Introduction of Drug

Delivery
Drug Delivery
⚫Definition
⚫ The appropriate administration of drugs through
various routes in the body for the purpose of
improving health
⚫ It is highly interdisciplinary
⚫ It is not a young field
⚫ It has recently evolved to take into consideration
⚫ Drug physico-chemical properties
⚫ Body effects and interactions Controlled
⚫ Improvement of drug effect Drug
⚫ Patient comfort and well being Delivery
 Drug Delivery

Conventional Controlled

Enteral Sustained

Extended
Parenteral
Site-specific
Other
Pulsatile
Oral Administration
⚫Advantages ⚫Disadvantages
⚫ Patient: Convenience,
not invasive, higher
compliance
⚫ Manufacture: well
established processes,
available infrastructure
⚫ Unconscious patients
cannot take dose
⚫ Low solubility
⚫ Low permeability
⚫ Degradation by GI
enzymes or flora
⚫ First pass metabolism
⚫ Food interactions
⚫ Irregular absorption
Oral Administration
⚫Traditional oral
delivery systems
⚫ Tablets
⚫ Capsules
⚫ Soft gelatin capsules
⚫ Suspensions
⚫ Elixirs
Buccal/Sublingual
⚫Advantages ⚫Traditional delivery
⚫ By-pass First pass system/devices
metabolism ⚫ Tablets
⚫ Rapid absorption ⚫ Chewing gum
⚫ Low enzymatic activity

⚫Disadvantages
⚫ Discomfort during
dissolution
⚫ Probability of swallowing-
lost of effect
⚫ Small doses
Rectal
⚫Advantages ⚫Traditional delivery
⚫ By-pass first pass system/devices
metabolism ⚫ Suppository
⚫ Useful for children ⚫ Enema
⚫Disadvantages
⚫ Absorption depends on
disease state
⚫ Degradation by
bacterial flora
⚫ Uncomfortable
Intravenous (IV)
⚫ Advantages ⚫Traditional delivery
⚫ Drug 100% bioavailable
⚫ Rapid response system/devices
⚫ Total control of blood
concentration ⚫Injection-bolus
⚫ Maximize incorporation ⚫IV bag - infusion
of degradable drugs
⚫ By-pass FPM
⚫ Disadvantages
⚫ Invasive
⚫ Trained personnel
⚫ Possible toxicity due to
incorrect dosing
⚫ sterility
Subcutaneous
⚫Advantages ⚫Disadvantages
⚫Patient self- ⚫Invasive
administration ⚫Irritation,
⚫Slow, complete inflammation
absorption ⚫Maximum dose
⚫By-pass FPM volume - 2mL
Intramuscular
⚫Advantages ⚫Disadvantages
⚫Patient can ⚫Invasive – patient
administer the drug disconfort
himself ⚫Irritation,
⚫Larger volume than inflamation
subcutaneous ⚫May require some
⚫By-pass first pass training
metabolism
Inhalers
⚫Advantages ⚫Disadvantages
⚫By-pass FPM ⚫Solids and liquids
⚫Gases are rapidly can be absorbed if
absorbed size is below 0.5um
 Example from Industry: Nektar Therapeutics
⚫Pulmonary delivery of aerosol
particle
Insulin
⚫ Amorphous aerosol
particles with ~1μm
diameters

lung
cell

capillary
solubilized
cell
drug
molecules

Glass stabilizer insulin molecules

Transdermal
⚫Advantages ⚫Requirements
⚫ Local effect ⚫Low dosage <10
⚫ Ease of administration mg/mL
⚫Disadvantages ⚫MW< 1,000
⚫ Low absorption for
some drugs
⚫ May cause allergic
reactions
Factors Influencing the Selection of the
Delivery Route
⚫Drug physico-chemical properties
⚫ Drug molecular size (molecular weight)
⚫ Half-life
⚫ Chemical stability
⚫ Loss of biological activity in aqueous solution
⚫ Proteins
⚫ Denaturation, degradation
Example from Industry: 3M Company
⚫Microstructured Transdermal System: MTS
⚫ Microneedle system
⚫ Drug-in-adhesive technology platform

(a) 3M microneedle system and (b)

histological section of microneedles in
guinea pig skin
Factors Influencing the Selection of the
Delivery Route
⚫ Solubility in aqueous solution
(hydrophobicity/hydrophilicity)
⚫ pH
⚫ pKa - ionization
⚫ Temperature
⚫ Concentration
⚫ Crystalinity
⚫ Particle size
⚫ State of hydration
Factors Influencing the Selection of the
Delivery Route
⚫Drug biological interactions
⚫ Sensitive to FPM
⚫ Low membrane permeabiltiy
⚫ Enzymatic degradation
⚫ Bacterial degradation
⚫ Half-life
⚫ Side effects
⚫ Irritation
Factors Influencing the Selection of the
Delivery Route
⚫Desired pharmacological effect
⚫ Local
⚫ topical, vaginal
⚫ Systemic
⚫ oral, buccal, IV, SC, IM, rectal, nasal
⚫ Immediate response
⚫ IV, SC, IM, nasal
⚫ Dose size
⚫ Drug molecular size
Manufacture of Classical Oral Delivery
Systems
⚫Formulation – combination of active ingredients
with the appropriate excipients
⚫Excipients – inactive ingredients employed for the
purpose of dilution, protection, stability, controlled
release, taste, fillers, coloring, disintegration, etc
Manufacture Process
for Tablets
Blendin
and Capsules g

We Granulatio Dr
t n y
Millin
g

Compression

Coating

Labelin
g

Packing
Pharmacokinetics and Pharmacodynamics
Pharmacokinetic Pharmacodynamics
s

Design
of dosage regimen Plasma Effects
• Where? Concentratio
Plasma refers to the clear
• How much? n supernatant fluid that
• How often? results from blood after
• How long? the cellular components
have been removed
Plasma Concentration
Plasma concentration

Toxicit
y
(mg/mL)

Therapeutic
window

No therapeutic
effect
Time
 Unsuccessful
Plasma concentration

therapy
(mg/mL)

Successful
therapy

Time
(min)
Magnitude of Drug Response
⚫Depends upon concentration achieved at the site of
action
⚫ Dosage
⚫ Extent of absorption
⚫ Distribution to the site
⚫ Rate/extent of elimination
From the Site of Delivery to Elimination…
steps in drug delivery, absorption, distribution and elimination
⚫Drug Delivery
⚫ Selection of drug delivery route
⚫ Knowledge of physicochemical properties
⚫ Design of dosing regimen
⚫Absorption
⚫ Knowledge of PK and PD
⚫ First pass effect
⚫ MDR or MRP
From the Site of Delivery to Elimination…
steps in drug delivery, absorption, distribution and elimination

⚫Distribution
⚫ Drugs must reach the site of action
⚫ Tissue Depends upon drug binding capabilities
⚫ Plasma
⚫Elimination
⚫ Metabolism
⚫ Liver, kidneys, cells
⚫ Excretion
⚫ Kidneys
⚫ Feces
 Oral Gastrointestina
Administratio l
n Tract

Intravenous Circulator

Excretio
Injection y
System

n
Intramuscula
r
Injection Metaboli
Tissues
c
Subcutaneous
Injection
Sites
 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
⚫Absorption of drugs could vary within the same
administration route
⚫Absorption of drugs could vary within the same
administration route