Release of isosorbide dinitrate from polymer film dosage forms and absorption of this drug through the oral mucosa of rats.
In vitro release tests and in vivo absorption measurements of oral cavity dosage forms of isosorbide dinitrate (ISDN) prepared from mixed polymer film systems were conducted. Hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose phthalate (HPMCP) were used to make the films, and the tests were conducted with films made from various ratios of these two polymers. The effects of the addition of the accelerator glycyrrhizic acid (GL), on dissolution and absorption were also examined. The mean dissolution time (MDT) in the in vitro dissolution tests varied with the nature of the polymers and drug, as well as with the pH of the testing solution. The MDT for the polymer film system with GL was smaller than that without GL. In the in vivo absorption tests using rats, the absorption of ISDN through the oral mucosa was observed in all the systems. In the mixed polymer film systems, the mean residence time (MRT) increased with increasing the ratio of HPMCP/HPC. The values of the area under the curve (AUC) for the systems with GL was larger than for those without GL. A good correlation was demonstrated between the absorption rate constant, ka and the dissolution rate constant, kd.
Danjo
K
K
Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Kitamura
Y
Y
Miyagawa
Y
Y
Otsuka
A
A
D000042:Absorption / Q000187:drug effects; D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D019695:Glycyrrhizic Acid; D065347:Hypromellose Derivatives; D007548:Isosorbide Dinitrate / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism*; D011108:Polymers; D051381:Rats; D013329:Structure-Activity Relationship
D003692:Delayed-Action Preparations; D004304:Dosage Forms; D011108:Polymers; D065347:Hypromellose Derivatives; D019695:Glycyrrhizic Acid; D002482:Cellulose; D008747:Methylcellulose; C008079:hydroxypropylcellulose; D007548:Isosorbide Dinitrate; D006034:Glycyrrhetinic Acid