Fentanyl is an opioid traditionally administered by infusion or injection and more recently in a rate-controlled transdermal dosage form. This system is a four-layer laminate on a protective liner. A backing layer seals and protects the drug reservoir, the source for continuous delivery of fentanyl. A membrane controls the release rate of fentanyl from the system. An adhesive layer attaches the system to skin and releases an initial loading dose of fentanyl. The rate of fentanyl delivery through skin is determined by the system and the skin at the application site. The release rate from the system is approximated by Fick's first law of diffusion and is controlled by the rate-controlling membrane. A complete simulation model that combines both in vitro release data and the pharmacokinetic model has been developed and used to show the influence of various physiologic and system variables on serum fentanyl concentrations.

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SynopsisThe kinetics of drug release from a series of partial esters of vinyl acetate-maleic anhydride has been investigated. These polymers in their un-ionized forms are hydrophobic and water insoluble, but in their ionized forms they are water soluble. Polymer dissolution is pH sensitive, and different half-esters have a characteristic pH range above which they are soluble and below which they are insoluble. When films are placed in buffered media, they erode a t a constant rate that depends on the pH of dissolution of the polymer and on the pH of the buffered medium. Dissolution of the polymer is limited to the polymer-buffer medium interface, and drugs dissolved or uniformly dispersed in the polymer are released by zero-order kinetics. A detailed model has been developed that successfully correlates dissolution behavior and various experimental parameters.

inlet pressure was 3 atm.abs. and the outlet pressure 2 atm.abs. The following temperature measurements were available: inlet, 600°C; 20% of coil length, 740°C; 80% of coil length, 812°C; outlet, 838°C. The following heat flux profile was generated from independent simulations of the heat transfer in the fire box: first tube, 22 kcal/ m2 s; second tube, 20; third, 18; fourth, 17; fifth, 15; sixth, 13; seventh, 11; eight, 8; ninth and tenth tube, 6. With this heat flux profile, the conversion, temperature, and total pressure profiles of Figure 13 were obtained. The Application of Hildebrand's theory of the solubility of microsolutes in ordinary solvents, and of the Flory-Huggins theory to the solubility of steroids in polymers, has permitted the derivation of a predictive correlation between polymer permeability and steroid crystalline melting temperature, other correlating parameters being the entropy of fusion of the steroid and the (computed) solubility parameters of steroid and polymer. The correlation permits prediction of the permeability of any steroid in any polymer with reasonable accuracy.

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