1. PHT 612 Selected Topics in Drug Delivery I
King Saud University
College of Pharmacy
Department of Pharmaceutics
PHT 612 Selected Topics in Drug Delivery I
Fundamentals of Drug Delivery Systems

2. Outlines Introduction Theoretical Aspects of TDD Experimental Design
Chemical Modulation of TDD
Physical and Technological Modulation
of TDD
Topical and Transdermal Formulations

3. Introduction

4. Drug Delivery Controlled 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
Improvement of drug effect
Patient comfort and well being
Controlled
Drug Delivery

5. Drug Delivery Conventional Controlled Enteral Sustained Extended
Parenteral
Pulsatile drug delivery systems (PDDS) have attracted attraction because of their multiple benefits over conventional dosage forms. They deliver the drug at the right time, at the right site of action and in the right amount, which provides more benefit than conventional dosages and increased patient compliance. These systems are designed according to the circadian rhythm of the body, and the drug is released rapidly and completely as a pulse after a lag time. These products follow the sigmoid release profile characterized by a time period.
Site-specific
Other
Pulsatile

6. Oral Administration Advantages Disadvantages
Patient: Convenience, not invasive, higher compliance
Manufacture: well established processes, available infrastructure
Disadvantages
Unconscious patients cannot take dose
Low solubility
Low permeability
Degradation by GI enzymes or flora
First pass metabolism
Food interactions
Irregular absorption

7. 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

8. 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

9. Pharmacokinetics and Pharmacodynamics
Design
of dosage regimen
Where?
How much?
How often?
How long?
Plasma
Concentration
Effects
Plasma refers to the clear supernatant fluid that results from blood after the cellular components have been removed

10. Plasma Concentration Toxicity Therapeutic window No therapeutic effect
(mg/mL)
Time (min)
Therapeutic window
Toxicity
No therapeutic effect

11. Unsuccessful therapy Successful
Time (min)
Plasma concentration
(mg/mL)
Unsuccessful
therapy
Successful

12. Excretion Gastrointestinal Tract Circulatory System Metabolic Tissues
Oral
Administration
Intravenous
Injection
Intramuscular
Subcutaneous
Gastrointestinal
Tract
Circulatory
System
Tissues
Metabolic
Sites
Excretion

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

14. Absorption of drugs could vary within
the same administration route

15. 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

16. Mathematical Modeling of Drug Disposition
Single compartment
Single compartment with absorption
Two compartments
Two compartments with absorption
Physiological Models

17. Single Compartment Model
Assumptions:
Body one compartment characterized by a volume of distribution (Vd)
Drug is confined to the plasma (small V) t
C/C0
C, Vd
absorption
elimination
k, C

18. 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/D0 t
M/D0

19. Two-Compartment Model
k1, C1
Drug rapidly injected
Drug distributed instantaneously throughout one compartment and slowly throughout second compartment
Describes drug concentration in plasma injected IV
C1, V1
k12
k21
k2, C2
C2, V2
Compartment 1
Compartment 2 t
Concentration after ingestion Concentration with slow absorption
C/C0

20. Where to Find PD and PK Information
United States Pharmacopeia
It is also paper published
Provides standards, chemical properties, and protocols to perform pharmacological experiments
Federal Drug Administration – if it has already being approved

21. Transdermal Drug Delivery

23. Disadvantages of TDDS

24. Disadvantages of TDDS…(cont.)
b) Stratum corneum is hydrophobic: (limits
drug penetration)
c) Epidermis is hydrophilic
d) Main entry to vasculature via pores: (small
% of surface)
e) Drugs bind to skin: desorption becomes
rate-limiting step
f) Allergic reaction: triggered by adhesive

25. Theoretical Aspects of TDD
a) Partition coefficient: a permeant must first
partition into the membrane log P(octanol/water) It is considered that rate limiting step in the permeation process.
According to the oil and water phases solubility:
log P(octanol/water) 1-3: intercellular route predominates
log P(octanol/water) > 3: intercellular route is the only route
log P(octanol/water) <1: transcellular route

27. Theoretical Aspects of TDD
b) Molecular size: the second major factor in determining the flux of a material through human skin is the size and shape of the molecules. Selected candidate for TDD
should fall within ( Dalton).
c) Solubility/melting point
d) Ionization
e) Other factors: binding forces, particle size,…etc.

28. Experimental Design Preparation of skin membranes:
In vitro/in vivo studies
Animal membrane: hairless mouse, guinea pig and mammalian skin
Artificial membrane:
- More simplistic model
- No regional variability
- Advantages of reproducibility and
control
- Simple permeation process
- Used for quality control purposes or
for testing formulation variables

29. Experimental Design…(cont.)
Diffusion cell for in-vitro studies:
Comprise of two compartments: donor and receptor sections
The receptor section of a fixed volume is kept at controlled T at 37 ºC and the fluid is agitated
A portal from the receptor compartment allows removal of receptor fluid at required time intervals.