Effect on the nasal bioavailability of co-processing drug and bioadhesive carrier via spray-drying.
A mucoadhesive combination of a maize starch (Amioca, mainly consisting of amylopectine) and a cross-linked acrylic acid-based polymer (Carbopol 974P) was spray-dried with metoprolol tartrate (used as model molecule) in order to develop a powder suitable for nasal drug delivery via a one-step manufacturing process. The bioavailability of metoprolol tartrate after nasal administration of this powder to rabbits was compared with powders manufactured via other procedures: (a) freeze-drying of a dispersion prepared using the co-spray-dried powder, (b) freeze-drying of a dispersion prepared using a physical mixture of drug and mucoadhesive polymers. After co-processing via spray-drying a low bioavailability (BA 10.8+/-2.3%) was obtained, whereas manufacturing procedures based on freeze-drying yielded a higher BA: 37.9+/-12.8% using the co-processed powder and 73.6+/-24.9% using the physical mixture. The higher bioavailability was due to the deprotonation of poly(acrylic acid) during neutralisation of the dispersion prior to freeze-drying. This induced repulsion of the ionised carboxyl groups and a lower interaction between poly(acrylic acid) and starch, creating a less compact matrix upon hydration of the polymer and allowing an easier escape of metoprolol tartrate from the matrix. This study showed that co-processing of a mucoadhesive Amioca/Carbopol 974P formulation with metoprolol tartrate via co-spray-drying did not provide any added value towards the bioavailability of the drug after nasal administration of the mucoadhesive powder.
Coucke
D
D
Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
Vervaet
C
C
Foreman
P
P
Adriaensens
P
P
Carleer
R
R
Remon
J P
JP
D000179:Acrylates / Q000737:chemistry*; D000268:Adhesiveness; D000281:Administration, Intranasal; D000687:Amylopectin / Q000737:chemistry*; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D005612:Freeze Drying; D008790:Metoprolol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011208:Powders; D011817:Rabbits
D000179:Acrylates; D004337:Drug Carriers; D011208:Powders; C117167:carbopol 974P NF; D000687:Amylopectin; D008790:Metoprolol