Bioadhesive starch microspheres and absorption enhancing agents act synergistically to enhance the nasal absorption of polypeptides.
This paper investigates the effect of starch microspheres on the absorption enhancing efficiency of various enhancer systems in formulations with insulin after application in the nasal cavity of sheep. The enhancers studied were lysophosphatidylcholine, glycodeoxycholate and sodium taurodihydroxyfusidate, a bile salt derivative. The enhancers were selected on the basis of their perceived or proven mechanism of action and worked predominantly by interacting with the lipid membrane. The bioadhesive starch microspheres were shown to increase synergistically the effect of the absorption enhancers on the transport of the insulin across the nasal membrane. Dependent on the potency of the enhancer system the increment in absorption enhancement was shown to be from 1.4 times to 5 times that obtained for the absorption enhancer in solution.
Illum
L
L
West Pharmaceutical Services, Drug Delivery and Clinical Research Centre Ltd., Albert Einstein Centre, Nottingham Science and Technology Park, University Boulevard, NG7 2TN, Nottingham, UK. lisbeth_illum@westpharma.com
Fisher
A N
AN
Jabbal-Gill
I
I
Davis
S S
SS
D000042:Absorption / Q000187:drug effects*; D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001682:Biological Availability; D001692:Biological Transport / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004357:Drug Synergism; D007328:Insulin / Q000493:pharmacokinetics*; D008863:Microspheres; D012756:Sheep; D013213:Starch / Q000494:pharmacology*
D001647:Bile Acids and Salts; D007328:Insulin; D013213:Starch