Preparation and IVIVC evaluation of salvianolic acid B micro-porous osmotic pump pellets.
OBJECTIVE
Salvianolic acid B micro-porous osmotic pump controlled release pellets (SalB-CRPs) with suitable in vitro release profiles and good in vitro and in vivo correlation (IVIVC) were developed.


METHODS
Extrusion-spheronization was used to prepare the starter cores containing SalB/MCC/Kollidon®CL-SF/Flowlac®100 of 30:40:15:15 [w/w, The formulation composition of SalB immediate-release pellets (SalB-IRPs)] and complexed with lactose. The pellets were subsequently coated with Surelease aqueous dispersion to achieve controlled-release properties. Furthermore, a single-dose pharmacokinetics study was carried out in New Zealand White (NZW) rabbits.


RESULTS
In the starter cores, the lactose content was 25% based on the SalB-IRPs constituent. The optimal coating polymer ratio of Surelease aqueous dispersion and polyvinyl alcohol-polyethylene glycol (PVA-PEG) graft copolymer (EC/PVA-PEG) was found to be 70:30 (w/w, %) with a coating weight of 5%. The prepared SalB-CRPs had similar in vitro release under three different pH release mediums. A good IVIVC was characterized by a high coefficient of determination (r=0.9801). The in vivo study indicated that the maximum plasma concentration (Cmax) of SalB-CRPs was decreased, peak concentration time (Tmax) and mean residence time (MRT) were all prolonged, as that of SalB-IRPs. In addition, the area under concentration-time curve from 0 to 24 h (AUC0-24 h) and 0 to infinity (AUC0-∞) were significantly higher, compared with those of SalB-IRPs.


CONCLUSIONS
Collectively, these results manifested that SalB-CRPs were likely to be a more suitable formulation in treating cardiovascular disease with improved in vivo retention, decreased plasma drug concentration fluctuation.
Department of Pharmaceutics, China Pharmaceutical University , Nanjing , PR China and.
Shu-Ling
SL
Kan
Jin
J
Li
Jian-Ping
JP
Liu
Yi
Y
Zhao
D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004343:Drug Implants / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D008297:Male; D016062:Porosity / Q000187:drug effects; D011817:Rabbits; D053630:Depsides
D001572:Benzofurans; D004343:Drug Implants; C076944:salvianolic acid B; D053630:Depsides
Drug release; fluid-bed coating; micro-porous osmotic pump pellets; pharmacokinetics; salvianolic acid B