug solubility in discovery and development. Pharmacol Rev 2013;65:315-499.

Nagarwal RC, Kumar R, Dhanawat M, Das N, Pandit JK. Nanocrystal technology in the delivery of poorly soluble drugs: an overview. Curr Drug Delivery 2011;8:398-406.

Gad SC. Evaluating products for their potential to cause dermal and ocular irritation and corrosion. J Toxicol Cutan Ocul Toxicol 2002;21:213-44.

Amin K, Dannenfelser RM, Zielinski J, Wang B. Lyophilization of polyethylene glycol mixtures. J Pharm Sci 2004;93:2244-9.

Lakshmi P, Ashwini KG. Nanosuspension technology: a review. Int J Pharm Sci 2010;2:35-40.

Muller RH, Gohla S, Keck CM. State of the art of nanocrystals-special features, production, nanotoxicology aspects and intracellular delivery. Eur J Pharm Biopharm 2011;78:1-9.

Moschwitzer JP. Drug nanocrystals in the commercial pharmaceutical development process. Int J Pharm 2013; 453:142-56.

Priti M, Ruchira C, Ujwala D, Rohini C. Review: nanosuspension. Int J Pharm Sci Rev Res 2012;13:118-24.

Kesisoglou F, Amitava M. Crystalline nanosuspensions as potential toxicology and clinical oral formulations for BCS II/IV compounds. AAPS J 2012;14:677-87.

Pignatello R, Bucolo C, Spedalieri G, Maltese A, Puglisi G. Flurbiprofen loaded acrylate polymer nanosuspensions for ophthalmic application. Biomater Sci 2002;23:3247-55.

O'Neil MJ. Ed. The Merck Index-An encyclopedia of chemicals, drugs, and biological. Cambridge. 15th ed. UK: Royal Society of Chemistry; 2013. p. 161.

Kohara Y, Kubo K, Imamiya E, Wada T, Inada Y, Naka T. Synthesis and angiotensin II receptor antagonistic activities of benzimidazole derivatives bearing acidic heterocycles as novel tetrazole bioisosteres. J Med Chem 1996;39:5228–35.

Sheetal G, Rashmita D, Ravindra S. Solubility enhancement of azilsartan medoxomil by solid dispersion technique. Int J Inst Pharm Life Sci 2015;5:262-81.

Ramesh R, Jai D, Rohit R, Shweta K. Azilsartan: novel angiotensin receptor blocker. J Assoc Physicians India 2016;64:96-8.

Jones JD, Jackson SH, Agboton C, Martin TS. Azilsartan medoximil (edarbi). The eighth angiotensin II receptor blocker. PT 2011;36:634-40.

British national formally. edit 71; 2016. p. 133.

Sweetman CS, Martindale. The Complete drug reference. 37ed. Pharmaceutical Press; 2011. p. 1345-6.

Kunal S, Ravindra B. UV spectrophotometric method for the estimation of azilsartan medoxomil in bulk and pharmaceutical formulations. World J Pharm Res 2015;4:1667-72.

Gandhi S, Mittal P, Pahade A, Rege S. Development and validation of stability indicating HPTLC method for estimation of azilsartan medoxomil. Pharm Sci Monitor 2015;6:224-32.

Kunal S, Ravindra B. Solubility enhancement of azilsartan medoxomel using mixed hydrotrophy. World J Pharm Pharm Sci 2015;4:1167-79.

Kumkum S, Bhawani S, Sonigar, Priyadarshani k, Ravindra K. A novel design and expansion of nanosuspension. Int J Appl Pharm Bio Res 2016;1:105-11.

Vikram M, Jayvadan K, Dhaval J. Formulation, optimization and characterization of simvastatin nanosuspension prepared by nanoprecipitation technique. Pharm Lett 2011;3:129-40.

Dandan L, Heming X, Baocheng T, Kun Y, Hao P, Shilin M, et al. Fabrication of carvedilol nanosuspensions through the anti-solvent precipitation–ultrasonication method for the improvement of dissolution rate and oral bioavailability. AAPS Pharm Sci Tech 2012;13:295-304.

Shekunov BY, Chattopadhyay P, Tong H, Chow A. Particle size analysis in pharmaceutics: principles, methods and applications. Pharma Res 2007;24:203-27.

Rajalakshmi R, Venkataramudu T, Kumar R, Divya K, Kiranmayi M. Design and characterization of valsartan nanosuspension. Int J Pharmacother 2012;2:70-81.

Erol Y, Hans-Hubert. Design of a phytosphingo sine containing, positively-charged nanoemulsion as a colloidal carrier system for dermal application of ceramides. Eur J Pharm Biopharm 2005;60:91-8.

Nakarani M, Misra AK, Patel JK, Vaghani SS. Itraconazole nanosuspension for oral delivery: formulation, characterization and in vitro comparison with marketed formulation. Daru J Pharm Sci 2010;18:84-90.

Sahu BP, Das MK. Nanosuspension for enhancement of oral bioavailability of felodipine. Appl Nanosci 2013;4:1-9.

Dolenc A, Govedarica B, Dreu R, Kocbek P, Srcic S, Kristl J. Nanosized particles of orlistat with enhanced in vitro dissolution rate and lipase inhibition. Int J Pharm 2010;396:149-55.

Dubhi M, Ghodasara U, Mori D, Patel K, Manek R, Sheth NR. Formulation, optimization and characterization of candesartan cilexetil nanosuspension for in vitro dissolution enhancement. Afr J Pharm Pharmacol 2015;9:102-13.

Ige PP, Baria RK, Gattani SG. Fabrication of fenofibrate nanocrystals by probe sonication method for enhancement of dissolution rate and oral bioavailability. Colloids Surf B 2013;108:366–73.

Raghad AN, Hind EZ. Enhancement of candesartan cilexetil dissolution rate by using different methods. Asian J Pharm Clin Res 2015;8:320-6.

Gandhi S, Mittal P, Pahade A, Rege S. Development and validation of stability indicating HPLC method for estimation of azilsartan medoxomil. Pharm Sci Monitor 2015 6:224-32.

Iswariya V, Soujanya G, Santhoshi S, Rani S, Haseeba, Sabitha. Formulation development and optimization of extend release matrix tablet of azilsartan medoxomil using natural and synthetic polymers. Eur j Pharm Med Res 2016;3:294-304.

Gao L, Zhang D, Chen M, Zheng T, Wang S. Preparation and characterization of an oridonin nanosuspension for solubility and dissolution velocity enhancement. Drug Dev Ind Pharm 2007;33:1332-9.

Kocbek P, Baumgartner S, Kristl J. Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs. Int J Pharm 2006;312:179-86.

Mcclements D. Crystals and crystallization in oil-in-water emulsions: implications for emulsion-based delivery systems. Adv Colloid Interface Sci 2012;174:1-30.

Helgason T, Awad TS, Kristbergsson K, McClements DJ, Weiss J. Effect of surfactant surface coverage on formation of solid lipid nanoparticles (SLN). J Colloid Interface Sci 2009;334:75-81.

Van Eerdenbrugh B, Vermant J, Martens JA, Froyen L, Van Humbeeck J, Augustijns P. A screening study of surface stabilization during the production of drug nanocrystals. J Pharm Sci 2009;98:2091-103.

Merisko-Liversidge E, Sarpotdar P, Bruno J, Hajj S, Wei L, Peltier N, et al. Formulation and antitumor activity evaluation of nanocrystalline suspensions of poorly soluble anticancer drugs. Pharm Res 1996;13:272-8.

Patravale VB. Nanosuspensions: a promising drug delivery strategy. J Pharm Pharmacol 2004;56:827-40.

Wu L, Zhang J, Watanabe W. Physical and chemical stability of drug nanoparticles. Adv Drug Delivery Rev 2011;63:456-69.

Jenning V, Gohla S. Encapsulation of retinoids in solid lipid nanoparticles (SLN). J Microencapsulation 2001;18:149-58

Senthil Kumar P, Arivuchelvan A, Jagadeeswaran A, Subramanian N, Senthil Kumar C, Mekala P. Formulation, optimization and evaluation of enrofloxacin solid lipid nanoparticles for sustained oral delivery. Asian J Pharm Clin Res 2015;8:231-6.

Patil P, Bhoskar M. Optimization and evaluation of spray dried chitosan nanoparticles containing doxorubicin. Int J Curr Pharm Res 2014;6:7-15.

Bagul R, Mahajan V, Dhake A. New approaches in nanoparticulate drug delivery system-a review. Int J Curr Pharm Res 2012;4:29-38.

Mou D, Chen H, Wan J, Xu H, Yang X. Potent dried drug nanosuspensions for oral bioavailability enhancement of poorly soluble drugs with pH-dependent solubility. Int J Pharm 2011;413:237-44.

Mahapatra A, Murthy P. Solubility and dissolution rate enhancement of efavirenz by inclusion complexation and liquid anti-solvent precipitation technique. J Chem Pharm Res 2014;6:1099-106.

Tugba G, Reyhan N, Levent O. Design and characterization of nanocrystal formulations containing ezetimibe. Chem Pharm Bull 2011;59:41-5.




About this article

Title

FORMULATION AND IN VITRO EVALUATION OF AZILSARTAN MEDOXOMIL NANOSUSPENSION

Keywords

Azilsartan medoxomil, Solubility, Bioavailabilit

DOI

10.22159/ijpps.2017v9i7.18917

Date

01-07-2017

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 7, 2017 Page: 110-119

Online ISSN

0975-1491

Statistics

201 Views | 161 Downloads

Authors & Affiliations

Nizar Awish Jassem
Al – Rifai General Hospital, Thi-Qar Health Directorate, Ministry of Health, Iraq
Iraq

Nawal Ayash Rajab
Department of Pharmaceutics, Collage of Pharmacy, University of Baghdad, Iraq
Iraq


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