Drug release from a suspension with a finite dissolution rate: theory and its application to a betamethasone 17-valerate patch.
A random walk method for a diffusion equation is applied to the model for a suspension with a finite dissolution rate developed by Ayres and Lindstrom in 1977. In the method, the diffusion of dissolved drug and dissolution of crystal are calculated separately using a simple BASIC program. The random walk method strictly meets the principle of the conservation of mass as the drug amount in each sublayer rather than the concentration at each subinterval is concerned in the ointment. The model is used to analyze the release of betamethasone 17-valerate from a pressure-sensitive silicone adhesive into a sink. The drug release from the 1.50 mg/mL patch shows no substantial discrepancy from that predicted by the classic suspension model assuming an infinite dissolution rate. However, the classic model overestimates the release from the 3.08 and 5.88 mg/mL patches. The disagreement is lessened when the dissolution rate is assumed to be finite. However, the model does not give a perfect explanation because the drug release from the 3.08 and 5.88 mg/mL patches in the early phase is faster than the model predicts.
Kubota
K
K
Department of Dermatology, University of California--San Francisco, School of Medicine 94143-0989.
Twizell
E H
EH
Maibach
H I
HI
D000279:Administration, Cutaneous; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008962:Models, Theoretical; D012828:Silicones; D012995:Solubility; D012996:Solutions; D013535:Suspensions
D012828:Silicones; D012996:Solutions; D013535:Suspensions; D003907:Dexamethasone; C030949:dexamethasone 17-valerate