[Preparation of transdermal drug delivery system of felodipine-metoprolol and its bioavailability in rabbits].
To prepare transdermal drug delivery system (TDDS) of felodipine and metoprolol and to study its pharmaceutical characteristics, pharmacokinetics and bioavailability in rabbits, an HPLC assay was established for the simultaneous determination of felodipine and metoprolol in the permeation receptor and patch. The permeation rate and permeation mechanism of felodipine-metoprolol-TDDS through rabbit skin in vitro was examined. The determination of drug content, the examination of content uniformity and stability of the TDDS were carried out. GC-ECD assays were established for the determination of felodipine and metoprolol in plasma separately and then employed to study the pharmacokinetics and bioavailability of felodipine and metoprolol after a single dose of oral or transdermal administration in rabbits. The results indicated that the permeation of flodipine and metoprolol from the patch through excised rabbit skin exhibited zero-order kinetic characteristics. The determination of drug content and the quality control of content uniformity of the patch accorded with Pharmacopoeia of the People's Republic of China of 2005 edition and the pharmaceutical characterization showed good stability. In contrast to oral delivery, relatively constant, sustained blood concentration with minimal fluctuation and prolonged peak time were observed over a long period after transdermal administration. The relative bioavailability of felodipine and metoprolol were 275.37% and 189.76% versus oral administration respectively. It was evident that the felodipine-metoprolol-TDDS exhibited good controlled release properties that satisfied the demands of original design that enhancing bioavailability and maintaining appropriate blood levels for a prolonged time without adverse effects associated with frequent oral administration.
Wang
Wen-gang
WG
Department of Pharmacy, Affiliated Hospital, Academy of Military Medical Sciences, Beijing 100071, China. Jason_wwg@hotmail.com
Yun
Liu-hong
LH
Wang
Rui
R
Fu
Gui-ying
GY
Liu
Ze-yuan
ZY
D000279:Administration, Cutaneous; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D001381:Azepines / Q000737:chemistry; D001682:Biological Availability; D003511:Cyclohexanols / Q000737:chemistry; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004355:Drug Stability; D000077591:Eucalyptol; D015736:Felodipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D039821:Monoterpenes / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D011817:Rabbits; D012869:Skin Absorption
D000959:Antihypertensive Agents; D001381:Azepines; D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D039821:Monoterpenes; D011409:Propylene Glycols; C035229:laurocapram; D008790:Metoprolol; D015736:Felodipine; D000077591:Eucalyptol