Poly(lactide-co-glycolide) microspheres containing bupivacaine: comparison between gamma and beta irradiation effects

• Published in: Journal of controlled release Vol. 90; no. 3; pp. 281 - 290
• Main Authors: Montanari, L, Cilurzo, F, Selmin, F, Conti, B, Genta, I, Poletti, G, Orsini, F, Valvo, L
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 31.07.2003; Elsevier
• Subjects: AFM; Anesthetics, Local - chemistry; Anesthetics. Neuromuscular blocking agents; Beta Particles; Beta-irradiation; Biological and medical sciences; Bupivacaine; Bupivacaine - chemistry; Calorimetry, Differential Scanning; Drug Carriers; Drug Stability; Gamma Rays; Gamma-irradiation; General pharmacology; Glycolates - chemistry; Glycolates - radiation effects; Lactic Acid; Medical sciences; Microspheres; Neuropharmacology; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; PLGA; Polyglycolic Acid; Spectroscopy, Fourier Transform Infrared; Sterilization - methods; Temperature; Time Factors; Gamma-irradiation; AFM; Beta-irradiation; Bupivacaine; PLGA; Encapsulation; Anhydride copolymer; Beta radiation; Anilide; Release; Glycolic acid copolymer; Microsphere; Pharmaceutical technology; Control release polymer; Spray drying; Anhydride polymer; In vitro; Local anesthetic; Ester copolymer; Lactic acid polymer; Gamma radiation; Dosage form; Irradiation; Active ingredient; Organic amide; Physicochemical properties
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(03)00153-6

The β- and γ-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 β- and γ-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 γ-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 β-irradiated microspheres are concerned, BU content decreased in a significant way (≈3%) only in microspheres containing 10% w/w of BU. Immediately after irradiation, drug release rate in β-irradiated microspheres increased less than in the corresponding γ-irradiated microspheres, and it did not change further over the following storage period. BU-loaded microspheres have been shown to be more stable against β- than γ-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.