Now let’s consider delivery from a solid drug in a polymeric matrix. The drug is initially well above its solubility limit CS in the matrix. At later times, dissolution of the drug occurs into the exterior of the matrix, and drug is then replenished by diffusion from the supersaturated core. The supersaturated core region becomes thinner with time hence we have a moving interface. There is however, no concentration gradient within the core. In the exterior region of thickness x there is a concentration gradient. See the figure below. (solution discussed on the PDF file)

1st order Drug Absorption and Elimination

These routes give absorption then elimination

Also see http://en.wikipedia.org/wiki/Inhalable_insulin

Absorption limiting Dissolution limiting

hysteresis

1st Order Drug Absorption and Elimination Need mass balance on the drug at the site of absorption and in the body. 8.68 8.68 See pages 429-433

Here is the Matlab solution for this example 8 Here is the Matlab solution for this example 8.7, the code is on the blog: fD/Vapp, mg/L = 19.8893 ka, 1/min = 0.070863 kte, 1/min = 0.014885 Vplasma, L = 20.1113

Two Compartment Models for IV and 1st Order Absorption See pages 433-440

Note the biphasic elimination with two different elimination rate constants represented by the slopes of these lines.

Superposition Principle States that each drug dose behaves independently of all other drug doses that have been administered. Hence, we can write Ctotal = CD1 + CD2 + CD3 + … Be careful though in your computer models since the single dose model equations for a given dose are in terms of the time since that particular dose was administered which can be called for example t’, so if doses D1, D2, D3 etc are given at t1, t2, t3 respectively, then t’1 = t – t1, t’2 = t – t2, t’3 = t – t3, and t is the time when the first dose was taken. Superposition works as long as all elimination processes and absorption processes are first order. It also works for multiple drug doses given by two or more different types of drug delivery methods.

Superposition Principle