Sustained release pellets based on poly(N-isopropyl acrylamide): matrix and in situ photopolymerization-coated systems.
The usefulness of poly(N-isopropyl acrylamide), PNIPA, for preparing sustained release matrix or photopolymerization-coated cellulosic pellets was evaluated. Theophylline pellets and granules were prepared using powdered cellulose (PC), poly(vinylpyrrolidone) (PVP), and PNIPA of Mw approximately 330 kDa, Mn approximately 93 kDa and low critical solubility temperature approximately 32 degrees C. The low consistency of wet mass, evaluated by torsion rheometry, due to hydrophilic character of PNIPA at room temperature, favored extrusion-spheronization. Theophylline (20%) pellets prepared with 15% PNIPA, 20% PVP and 45% PC, and granules obtained using 40% PNIPA and 40% PC showed an enhanced, although limited, ability to sustain the release. This effect was notably promoted after compression (which provides slowly eroding tablets) or coating of individualized pellets. A new coating technique consisting in forming the polymer film by photo-polymerization/cross-linking of NIPA monomers on pellets surface, using a photoinitiator and UV-irradiation at 366 nm, was developed. The composition of coating mixture and the time of irradiation were optimized using oscillatory rheometry. Coating did not significantly change the shape, size, or friability of the pellets but remarkably decreased the porosity and sustained drug release for several hours. In situ formation and cross-linking of PNIPA on the pellet appears as a feasible way for controlling drug release.
Mayo-Pedrosa
Marcos
M
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782-Santiago de Compostela, Spain.
Alvarez-Lorenzo
Carmen
C
Lacík
Igor
I
Martinez-Pacheco
Ramon
R
Concheiro
Angel
A
D000178:Acrylamides / Q000737:chemistry; D000180:Acrylic Resins / Q000737:chemistry* / Q000528:radiation effects; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003432:Cross-Linking Reagents / Q000737:chemistry; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients / Q000737:chemistry* / Q000528:radiation effects; D008855:Microscopy, Electron, Scanning; D010777:Photochemistry; D016062:Porosity; D011205:Povidone / Q000737:chemistry; D011208:Powders; D012212:Rheology; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D013806:Theophylline / Q000737:chemistry; D013997:Time Factors; D019415:Torque; D014466:Ultraviolet Rays
D000178:Acrylamides; D000180:Acrylic Resins; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D011208:Powders; D013607:Tablets; C052970:poly-N-isopropylacrylamide; D002482:Cellulose; D013806:Theophylline; C021221:N,N'-methylenebisacrylamide; D011205:Povidone; C109691:microcrystalline cellulose