Scintigraphic evaluation in rabbits of nasal drug delivery systems based on carbopol 971p((R)) and carboxymethylcellulose.
The residence time of apomorphine mucoadhesive preparations incorporating 99mTc labeled colloidal albumin in rabbit nasal cavity was evaluated by gamma scintigraphy. This technique was used to compare the nasal clearance of preparations based either on Carbopol 971P((R)) or lactose (control), each with and without apomorphine, or carboxymethylcellulose with apomorphine. The planar 1-min images showed an excipient-dependent progressive migration of radioactivity with time from the nasal cavity to the stomach and intestine. Thirty minutes post insufflation, the percentages of the formulations cleared from the nasal cavity were 47% for lactose, 26% for lactose/apomorphine, 10% for Carbopol 971P((R)), and 3% for both Carbopol 971P((R))/apomorphine and carboxymethylcellulose/apomorphine. Three hours post insufflation, the percentages of the formulations cleared from the nasal cavity were 70% for lactose, 58% for lactose/apomorphine, 24% for Carbopol 971P((R)), 12% for Carbopol 971P((R))/apomorphine, and 27% for carboxymethylcellulose/apomorphine. Apomorphine inhibited nasal mucociliary clearance since migration of the radioactivity administered with apomorphine containing preparations was in all cases slower than that of the corresponding powder without apomorphine. The peak plasma concentration of apomorphine was attained while all the formulations were still within the nasal cavity. The use of mucoadhesive polymers such as Carbopol 971P((R)) or carboxymethylcellulose in nasal dosage forms increases their residence time within the nasal cavity and provides the opportunity for sustained nasal drug delivery.
Laboratorium voor Farmacotechnologie en Biofarmacie, Campus Gasthuisberg O&N, Katholieke Universiteit Leuven, B-3000, Leuven, Belgium.
M I
MI
Ugwoke
R U
RU
Agu
H
H
Vanbilloen
J
J
Baetens
P
P
Augustijns
N
N
Verbeke
L
L
Mortelmans
A
A
Verbruggen
R
R
Kinget
G
G
Bormans
D000180:Acrylic Resins; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D008297:Male; D009079:Mucociliary Clearance; D009297:Nasal Mucosa / Q000378:metabolism*; D011145:Polyvinyls / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits; D013667:Technetium
D000180:Acrylic Resins; D011145:Polyvinyls; C006912:carboxypolymethylene; D013667:Technetium; D002266:Carboxymethylcellulose Sodium; D001058:Apomorphine