Improvement of dissolution rate of piroxicam by inclusion into MCM-41 mesoporous silicate.
The aim of the present paper was the use of mesoporous silicate MCM-41 to increase the dissolution rate of piroxicam, a non-steroidal anti-inflammatory drug-class II of the Biopharmaceutic Classification System. The inclusion/adsorption compound of piroxicam in MCM-41 was obtained with a drug loading of about 14%. X-ray powder diffraction and differential scanning calorimetry (DSC) revealed the presence of piroxicam not arranged in crystalline form and FT-IR spectroscopy showed the presence of light interactions (hydrogen bonds) between the silicate silanols and the drug. The decrease of Brunauer, Emmett and Teller (B.E.T.) specific surface area and pore volume between free MCM-41 and the inclusion/adsorption compound was a prove of the presence of piroxicam inside the mesopores. The inclusion compound was submitted to in vitro dissolution tests and a remarkable dissolution rate improvement was observed in comparison to the crystalline drug in all tested conditions. The dissolution profile at pH 1.2 was comparable to that of the marketed product Brexin, a formulation with rapid analgesic effect onset. The improvement of dissolution rate is due to both the lack of drug in the crystalline form and to the extremely large surface area of the siliceous support. Physical stability tests of the free drug and the inclusion/adsorption complex were conducted as well over one month storage at 40 degrees C at different relative humidity.
Ambrogi
V
V
Dipartimento di Chimica e Tecnologia del Farmaco, Via del liceo 1, Perugia, Italy. valeria.ambrogi@unipg.it
Perioli
L
L
Marmottini
F
F
Giovagnoli
S
S
Esposito
M
M
Rossi
C
C
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D006813:Humidity; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010894:Piroxicam / Q000737:chemistry*; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013696:Temperature; D013818:Thermogravimetry