Poly(lactide-co-glycolide) microspheres containing bupivacaine: comparison between gamma and beta irradiation effects.
The beta- and gamma-irradiation effects on stability of microspheres made of poly(lactide-co-glycolide) 50:50 copolymer (PLGA) containing bupivacaine (BU) were studied. Microspheres containing 10, 25, and 40% w/w, respectively, of BU were prepared by spray drying and irradiated in air with beta- and gamma-irradiation at a dose of 25 kGy. Morphology (atomic force microscopy, particle-size analysis), physico-chemical characteristics (DSC and FT-IR spectroscopy), drug content and in vitro dissolution profile of microspheres were all determined; the stability of irradiated microspheres was evaluated over a 9-month period. The decrease of BU content in gamma-irradiated microspheres was almost always constant independent of the amount of BU per sample, therefore it was in inverse proportion to drug loading (range between 5 and 15%). BU release rate increased immediately after irradiation and increased slightly until 90 days of storage. As far as beta-irradiated microspheres are concerned, BU content decreased in a significant way (approximately 3%) only in microspheres containing 10% w/w of BU. Immediately after irradiation, drug release rate in beta-irradiated microspheres increased less than in the corresponding gamma-irradiated microspheres, and it did not change further over the following storage period. BU-loaded microspheres have been shown to be more stable against beta- than gamma-irradiation. AFM revealed that the surface roughness of the irradiated microspheres increases depending on irradiation. As such, if a parameter is quantifiable, it is proposed as a marker of degradation due to ionizing radiation.
Montanari
L
L
Istituto di Chimica Farmaceutica e Tossicologica, Via le Abruzzi 42, 20131 Milan, Italy. luisa.montanari@unimi.it
Cilurzo
F
F
Selmin
F
F
Conti
B
B
Genta
I
I
Poletti
G
G
Orsini
F
F
Valvo
L
L
D000779:Anesthetics, Local / Q000737:chemistry*; D001610:Beta Particles; D002045:Bupivacaine / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers; D004355:Drug Stability; D005720:Gamma Rays; D006016:Glycolates / Q000737:chemistry / Q000528:radiation effects*; D019344:Lactic Acid; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017550:Spectroscopy, Fourier Transform Infrared; D013242:Sterilization / Q000379:methods; D013696:Temperature; D013997:Time Factors
D000779:Anesthetics, Local; D004337:Drug Carriers; D006016:Glycolates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002045:Bupivacaine