Gastro-resistant microspheres containing ketoprofen.
Ketoprofen gastroresistant microspheres were prepared by spray-drying using common pH dependent polymers, such as Eudragit S and L, CAP, CAT and HPMCP. The long ketoprofen recrystallization time was a serious hindrance to the preparation of microspheres having a drug content higher than 35%. Microspheres were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray diffractometry and in vitro dissolution studies, and used for the preparation of tablets. During this step, the compaction ability of the spray-dried powders was measured. While the compressibility of the microspheres containing the enteric cellulosic derivatives are not acceptable and different from those of the microcrystalline cellulose, the compaction properties of ketoprofen/Eudragit L or S microspheres are comparable to those of the Avicel PH 101. In vitro dissolution studies were performed on the microspheres and the tablets. All microspheres showed a good gastroresistance, but some differences among the five polymers in reducing drug release at low pH values are present. Acrylic polymers (Eudragit L or S) are considerably more effective than the cellulosic derivatives CAP and CAT, while the HPMCP profile is in an intermediate position. These differences are erased by the microspheres compression process. In HCl 0.1 N, the percentage of ketoprofen released from the tablets is always close to zero, independently from the polymer used.
Palmieri
G F
GF
Università di Camerino, Dipartimento di Scienze Chimiche, Italy. gianpalm@camserv.unicam.it
Bonacucina
G
G
Di Martino
P
P
Martelli
S
S
D000179:Acrylates; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002482:Cellulose; D004339:Drug Compounding; D005753:Gastric Mucosa / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007660:Ketoprofen / Q000008:administration & dosage* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011108:Polymers; D011109:Polymethacrylic Acids; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013607:Tablets; D014961:X-Ray Diffraction
D000179:Acrylates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011108:Polymers; D011109:Polymethacrylic Acids; D013607:Tablets; C038300:methylmethacrylate-methacrylic acid copolymer; D002482:Cellulose; D007660:Ketoprofen