Lecture 1

Question 1

Pros of Oral Formulations (3)

Answer 1

easy, painless, self administered

Question 2

Cons of Oral Formulations (3)

Answer 2

can be degraded in intestines, must be taken frequently, requires patient compliance

Question 3

What is pharmacokinetics? What are the 4 stages?

Answer 3

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

Question 4

Ways to Administer Drugs

Answer 4

injection, oral, buccal, ocular, respiratory, transdermal

Question 5

Ways to increase drug effectiveness

Answer 5

more powerful drug, Identify physiological targets which lower barriers, Increase duration of activity, Decrease elimination rate, Increase permeability or solubility

Question 6

Types of Sustained Release Formulations & Characteristics

Answer 6

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)

Question 7

Controlled Release Formulations & Characteristics

Answer 7

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)

Question 8

Applications of Controlled Release

Answer 8

pharma/medical, biological, agricultural, environmental, food, household products

Question 9

Commercial Reasons for Controlled Drug Release

Answer 9

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

Question 10

Critical Factors in Design

Answer 10

drug properties, intended administration route, targeted organ or tissue, patient details

Question 11

Polymeric Controlled Release Systems

Answer 11

Diffusion Controlled (Reservoir Systems, Matrices), Chemically Controlled (Bioerodible, Pendant Chain) , Solvent Controlled (swelling,Osmosis), Externally Activated or Modulated

Question 12

Reservoir System forms and common polymers

Answer 12

Diffusion Controlled (fick’s law)
Forms — Capsules, Microcapsules, Hollow Fibers, Membranes
Most Commonly Polymers — Silicone, EVA, Hydrogels

Question 13

Reservoir System Advantages & Disadvantages

Answer 13

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

Question 14

Non-Erodible Matrix System pro and con

Answer 14

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

Question 15

Bioerodible Systems

Answer 15

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

Question 16

Pendant Chain

Answer 16

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

Question 17

Swelling Controlled Matrix

Answer 17

solvent controlled
Advantages
 Reformulation of vehicle
not necessary for
different drugs
 No burst effect
Disadvantages
 Shorter release times

Question 18

Osmotically Controlled System

Answer 18

Advantages
 Osmosis is a constant
driving force
Disadvantages
 Hard to achieve zero-
order release unless put
in a pump formulation

Question 19

Pumps Advantages and Disadvantages

Answer 19

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

Question 20

Smart Drug Delivery Systems

Answer 20

Targeting
Diagnostics
Stimuli-responsive

Question 21

Delivery to Cells

Answer 21

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

Question 22

Smart systems

Answer 22

Main advantage: level of control and
increase in effectiveness
 Main disadvantage: complexity and
regulatory issues