In vitro evaluation of intestinal absorption of desmopressin using drug-delivery systems based on superporous hydrogels.
The aim of this study was to investigate and modify the potential of drug-delivery systems based on superporous hydrogel (SPH) for improving the intestinal transport of the peptide drug desmopressin in vitro. The swelling properties and mechanical strength of SPHs were studied. The release profile of desmopressin was investigated by changing the composition of excipients in the formulations. Subsequently, the ability of the SPH-based drug-delivery systems to enhance the transport of desmopressin across porcine intestine was performed in vitro. The swelling properties and mechanical strength of SPHs were affected by the addition of the disintregrant AcDiSol. This disintregrant reduced the swelling ratio to 10% and the time to 80% swelling was retarded by 3-5 min in comparison to the negative control. AcDiSol increased the mechanical strength, according to the increasing of penetration pressure value, the pressure that the punch can penetrate the gel, of the SPHs. The transport of desmopressin across the intestinal mucosa in vitro was enhanced four- and six-fold by applying SPH, with AcDiSol, in the absence and presence of the additional absorption enhancer trimethyl chitosan chloride, respectively, in comparison to the negative control. It is concluded that drug-delivery systems based on SPHs are promising for enhancing the intestinal absorption of desmopressin.
Polnok
Assadang
A
Department of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Verhoef
J Coos
JC
Borchard
Gerrit
G
Sarisuta
Narong
N
Junginger
Hans E
HE
D000818:Animals; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D020100:Hydrogels / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D012076:Renal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013552:Swine
D020100:Hydrogels; D012076:Renal Agents; D003894:Deamino Arginine Vasopressin