Drug Delivery and Mass Balance BIOE201-B. The concentration of the drug at the site of action, over...
If you can't read please download the document
Drug Delivery and Mass Balance BIOE201-B. The concentration of the drug at the site of action, over time. Drug delivery is about the complex mechanisms
The concentration of the drug at the site of action, over time.
Drug delivery is about the complex mechanisms to getting that
concentration profile to happen. Delivery methods can be classified
by the anatomical site they target (oral, injection, topical,
transdermal, pulmonary, ophthalmic, rectal/vaginal, implantable
depot device, etc.). Drug Delivery and Mass Balance
Even with controlled delivery side effects cannot be avoided
Might cause severe side effects- spread over body Site specific
delivery- active or passive targeting
Slide 5
RES Lungs Liver Spleen Reticuloendothelial System (RES) Site
Specific Delivery
Slide 6
Enhanced permeability and retention (EPR) effect
Disorganization of tumor vasculature Poor lymphatic drainage
Passive Targeting of Particulate by EPR Mechanism
Slide 7
Ringsdorfs Model Active Targeting
Slide 8
Various Drug Delivery System
Slide 9
Chemically-Controlled DDS
Slide 10
Major Classes of Matrix in DDS
Slide 11
Environmentally Responsive System
Slide 12
pH Responsive System
Slide 13
Absorption of drugs could vary within different administration
routes 500 mg dose given intramuscularly orally **to the same
subject on separate occasions Biological barriers greatly affect
the extent of drug absorption
Slide 14
Absorption of drugs could vary within the same administration
route
Slide 15
Slide 16
Drug Delivery System (DDS) Controlled delivery system Site
specific delivery of drugs Toxicity Therapeutic Window No
Therapeutic Effect
Slide 17
Time (min) Plasma concentration (mg/mL) Unsuccessful therapy
Successful therapy
Slide 18
All drugs must diffuse through various barriers when
administered to the body. Some drugs must diffuse through the skin,
gastric mucosa, or some other barrier to gain access to the
interior of the body. Parenteral drugs must diffuse through muscle,
connective tissue, and so on, to get to the site of action.
Intravenous drugs must diffuse from the blood to the site of
action. Drugs must also diffuse through various barriers for
metabolism and excretion. Laws governing diffusion are important to
drug delivery systems
Slide 19
Ficks law for diffusion, compartmental analysis, and the
general use of mass conservation equations. The mass conservation
equation: In out + Generation - Consumption = Accumulation This
equation, when properly replaced with mathematical terms, is used
to describe transport everywhere. We can use simplified experiments
and model fitting to calculate the value of drug diffusion
constants, which can then be used to predict concentration profiles
in relevant drug delivery scenarios.
Slide 20
Bioavailability is defined as a ratio of the areas under the
curves (AUCs) of plasma concentration versus time. The AUC for
intravenous injection is the standard, and any other delivery
method is compared against that. Bioavailability and Area Under the
Curve
Slide 21
Important Concepts Volume of distribution apparent volume into
which a drug distributes in the body at equilibrium direct measure
of the extent of distribution V = amount of drug in the body/Plasma
drug concentration
Slide 22
Mathematical Modeling of Drug Disposition Single compartment
Single compartment with absorption Two compartments Two
compartments with absorption Physiological Models
Slide 23
These compartments don't usually correspond to actual bodily
compartments, but they're still useful. The simplest case is the
singlecompartment model. All the compartments are considered to be
uniform and wellmixed. Compartmental analysis In cases where the
drug doesn't readily distribute to the whole body immediately, it's
better to model things with more than one model. For example, using
two of them:
Slide 24
Single Compartment Model Assumptions: Body one compartment
characterized by a volume of distribution (V d ) Drug is confined
to the plasma (small V) C, V d absorption elimination k, C t C/C
0
Slide 25
One-Compartment Model with Absorption Low absorption occurs
Absorption is the rate- limiting step Slow absorption may represent
drug entry through GI tract or leakage into circulation after SC
injection Drugs require multiple doses to maintain drug
concentration within therapeutic window t M/D 0 t
Slide 26
Two-Compartment Model Drug rapidly injected Drug distributed
instantaneously throughout one compartment and slowly throughout
second compartment Describes drug concentration in plasma injected
IV C 1, V 1 C 2, V 2 k 2, C 2 k 12 k 21 k 1, C 1 Compartment 1
Compartment 2 tt Concentration after ingestion Concentration with
slow absorption C/C 0
Slide 27
Diffusion occurs when individual molecules move within a
substance, as the result of a concentration gradient or by random
molecular motion. Molecular diffusion from a microscopic and
macroscopic point of view. Initially, there are solute molecules on
the left side of a barrier (purple line) and none on the right. The
barrier is removed, and the solute diffuses to fill the whole
container. Top: A single molecule moves around randomly. Middle:
With more molecules, there is a clear trend where the solute fills
the container more and more uniformly. Bottom: With an enormous
number of solute molecules, randomness becomes undetectable: The
solute appears to move smoothly and systematically from high-
concentration areas to low-concentration areas. This smooth flow is
described by Fick's laws. Ficks Law
Slide 28
Ficks first law relates to a steady-state flow J = dM/(S dt)=
-DdC/dX J = Flux (in g/cm 2 s) M = material (in g) S = surface area
(in cm 2 ) t = time (in s) D = diffusion coefficient (in cm 2 /s) C
= concentration (in g/cm 3 ) X = distance of movement (in cm)
units: g/cm^2*s Steady State Diffusion Ficks second law relates to
a change in concentration of drug with time, at any distance, or an
unsteady state of flow. J= -D*(C1-C2)/h D = diffusion coefficient
(in cm 2 /s) C = concentration (in g/cm 3 ) h = thickness of
membrane (in cm) Non-Steady State Diffusion Partition Coefficient
K=C1/Cd=C2/Cr K=[Drug]oil/[Drug]water determines concentration of
drug in the membrane
Slide 29
29 A Versatile Prodrug Platform API= ACTIVE PHARMACEUTICS
INGREDIENT SN-2
Slide 30
30g/kg x 3 times (3, 6, 9 days) BiomaterialsBiomaterials, 2012,
33 (33), 8632864033 (33 Pan et. al. Nanomedicine (UK), 2012 Treated
Un-treated AntiAngiogenic Therapy Pan et. al. Circulation. 2009,
120, S322. Comparison of MR Contrast Enhanced Images presented as
2D Slice and 3D Volume THERAPY NO THERAPY