A novel differentiation method of vehicle models for topically applied drugs: application to a therapeutic timolol patch.
A novel method to differentiate basic vehicle models for topically applied drugs is proposed. In this method, the rate of drug release as a function of time, obtained by using a flow-through cell, is plotted on both semilogarithmic and logarithmic scales. In the Solution Case, where all of the drug is dissolved in the vehicle, the profiles become linear on the semilogarithmic scale. However, in the Suspension Case, where the initial drug amount per vehicle volume is greater than the solubility of the drug and the vehicle contains finely dispersed drug, the profiles are linear on the logarithmic scale with a slope of -0.5. They abruptly depart from this pattern upon depletion of the suspended phase. The different attributes of the profiles for the drug release rate-time curves in these two cases can be visualized more clearly when vehicle thickness and drug concentration are varied. The theoretical principles are illustrated in profiles for the drug release-rate time plots of therapeutic patches containing the beta blocker timolol. This was formulated at different concentrations in an acryl copolymer with varied thickness. The release profiles were best fitted to the Solution Case treatment of the data.
Kubota
K
K
Division of Clinical Pharmacology, National Medical Center, Tokyo, Japan.
Yamada
T
T
Ogura
A
A
Ishizaki
T
T
D000287:Administration, Topical; D003692:Delayed-Action Preparations; D004058:Diffusion; D006207:Half-Life; D008567:Membranes, Artificial; D008954:Models, Biological; D009824:Ointments; D014677:Pharmaceutical Vehicles; D011108:Polymers; D013999:Timolol / Q000008:administration & dosage*
D003692:Delayed-Action Preparations; D008567:Membranes, Artificial; D009824:Ointments; D014677:Pharmaceutical Vehicles; D011108:Polymers; D013999:Timolol