[Influence of suspending agents on relative bioavailability of cyclosporine A-loaded HPMCP nanoparticles for oral administration to rats].
OBJECTIVE
To study the influence of suspending agents on the relative bioavailability of Cyclosporine A-loaded HPMCP(HP55) nanoparticles for oral administration.


METHODS
Suspending agents such as Vanzan, HPMC, Carbopol were added into cyclosporine A-loaded HP55 nanoparticles. The suspended nanoparticle formulations and Neoral were administered orally in a dosage of 15 mg/kg to rats. The CyA concentrations in the blood sample were determined by HPLC. Pharmacokinetic parameters were calculated by 3P97.


RESULTS
The concentration-time data of these preparations were best fit by two compartment model with a weight of 1/C(2). Compared with the reference Neoral microemulsion, the relative bioavailability of 2 g/L Carbopol, 5 g/L Vanzan, 8, 5, 3 g/L HPMC suspended nanoparticles were 70.2%, 84.3%, 90.0%, 94.5% and 97.7%, respectively. Their viscosity values were 550, 362, 105, 30 and 15 mPaxs, respectively.


CONCLUSIONS
With the increase in viscosity, the relative bioavailability of nanoparticle formulations decreased. So, it is important to select the appropriate viscosity of suspending agents in the formulation design.
Wang
Xun-qing
XQ
Department of Pharmaceutics, Peking University School of Pharmaceutical Sciences, Beijing 100083, China.
Chen
Zhen
Z
Dai
Jun-dong
JD
Zhang
Tao
T
Xia
Gui-min
GM
Zhang
Qiang
Q
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005079:Excipients / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008747:Methylcellulose / Q000008:administration & dosage* / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D014783:Viscosity
D005079:Excipients; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate