ENHANCEMENT OF DISSOLUTION RATE OF POORLY SOLUBLE DRUG ITRACONAZOLE BY NANOSUSPENSION TECHNOLOGY: ITS PREPARATION AND EVALUATION STUDIES
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i4.19933Keywords:
Itraconazole, Eudragit RL-100, Tween 80, Nanoprecipitationsolvent displacement, Dissolution rateAbstract
 Objective: The objective of this study was to prepare and evaluate itraconazole (ITZ) nanosuspensionsusing polymer Eudragit RL-100 and stabilizer Tween-80 by nanoprecipitation method.
Materials and Methods: Itraconazole is a potent broad-spectrum Biopharmaceutical Classification System Class II triazole antifungal drug. Nanosuspensions were prepared using solvent displacement/nanoprecipitation method with the help of Eudragit RL-100 as rate-controlled polymer in different ratios and using Tween-80 as stabilizer. The nanosuspension preparation was optimized for particle size by investigating two factors that are solvent:anti-solvent ratio and surfactant concentration, at three levels. The prepared nanosuspensions were evaluated and characterized for particle size, drug excipient compatibility, percentage yield, drug entrapment efficiency, surface morphology, zeta potential, saturation solubility, solid state, and in vitro drug release studies.
Results: The nanosuspensions of itraconazole were successfully prepared using solvent displacement/nanoprecipitation method. The two factors solvent: anti-solvent ratio and surfactant concentration influenced the particle size of the nanosuspensions prepared. The Fourier-transform infrared spectroscopy studies confirmed that drug and excipients are compatible, and the X-ray powdered diffraction and differential scanning calorimetry results indicated that the nanoprecipitation method led to the amorphization of itraconazole. Itraconazolenanosuspensions increased the saturation solubility to an extent of 4 times. Itraconazole nanosuspensions completely dissolved in the dissolution medium within 10 s and 72% drug release within 5 min, while the pure drug was dissolved only up to 20% in 15 min and nanosuspensions showed increased dissolution rate of 3 folds, the active drug.
Conclusions: Stable itraconazole nanosuspensions were successfully prepared and these nanosuspensions demonstrated dramatic improvement in dissolution rate of the active drug.
Downloads
References
Nallaguntla L, Muzib YI, Aukunuru J, Balekari U. Novel nanoparticles for oral delivery of low molecular weight heparin: In vitro and in vivo assessment. Asian J Pharm Clin Res 2017;10:254-61.
Hiendrawan S, Hartanti AW, Veriansyah B, Widjojosusumo E, Tjandrawinata RR. Solubility enhancement of ketoconazole via salt and cocrystal formation. Int J Pharm Pharm Sci 2015;7:160-4.
Pragna S, Mandowaraa VK, Deepak G, Shetulv P. Formulation of curcuminoid loaded solid lipid nanoparticles in order to improve oral bioavailability. Int J Pharm Pharm Sci 2015;7:278-82.
Thadkala K, Nanam PK, Rambabu B, Sailu C, Aukunuru J. Preparation and characterization of amorphous ezetimibe nanosuspensions intended for enhancement of oral bioavailability. Int J Pharm Investig 2014;4:131-7.
Nanam PK, Thadkala K, Chinta S, Aukunuru J. Investigation of various practical techniques to enhance dissolution of ezetimibe from oral tablets. J Young Pharm 2014;6:8-15.
Yi Y, Tu L, Hu K, Wu W, Feng J. The construction of peurarin nanocrystals and its pharmacokinetic and in vivo-in vitro correlation (IVIVC) studies on beagle dog. Coll Surf B Biointerf 2015;133:164-70.
Ho C, Davies AM, Sangha RS, Lau D, Lara P Jr., Chew HK, et al. Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer. Invest New Drugs 2013;31:1587-91.
Kompella UB, Bandi N, Ayalasomayajula SP. Subconjunctival nano- and microparticles sustain retinal delivery of budesonide, a corticosteroid capable of inhibiting VEGF expression. Invest Ophthalmol Vis Sci 2003;44:1192-201.
Kolluru LP, Rizvi SA, D’Souza M, D’Souza MJ. Formulation development of albumin based theragnostic nanoparticles as a potential delivery system for tumor targeting. J Drug Target 2013;21:77-86.
Raju A, Reddy AJ, Satheesh J, Jithan AV. Preparation and characterization of nevirapine oral nanosuspensions. Indian J Pharm Sci 2014;76:62-72.
Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a bio-pharmaceutic drug classification: The correlation of in vitro drug product dissolution and in-vivo bioavailablility. Pharm Res 1995;12:413-20.
Yohei K. Formulation design for poorly water soluble drugs based on bio-pharmaceutics classification system. Int J Pharm Sci 2011;420:1 10.
Liversidge GG, Higak K, Kimura T. Effect of particle size reduction on dissolution and oral absorption of a poorly water-soluble drug cilostazol in beagle dogs. J Control Release 2006;111:56-64.
Yellela S, Krishniah R. Pharmaceutical technologies for enhancing oral bioavailability of poorly soluble drugs. J Bioequiv Availab 2010;2:28 36.
Hsu CH, Cui Z, Mumper RJ, Jay M. Micellarsolubilization of some poorly soluble antidiabetic drugs. AAPS Pharm Sci Technol 2010;9:939-43.
Chiba Y, Kohri N, Iseki K, Miyazaki K. Improvement of dissolution and bioavailability for mebendazole, an agent for human echinococcosis, by preparing solid dispersion with polyethylene glycol. Chem Pharm Bull (Tokyo) 1991;39:2158-60.
Desai PP. Overcoming poor oral bioavailability using nanoparticle formulations. Drug Discov Today Technol 2012;9:87-95.
Müller 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 Deliv Rev 2001;47:3-19.
Hetal P, Vishnu P, SnehaP. Nanosuspensions of olmesartanmedoxmil for bioavailability enhancement. J Pharma Bioallied Sci 2011;3:426-34.
Ana M, Marco M, Bruno G. Miconazole nanosuspensions. Int J Pharm 2010;396:210-3.
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.
Vishal R, Agarwal YK. Nanosuspension: An approach to enhance solubility of drugs. J Adv Pharm Tech Res 2011;2:81-7.
Odds FC, Oris M, Van Dorsselaer P, Van Gerven F. Activities of an intravenous formulation of itraconazole in experimental disseminated aspergillus, candida, and cryptococcus infections. Antimicrob Agents Chemother 2000;44:3180-3.
Xu Y, Liuc X, Liana R, Zheng S. Enhanced dissolution and oral bioavailability of aripiprazole nanosuspensions prepared by nanoprecipitation/homogenization based on acid-base neutralization. Int J Pharm 2012;438:287-95.
Mansour M, Pouretedal HR, Vida V. Preparation and characterization of ibuprofen nanoparticles by using solvent-anti-solvent precipitation. Open Conf Proc J 2011;2:88-94.
Kakran M, Sahoo NG, Li L, Judeh Z, Wang Y, Chong K, et al. Fabrication of drug nanoparticles by evaporative precipitation of nanosuspension. Int J Pharm 2010;383:285-92.
Xia D, Quan P, Piao H, Piao H, Sun S. Preparation of stable nitrindepine nano suspensions using precipitation-ultrasonication method for enhancement of dissolution of oral bioavailability. Adv Drug Deliv Rev 2011;47:19-25.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
