Download PHARMACEUTICAL PROCESS ENGINEERING CHAPTER 1

(1) Course code:
(2) Course title:
ERT430 Introduction
ERT 430
Pharmaceutical Process Engineering
(3) Number of unit: 3
(4) Course type:
Elective
(5) Prerequisite:
Nil
(6) Course synopsis:
The course includes the principles of drug pharmacokinetics: absorption, distribution,
metabolism and excretion of drugs. This course also covers the scientific and technological
aspects of the designing and manufacturing of pharmaceutical products.
(7) ) Learning Outcomes:
At the end of the course, students are expected to be:
1. Able to explain the basic concept of drug absorption and disposition and analyze the
related pharmacokinetics.
2. Able to evaluate the pharmaceutical engineering processes in pharmaceutical formulation
and production.
3. Able to design pharmaceutical facilities.
(8) List of possible experiments:
Nil
(9) Learning approach:
Lecture
: 100% (42 hours)
(10) Evaluation contribution:
(i) Examination: 70%
 Midterm Examinations = 20%
 Final Examination
= 50%
(ii) Continual Assessment: 30%
 Assignments = 20%
 Quizzes
= 10%
ERT430 Introduction
(11) Lecturers
i.
ii.
iii.
Dr Khairul Farihan Kasim (C)
Mrs Anis Atikah binti Ahmad
Mrs Syazwani binti Mahmad Puzi
(12) List of text books and references
Textbook:
i) Bennet, B. and Cole, G. Pharmaceutical Production: An Engineering Guide. Warwickshire:
Institution of Chemical Engineers (IChemE)., 2003.
Reference Books:
i)
Aulton M. E., Pharmaceutics. The science of dosage form design. 2nd Edition. London: Churchill
Livingstone., 2002.
ii)
David J. am Ende, Chemical Engineering in the Pharmaceutical Industry: R&D to
Manufacturing, New Jersey, USA: John Wiley & Sons, Inc., 2011.
iii)
Blacker A. John, Williams Mike T., Pharmaceutical Process Development - Current Chemical
and Engineering Challenges, Royal Society of Chemistry, UK: Cambridge., 2011.
iv)
Anthony J. Hickey, David Ganderton. Pharmaceutical Process Engineering: 2nd Edition. New
York: Informa Healthcare., 2009
v)
Sambamurthy K., Pharmaceutical Engineering. New Delhi: New Age International Publishers.
2012
ERT430 Lesson Plan
Week
Week 1
(13 Feb 17)
Week 2-3
(20 Feb 17)
(27 Feb 17)
Week 4-5
(6 Mac 17)
(13 Mac 17)
Course Contents
(Guidelines)
INTRODUCTION TO PHARMACEUTICAL PROCESS
Compare the traditional and modern way of drug usage and
production. Discuss several routes for synthetic drug formation.
Distinguish different flow processes /stages of new product
launch.
(3 hours)
PHARMACEUTICS AND PHARMACOKINETICS
Discuss the physiological issues involved in drug therapy;
Analyze the pharmacokinetic models such as adsorption,
distribution, metabolism and elimination kinetics;
Analyze bioavailability, clearance and repetitive dosing;
Demonstrate membrane transport of orally delivered drugs.
Discuss factor influencing drug adsorption and availability.
Discuss and demonstrate route of delivery on drug action;
Calculate chemical kinetics and drug stability.
(6 hours)
PHARMACEUTICAL PARENTERAL FORMULATION:
SOLUTIONS, SUSPENSIONS and EMULSIONS
Discuss and define parenteral formulated products;
Formulate and evaluate solutions, suspensions and emulsions;
Discuss and demonstrate production eye drops, eye lotions and
eye ointments; Discuss and design production facilities;
Formulate and evaluate ophthalmic products.
(6 hours)
Lecturer
Mrs Anis Atikah
Mrs Anis Atikah
Mrs Anis Atikah
ERT430 Lesson Plan – cont.
Week 6-7
(20 Mac 17)
(27 Mac 17)
Week 8
(3 April 17)
Week 9
(10 April 17)
Week 10-11
(17 Apr 17)
(24 Apr 17)
PHARMACEUTICAL SOLID DOSE FORMULATION: TABLETS and
CAPSULES
Illustrate, formulate and evaluate of different types of solid dose
formulation;
Discuss, analyze and evaluate methods of preparation,
processing problems, formulation and manufacturing techniques
of different compressed tablets and capsules.
(6 hours)
Dr Khairul
Farihan
CUTI PERTENGAHAN SEMESTER/MID-TERM BREAK
PHARMACEUTICAL SOLID DOSE FORMULATION: POWDERS and
GRANULES
Discuss, demonstrate and analyze methods of preparation,
processing problems, formulation and manufacturing techniques
of powders and granules.
(3 hours)
PHARMACEUTICAL PROCESSING
Describe, discuss and illustrate general technique used for
extraction and isolation of phytopharmaceuticals;
illustrate principles and design pilot plant for Isolation of
active pharmaceuticals.
(6 hours)
Dr Khairul
Farihan
Dr Khairul
Farihan
ERT430 Lesson Plan – cont.
Week 12-13
(1 May 17)
( 8 May 17)
Week 14-15
(15 May 17)
(22 May 17)
PHARMACEUTICAL FACILITIES
Discuss, illustrate and design utilities and services for the
pharmaceutical (laboratory and plant) facility.
(6 hours)
PILOT MANUFACTURING FACILITIES
Design pilot manufacturing facilities for the development and
manufacture of pharmaceutical products.
Discuss regulatory, design and operating conditions for primary
and secondary production. Design of facilities and equipment.
(6 hours)
Week 16
(29 May 17)
REVISION WEEK
Week 17-19
65June -23
June 17)
FINAL EXAMINATION
Mrs
Syazwani
Mrs
Syazwani
PHARMACEUTICAL PROCESS
ENGINEERING
CHAPTER 1 – INTRODUCTION
MRS ANIS ATIKAH AHMAD
[email protected]
PHARMACEUTICAL ENGINEERING
• Pharmaceutical process engineering: involves the
manufacturing process of pharmaceuticals and related
therapies.
• Pharmaceutical engineers: are the professionals
who help develop the manufacturing plants and design
pharmaceutical products.
DEFINITION OF DRUG
• Substances intended for use in the diagnosis,
cure, mitigation or prevention of disease in man
or animals;
• substances (other than food) intended to affect
the structure or any function of the body of man
or animals;
• substances intended for use as a component of
any substances specified above but does not
include devices or their components, parts or
accessories
TRADITIONAL VS MODERN WAY
OF DRUG USAGE & PRODUCTION
1. TRADITIONAL WAY:
• Trial & error : by looking at the effect of consumption
• Discovered that small quantities of drugs are useful
and larger quantities intake are not necessarily better
(usually harmful)
• Direct consumption of medication: coca leaves
(cocaine), poppy juice (morphine).
TRADITIONAL VS MODERN WAY
OF DRUG USAGE & PRODUCTION
MODERN WAY:
• Needs to follow a path or process before can be sold
• Once an active product has been discovered and proven to be
medically effective, the manufacturer has to produce the
active ingredient and process it into the most suitable dosage
form
• Very costly: can cost up to 300 million USD/drug (involves
R&D, manufacturing, distribution, marketing & sales.)
SYNTHETIC DRUG FORMATION
Synthetic route for phenylbutazone
Synthetic route for 6a methylprednisolone (steroid)
STAGES IN NEW PRODUCT LAUNCH
The time cycle from discovery to launch takes many years and will probably not be less than
four years for a New Chemical Entity (NCE).
Activity & pre-clinical safety 2-4yrs
Discovery of
active
substance
Pre-clinical
trials
Approx 8-10,000
potential candidate
substances screened for
therapeutic activity
Synthesis of
active
substance
Screened for
pharmacological activity
Toxicity trials
0.5 yr
Pharmacokinetic
trials
2/3 yr
Clinical trials
Approx 1 yr
Phase 1
Phase 2
Approx 1 yr
Phase 3
Approx 2 yr
Registration &
Launch
Registration with
health
authorities
Launch & sales
2/3 yr
• Development of formulations
•Bioavailability of formulations
•Stability tests on drugs & formulations
•Quality control methods devised
•Process development
•Detailed animal pharmacology
•Synthesis of radio labelled material
•Blood level methods developed
•Acute & 6 month toxicity studies
•Reproduction studies & teratology
•Absorption, excretion, & metabolism on
animal species
•Outline clinical trial programmes
• Establishment of manufacturing
processes
•Plant design & buildings
•Development of sales formulation
•Bioavailability studies
•Package development
•Stability studies
•International clinical trials
•Detailed absorption, excretion &
metabolism studies in man
Pre-Clinical Testing (on animal)
• it is used as an aid to assessing whether initial human studies
will be acceptably safe, and
• to predict the therapeutic activity of the drug
• If the drug looks promising, human clinical studies are
proposed.
Clinical Testing
•
PHASE 1:includes the initial introduction of an investigational drug into
humans and consists of short-term studies in a small number of healthy
subjects, or patients with the target disease, to determine the metabolism and
basic pharmacological and toxicological properties of the drug, and if
possible, to obtain preliminary evidence of effectiveness.
•
PHASE 2: consists of larger, more detailed studies; usually including the first
controlled clinical studies intended to assess the effectiveness of the drug and
to determine the common short-term side effects and risks of the drug.
•
PHASE 3 studies are expanded controlled and uncontrolled trials. They are
performed after preliminary evidence of effectiveness has been established
and are designed to gather the additional information necessary to evaluate
the overall benefit-risk relationship of the drug and to provide an adequate
basis for professional labelling.
Common terms
• Primary Production: manufacture of the
active ingredient
• Secondary Production: turning the active
ingredient into the dosage forms
Dosage forms available for different
administration routes
Administration routes
Dosage forms
Oral
Solution, syrup, suspension, emulsion, gel, powders,
granules, capsules, tablets
Rectal
Suppositories, oitments, creams, powders, solutions
Topical
Ointments, creams, paste, lotions, gel, solutions,
topical aerosols
Parenteral
Injection (solution, suspension, emulsion forms),
implants, irrigation and dialysis solutions
Respiratory
Aerosols (solution, suspension, emulsion, powder
forms), inhalations, sprays, gases
Nasal
Solutions, inhalations
Eye
Solutions, creams, ointments
Ear
Solutions, suspension, creams, ointments
Common terms
• Pharmacokinetics: The study and characterization of the time
course of drug absorption, distribution, metabolism and
elimination (ADME). It is the measure of the rate (kinetics) of
ADME. All the four processes involve drug movement across the
membranes.
• The time course of drug action depends on:
1. Drug dose, route of administration, rate and extent of
absorption, distribution rate (particularly to site of action) and rate
of elimination.
2. The minimum effective concentration and concentration-effect
relationship. Consideration of the time course of drug action is
important since usually it is necessary to maintain a certain
concentration of drug at its site of action for a finite period of time.
ADME
ADME
• Absorption: is the process by which a drug
enters the bloodstream without being
chemically altered.
• Absorption is the movement of a drug from its site of
administration into the blood. Most drugs are absorbed by passive
absorption but some drugs need carrier mediated transport. Small
molecules diffuse more rapidly than large molecules.
• Most drugs are absorbed in small intestine.
ADME
• Distribution
• Distribution is the movement of drugs throughout the body. Determined
by the blood flow to the tissues, it is ability of the drug to enter the
vasculature system and the ability of the drug to enter the cell if required.
ADME
• Metabolism or Biotransformation
• It is the process of transformation of a drug within the body to make it
more hydrophilic so that it can be excreted out from the body by the
kidneys. This needs to be done since drugs and chemicals are foreign
substances in our body.
• Metabolism is one of the most important mechanisms that the body has
for detoxifying and eliminating drugs and other foreign substances.
• Drugs delivered by the oral route must pass through the liver before
reaching the general circulation.
• Metabolism at this point is called “first-pass metabolism,” which can limit
systemic exposure for drugs despite good absorption.
• The greater the first pass effect, the lesser the drug that will reach the
systemic circulation when the drug is administered orally.
FIRST PASS METABOLISM
FIRST PASS METABOLISM
ADME
• Elimination/Excretion
•
Excretion is the removal of the substance from the body. Some drugs are either
excreted out unchanged or some are excreted out as metabolites in urine or bile.
•
Drugs may also leave the body by natural routes such as tears, sweat, breath and
saliva. Patients with kidney or liver problem can have elevated levels of drug in the
system and it may be necessary to monitor the dose of the drug appropriately
since a high dose in the blood can lead to drug toxicity.
Common Terms (Cont.)
•
Bioavailability: The relative amount/percentage/fraction of an administered dose of a
particular drug that reaches the systemic circulation in unchanged form and the rate at
which this occurs (the rate and extent of drug absorption).
(the amount of drug that is available to the body to produce a therapeutic effect.)
•
Half life of a drug : is the time for the drug to decrease to half of its concentration.
•
Minimum effective concentration: below which there will be no therapeutic effect.
•
Maximum safe concentration: above which there will be a toxic effect. The larger the
therapeutic index the more safer the drug.
•
Onset of action : it is the time taken for the drug to reach the minimum effective
concentration after a drug has been administered.
•
Duration of action: is the length of time the drug has a pharmacological action.
Tablet / Pill
Some tablet shape possibilities
Capsules
Pellets and other extrudates
THANK YOU

QUIZ 1
1.
After administering a drug, the time when the body first starts to respond to the medication is
called:
A. Plateau
B. Peak plasma level
C. Onset of action
D. Drug half-life
2.
Two most important sites for drug elimination:
A) pulmonary and liver
B) liver and gastrointestinal tract
C) kidney and liver
D) skin and liver
E) pulmonary and kidney
3.
Parenteral administration:
A) Cannot be used with unconsciousness patients
B) Generally results in a less accurate dosage than oral administration
C) Usually produces a more rapid response than oral administration
D) Is too slow for emergency use
QUIZ 1
4.
Which route of drug administration is most likely to lead to the first-pass effect?
A) Sublingual
B) Oral
C) Intravenous
D) Intramuscular
5.
Pharmacokinetics is:
A) The study of biological and therapeutic effects of drugs
B) The study of absorption, distribution, metabolism and excretion of drugs
C) The study of mechanisms of drug action
D) The study of methods of new drug development
6.
What does the term “bioavailability” mean?
A) Plasma protein binding degree of substance
B) Permeability through the brain-blood barrier
C) Fraction of an uncharged drug reaching the systemic circulation following any route
administration
D) Amount of a substance in urine relative to the initial doze
REFERENCES
• Goodman & Gilman’s The Pharmacological Basis of
Therapeutics by. Joel Griffith Hardman, Lee E. Limbird, Alfred G.
Gilman. 10th Ed.
• Rang & Dale’s Pharmacology by. Humphrey Rang, Maureen Dale,
James Ritter, Rod Flower. 6th Ed.
• PK/DB – Database for Pharmacokinetic Properties – IFSC/USP
(URL= http://miro.ifsc.usp.br/pkdb/) accessed