Lecture 1 Flashcards
Pros of Oral Formulations (3)
easy, painless, self administered
Cons of Oral Formulations (3)
can be degraded in intestines, must be taken frequently, requires patient compliance
What is pharmacokinetics? What are the 4 stages?
pharmacokinetics is concerned with the movement of drugs in the body. The 4 stages of ADME are Absorption, Distribution, Metabolism, and Excretion.
Absorption: how a drug moves from administered site to the site of action
Distribution: journey of a drug through the blood/tissue
Metabolism: process that breaks down the drug
Excretion: removal of the drug from the body
Ways to Administer Drugs
injection, oral, buccal, ocular, respiratory, transdermal
Ways to increase drug effectiveness
more powerful drug, Identify physiological targets which lower barriers, Increase duration of activity, Decrease elimination rate, Increase permeability or solubility
Types of Sustained Release Formulations & Characteristics
complexes, slowly dissolving coatings, suspensions, emulsions, compressed tablets
Still for short periods of time (e.g. hours) and require repeat administration
Release rates are strongly influenced by environmental conditions
(increase a bit above desired level and then gradual decrease through desired range)
Controlled Release Formulations & Characteristics
Most basic form is an IV drip, Polymers, Pumps (balance between release rate and drug clearance rate)
For long periods of time (days to months)
Release rates are only weakly influenced by environmental conditions (fixed predetermined pattern for a definite period of time)
Applications of Controlled Release
pharma/medical, biological, agricultural, environmental, food, household products
Commercial Reasons for Controlled Drug Release
improve drug performance, lower cost than new drug, alternative uses for old drugs, decrease side effect, legal protection for a drug coming off patent, ease of use/more convenient, fewer problems
Critical Factors in Design
drug properties, intended administration route, targeted organ or tissue, patient details
Polymeric Controlled Release Systems
Diffusion Controlled (Reservoir Systems, Matrices), Chemically Controlled (Bioerodible, Pendant Chain) , Solvent Controlled (swelling,Osmosis), Externally Activated or Modulated
Reservoir System forms and common polymers
Diffusion Controlled (fick’s law)
Forms — Capsules, Microcapsules, Hollow Fibers, Membranes
Most Commonly Polymers — Silicone, EVA, Hydrogels
Reservoir System Advantages & Disadvantages
pro: Zero-Order Release, Easy to control kinetics by design parameters
cons: They must be removed, Impermeable to high M.W. drugs, Cost (high drug level), Leaks would be dangerous
Non-Erodible Matrix System pro and con
Chemically Controlled, Drug Dispersed in Polymer
Advantages
Easy to make
Leaks do not create as severe a problem
Can be made to release high M.W. drugs
Disadvantages
Release rates are not generally zero-order
They must be removed
Bioerodible Systems
Zero-order if only surface erosion occurs and surface area
does not change significantly over a given time period
Examples of bioerodible systems include poly-lactic acid,
polyaminoacids, polyorthoesters, and polyanhydrides
Advantages
Removal is not a problem
Disadvantages
Release kinetics are often harder to control
By-products of degradation may cause toxicity or
tissue damage
Pendant Chain
chemically controlled
polymer backbone w drug attached that breaks w water or enzyme interaction
Primary Advantage
Very high drug loadings
Primary Disadvantage
New chemical entity
Swelling Controlled Matrix
solvent controlled
Advantages
Reformulation of vehicle
not necessary for
different drugs
No burst effect
Disadvantages
Shorter release times
Osmotically Controlled System
Advantages
Osmosis is a constant
driving force
Disadvantages
Hard to achieve zero-
order release unless put
in a pump formulation
Pumps Advantages and Disadvantages
Advantages
Can release drug directly into blood at near zero-order rate
Large volumes
Some are refillable
Releases drug independently of the drug’s properties
Disadvantages
Expense
Need for surgical implantation
Contents are in solution
Difficult to reformulate
Smart Drug Delivery Systems
Targeting
Diagnostics
Stimuli-responsive
Delivery to Cells
Cellular targeting through ligand-receptor
Targeting for uptake using passive and
active mechanisms
Cellular Barriers
Avoid cellular degradation (protection)
If needed, release into cytoplasm
If needed, transport to relevant intracellular
compartment
Advantages
Exquisite control over what is delivered where
Increase in therapeutic index
Many ways to engineer effectiveness of the
formulation
Disadvantages
Exquisite control sometimes requires a profound
amount of complexity
Expensive/regulatory
Many cellular barriers are not understood
Smart systems
Main advantage: level of control and
increase in effectiveness
Main disadvantage: complexity and
regulatory issues
