Introduction to

Pharmaceutical Technology
Dr. Pharm. Beyza Betül Gökçe
E-mail: [email protected]

Istinye University Faculty of Pharmacy

Department of Pharmaceutical Technology

Genel Kimya/Maddenin Özellikleri Ve Ölçümü 1

Course Schedule and Outcomes

Principles
World Pharmaceutical Market
• The world pharmaceutical market reached 1.5 trillion USD in
2022.
• Turkey ranked 21th in 2022.

Market share of leading 5 pharmaceutical markets worldwide in 2022

Source: IQVIA

Source: IQVIA, İEİS

World Pharmaceutical Market
A remarkable change is expected
in 2025 with the rise of India to
one of the top 10 countries in
the global pharma industry.

Turkey is projected to rise in the

rankings in the global pharma
industry in 2025.

Brazil keeps rising up to the top

in the global market list.

China retains its position as the

number two ranked market.

Japan, the EU 4 (France,

Germany, Italy, and Spain), and
the UK are also projected to be
present among the top 10
pharma markets for 2025.

https://www.dcatvci.org/features/pharma-industry-outlook-the-challenges-and-opportunities/
 Pharmaceutical Technology
• In pharmaceutical sciences, the term is used to express the topics from the
beginning to the end of the development of a dosage form
• The steps following the synthesis or discovery of a drug are first the isolation
and purification of the drug, testing its pharmacological effects and
investigating the presence of side effects.
Pharmaceutical technology briefly refers to the process
of transforming the active substance into a drug

It is also known as ‘Galenic Pharmacy’, which comes

from the name of Galenos of Pergamon, who is
considered the founder of pharmacy.
 Pharmaceutical Technology Process

• Understanding the chemical structure of the active substances and

excipients used for the design of dosage forms
• Selection of active ingredients and excipients
• Control of the purity and compatibility of the active substance and
excipients
• Design of dosage form
 Pharmaceutical Technology Process

• Understanding the characteristics of the

dosage form related to the route of
administration and how the active
ingredient reaches the site of action
• All the steps of designing and achieving
both small and large scale production of
the designed dosage form are included.
Pharmaceutical Technology Process
 Pharmaceutical Technology
In general terms, pharmaceutical technology deals with;
• production of dosage forms,
• inspection of all stages and inputs, elimination of problems, which ensure
quality assurance in this production,
• bioavailability and stability of the produced drug forms,
• designing particular drug release systems,
• active substance targeting and related dosage forms,
• ensuring invariability of the properties of the active substance,
• determination and development of the properties of excipients,
• development of new drug delivery systems.
 Classification of Dosage Forms
• Solid Pharmaceutical Forms: Powder, cachet, packages, capsules, tablets,
lozenges, dragees.
• Semi-Solid Pharmaceutical Forms: Suppositories, ovules, ointments,
creams and gels.
• Liquid Pharmaceutical Forms: Solutions (oral, injection, eye and nasal, oral
cavity, rectal and vaginal, inhalation), syrups, lotions and enemas.
• Two Phase Systems: Suspension, emulsion and
aerosols
• New Drug Delivery Systems: Microcapsules,
microspheres, nanoparticles, solid lipid
nanoparticles, microsponges and liposomes.
Steps in the development of a new drug as a pharmaceutical product
STEP 0:

1. Idea, synthesis, synthesis of radioactive compound

2. Physicochemical investigations

3. Preliminary analytical studies

4. Biological activity screening

5. Acute and subchronic toxicity tests

6. Pre-formulation tests

7. Marketing recommendations
STEP 1:
1. Clinical Phase I. Study in healthy human volunteers. Proper pharmaceutical dosage form and dose
selection determined by short-term pre-Absorption Dispersion, Metabolization, Elimination (ADME)
tests and predicted pharmacokinetic parameters

2. Investigation of metabolic pathways of the drug

3. Chronic toxicity tests
4. Investigation of mutagenic, teratogenic and carcinogenic effects

5. Investigation of active substance-DNA repair system

6. Synthetic chemistry research involving scale up and experimental industrial product production

7. Drug formulation research (stability, incompatibility, biopharmaceutical, dosing design)

8. Analytical studies of the active substance, stability test methods and testing methods for specific
measurements of metabolites

9. Examining the marketing plan

STEP 2:

1. Clinical phase II. Randomized double-blind controlled clinical trials to measure pharmacological
efficacy for the relevant patient population. Long-term ADME tests and pharmacokinetic
parameters estimation.

2. Drug formulation trials. Determination of bioavailability. Preparation of production guides.

Pharmaceutical pilot production experimental study. Scale magnification experiments. Medium-
scale production of clinical specimens

3. Analytical examination of pharmaceutical product

4. Management work in accordance with marketing plans

5. Marketing
STEP 3:

1. Common clinical trials. Evaluation of side effects and possible drug interactions

2. Large-scale production of pharmaceutical products. Determination of shelf life.

3. Determination of quality norms for the product

4. Management work in accordance with marketing plans. Licensing certificate

5. Marketing
STEP 4 (Summary, evaluation)

1. Data on synthesis

2. Analytical data

3. Preparation data

4. Clinical data (indication area, rules of use)

5. Licensing

6. Marketing data

7. Production data

8. Patent status
PHASES OF DEVELOPMENT PROCESS OF A DRUG
• The process involving the discovery of a drug into a safe and effective
dosage form is quite long, difficult and expensive.
• After the discovery of a new drug, its pharmacological, toxicological and
potential therapeutic effect is investigated. Then, it must be approved
by the relevant institutions (such as the FDA) within the framework of
the laws governing that country.

• On average, it costs a company $800 million to

reach a new drug from the laboratory to the
patient.
• It takes at least 10-15 years.
• Only about 5 of the 5,000 compounds that have been subjected to
preliminary clinical testing, can be tested in humans, and only one of
these candidates receives the necessary approval to be available in the
pharmaceutical market.
• A classic business development process begins with revealing the
chemical structure of the active substance. Subsequently, the necessary
processes are carried out for its synthesis or production. In vitro studies
are carried out on the resulting product to demonstrate its
effectiveness in every aspect.
• The activity of the new drug is investigated by animal testing.
Pharmacokinetics and toxicological studies are also performed in
animals.
• In preclinical studies, suspension or solution of the drug, the simplest
drug forms, are used.
 THE DRUG DISCOVERY PROCESS

www.PhRMA.org, January 2012, Washington, US

There are 3 important issues in dosage form design
1. Physicochemical properties of the active substance
2. The effect of the dosage form on the absorption of the active substance
3. Existing therapeutic effect of the active substance
 Dosage form design
• As a result of the examinations made on these issues, the most
appropriate, the optimum dosage form for that active substance is
decided.
• Dosage forms can vary in a range from simple solutions to complex drug
forms designed with specific excipients.
• The physical properties of the active substance such as solubility,
dispersion, viscosity, emulsification, compressibility, compactibility or
color, taste can be changed by means of excipients used in the
preparation of the dosage form.
The main purpose of the dosage form design is to provide a formulation
containing the active substance with a product quality that can be
introduced to the market through large-scale production systems.

✓Chemical and physical stability

✓Homogeneity of active substance in the
formulation
✓Acceptability by patients
✓Proper packaging and labeling of this
formulation is important.
Absorption of the drug is only possible when in solution.
The absorption of the drug depends on its solubility in fat, its
formulation and route of administration.
In order to achieve the proper design of a dosage form; the physical,
chemical and biological properties of the drug and excipients it contains
must be known.

Furthermore, the compatibility of the drug and

excipients with each other is important to ensure
that the dosage form is stable, effective, easy to
administer and safe.
 Drug administration in different ways is as follows.
Route of
Dosage Form
Administration

Solutions, syrups, suspensions, emulsions, gels, powders, granules, capsules, tablets

Oral

Rectal Suppositories, creams, ointments, powders and solutions

Ointments, creams, pastes, lotions, gels, solutions, topical aerosols, transdermal films
Topical

Parenteral forms in the form of solutions, suspensions and emulsions and dialysis solutions
Parenteral

Aerosols and inhalations in the form of solutions, suspensions, emulsions and powders
Inhalation

Intranasal Aerosols and inhalations

Ocular Solutions, suspensions and cream

Ear Solutions, suspensions, ointments and cream

 In an ideal dosage :
✓The drug should be protected from the influence of air humidity and oxygen (Coated
tablets).
✓Following oral administration of the drug, it must be protected from the acid effect of
the gastrointestinal tract (Enteric coated tablets).
✓The bitter, salty or bad taste or smell of the drug should be hidden (Capsules, coated
tablets and flavored syrups).
✓The preparation of a solution formulation of the drug that is insoluble or unstable in the
desired solvent should be ensured (Suspensions).
✓The release rate of the drug should be able to controlled (All controlled release tablets,
capsules and suspensions).
✓The release of the drug should be able to achieved in a specific area or locally (Rectal or
vaginal suppositories).
✓The release of the drug should be able to achieved in the targeted tissue (Nanoparticles
and liposomes).
 Classification of dosage forms according to their onset of
action
Drug on set of Dosage Form
action
Seconds i.v. injection

Minutes i.m. and s.c. injection, buccal tablets, aerosols

Minutes to hours Injections with short term storage effect, suspensions, powders, granules,
capsules, tablets, modified release tablets

Hours Enteric coated tablets

Days to weeks Injections with storage effect, implants

Various times Topical applications

THANK YOU
Basic Applications of Drug Preparation
Pharmaceutical Mixing

Dr.Pharm. Beyza Betül GÖKÇE

E-mail: [email protected]

Genel Kimya/Maddenin Özellikleri Ve Ölçümü 31

 Mixing
• Mixing is the process of randomly distributing dissimilar particles within a
system.
• The process of dispersing powders or solvents within each other, as
thoroughly and completely as possible is called mixing, and the
homogeneous system prepared is called mixture.
• The basis of the drug preparation process is based on homogeneous mixing
of the substances.
• A poorly mixed powder, granule or pomade cannot be accurately dosed.
• The main purpose of mixing process is to ensure the amount of active
substance reported on the label in unit doses of the prepared drugs.
Purpose of Mixing Process
• Mixing two or more miscible liquids or powders,
• Mixing insoluble solids in a liquid (e.g. suspension),
• Dispersion of particles with a carrier such as emulsion, suspension,
liquid, ointment.
In cases where no external energy is required to prepare the mixture;
liquids, gases and vapors that mix easily with each other instantly mix
through diffusion, this is positive mixing.

The process of mixing solid particles in a liquid, which are insoluble

and precipitated when mixing stops is defined as negative mixing.
Mixing process can be categorized as;
• Mixing of liquids (solutions and emulsions)
• Mixing a solid in a liquid (real solutions, colloidal solutions,
suspensions and wet granulation)
• Mixing of powders (tablets and capsules)
• Mixing of semi-solids (creams, ointments, pastes and suppositories)
 Tools Used in Mixing Process
• There are various types of mixers in the industry that mix on a large scale
and for different purposes.

• Generally two types of mixers can be mentioned:

❑Batch Mixing
Mixing certain amounts of substances
❑Continuous Mixing
Mixing of large volumes by constantly refreshing the mixed material
Powder Mixing

What would be an ideal mix?

Two separate sets of unmixed powder
Ideally mixed powder cluster (*perfect)
Set of randomly mixed powders
 Powder Mixing
• Mixing by conveying: It is the mass displacement of the material to be mixed.
Depending on the type of mixing applied, it is done by turning the powder upside
down or by moving it from one place to another with the help of shovels or
wings.
• Shear mixing: A shear plane is formed by the forces in the powder mass. As a
result, the powder mass slides through this plane and a laminar flow is occurs. As
a result of this flow, the layers of the different powders to be mixed in the
environment gradually become thinner and the powders mix with each other
• Diffusion mixing: Mixing occurs as a result of random movements of the particles
in the mixture. The particles are moved from one place to another in the mixture
and change their position relative to each other. In other words, it is formed by
the spontaneous self-diffusion of particles within each other between layers as a
result of shear mixing.
 Different particle sizes of powders
• When the particle sizes of the powders to be mixed are different, the
smaller ones tend to remain at the bottom and the larger ones at the top.
• While particles with a particle size of 200-250 µm flow well; in powders with
particle sizes between 200-75 µm, flow problems may occur due to the
increase in surface area and the effect of forces on the surface
• As the particle size of the powders decreases below 75 µm, the flow
problem increases due to both static electricity and cohesion. If there is a
density difference between the powders, separation will be easier.
Shapes and formes of particles
• Smooth, spherical particles mix well with each other.

• Segregation is mostly seen in powder mixtures consisting of

amorphous particles and fibrous and fine flake particles.
 Agglomeration of particles
• Fine particles attract each other by the effect of electrical forces on the
surface (cohesive forces).

• As the particle size of the powders becomes smaller, the increased surface
area and static electricity cause agglomeration, which reduces the fluidity
of the powder.
 Separation of particles (Segregation)
• Particles that are not of the same size and density tend to separate.

• Electrical charge and shapes are also effective in separation.

• Mixing powders for too long is one of the causes of separation.

 Relative ratios of the substances to be mixed
• The proportions of the two substances constituting the mixture may be
different, for example 50/50 or 1/99.
• The smaller the ratio, the more difficult the homogeneous mixing of the
powders is.
• In such cases, the powders must be mixed by the geometric dilution
method in order to prevent separation and provide a good mixture.
• That is to say, at the beginning, the same amounts of both substances,
equal to the substance present less in quantity are taken and mixed.
• Then, more substance is added as equal to the total substance in the
medium, and the mixing process continues, and so on.
 Mixers for Powder Mixing
• Hand tools: Mortar, pestle and spatula are most commonly used for
mixing small amounts of powders in a pharmacy or laboratory.
• Grinding and mixing take place simultaneously.
• Mixing in mortar should be done on the basis of geometric dilution.
 Powder Mixers Used in Industry
• Tools that mix by turning upside down
❑V, cylindrical or cube shaped mixers
❑Müller mixers

• Tools that mix by digging

❑Ribbon, drum mixers

• Other mixers also used for mixing semi-solid preparations

❑Sigma, planetary mixers
 Powder Mixers Used in Industry
• Mixing devices that have different geometric shapes and rotate around
themselves are available.
• In such devices, the diffusive mixing mechanism is generally effective.
Powders are moved from one place to another and turned upside down.
• The most commonly used mixers are cubic, V type, cylindrical and
double- cone mixers.
CUBIC MIXER
V-type mixer
• https://www.youtube.com/watch?v=OWfHoB_t948

• https://www.youtube.com/watch?v=5WuNalI71IU

• https://www.youtube.com/watch?v=jRkRLPnAWh0
Cylinder Mixer
Double-cone mixers
Müller Mixers
• Mixing is achieved by the breaking mechanism. They do not take up
much space as they are in vertical position. The improved form of this
tool is the mixers which mix with air stream.
Mixers mixing with air flow
• Other mixers that make batch mixing are mixers with mixing blades.
They can be used for both wet and dry mixing.
• These tools are mainly used in processes such as granulating.
• Ribbon mixers, Sigma mixers are examples of this group.
Ribbon Mixer
• https://www.youtube.com/watch?v=18ypfMT7Rvo
Planet Mixer
• When selecting powder mixers, care must be taken to ensure that the
mixer can move the ingredients in three directions and that there are no
dead spots in the container.
Mixing of Liquids
1- Bulk transport: It is the process of transporting the material to be
mixed from one region to another within the system.
2- Vortex mixing (Turbulent mixing): It is the process of mixing liquids
with non-uniform turbulent flow. Its feature is that the flow rate and
mixture of the liquid during the mixing process is random. Therefore,
turbulence occurs in the system due to the temporary and variable
speed difference and makes the mixing process random. This
mechanism is very effective in mixing. The density of the liquid is also
very important for vortex mixing in terms of mixing speed.
 Mixing of Liquids

3- Laminar mixing: Laminar mixing occurs during smooth flows of viscous

liquids. It occurs when two dissimilar liquid layers slide over each other
and mix. These layers may also be more than one.
4- Molecular diffusion: The mechanism responsible for mixing at the
molecular level is the diffusion, caused by the thermal movement of
molecules. Basically, mixing occurs when the liquid molecules to be mixed
move randomly within each other.
 Tools for Mixing Liquids
Propeller mixers:
Various machines are used for industrial production. These machines can
be in various capacities depending on the amount of production.
A propeller mixer can be used to mix soluble substances within a liquid,
such as in the manufacture of solutions or syrups.
The shaft, consisting of a stainless steel rod, is connected to a rotating
motor from the top. The wings rotating at the end of the rod are called
propellers.
Propeller mixers:

Mixer with handle

Simple propeller mixer Inclined mixer
Propeller mixers:
Airflow Mixing
Air and, in some cases, inert gases are sent to the liquid to be mixed
through a pipe to provide mixing by means of pressure.
The air, pushed upwards by the pipe and released into the environment
enables the turbulent flow of the liquid in the container in all
directions.
In order for such mixing to be done effectively, the liquid must be of
low viscosity, not foaming, not reacting with gas, and be non-volatile.
Airflow Mixing

AIRFLOW
Mixing with Liquid Flow
The liquid to be mixed is circulated in the container with a particular
pipe.
Liquid is pumped through holes to ensure good mixing in all sides.
 Mixing a Solid in a Liquid
(Real Solutions, Colloidal Solutions, Suspensions, Wet Granulation
Formation)

Low viscosity liquids are easier to mix.

However, the addition of powders to these liquids, i.e., the mixing
process to form suspensions, is more difficult; because as soon as
mixing stops, the powder particles begin to descend.
When a viscous liquid is used, the descending is slower, but mixing is
more difficult.
THANK YOU