Rate-modulating PHBHV/PCL microparticles containing weak acid model drugs.
In this work, we aimed to evaluate the influence of the proportions of poly(epsilon-caprolactone) (PCL) in the poly(hydroxybutyrate-co-hydroxyvalerate) (PHBHV) blended microparticles on the drug release profiles of drug models and to determine the drug release mechanism. Diclofenac and indomethacin used as drug models showed encapsulation efficiencies close to 85%. The average diameters (122-273microm) and the specific surface areas (26-120m(2)g(-1)) of the microparticles were dependent on the PCL concentration in the blends. Differential scanning calorimetry (DSC) analyses showed that the microparticle preparation process influenced the thermal behavior of PHBHV, as well as the glass transition temperature of PHBHV increased with the presence of indomethacin. The release profiles, described by a biexponential equation, showed sustained phase half-lives varying from 131 to 912min (diclofenac) and from 502 to 6300min (indomethacin) depending on the decrease of the PCL concentration. The product between the diffusion coefficient and the drug solubility in the matrix (DC(s,m)), which was proportional to the PCL concentration, was calculated by fitting the release data to the Baker-Lonsdale equation. The mechanism of release was mainly controlled by the drug diffusion and the drug release profiles were controlled by varying the PCL concentration systematically in the blended PHBHV/PCL microparticles.
Poletto
Fernanda S
FS
Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Jäger
Eliézer
E
Ré
Maria I
MI
Guterres
Sílvia S
SS
Pohlmann
Adriana R
AR
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002214:Capsules; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry; D004339:Drug Compounding; D006207:Half-Life; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D015233:Models, Statistical; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D016062:Porosity; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013499:Surface Properties; D014867:Water; D000094122:Polyhydroxybutyrates
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D004008:Diclofenac; D007213:Indomethacin; D011091:Polyesters; D014867:Water; C052620:poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate); D000094122:Polyhydroxybutyrates; C016240:polycaprolactone