Effect of diethyl-beta-cyclodextrin on the release of nitroglycerin from formulations.
The complex-forming abilities of 2,6-di-O-ethyl-beta-cyclodextrin (DE-beta-CD), and its effect on the release of nitroglycerin (TNG) from formulations of the compound, were studied and compared with corresponding properties of beta-cyclodextrin (beta-CD) and 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CD). Complex formation was confirmed by differential scanning calorimetry and infrared absorption spectroscopy. In an accelerator test involving temperature and reduced pressure, marked depression of the volatility of TNG was observed as a result of CD complex formation. Dissolution rates of TNG from powdery TNG/DE-beta-CD complex and its tablets were retarded in comparison with the rates from other CD complexes. The release rate of TNG from ointments was accelerated by complexation with DE-beta-CD, and retarded by complexation with beta-CD. To evaluate their in vivo percutaneous absorption, samples were applied to the inside tip of the cheek pouch of male golden hamsters. The amount of TNG remaining in the cheek pouch was lowest in the case of the TNG/DE-beta-CD complex ointment, and relatively high in the case of the TNG/beta-CD complex ointment, in agreement with the in vitro results. We suggest that the combination of DE-beta-CD complex and beta-CD complex might be applicable to sustained-release preparations for percutaneous administration.
Umemura
M
M
Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Ueda
H
H
Tomono
K
K
Nagai
T
T
D000818:Animals; D002152:Calorimetry, Differential Scanning; D006224:Cricetinae; D003505:Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*; D004355:Drug Stability; D007408:Intestinal Absorption; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008647:Mesocricetus; D005996:Nitroglycerin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009823:Ointment Bases; D009824:Ointments; D010577:Petrolatum; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013607:Tablets; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D009823:Ointment Bases; D009824:Ointments; D013607:Tablets; D047392:beta-Cyclodextrins; C055959:heptakis(2,6-diethyl)beta-cyclodextrin; D010577:Petrolatum; D005996:Nitroglycerin