ARTEMETHER LOADED ETHYLCELLULOSE NANOSUSPENSIONS: EFFECTS OF FORMULATION VARIABLES, PHYSICAL STABILITY AND DRUG RELEASE PROFILE
DOI:
https://doi.org/10.22159/ijpps.2017v9i6.18321Keywords:
Artemether nanosuspensions, Effects of variables, Dynamic light scattering, Particle size, Size distribution, Stability, Drug releaseAbstract
Objective: The aim of this study was to explore the individual and joint effects of drug: ethylcellulose ratio, content of tween 80 and chloroform: water volume ratio on particles' size and size distribution of artemether loaded ethyl cellulose nanosuspension formulations, aiming to achieve nanosuspension with desired particles properties, stability and drug release profile.
Methods: Mixed levels design was used to generate a series of artemether loaded ethylcellulose nanosuspensions that produced by emulsification-solvent evaporation technique. Formulations were qualified for particle size and size distribution using dynamic light scattering technique. Best ranked formulation was then evaluated for stability and drug release rate and kinetics.
Results: Drug: polymer ratio, content of surfactant and organic: water volume ratio were found to exert considerable influences (p<0.05) on particle size of produced nanosuspensions, either individually or as joint variables. Peak intensity property of nanosuspensions was found to be influenced by drug: polymer ratio (p<0.05) whereas the influences of different variables on the polydisperse index property appear inconsequential (p>0.05). Best ranked (optimal) artemether nanosuspension proved stable and capable to improve and maintain the release of loaded drug over 24 h, at least under the setting conditions of this study.
Conclusion: Focusing on both the individual and joint influences of formulation variables assist in achieving nanosuspension with desired particles characteristics, stability and drug release profile.
Downloads
References
Muller RH, Jacobs C, Kayser O. Nanosuspensions as particulate drug formulations in therapy: rationale for development and what we can expect for the future. Adv Drug Delivery Rev 2001;47:3-19.
Patel VR, Agrawal YK. Nanosuspension: an approach to enhance solubility of drugs. J Adv Pharm Tech Res 2011;2 Suppl 2:81-7.
Silamut K, Newton PN, Teja-Isavadharm P, Suputtamongkol Y, Siriyanonda D, Rasameesoraj M, et al. Artemether bioavailability after oral or intramuscular administration in uncomplicated falciparum malaria. Antimicrob Agents Chemother 2003;47 Suppl 12:3795-8.
Laxmi M, Bhardwaj A, Mehta S, Mehta A. Development and characterization of nanoemulsion as carrier for the enhancement of bioavailability of artemether. Artif Cells Nanomed Biotechnol 2015;43 Suppl 5:334-44.
Anna B, Harisha KM, Uday K. Development, charecterization and evaluation of solid dispersion of artemether and Lumefantrine by solvent evaporation method using hydrophilic polymers. Int J Pharm Pharm Sci 2010;6 Suppl 2:180-5.
Somasundaram I, Sathesh Kumar S. Pramipexole dihydrochloride loaded MPEGPCL nanosuspension by modified nanoprecipitation: in vitro and in vivo evaluation. Asian J Pharm Clin Res 2016;9 Suppl 6:1-7.
Kilor V, Sapkal N, Daud A, Humne S, Gupta T. Development of stable nanosuspension loaded oral films of glimepiride with improved bioavailability. Int J Appl Pharm 2017;9 Suppl 2:28-33.
George M, Ghosh I. Identifying the correlation between drug/stabilizer properties and critical quality attributes (CQAs) of nanosuspension formulation prepared by wet media milling technology. Eur J Pharm Sci 2013;48 Suppl 1-2:142-52.
Bonhoeffer B, Kwade A, Juhnke M. Impact of formulation properties and process parameters on the dispensing and depositioning of drug nanosuspensions using micro-valve technology. J Pharm Sci 2017;106 Suppl 4:1102-10.
Sarmaha JK, Mahantab R, Bhattacharjeea SK, Ranadeep M, Angshuman B. Controlled release of tamoxifen citrate encapsulated in cross-linked guar gum nanoparticles. Int J Biol Macromol 2011;49:390-6.
Derringer G, Suich R. Simultaneous optimization of several response variables. J Qual Technol 1980;12 Suppl 4:214-9.
Kumar R, Nagarwal RC, Dhanawat M, Pandit JK. In vitro and in vivo study of indomethacin loaded gelatin nanoparticles. J Biomed Nanotechnol 2011;7 Suppl 3:325-33.
International Pharmacopoeia, Artemether assay specific monograph. 6th edition, Geneva: WHO publications; 2016. Available from: http://apps.who.int/phint/2016/ index.html#d/b.6.2.2.16. [Last accessed on 10 Feb 2017]
Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophillic polymers. Int J Pharm 1983;15:25-35.
Liversidge GG, Cundy KC. Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: absolute oral bioavailability of nanocrystalline danazol in beagle dogs. Int J Pharm 1995;125:91-7.
Chen Y, Liu J, Yang X, Zhao X, Xu H. Oleanolic acid nanosuspensions: preparation, in vitro characterization and enhanced hepatoprotective effect. J Pharm Pharmacol 2005;57:259-64.
Nur AO, Elamin KM, Osman ZA. Individul and mutual effects of applied compression force, mixing time and manufacturing method on properties of HPMC oral matrices. World J Pharm Pharm Sci 2015;4 Suppl 6:1327-44.
Dinarvand R, Mirfattahi S, Atyabi F. Preparation, characterization and in vitro drug release of isosorbide dinitrate microspheres. J Microencapsul 2002;19 Suppl 1:73-81.
Kalimuthu S, Yadav AV. Formulation and evaluation of carvedilol loaded Eudragite 100 nanoparticles. Int J PharmTech Res 2009;1 Suppl 2:179-83.
Rao KR, Senapati P, Das MK. Formulation and in vitro evaluation of ethyl cellulose microspheres containing zidovudine. J Microencapsul 2005;22 Suppl 8:863-76.
Zimmermann E, Müller RH, Mäder K. Influence of different parameters on reconstitution of lyophilized SLN. Int J Pharm 2000;196 Suppl 2:211-3.
Verma S, Kumar S, Gokhale R, Burgess DJ. Physical stability of nanosuspensions: Investigation of the role of stabilizers on Ostwald ripening. Int J Pharm 2011;406 Suppl 1-2:145-52.
Published
How to Cite
Issue
Section
