NANOCRYSTAL TECHNOLOGY AS A TOOL FOR IMPROVING DISSOLUTION OF POORLY SOLUBLE DRUG, LORNOXICAM
DOI:
https://doi.org/10.22159/ijap.2018v10i3.25624Keywords:
Lornoxicam, Nanocrystals, Cyclodextrin, PVP K-30, PrecipitationAbstract
Objective: The aim of this study was to enhance the dissolution of a poorly water-soluble drug, lornoxicam by fabricating as nanoparticles using anti-solvent precipitation method and to investigate the effect of stabilizers on the particle size.
Methods: Nanocrystals of lornoxicam were prepared by precipitation method using water as antisolvent with stabilizers, β cyclodextrin, and PVP-K30. Characterization of the unmilled lornoxicam powder and nanocrystals was carried out by the Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and dissolution tester.
Results: Nano range (130-280 nm) particles were obtained which was confirmed by particle size analyzer. The dissolution of the drug nanoparticles (LBCD, LPVP) was carried out in pH 6.8 phosphate buffer solution and was significantly higher and almost complete compared with the pure drug. According to DSC, X-ray diffraction analysis, the nanocrystals were still in crystalline state after the preparation procedure. By reducing the particle size, the in vitro dissolution of lornoxicam was complete, 100% within 1 hr compared to the pure drug which showed an incomplete release of 37.35±1.09%.
Conclusion: Nanocrystals of lornoxicam was prepared and nanocrystal technology can be an effective tool for enhancing the solubility of poorly soluble drugs
Downloads
References
Balfour JA, Fitton A, Barradell LB. Lornoxicam: a review of its pharmacology and therapeutic potential in the management of painful and inflammatory conditions. Drugs 1996;51:639-57.
Martindale. The Complete Drug Reference. 4th edition. Pharmaceutical Press; London, Chicago: 2005;3:54.
Nawal AR. Preparation and in vitro evaluation of lacidipine oral liquid solid tablet as an approach of solubility and dissolution rate enhancement. Int J Appl Pharm 2018;10:145-53.
Patravale VB, Date AA, Kulkarni RM. Nanosuspensions: a promising drug delivery strategy. J Pharm Pharmacol 2004;56:827-40.
Shahira FE, Essam E, Adel AA, Ahmed AA. Enhancement of lornoxicam solubility by inclusion complexation with cyclodextrin: preparation and characterization. Int J Pharm Pharm Sci 2017;9:132-8.
Riehemann K, Schneider SW, Luger TA, Godin B, Ferrari M, Fuchs H. Nanomedicine-challenge and perspectives. Chem Int Ed Engl 2009;48:872-97.
Prakash K, Jieun RO, Hyeongmin K. Pharmaceutical particle technologies: an approach to improve drug solubility, dissolution and bioavailability. Asian J Pharm Sci 2014;9:304-16.
Ijeoma FU, Andreas GS, Woei PC, Aikaterini L. Fundamentals of Pharmaceutical Nanoscience. 1st edition. Springer-Verlag, New York; 2013. p. 277.
Xun W, Jing Z, Qing P, Yadong L. A general strategy for nanocrystal synthesis. Nature 2005;437:121–4.
Varaporn BJ, Boontida M. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian J Pharm Sci 2015;10:13-23.
Merisko LE, Liversidge GG, Cooper ER. Nanosizing: a formulation approach for poorly-water-soluble compounds. Eur J Pharm Sci 2003;18:113-20.
Anju G, Rupa M, Kamla P. Formulation, optimization and characterization of ziprasidone nanocrystals prepared by media milling technique. Int J Pharm Pharm Sci 2015;7:146-50.
Hanafy A, Spahn LH, Vergnault G, Grenier P, Tubic GM, Lenhardt T, et al. Pharmacokinetic evaluation of oral fenofibrate nanosuspensions and SLN in comparison to conventional suspensions of micronized drug. Adv Drug Delivery Rev 2007;59:419-26.
Ali HSM, York P, Ali AMA, Blagden N. Hydrocortisone nanosuspensions for ophthalmic delivery: a comparative study between microfluidic nanoprecipitation and wet milling. J Controlled Release 2011;149:175-81.
Gao L, Zhang D, Chen M, Duan C, Daia W, Jia L, et al. Studies on pharmacokinetics and tissue distribution of oridonin nanosuspensions. Int J Pharm 2008;355:321-7.
Mitri K, Shegokar R, Gohla S, Anselmi C, Müller RH. Lutein nanocrystals as antioxidant formulation for oral and dermal delivery. Int J Pharm 2011;420:141-6.
El-Gendy N, Pornputtapitak W, Berkland C. Nanoparticle agglomerates of fluticasone propionate in combination with albuterol sulfate as dry powder aerosols. Eur J Pharm Sci 2011;44:522-33.
Muller RH, Jacobs C. Buparvaquone mucoadhesive nanosuspension: preparation, optimisation and long-term stability. Int J Pharm 2002;237:151-61.
Krishna RSM, Shivakumar HG, Gowda DV, Banarjee S. Nanoparticles-a novel colloidal drug delivery system. Indian J Pharm Educ Res 2006;40:15-9.
Müller RH, Sven G, Cornelia MK. State of the art of nanocrystals–special features, production, nanotoxicology aspects and intracellular delivery. Eur J Pharm Biopharm 2011;78:1–9.
Biswadip S, Muller RH, Moschwitzera JP. Bottom-up approaches for preparing drug nanocrystals: formulations and factors affecting particle size. Int J Pharm 2013;453:126-41.
Eerdenbrugh VB, Van den MG, Augustijns P. Top-down production of drug nanocrystals: nanosuspension stabilization, miniaturization and transformation into solid products. Int J Pharm 2008;364:64–75.
Mitali K, Ranjita S, Nanda GS, Sven G, Lin L, Müller RH. Long-term stability of quercetin nanocrystals prepared by different methods. J Pharm Pharmacol 2012;64:1394–402.
Alessandra V, Jean J, Fabienneespitalier, Mariaines R, Vicosa A. An innovative antisolvent precipitation process as a promising technique to prepare ultrafine rifampicin particles. J Cryst Growth 2012;342:80–7.
Basavaraj KN, Ganesh KD, Hiren MB, Veerendra KN, Manvi FV. Design and characterization of nanocrystals of lovastatin for solubility and dissolution enhancement. J Nanomed Nanotechnol 2011;2:1-7.
Donald LP, Gary ML, James RV. Introduction to spectroscopy. 4th ed. USA: Brooks and Cole; 2009.
Maryadele JON. The Merck Index. 14th ed. USA: Merck and Co., Inc whitehouse station; 2006. p. 1000.