INFLUENCE OF STABILIZERS IN MELOXICAM NANOCRYSTAL FORMATION AND ITS APPLICATION ON SUSPENSION ORAL DOSAGE FORM

Magdalena Yuni Kristanti; Rachmat Mauludin; Heni Rachmawati

doi:10.14499/indonesianjpharm0iss0pp259-266

INFLUENCE OF STABILIZERS IN MELOXICAM NANOCRYSTAL FORMATION AND ITS APPLICATION ON SUSPENSION ORAL DOSAGE FORM

Magdalena Yuni Kristanti, Rachmat Mauludin, Heni Rachmawati

Abstract

Meloxicam is a non steroid anti inflammatory drug that is classified as Biopharmaceutics Classification System (BCS) class II. Meloxicam is poorly soluble in water, therefore its solubility would be the rate limiting step for drug absorption. This study was conducted to improve meloxicam solubility using nanotechnology approach. Meloxicam nanocrystal was prepared using high pressure homogenization technique. Several stabilizers were investigated for suitable nanocrystal production. Formulation of suspension on the meloxicam nanocrystal was developed. Short physical stability was performed to assess the potential use of the stabilizer. Nanocrystal containing 10% meloxicam and 5% PVP K25 was formed faster with better physical stability compared to other stabilizers (xanthan gum, HPMC 2910 type 603 dan 645). Meloxicam nanocyrstal suspension containing meloxicam nanocrystal with stabilizer 5% or 10% of PVP K25 showed excellent particle size stability (with particle size 466.6nm and 486.9nm) and dissolution rate compared to reference product (without nanonization). Particle size and dissolution rate of meloxicam nanocrystal suspensions (containing 5% or 10% of PVP K25) were stable after storage for 30 days at room temperature. Kinetic solubility of meloxicam nanocrystal was three times higher than that of meloxicam. According to XRD profile, there was no differences in crystallinity between meloxicam and meloxicam nanocrystal.
Key words: meloxicam, high pressure homogenizer, nanocrystal,dissolution rate, kinetic solubility

Full Text:

Untitled

References

Ambrus R., Kocbek P., Kristl J., Šibanc R., Rajkó R., and Szabó-Révész P., 2009, Investigastion of Preparation Parameters to Improve the Dissolution of Poorly Water-Soluble Meloxicam, Int. J. Pharm.,pp. 153 – 159

Buckton G., and Beezer A., 1992, The Relationship Between Particle Size and Solubility, Int. J. Pharm., 82, pp. R7 – R10 Comba S., and Sethi R., 2009, Stabilization of Highly Concentrated Suspensions of Iron Nanoparticles Using Shear-Thinning Gels of Xanthan Gum, Water Research, 43, pp. 3717 – 3726

Khanam J., 2007, Crystallization, Pharm. Engineering Kürti L., Kukovecz A., Kozma G., Ambrus R., Deli MA., Szabó-Révész P., 2011, Study of the parameters influencing the cogrinding process for the production of meloxicam nanoparticles, Powder Technology, 212 , pp. 210–217

Mauludin R., 2008, Nanosuspensions of Poorly Soluble Drugs for Oral Administration, , Thesis, Freie Universität Berlin, Berlin. Mauludin R., Muller RH., Keck CM., 2008, Kinetic Solubility and Dissolution velocity of Rutin Nanocrystal, Euro. J Pharm. Scie., 36, pp. 502–510

Müller RH., and Akkar A., 2004, Drug Nanocrystals of poorly soluble drugs, Ensiclopedia of nanoscience and nanotechnology, 2, pp. 627 - 638

Naidu NB., Chowdary KPR., Murthy KVR., Satyanarayana V., Hayman AR., Becket G., 2006, Physicochemical Characterization of Meloxicam-Cyclodextrin Binary Systems, J. Pharm. Bio. Anal., 35 (1), pp.75 – 86

Nassab PR., Rajkó R., Szabó-Révész P., 2006 Physicochemical Characterization of Meloxicam–Mannitol Binary Systems, J. Pharm. Biomed Anal, pp. 1191 - 1197

Rachmawati H., Al Shaal L., Keck CM., 2009, Development of Curcumin Nanocrystals for Oral Bioavailability Enhancement : Preparation Characterization, Annual Meeting of the German Pharmaceutical Society (DPhG)

Rowe RC., 2009, Handbook of Pharmaceutical Excipient, Pharmaceutical Press, London, 6, pp. 326 – 329; 581 – 583; 549 – 553; 651 – 653; 782 – 784

Shi J, 2002, Steric Stabilization, Center for Industrial Sensor and Measurement Departement Materials Science and Enginering Group Inorganic Materials Science, pp. 1 – 13

Suman K., 2009, Drug Nanocrystals : A Novel Formulation Approach for Poorly Soluble Drugs, Int. J. Pharm Tech Res., 1(3), pp. 682-694

United States, PC., 2011 The United States Pharmacopoeia, The United States Pharmacopoeia Conventional Inc, 34

Verma S., Kumar S., Gokhale R., Burgess DJ., 2004, Physical stability of nanosuspensions: Investigation of the role of stabilizers on Ostwald ripening, Int. J.Pharm, 406, pp. 145 – 152.

DOI: http://dx.doi.org/10.14499/indonesianjpharm0iss0pp259-266