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Excipients to enhance the nasal delivery of peptides
ELSEVIER
European
Excipients
Journal
of Pharmaceutical
E. Marttin, S.G. Romeijn,
LeidenlAmsterdam Centre
(1996)S35
N.G.M. Schipper,
J. Verhoef
for Drug Research, P.O. Box 9502, 2300 RA, Leiden. Netherlands
Excipients of widely differing chemical structure have been investigated as potential nasal absorption enhancers foe the delivery of peptide and protein drugs. They include surfactants, bile salts, fusidic acid derivatives, fatty acids, phospholipids, bioadhesive polymers, starch microspheres, enzyme inhibitors, glycyrrhetinic acid derivatives and cyclodextrins. Generally, absorption enhancers act via one or a combination of the following mechanisms: they increase membrane fluidity, inhibit enzyme activity, reduce mucus viscosity or elasticity, decrease mucociliary clearance, open up tight junctions, or they solubilize or stabilize the drug. Ideally, absorption enhancers to be used in nasal therapy should have an immediate and predictable duration of action, their effect on the barrier properties of the nasal mucosa should be reversible, they
author.
0928-0987/96/$32.00 0 PII SO928-0987(96)00038-3
4 Suppl.
to enhance the nasal delivery of peptides
F.W.H.M. Merkus”,
*Corresponding
Sciences
1996 Elsevier Science B.V. All rights reserved
should be systematically inert, and devoid of any toxic, or allergenic activity. They should not give entry to potentially dangerous environmental material and should be compatible with drugs and adjuvants in the nasal formulation. Large interspecies differences appear to exist between the absorption enhancement efficacy of most nasal absorption enhancers. Increased nasal bioavailability measured in animal models does not mean that a clinically useful nasal absorption in human subjects can be expected. Thus, clinical efficacy of absorption enhancement and lack of nasal toxicity are crucial issues in the selection and approval of absorption enhancers. Nasal toxicity screening can be done by studying the nasal histopathology, the release of marker compounds from nasal epithelium and the influence on ciliary movement.
European
Excipients
Journal
of Pharmaceutical
E. Marttin, S.G. Romeijn,
LeidenlAmsterdam Centre
(1996)S35
N.G.M. Schipper,
J. Verhoef
for Drug Research, P.O. Box 9502, 2300 RA, Leiden. Netherlands
Excipients of widely differing chemical structure have been investigated as potential nasal absorption enhancers foe the delivery of peptide and protein drugs. They include surfactants, bile salts, fusidic acid derivatives, fatty acids, phospholipids, bioadhesive polymers, starch microspheres, enzyme inhibitors, glycyrrhetinic acid derivatives and cyclodextrins. Generally, absorption enhancers act via one or a combination of the following mechanisms: they increase membrane fluidity, inhibit enzyme activity, reduce mucus viscosity or elasticity, decrease mucociliary clearance, open up tight junctions, or they solubilize or stabilize the drug. Ideally, absorption enhancers to be used in nasal therapy should have an immediate and predictable duration of action, their effect on the barrier properties of the nasal mucosa should be reversible, they
author.
0928-0987/96/$32.00 0 PII SO928-0987(96)00038-3
4 Suppl.
to enhance the nasal delivery of peptides
F.W.H.M. Merkus”,
*Corresponding
Sciences
1996 Elsevier Science B.V. All rights reserved
should be systematically inert, and devoid of any toxic, or allergenic activity. They should not give entry to potentially dangerous environmental material and should be compatible with drugs and adjuvants in the nasal formulation. Large interspecies differences appear to exist between the absorption enhancement efficacy of most nasal absorption enhancers. Increased nasal bioavailability measured in animal models does not mean that a clinically useful nasal absorption in human subjects can be expected. Thus, clinical efficacy of absorption enhancement and lack of nasal toxicity are crucial issues in the selection and approval of absorption enhancers. Nasal toxicity screening can be done by studying the nasal histopathology, the release of marker compounds from nasal epithelium and the influence on ciliary movement.