Investigation of preparation parameters to improve the dissolution of poorly water-soluble meloxicam.

The rate of dissolution of drugs remains one of the most challenging aspects in formulation development of poorly water-soluble drugs. The meloxicam, a low molecular analgetic for oral administration, exhibits a slow dissolution. To improve the dissolution rate, the drug was formulated in a nanosuspension by using an emulsion-diffusion method, high-pressure homogenization or sonication. Optimization of the technological parameters (organic solvents, stabilizers, homogenization procedure and recovery of particles) allowed the formation of nanosuspensions with a particle size of 200-900 nm. SEM imaging confirmed the nanosized drug particles. Use of an SMCR method on the XRPD patterns of the nanosuspensions revealed the crystalline form of the drug and the strong interaction between meloxicam and the stabilizer. The rate of dissolution of the dried meloxicam nanosuspension was enhanced (90% in 5 min), relative to that of raw meloxicam (15% in 5 min), mainly due to the formation of nanosized particles. These results indicate the suitability of formulation procedure for preparation of nanosized poorly water-soluble drug with significantly improved in vitro dissolution rate, and thus possibly enhance fast onset of therapeutic drug effect.

[1]  M. Fathy.  Ca-alginate beads loaded with meloxicam: effect of alginate chemical composition on the properties of the beads and ulcerogenicity of the drug , 2006 .

[2]  M. Yazdanian,et al.  Evaluation of an accelerated Caco-2 cell permeability model. , 2000, Journal of pharmaceutical sciences.

[3]  G. Liversidge,et al.  Drug particle size reduction for decreasing gastric irritancy and enhancing absorption of naproxen in rats , 1995 .

[4]  E. A. Sylvestre,et al.  Self Modeling Curve Resolution , 1971 .

[5]  J. Morrow,et al.  Meloxicam inhibits the growth of colorectal cancer cells. , 1998, Carcinogenesis.

[6]  R. Rajkó,et al.  Physicochemical characterization of meloxicam-mannitol binary systems. , 2006, Journal of pharmaceutical and biomedical analysis.

[7]  Rolf Ergon.  PLS post‐processing by similarity transformation (PLS + ST): a simple alternative to OPLS , 2005 .

[8]  K Borner,et al.  Preparation of a clofazimine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine Mycobacterium avium infection. , 2000, The Journal of antimicrobial chemotherapy.

[9]  S. Baumgartner,et al.  Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs. , 2006, International journal of pharmaceutics.

[10]  Róbert Rajkó,et al.  Analytical solution for determining feasible regions of self‐modeling curve resolution (SMCR) method based on computational geometry , 2005 .

[11]  Róbert Rajkó,et al.  Natural duality in minimal constrained self modeling curve resolution , 2006 .

[12]  Rakesh Rathi,et al.  Encyclopedia of Nanotechnology , 2009 .

[13]  J. Breitenbach.  Melt extrusion: from process to drug delivery technology. , 2002, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[14]  Georg Achleitner,et al.  Development of an intravenously injectable chemically stable aqueous omeprazole formulation using nanosuspension technology. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[15]  Barrett E. Rabinow,et al.  Nanosuspensions in drug delivery , 2004, Nature Reviews Drug Discovery.

[16]  Kinam Park,et al.  A new process for making reservoir-type microcapsules using ink-jet technology and interfacial phase separation. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[17]  P Amsa,et al.  Nanosuspensions: A Promising Drug Delivery Strategy , 2010 .

[18]  K. Amighi,et al.  Preparation and characterization of nanocrystals for solubility and dissolution rate enhancement of nifedipine. , 2005, International journal of pharmaceutics.

[19]  R. Rajkó,et al.  Preparation of a solid dispersion by a dropping method to improve the rate of dissolution of meloxicam. , 2008, Drug development and industrial pharmacy.

[20]  Bruce R. Kowalski,et al.  An extension of the multivariate component-resolution method to three components , 1985 .

[21]  M. Gallarate,et al.  Emulsions containing partially water-miscible solvents for the preparation of drug nanosuspensions. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[22]  D. Türck,et al.  Meloxicam oral suspension: a treatment alternative to solid meloxicam formulations , 2001, Inflammation Research.

[23]  Christophe Collet,et al.  Self-Modelling Curve Resolution of near Infrared Imaging Data , 2008 .

[24]  Odd S. Borgen,et al.  The multivariate N-Component resolution problem with minimum assumptions , 1986 .

[25]  J Dressman,et al.  Improving drug solubility for oral delivery using solid dispersions. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[26]  Romà Tauler,et al.  Multivariate Curve Resolution (MCR) from 2000: Progress in Concepts and Applications , 2006 .

[27]  Filippos Kesisoglou,et al.  Nanosizing--oral formulation development and biopharmaceutical evaluation. , 2007, Advanced drug delivery reviews.

[28]  J. Nagy,et al.  Synthesis of Nimesulide Nanoparticles in the Microemulsion Epikuron/Isopropyl Myristate/Water/n-Butanol (or Isopropanol) , 2001 .

[29]  A. Pandit,et al.  Cavitation--a novel technique for making stable nano-suspensions. , 2007, Ultrasonics sonochemistry.

[30]  R. Rajkó,et al.  Preparation of a Solid Dispersion by a Dropping Methodto Improve the Rate of Dissolution of Meloxicam , 2008 .

[31]  J. Fiala.  Powder diffraction analysis of a three-component sample , 1980 .

[32]  M. Fornai,et al.  Efficacy and Tolerability of Meloxicam, a COX-2 Preferential Nonsteroidal Anti-Inflammatory Drug , 2002 .