Differential scanning calorimetry differences in micronized and unmicronized nimesulide uptake processes in biomembrane models.
Nimesulide release from micronized and unmicronized drug particles was tested at pH 7.4 by measuring the transfer to dimyristoylphosphatidylcholine liposomes (multilamellar and unilamellar vesicles), chosen as a biomembrane model. The perturbing effect of increasing molar fractions of pure nimesulide on the thermotropic behaviour of dimyristoylphosphatidylcholine liposomes was investigated by differential scanning calorimetry. In order to study the drug dissolution process by its uptake into void liposomes, measurements were carried out on suspensions of blank liposomes added to weighed amounts of free powdered nimesulide (micronized and unmicronized). The amount of drug transferred was quantified by comparing the effect caused by the dissolved and released drug to that caused by the free drug that had been previously molecularly dissolved in the liposomes. The calorimetric results show that the dissolution rate depends on the nimesulide form (micronized or unmicronized), and that the transfer to the void liposomes is quicker when the drug is in a micronized form. The uptake was faster when unilamellar vesicles were used instead of multilamellar vesicles because of the greater lipid surface. The calorimetric technique could represent an alternative 'in vitro' method that can be applied to the study of the dissolution kinetics directly at the site of drug uptake, mimicking a biological system.
Castelli
Francesco
F
Dipartimento di Scienze Chimiche, Universita di Catania, Viale Andrea Doria, 6, 95125, Catania, Italy. fcastelli@dipchi.unict.it
Grazia Sarpietro
Maria
M
Messina
Chiara
C
De Lazzari
Alessandra
A
Di Rosa
Dario
D
Giannetto
Antonino
A
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D001692:Biological Transport; D002152:Calorimetry, Differential Scanning / Q000379:methods; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008567:Membranes, Artificial; D008954:Models, Biological; D010539:Permeability; D013449:Sulfonamides / Q000737:chemistry* / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008081:Liposomes; D008567:Membranes, Artificial; D013449:Sulfonamides; D004134:Dimyristoylphosphatidylcholine; C012655:nimesulide