Improved pH-independent dissolution and oral absorption of valsartan via the preparation of solid dispersion.
This study aimed to improve the pH-independent solubility and dissolution characteristics of valsartan via the preparation of solid dispersions (SD) with poloxamer 407. SDs was prepared by using the solvent method at various drug-polymer ratios and their dissolution characteristics were examined at different pHs. Oral pharmacokinetics of SDs was also evaluated in rats. Compared to the untreated powder, SDs significantly improved the dissolution rate as well as the extent of drug release at low pH. Particularly, SD having the drug-polymer ratio of 1:5 exhibited pH-independent dissolution of valsartan, resulting in the rapid and complete drug release over the pH range of 1.2 to 6.8. The improved dissolution of valsartan via SD formulation appeared to be well correlated with the enhanced oral exposure of valsartan in rats. SDs increased C(max) and AUC(0-24) of valsartan by 2-7 folds in rats, implying that SDs should be effective to improve the bioavailability of valsartan. In conclusion, SDs containing poloxamer 407 appeared to be effective to improve the pH-independent dissolution and oral absorption of valsartan.
Park
Young Joon
YJ
Samil-pharm. Co. Ltd., Anyang, 431-060, Korea.
Lee
Hyoung-Kyu
HK
Im
Young Bin
YB
Lee
Wonjae
W
Han
Hyo-Kyung
HK
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008297:Male; D020442:Poloxamer / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013777:Tetrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000068756:Valsartan
D000959:Antihypertensive Agents; D004337:Drug Carriers; D012997:Solvents; D013777:Tetrazoles; D020442:Poloxamer; D000068756:Valsartan; D014633:Valine