Miconazole Nitrate Oral Disintegrating Tablets: In Vivo Performance and Stability Study
- 617 Downloads
The interest in and need for formulating miconazole nitrate (MN), a broad-spectrum antifungal, as an oral disintegrating tablet for treatment of some forms of candidiasis have increased. Formulation of MN in this dosage form will be more advantageous, producing dual effect: local in the buccal cavity and systemic with rapid absorption. Four formulations were prepared utilizing the foam granulation technique. The prepared tablets were characterized by measuring the weight uniformity, thickness, tensile strength, friability, and drug content. In addition, tablet disintegration time, in vitro dissolution, and in vivo disintegration time were also evaluated. Stability testing for the prepared tablets under stress and accelerated conditions in two different packs were investigated. Each pack was incubated at two different elevated temperature and relative humidity (RH), namely 40 ± 2°C/75 ± 5% RH and 50 ± 2°C/75 ± 5% RH. The purpose of the study is to monitor any degradation reactions which will help to predict the shelf life of the product under the defined storage conditions. Finally, in vivo study was performed on the most stable formula to determine its pharmacokinetic parameters. The results revealed that all the prepared tablets showed acceptable tablet characteristics and were stable under the tested conditions. The most stable formula was that containing magnesium stearate as lubricant, hydrophobic Aerosil R972 as glidant, low urea content, mannitol/microcrystalline cellulose ratio 2:1, and 9% Plasdone XL100 as superdisintegrant. The in vivo results revealed that the tested formula showed rapid absorption compared to the physical blend (t max were 1 and 4 h, respectively), while the extent of absorption was almost the same.
KEY WORDSaccelerated stability testing bioavailability foam granulation technique miconazole nitrate oral disintegrating tablet
The authors highly appreciated the cooperation of DEEF Pharmaceutical Industries Company for giving the research team the permission to use the foam granulation machine.
- 1.Himanshu KS, Tarashankar B, Jalaram HT, Chirag AP. Recent advances in granulation technology. Int J Pharm Sci Rev Res. 2010;5(3):Article-008.Google Scholar
- 3.Powder pro (2012) http://www.powderpro.se/products/technology/. Accessed 8 Apr 2012.
- 6.Ismat U, Jennifer W, Shih-Ying C, Gary JW, Nemichand BJ, San K. Moisture activated dry granulation—part I: a guide to excipient and equipment selection and formulation development. Pharm Technol. 2009;33(11):62–70.Google Scholar
- 8.Paul J, Shesky R, Colin K. New foam binder technology from Dow improves granulation process. Pharm Can. 2006; 19–22.Google Scholar
- 14.ICH. Stability testing of new drug substances and products. Geneva: International Conference on Harmonization, IFPMA; 1993.Google Scholar
- 15.ICH. Impurities in new drug products. Geneva: International Conference on Harmonization, IFPMA; 1996.Google Scholar
- 17.EMEA, The European Agency for the Evaluation of Medicinal Products, Human Medicines Evaluation Unit. Committee for Proprietary Medicinal Products (CPMP). Note for guidance on quality of modified release products. A: oral dosage forms. B: transdermal dosage forms, Section I (quality). 1999. CPMP/QWP/604/96, 1–15.Google Scholar
- 18.USP 28, the United States Pharmacopoeia, 28th Revision. Rockville, MD: Pharmacopoeial Convention, Inc. 2005.Google Scholar
- 20.Harshal AP, Priscilla MD. Development and evaluation of herbal laxative granules. J Chem Pharm Res. 2011;3(3):646–50.Google Scholar
- 21.Aulton ME. Pharmaceutics: the science of dosage form design. 2nd ed. New York: Churchill Livingstone; 2002. p. 154–5.Google Scholar
- 22.Wells J. Pharmaceutical preformulation. In: Aulton ME, editor. Pharmaceutics the science of dosage form design. 2nd ed. Edinburgh: Churchill Livingstone; 2003. p. 133–4.Google Scholar
- 23.Haririan I, Newton JM. Tensile strength of circular flat and convex-faced avicel PH102 tablets. Daru. 1999;7(3):36–9.Google Scholar
- 24.USFDA. Dissolution methods database. 2010. accessdata.fda.gov/scripts/cder/dissolution. Accessed on 15 Jun 2010.
- 26.USFDA. Bioequivalence guidelines. 2010. accessdata.fda.gov/scripts/cder/dissolution. Accessed 15 Jun 2010.
- 28.Sheskey P, Keary C, Clark D, Balwinski K. Scale up formulae of foam granulation technology-high shear. Pharm Technol. 2007;31(4):94–9.Google Scholar
- 30.Barillaro V, Dive G, Bertholet P, Evrard B, Delattre L, Frederich M, Ziemons E, Piel G. Theoretical and experimental investigations of organic acids/ cyclodextrin complexes and their consequences upon the formation of miconazole/previous termcyclodextrin/acid ternary inclusion complexes. Int J Pharm. 2007;342:152–60.PubMedCrossRefGoogle Scholar
- 32.Nie X. Heat and moisture migration within a porous urea particle bed. PhD thesis, University of Saskatchewan, 2010; p. 8–9.Google Scholar
- 33.USP, the United States Pharmacopoeia. 34th edn., Rockville, MD: Pharmacopoeial Convention, Inc. 2011.Google Scholar
- 36.ICH. International Conference on Harmonization of technical requirements for registration of pharmaceuticals for human use, by the ICH Steering Committee, version 2, 2005.Google Scholar
- 37.The European Pharmacopoeia (Ph.Eur.). 6th ed., Strasbourg, France: European Directorate for the Quality of Medicines, Council of Europe. 2010.Google Scholar
- 38.Faroongsarng D, Peck GE. Thermal porosity analysis of croscarmellose sodium and sodium starch glycolate by differential scanning calorimetry. AAPS Pharma Sci Tech. 2003;4:E67.Google Scholar
- 40.Rowe RC, Shesky PJ, Quinn ME. Handbook of pharmaceutical excipients. 6th ed. London: Pharmaceutical Press; 2009. p. 196–8.Google Scholar
- 42.Barillaro V, Bertholet P, Sandrine HH. Effect of acidic ternary compounds on the formation of miconazole/cyclodextrin inclusion complexes by means of supercritical carbon dioxide. J Pharm Sci. 2004;7(3):378–88.Google Scholar