Influence of heat treatment on spray-dried mixtures of Amioca starch and Carbopol 974P used as carriers for nasal drug delivery.
A mucoadhesive spray-dried starch/poly(acrylic acid) powder underwent different heat treatments in order to induce cross-linking between the functional groups of starch (Amioca) and poly(acrylic acid) (Carbopol 974P). After heat treatment the water-absorbing capacity, viscosity and elasticity of the mucoadhesive powder increased. NMR analysis in combination with FT-IR indicated that heat treatment induced a low degree of cross-linking between the polymers. Nasal administration of Amioca/Carbopol 974P powders without heat treatment resulted in an absolute bioavailability in rabbits of 8.2+/-3.0% for insulin. Due to the difference in water-absorbing capacity (which opened the tight junctions of the nasal mucosa), elasticity and plasticity (which reduced mucociliairy clearance and prolonged residence time) heat treatment at 120 degrees C improved the bioavailability: 26.4+/-21.9, 36.5+/-11.0 and 19.3+/-17.3% after heat treatment during 30 min, 1 h and 4 h, respectively. Heat treatment at 60 degrees C was less efficient. This study demonstrated that the nasal insulin absorption improved via heat treatment of the Amioca/Carbopol 974P powder (prior to the addition of insulin). The bioavailability-enhancing effect of a 1 h heat treatment at 120 degrees C was confirmed using the same polymer matrix in combination with different drugs (salmon calcitonin, human growth hormone and metoprolol tartrate).
Coucke
D
D
Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
Pringels
E
E
Foreman
P
P
Adriaensens
P
P
Carleer
R
R
Remon
J P
JP
Vervaet
C
C
D000179:Acrylates / Q000737:chemistry*; D000268:Adhesiveness; D000281:Administration, Intranasal; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D004548:Elasticity; D006358:Hot Temperature; D008790:Metoprolol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011208:Powders; D011817:Rabbits; D013213:Starch / Q000737:chemistry*; D014783:Viscosity; D003313:Zea mays / Q000737:chemistry
D000179:Acrylates; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D010455:Peptides; D011208:Powders; C117167:carbopol 974P NF; D013213:Starch; D008790:Metoprolol