Introduction to Drug

Delivery Systems
By Ms. N. Akombaetwa
Introduction

• Method or process of administering an active

pharmaceutical ingredient (API) to achieve
therapeutic effect in humans or animals.

• Modify drug release profile and pharmacokinetic

parameters for the benefit of improving product
efficacy as well as patient convenience and
compliance.
Introduction

• Aims to deliver the drug at a rate directed by

the needs of the body during the period of
treatment, and target the active entity to the
site of action
Introduction - Challenges in administering Drugs

• Can be inactivation by gastric juice

• Can be metabolism before reaching targeted site – First pass

(metabolism in lung / liver / Intestine)

• Can exhibit too many adverse reactions

Introduction - How to overcome this?
• By improving rate of drug delivery
• By preparing medicines that decrease biodegradation
• By preparing time release medications
• By preparing medicines that have site-specific target capabilities
• Administer injectable only medications in oral form
• By preparing medicines that cost effective, multiple-dose, long-term
therapies which are inexpensive and potent
• Preparing drugs through different delivery systems (Solids, liquids,
semisolid and gaseous) which can be administered through different
routes
Introduction
• Molecules existence in different states of matter is influence by
• intermolecular forces
• intramolecular bonding energies
• Covalent bonding governs intramolecular interactions
• While electron orbital interactions govern intermolecular forces
• These forces are attractive and repulsive forces

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Introduction cont…….
• Attraction pulls molecules together and can either be cohesive or
adhesive
• Repulsion is a reaction between molecules that forces them apart
• Interactions between molecules results from a balance between
attractive and repulsive forces
• The balance obtains an energetically favored arrangement described
by intermolecular distance and intramolecular conformation
• The balance of these forces explains properties of gases, liquids and
solids

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Introduction cont….
• Repulsion results from interpenetration of electron clouds of the
molecules
• Repulsion increases exponentially with decreasing distance between
the molecules
• When attractive and repulsion forces are equal the potential energy
of the two molecules is at a minimum and the system is most stable
• States of matter are determined by the distance between atoms,
molecules and ions as well as kinetic energy of these particles

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States of matter
• In the solid phase particles are held in close proximity by
intermolecular/interatomic/interionic forces
• The particles oscillate about a fixed position.
• As temperature rises, particles acquire energy to disrupt the ordered
matter and pass to fluid
• When more energy is acquired, particles pass into gaseous state

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Gaseous Drug Delivery
Systems
Gaseous State
• In gaseous state molecules have vigorous and rapid movement.
• This leads to collisions between the molecules themselves and walls
of the container they are confined in
• As a result of these collisions, gases tend to exert pressure which is
measured in dynes, atm or mmHg.
• Volume(cm³/L) and temperature (˚C/K) are also important parameters
when considering gases
• When it is assumed that intermolecular forces are absent and
collisions are perfectly elastic, gases obey Boyel’s law

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Gaseous State cont….
1. Boyel’s law states that at constant temperature, pressure of the gas is
inversely proportional to volume
P
PV= k

2. Gay-Lussac and Charles law state that At constant pressure, volume is

directly proportional to absolute temperature of a given mass of gas. Gay-
Lussac and Charles law states that
V
V=kT
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Ideal gas law
• Combination of these laws gives rise to
PV=nRT
Where P= pressure
V= volume
n= number of moles
T= temperature
R= ideal gas constant

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Kinetic molecular theory
• The behavior of gases is explained by the kinetic molecular theory
which has the following important statements:
1. Actual volume of the gas is almost negligible in relation to the volume of
space occupied. This approximated in low pressures and high temperatures
2. Particles do not attract each other but move in complete
independence(applicable at low pressure)
3. Particles exhibit continuous random motion where kinetic energy is directly
proportional to absolute temperature and is expressed as
E
4. The molecules exhibit perfect elasticity

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Behavior of gases
• When a gas is cooled it loses some kinetic energy in the form of heat
resulting in reduction of the molecules’ velocity
• When pressure is applied and molecules are brought together within
a sphere of van dar Waals forces, they interact and pass into liquid
state
• This makes liquids denser than gases, they occupy a definite volume
• Passage of gases to liquid and then to solid state depends on both
temperature and pressure

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Liquefaction of a gas
• If temperature of a gas is elevated sufficiently, a value is reached
above which it is impossible to liquefy a gas regardless of the pressure
applied
• This temperature, above which a liquid can no longer exist, is known
as the critical temperature.
• The pressure required to liquefy a gas at its critical temperature is
the critical pressure
• Critical pressure is the highest vapor pressure that a liquid can have

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Liquefaction of a gas
• The further a gas is cooled below its critical temperature, the less
pressure is required to liquefy it.
• Gas liquefaction is usually achieved by subjecting the molecules to
intense cold using freezing mixtures
• The other methods of liquefaction depend on the cooling effect
produced by a gas as it expands

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Experimental model of gas expansion
1. Adiabetic expansion
• when a gas is allowed to expand rapidly while restricting entry of heat to
the system
• Using a vacuum flask where the system is effectively insulated from
external heat
• The work done to bring about expansion therefore must come from the gas
itself at the expense of its own heat energy content (collision frequency).
• As a result, the temperature of the gas falls.
• If this procedure is repeated a sufficient number of times, the total drop in
temperature may be sufficient to cause liquefaction of the gas
• This expansion is observed in ideal gases
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2. Joule-Thomson expansion
• A cooling effect is also observed when a highly compressed nonideal gas expands into a
region of low pressure.

• In this case, the drop in temperature results from the energy expended in overcoming
the cohesive forces of attraction between the molecules.

• This cooling effect is known as the Joule–Thomson effect and differs from the cooling
produced in adiabatic expansion, in which the gas does external work.

• To bring about liquefaction by the Joule–Thomson effect, it may be necessary to

precool the gas before allowing it to expand.
• Liquid oxygen and liquid air are obtained by methods based on this effect
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Aerosols

• The principles of liquefaction are applicable in aerosols

• Gases can be liquefied under high pressures in a closed chamber as long as
the chamber is maintained below the critical temperature.
• When the pressure is reduced, the molecules expand and the liquid reverts
to a gas.
• This reversible change of state is the basic principle involved in the
preparation of pharmaceutical aerosols
• This is achieved by dissolving or suspending a drug in a material that exists in
liquid state under pressure but transitions to gas under normal atmospheric
conditions
• This material is referred to as a propellant
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Aerosols cont..
• The container is designed that, by depressing a valve, some of the
drug–propellant mixture is expelled

• If the drug is nonvolatile, it forms a fine spray as it leaves the valve

orifice;

• at the same time, the liquid propellant vaporizes off

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Aerosols cont..
• Chlorofluorocarbons and hydrofluorocarbons were traditional
propellants
• More recently other gases such as nitrogen and carbon dioxide are
increasingly being used as propellants
• Examples of pharmaceutical aerosols include
• antiseptic materials can be sprayed onto abraded skin with a minimum of
discomfort to the patient
• Ethyl chloride, cools sufficiently on expansion so that when sprayed on the
skin, it freezes the tissue and produces a local anesthesia
• Most widely used application is delivery of pharmaceutical products to the
respiratory system
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Other drug administered via respiratory route
1. Volatile solvents: popular in aromatherapy
2. Gases: mainly anesthetics (halothane, ether, nitrous oxide)
3. Nebulizing solutions
• Alexander TF (2011). Physicochemical Principles of Pharmacy, 5th
Edition Pharmaceutical Press. ISBN-10-1-4200-6566-1