title: Tracking the effect of microspheres size on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot in vitro and in vivo.
abstract: The effects of particle size of microspheres on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot (m-SAIB) was investigated to develop a long-term sustained release drug delivery system with low burst release both in vitro and in vivo. A model drug, risperidone, was first encapsulated into PLGA microspheres with different particle sizes using conventional emulsification and membrane emulsification methods. The m-SAIB was prepared by dispersing the risperidone-microspheres in the SAIB depot. The drug release from m-SAIB was double controlled by the drug diffusion from the microspheres into SAIB matrix and the drug diffusion from the SAIB matrix into the medium. Large microspheres (18.95 ± 18.88 µm) prepared by the conventional homogenization method exhibited porous interior structure, which contributed to the increased drug diffusion rate from microspheres into SAIB matrix. Consequently, m-SAIB containing such microspheres showed rapid initial drug release (Cmax = 110.1 ±54.2 ng/ml) and subsequent slow drug release (Cs(4-54d)= 2.7 ± 0.8 ng/ml) in vivo. Small microspheres (5.91 ± 2.24 µm) showed dense interior structure with a decreased drug diffusion rate from microspheres into SAIB matrix. The initial drug release from the corresponding m-SAIB was significantly decreased (Cmax = 40.9 ± 13.7 ng/ml), whereas the drug release rate from 4 to 54 d was increased (Cs(4-54d)=4.1 ± 1.0 ng/ml). By further decreasing the size of microspheres to 3.38 ± 0.70 µm, the drug diffusion surface area was increased, which subsequently increased the drug release from the m-SAIB. These results demonstrate that drug release from the m-SAIB can be tailored by varying the size of microspheres to reduce the in vivo burst release of SAIB system alone.
authors.affiliation: a School of Pharmaceutical Science , Jiangnan University , Wuxi , People's Republic of China ;
authors.forename: Xia
authors.initials: X
authors.lastname: Lin
authors.affiliation: b Department of Pharmaceutics Science , Shenyang Pharmaceutical University , Shenyang , People's Republic of China ;|c Shenyang Bozhixinda Drug Research Co. Ltd , Shenyang , People's Republic of China ;
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: d School of Pharmacy , Shanghai Jiao Tong University , Shanghai , People's Republic of China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: b Department of Pharmaceutics Science , Shenyang Pharmaceutical University , Shenyang , People's Republic of China ;
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
authors.affiliation: d School of Pharmacy , Shanghai Jiao Tong University , Shanghai , People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: b Department of Pharmaceutics Science , Shenyang Pharmaceutical University , Shenyang , People's Republic of China ;
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: b Department of Pharmaceutics Science , Shenyang Pharmaceutical University , Shenyang , People's Republic of China ;
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: a School of Pharmaceutical Science , Jiangnan University , Wuxi , People's Republic of China ;
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000737:chemistry; D013395:Sucrose / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013395:Sucrose; C002885:sucrose acetate isobutyrate; D018967:Risperidone
keywords: Burst release; PLGA microspheres; controlled release; microsphere/SAIB hybrid depot; risperidone