Drug Delivery Flashcards
Define drug delivery.
a. The appropriate administration of drugs through various routes in the body for the
purpose of improving health
What are some examples of controlled drug delivery?
a. Drug physio-chemical properties
b. Body effects and interactions
c. Improvement of drug effect
d. Patient comfort and well being
Define pharmacokinetics and what does it affect?
a. time course of drugs and drug delivery systems through the body
b. Adsorption, distribution, metabolism, and excretion
Define pharmacodynamics.
a. What the drug does to the body
b. Toxicity, therapeutic efficacy
State and define 3 different routes of adminstration.
a. Sublingual, drug is placed under the tongue and allowed to dissolve
b. Oral, drug is delivered by mouth and absorbed in the gastrointestinal (GI) tract
c. Parenteral, delivery with a needle or syringe
d. Transdermal, absorption of drug through the skin
e. Inhalation, administration through the respiratory tract
f. Nasal, absorption of drug by olfactory epithelia
g. Rectal, absorption through colon epithelium
Give 3 examples of sublingual and oral tablets. How do they work?
a. Nitroglycerin for angina, Claritin for allergies
b. Drug diffuses directly into the capillaries of the mouth and allows for rapid
resolution of symptoms, within minutes
What are the advantages and disadvantages of oral administration?
a. Adv:
i. For the patient: Convenience, not invasive, higher compliance
ii. For the manufacturer: well established processes, available infrastructure
b. Disadv:
i. Unconscious patients cannot take dose
ii. Low solubility
iii. Low permeability
iv. Degradation by GI enzymes
v. Food interactions
vi. Irregular absorption
Name 3 examples of traditional oral delivery systems:
a. Tablets
b. Capsules
c. Soft gelatin capsules
d. Suspensions
State the advantages and disadvantages of sublingual administration. Give examples.
a. Adv: Rapid absorption, low enzymatic activity
b. Disadv: Discomfort during dissolution, small doses
c. Ex: Tablets, chewing gum
State the advantages and disadvantages of intravenous (IV) administration. Give
examples
a. Adv: Drug 100% bioavailable, Rapid response, Total control of blood
concentration
b. Disadv: Invasive, trained personnel, Possible toxicity due to incorrect dosing,
sterility
c. Ex: Injection, IV bag (infusion)
State the requirements, advantages and disadvantages of transdermal administration.
a. Requires: Low dosage
b. Adv: Local effect, ease of administration
c. Disadv: low absorption for some drugs, may cause allergic reaction
What are the 4 factors that influence the selection of the delivery route?
a. Drug physico-chemical properties
b. Drug biological interactions
c. Solubility in aqueous solution (hydrophobicity/hydrophilicity)
d. Desired pharmacological effect
- Drug physico-chemical properties
- Drug molecular size (molecular weight)
- Half-life
- Chemical stability
- Loss of biological activity in aqueous solution
- Proteins
- – Denaturation, degradation
- Proteins
- Drug biological interactions
- Enzymatic degradation
- Half-life
- Side effects
- Irritation
- Solubility in aqueous solution (hydrophobicity/hydrophilicity)
- pH
- Temperature
- Concentration
- Particle size
- Desired pharmacological effect
- Immediate response
- IV, nasal
- Dose size
- Local
- Systematic
Define systemic effects and give an example.
a. Delivered drugs circulate through the entire body
b. Orally delivered pain reliever for a sore toe
Define local effects and give an example.
a. Restricted to region of delivery
b. Nasal spray for stuffy nose
Problems associated with conventional drug delivery?
a. Reduced potencies because of partial degradation
b. Toxic levels of administration
c. Increase costs associated with excess dosing
Label a polymeric drug delivery graph.
Look at image
What are the goals of more sophisticated drug delivery techniques?
a. Deploy to a target site to limit side effects
b. Shepard drugs through specific areas of the body without degradation
c. Maintain a therapeutic drug level for prolonged periods of time
d. Predictable controllable release rates
What are the pharmacokinetic steps?
a. Drug delivery
- Selection of drug delivery route
- - Knowledge of physicochemical properties
- Design of dosing regimen
b. Magnitude of drug response
- Depends upon concentration achieved a the site of action
- Dosage
- Extend of absorption
- Distribution to the site
c. Absorption
- Knowledge of Pharmokinetics
d. Distribution
- Drugs must reach the site of action
- - Tissue
- – Depends upon drug binding capabilities
e. Elimination
- Metabolism
- - Liver
- Excretion
- - KIdneys
What are the challenges of drug delivery?
a. Challenges for drug molecule to reach its target organ and have its desired effect
b. In vivo drug solubility
c. In vivo drug stability
d. Physical barriers to absorption
What are the physical barriers to drug delivery?
a. Epithelial Membranes – Interior and exterior of numerous organs
b. Endothelial membranes – Blood vessels
c. Blood brain barrier – System of membranes keeping the central nervous system
impermeable to molecules from systemic circulation
Polymer based drug delivery aims to increase:
a. circulation time by increasing size
b. Targeting of drugs
c. Applicability to wide range of drugs
d. biocompatibility
e. Acceptability by regulatory agencies (FDA)
f. All of the above
f. All of the above
Why are micro particles being researched for better drug delivery?
a. Larger particles, higher loading, longer controlled release
b. Location and how long controlled delivery
Define encapsulation.
a. surrounding drug molecules with a solid polymer shell
Define entrapment.
a. the suspension of drug molecules within a polymer matrix
Describe drug release by diffusion.
a. Early encapsulation and entrapment systems released the drug from within the
polymer via molecular diffusion
b. Process:
i. When the polymer absorbs water it swells in size
ii. Swelling created voids throughout the interior polymer
iii. Smaller molecule drugs can escape via the voids at a known rate
controlled by molecular diffusion (a function of temperature and drug size)
Describe drug release by erosion.
a. Modern delivery systems employ biodegradable polymers:
i. When the polymer is exposed to water hydrolysis occurs
ii. Hydrolysis degrades the large polymers into smaller biocompatible
compounds
iii. 2 processes: bulk erosion and surface erosion
Describe the process of bulk erosion and give an example material that undergoes this
process.
a. When the polymer is exposed to water hydrolysis occurs
b. Hydrolysis degrades the large polymers into smaller biocompatible compounds
c. These small compound diffuse out of the matrix through the voids caused by
swelling
d. Loss of the small compounds accelerates the formation of voids thus the exit of
drug molecules
e. Ex: Poly lactide, polyglycolic acid
Describe the process of surface erosion and give an example material that undergoes
this process.
a. When the polymer is exposed to water hydrolysis occurs
b. Hydrolysis degrades the large polymers into smaller biocompatible compounds
c. These small compound diffuse from the interface of the polymer
d. Loss of the small compounds reveals drug trapped within
e. Note these polymer do not swell
f. Ex: polyanhydrides
How is entrapment or encapsulation obtained?
a. Wurster - coating process applied after a drug core is formed. The polymer shell
is applied via spraying while the drug cores (liquid or solid) is suspended and
recirculated in a gas stream
b. Coacervation
i. STEP #1: – Polymer dissolved in a solvent (or oil) – Drug dissolved in
water
ii. STEP #2: – 2 liquids are rapidly mixed – water droplets form within the
solvent
iii. STEP # 3: – Emulsion from step #2 is mixed rapidly with fresh water – Oil
droplets within the fresh water phase – Oil droplets contain original
dispersed water/drug phase – Oil diffuses into the fresh water phase
precipitating the polymer & entrapping the drug
c. Coextrustion - the polymer shell is flowed concentrically around a pipe containing
the drug formulation
i. These concentric cylinders then breakup into individual packets either
driven by air flow, electrostatic or mechanical vibration
d. Self-assembly methods (2 methods):
i. Using a molecule that has a hydrophilic head and hydrophobic tail to form
a shell, or
ii. Electrostatic interaction to entrap drug molecules
Wurster
a. Coating process applied after a drug core is formed. The polymer shell
is applied via spraying while the drug cores (liquid or solid) is suspended and
recirculated in a gas stream
Coacervation
i. STEP #1: – Polymer dissolved in a solvent (or oil) – Drug dissolved in
water
ii. STEP #2: – 2 liquids are rapidly mixed – water droplets form within the
solvent
iii. STEP # 3: – Emulsion from step #2 is mixed rapidly with fresh water – Oil
droplets within the fresh water phase – Oil droplets contain original
dispersed water/drug phase – Oil diffuses into the fresh water phase
precipitating the polymer & entrapping the drug
Coextrustion
- the polymer shell is flowed concentrically around a pipe containing
the drug formulation
i. These concentric cylinders then breakup into individual packets either
driven by air flow, electrostatic or mechanical vibration
Self-assembly methods (2 methods):
i. Using a molecule that has a hydrophilic head and hydrophobic tail to form
a shell, or
ii. Electrostatic interaction to entrap drug molecules
How do surfactants enhance targeting?
a. Increase absorption into cell membrane – Acting as a wetting agent surfactants,
increases the contact area between the drug and cell wall, facilitating the
absorption of molecules into the cell membrane
b. Increase solubility of drug into carrier – Introduction of a surfactant into a solvent
lowers the surface tension thereby increasing solubility limits
c. Increase stability of vehicle
How can antibodies enhance delivery?
a. Increase tissue sensitivity
. Why are nanoparticles being researched for drug delivery?
a. Nanoparticles are highly charged coupled with high surface to volume ratio – this
property can effect cellular interaction
b. Particle size alone can significantly effect biodistribution
. What are the design criterion for drug delivery?
a. What is desired outcome
i. Protecting drug
ii. Extended release
iii. Release location
b. Design questions
i. What is target area
ii. What is desired delivery route
iii. What time frame
c. Polymer consideration
i. What polymer
ii. What type of micro/nano particle
iii. What type of synthesis method
Define nanotechnology.
a. the creation of functional materials, devices and systems, through the
understanding and control of matter at dimensions in the nanometer scale length
(1-100 nm), where new functionalities and properties of matter are observed and
harnessed for a broad range of applications
What are novel phenomena and properties change due to the nanoscale size effect?
a. Physical Properties (e.g. melting point)
b. Chemical Properties (e.g. reactivity)
c. Electrical Properties (e.g. conductivity)
d. Mechanical Properties (e.g. strength)
e. Optical Properties (e.g. light emission)
Give 3 different industry examples of nanotechnology applications.
a. IT: Smaller, faster, more energy efficient and powerful computing and other
IT-based systems
b. Medicine: Cancer treatment • Bone treatment • Drug delivery • Appetite control •
Drug development • Medical tools • Diagnostic tests • Imaging
c. Energy: More efficient and cost effective technologies for energy production
i. Solar cells − Fuel cells − Batteries − Bio fuels
d. Consumer Goods:
i. Foods and beverages −Advanced packaging materials, sensors, and
lab-on-chips for food quality testing
ii. Appliances and textiles −Stain proof, water proof and wrinkle free textiles
iii. Household and cosmetics − Self-cleaning and scratch free products,
paints, and better cosmetics
Why is nanotechnology based drug delivery being researched?
a. Ideally delivery system should provide:
i. Long circulation time
ii. Present at target in sufficient quantity
iii. No loss of efficacy
b. Minimizing the drug use would significantly reduce the effective cost of drug
which would give financial relief to the patients
c. Drug delivery formulations involve low cost research compared to that for
discovery of new molecule
d. Delivery systems increase commercial opportunity by distinguishing a drug from
competitive threats posed by generic drugs
Name 2 nanoparticle structures:
a. Nanotubes • Nanogels • Dendrimers • Nanocapsules / Nanoparticles
Nanotubes
- Larger internal volume
- Inner and outer surfaces can be separately functionalized
- Can be grown on templates
- Control of size and shape
- Typically carbon or silica
- Can be “corked” with a bioactive or actively triggered particle
Nanogels
- Can be synthesized and stored
- Extended stability
- Low toxicity
Dendrimers
- Controlled shape
- Relatively easy to isolate
- Drugs can be “enveloped” by structure or bonded to branches
- Increasing size increases solubility, toxicity
Nanocapsules
- Fully enclosed structures nanocapsules,
- Encapsulated structures protect drugs, allow for surface modification
- Partially enclosed and plugged structures: nanoshells and nanotubes
What are the challenges and opportunities that NPs can provide:
a. Prevention of drug from biological degradation
b. Effective Targeting
c. Cost effectiveness
d. Product life extension
Why have biodegradable polymeric NPs attracted more attention?
a. potential drug delivery devices in view of their applications in drug targeting to
particular organs/tissues,
b. carriers of DNA in gene therapy,
c. ability to deliver proteins, peptides and genes
- What should be considered in preparation of NPs?
a. Size of desired NPs
b. Properties of drug (aqueous solubility, stability) to be encapsulated in the polymer
c. Surface characteristics and functionality
d. Degree of biocompatibility and biodegradability
e. Drug release profile
f. Dispersion of preformed polymers – Solvent evaporation method
g. Polymerization of monomers
h. Ionic gelation methods for hydrophilic polymers
Solvent Evaporation
- Providing continuous agitation and letting solvent evaporate at the same time
Polimerization of monomers
- NPs are prepared from monomers to form NPs in an aqueous solution
- Drug dissolved in polymerized medium
- Adsorption/attachment of drug onto polymerized NPs
Ionic gelation for hydrophilic polymers
- Gelatin, alginates. chitosan
- Polymer gels to form hydrogels by introducing appropriate salt
Eg: gelation of chitosan solution dispersed in an emulsion
