Formulation approaches to improving the delivery of an antiviral drug with activity against seasonal flu.
The main objective of the present study was to develop formulations of noscapine hydrochloride hydrate with enhanced solubility and bioavailability using co-solvent- and cyclodextrin-based approaches. Different combinations of co-solvents, which were selected on the basis of high-throughput solubility screening, were subjected to in vitro intestinal drug permeability studies conducted with Ussing chambers. Vitamin E tocopherol polyethylene glycol succinate and propylene glycol based co-solvent formulations provided the maximum permeability coefficient for the drug. Inclusion complexes of the drug were prepared using hydroxypropyl-β-cyclodextrin and sulphobutylether cyclodextrins. Pharmacokinetic studies were carried out in male Sprague-Dawley rats for the selected formulations. The relative bioavailabilities of the drug with the co-solvent- and cyclodextrin-based formulations were found to be similar.
Pharmaceutical Development, Biosciences Division, SRI International , Menlo Park, CA , USA .
Srinivasa M
SM
Sammeta
Li
L
Wang
Shravan K
SK
Mutyam
Kathleen
K
O'Loughlin
Carol E
CE
Green
Milton H
MH
Werner
Terence
T
Kelly
Gita N
GN
Shankar
D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D016503:Drug Delivery Systems; D015195:Drug Design; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy; D007408:Intestinal Absorption; D008297:Male; D009665:Noscapine / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry*
D000998:Antiviral Agents; D005079:Excipients; D012997:Solvents; D009665:Noscapine
Bioavailability; Ussing chambers; co-solvents; cyclodextrins; solubility