Drugs and Dosage forms

1. Drugs and dosage forms
Fakhrul Ahsan, Ph.D.
E-mail: fakhrul.ahsan@ttuhsc.edu
Room # SOP 214
I have used the above book to prepare this note. I have used a large
number of pictures from various websites and books, but I did not cite all
to avoid clutters. A few pictures were drawn by Dr. Nilesh Gupta.

2. Learning objectives
1. Know the discipline of pharmaceutics and its
branches
2. Define drugs and know the process of drug
development and discovery
3. Explain pharmaceutics and drug delivery
4. Differentiate drugs, formulations and dosage
forms
5. Distinguish between active ingredients and
excipients
6. Appreciate the standardization process of drugs
7. Learn the nomenclature of drugs
8. Categorize drugs based on dispensing
regulations
9. Recognize official compendia for drug standards

3. The science of dosage forms
 Pharmaceutical principles
of dosage forms and
pharmacy calculations
based on different routes
of administration
 Physico-chemical
properties
 Bio-pharmaceutics,
stability, packaging, and
formulation of various
dosage forms.
 Radiopharmaceuticals

4. Pharmaceutics
 The methodologies and science
involved in transforming a new
chemical entity (NCE) or a
biological into a consumable
product that is safe for human
use but effective against a
given disease
 The science of dosage form
design and drug delivery
systems.
 Many chemicals have
pharmacological effects but you
cannot administer a raw
chemical as is.
 Branches of
Pharmaceutics:
 Pharmacokinetics
 Bio-pharmaceutics
 Pharmacodynamics
 Pharmacogenomics
 Pharmaceutical
Technology

5. Pharmaceutics
Pharmacokinetics
 Pharmacokinetics (in Greek: "pharmacon" meaning
drug, and "kinetikos" meaning putting in motion)
 A branch of pharmaceutics that studies the fate of
drugs after administration to human or animals
 Assess the extent and rate of absorption, distribution,
metabolism and excretion (ADME)
 What body does to the drug
oP2 spring
Pharmacodynamics:
 Study the relationship between drug concentration
and its effect
 What drug does to the body
oP2 spring

6. Pharmaceutics
 Bio-pharmaceutics
 Study the impact of physicochemical properties of
drugs and drug products on drug delivery and
absorption under normal or pathological condition.
oWill be covered in P1 spring
 Pharmacogenomics
 Cover the influence of genetic variation on the drugs’
efficacy and toxicity
 Pharmaceutical Technology
 Address the technologies involved in the development
of dosage forms
oWill be covered in P1 spring

7. Review
Pharmaceutics deals with all of the followings
EXCEPT
o A. Preparation of dosage forms
o B. Formulating a pure drug into a dosage forms
o C. Studying the physico-chemical properties of
pure drug substance
o D. Identifying the mechanism of action of a drug
o C. Study the rate and extent of drug absorption

8. Drug
• From the Greek pharmakon = drug
• Any chemical or biological substances used in the
diagnosis, mitigation, treatment, cure or
prevention of human or animal diseases.
• The process of drug discovery is very
complex
• Requires integrated efforts of a team of scientists
comprising chemists, biochemists, pharmaceutical
scientists, clinical pharmacists, medical doctors,
and statisticians

9. Drugs versus biologics
 Drugs
 In general, they have well-known chemical structures
 Manufactured via chemical synthesis
 Manufacturing in involves a ordered process
 Example: Acetaminophen, ibuprofen
 Biologics (also called biopharmaceuticals or biotech
products
 Manufactured in bacteria, plan or animal cells
 Very large molecules or may contain a mixture of
molecules
 Hard to know the exact structure or composition
 Difficult to control the manufacturing process
 Use recombinant DNA technology
 Example: Adalimumab (Humira)

10. Drug discovery
 Pharmaceutical industry discovers the vast majority of the
drugs
 To discover drugs, we must have well-designed research
program for screening, molecular modification and
mechanism based drug design
 You can isolate drugs from a variety of natural sources or
synthesize them in the laboratory.
 Natural drug sources include
 Plant: Taxol (paclitaxel), extracted from Pacific Yew
Tree, is used in the treatment of cancer
 Animal: Many vaccines were initially developed from
animals.

11. Prodrugs
 A drug that must change
to an active compound
after ingestion
 Such conversion occurs
through enzymatic and
biochemical cleavage.

12. Drug discovery and development
 Discovery
 Identify disease targets and potential therapeutic
compounds
 The least successful aspect of drug development
 Non-Clinical Development
 Translates chemical or biological substances into
therapeutic candidates
 Modify, scale-up, purify, test, produce chemical or
biological substances
 Use animals to conduct studies
 Clinical Development: Studies performed in humans
 Phase I, II, III and IV trials

13. Drug discovery

14. Terms used in drug discovery
 Target
 A protein, enzyme, receptor, signaling or other molecules that is/are
responsible for development of a disease
 Hit
 A test protein, peptide or compound that appears to act on targets.
 Lead
 Of the numerous hits or variants, the protein, peptide or organic
compound that show the highest degree of activity against the disease
 Candidate
 A protein, peptide or organic compound that has most or all of
properties of a desired therapeutic (a development candidate) agent
 IND
 Investigational New Drug application, filed for first human test
 Product
 A marketed therapeutic agent
From Drug and Biological Development by R.P. Evens

15. Terms used in drug discovery
►Target identification:
 You investigate potential targets, screen and prioritize
 Understand the disease process, such as up-regulation of
certain proteins in cancer cells
►Target validation:
 Identify the roles a target plays in a disease
 Use various in vitro and in vivo functional studies
►Lead identification:
 Potential therapeutics are screened and prioritized
 Utilizes knowledge of a specific target to identify/design
an appropriate agonist/antagonist
►Lead optimization/validation:
 The effects of a compound on a disease are confirmed
 You test compounds in animal models of the target
disease
 Redesign and re-assess the effects of variants of the same
compound

16. Target to candidate

17. Clinical development
 Phase I
 First studies in humans, usually healthy humans, after
obtaining an IND
 Single-dose followed by short-term multiple dose studies –
follow-up for days to weeks
 Phase II
 Determine effectiveness in conditions or diseases of
interest
 Phase III
 Confirm effectiveness in larger studies
 Phase IV
 Post-approval studies

18. Clinical trials
Pre
Clinical
Testing
FILE
IND
Phase I Phase II Phase III
FILE
NDA
FDA Approval
Years 3.5 1 - 2 2 - 4 4 - 6 1.5 Total = 12 -
17
Test
Population
Laborator
y and
Animal
Studies
20 to 100
Healthy
Volunteers
100 – 300
Patient
Volunteers
1,000 to 3,000
Patient Volunteers
Review
Post Marketing
Safety
Monitoring
Purpose
Assess
Safety
and
Biological
Activity
Determine
Safety and
Dosage
Evaluate
Effectiveness.
Look for Side
Effects.
Verify Effectiveness,
Monitor Adverse
Reactions from
Long-Term Use
Process
Large Scale
Manufacturing
--------------
Distribution
--------------
Education
%
of
all
new
drugs
that
pass
70% of INDs 30% of INDs 27% of INDs 20% of
INDs

19. Preclinical and clinical
development

20. Drug discovery timeline

21. Generic drug development
Does not involve
preclinical
development or drug
discovery process
Requires
bioequivalence study
or data showing that
the product is as
efficacious as its
brand counterpart

22. Generic drug development

23. Brand, Generic and biosimilars
 Brand
 Innovator’s product
 Innovators has the exclusive patent
 Nobody, but the innovator can make or sell during a certain time
 Generics
 The Hatch-Waxman Act of 1984 allows drug companies to copy an
innovator’s product when the patent expires
 Much cost effective
 Chemically identical to the original branded drug.
 Biosimilars
 Since biologics may not be an exact copy of the innovators’ product,
the generics of biologics are NOT called generic products, called
biosimilars
 They have the same clinical effect as that of innovators’ product, but
one cannot confirm that the chemical identity of the generic product
is the same as that of the innovator’s product

24. Review
Preclinical studies are performed in -------
Clinical studies are performed in -------- at --
------different phases
The correct definition of the term ‘hit’ is…..
 A protein, enzyme, receptor, signaling or other
molecule that may play a role in a Particular
disease process
 A test protein, peptide or compound that
appears to act on targets

25. Good manufacturing practices
(GMP)
 “A system to ensure that products are consistently produced
and controlled according to quality standards.
 Minimize the risks involved in any pharmaceutical production
that cannot be eliminated through testing the final product.
 Covers all aspects of production from the starting materials,
premises and equipment to the training and personal
hygiene of staff.
 Detailed, written procedures for each process that could
affect the quality of the finished products
 Provide documented proof that correct procedures are
consistently followed at each step in the manufacturing
process” (ISPE Website)

26. Good laboratory practice (GLP)
 A Federal regulation concerning the minimum quality
standards that pharmaceutical laboratories should adhere
to regarding the following:
 Personnel
 Management
 Quality assurance
 Facility
 Equipment
 Procedures required
 Testing issues
 Records and Reports

27. Good clinical practice (GCP)
 A set of standards for the design, conduct, performance,
monitoring, auditing, recording, analysis and reporting of
clinical trials or studies.
 Addresses:
 Ethical conduct of clinical trials
 Institutional approval prior to initiation of a trial
 Qualification to perform trials
 Informed consent
 Data quality and integrity
 Protects confidentiality of records
 Investigational products conform to GMP’s and used per
protocol

28. Drug product and drug substance
 Drug substance
 An active ingredient that produces
pharmacological action or other direct
effect in the diagnosis, cure, mitigation,
treatment, or prevention of a disease
 Does not include intermediates used in the
synthesis of such an ingredient.
 Drug product
 A finished dosage form, for example,
tablet, capsule, or solution, that contains a
drug substance, generally, but not always,
in association with one or more inert
ingredients.

29. Dosage forms
 You cannot administer drugs in their natural or pure state.
 You administer drugs with other pharmaceutical ingredients
in different forms, called dosage forms.
 Examples: tablets, capsules, injections, syrup, elixir
 We need a dosage form to
 Administer an accurate dose of a drug that would be safe
and convenient
 Ensure patient compliance, e.g. pediatric/geriatric
patients may have difficulty swallowing solid dosage
forms
 Protect the drug against chemical decomposition from
both the external (atmospheric oxygen and humidity)
and internal (gastric acid) environments
 Conceal any unpleasant odor or taste
 Ensure or control the release of drugs into the body

30. Dose, dosage forms and strengths
 An amount of a drug that
is enough to produce a
therapeutic response
without producing toxic
effects
 The amount of drug that
produces desired effect in
most adult patients is used
as the drug’s adult dose
 You should not confuse
the term ‘dose’ with
‘dosage form’ and ‘dose’
with strengths
 A drug product may be
available in different
strengths, your physician
chooses a dose for you

31. Review
 Which of the following statements are not correct
o A. Drug substance is the same as active
ingredient
o B. Tablet is a drug product
o C. The terms ‘drug product’ and ‘drug substance’
can be used interchangeably’
o D. Prodrugs requires bio-transformation to
become active
o E. ‘Dose’ and ‘Dosage forms’ are used as
synonyms

32. Review
 A dosage form offers which of the following
advantages?
o A. Provides a safe and convenient means of
administering a drug
o B. Enhances patient compliance,
o C. Protects the drug against chemical
decomposition
o D. Conceals any unpleasant odor or taste
o E. Ensures or control the release of drug into
the body
o F. All of the above

33. Review
Identify the correct statement:
o Some prescription drugs may not require FDA
registration
o Phase III trial is performed after FDA approval
of a drug
o Generic drug development involves all the steps
that are required for a brand drug
o Mutagenicity studies are performed in healthy
humans

34. Drug formulations
 A recipe or formula for a dosage
form that includes the following
information
 Name and quantities of ingredients
 Mixing sequence
 Processing steps
 A recipe for preparation of a
drug product is called
formulation
 A pharmaceutical formulation
contains
 One or more active ingredient
(Drug)
 Many additives called excipients

35. Drug formulations
 An optimized drug product should take into
account all factors to ensure maximal
effectiveness, the primary objective, along with
safety and reliability, the secondary objectives
 Important factors for drug formulations
 Drug factors
 Physical-chemical properties of the drug substance
 Therapeutic considerations
 Disease and patients
 Bio-pharmaceutic considerations
 Factors that affect absorption of a drug substance from
various routes of administration.

36. Ingredients in a drug product
 A drug product contains two groups of ingredients
 Active ingredients: one or more
 Responsible for pharmacological effects
 Inactive ingredients, called excipients
 Excipients do not have any pharmacological
effect
 Excipients contribute to the
• Physical form
• Texture
• Stability
• Taste
• Overall appearance

37. A drug formulation

38. Drug nomenclature
 Proprietary (Brand) names
 A trademark officially registered (®) by a company
• Example: Tylenol® from Johnson & Johnson
 Non-proprietary (Generic) names
 The generally recognized or "common" name for a drug
 Standardized nomenclature established by:
• USAN Council (United States Adopted Names)
• WHO (World Health Organization)
• Example, acetaminophen
 Generic products
 A copy of a brand drug product, comprising the same
active ingredient(s), strength, and dosage form.
• Tylenol from Walgreen

39. Review
Identify true or false statements
o A. Proprietary name is the chemical name of a
drug
o B. The terms, ‘generic name’ and ‘generic
product’ describe the same nomenclature
o C. Generic name is the common name of a drug
o D. Generic product is an imitation of a brand
product

40. Drug class according to the food
and drug act
 OTC Drugs
 Not considered dangerous for self-medication and you
can get these drugs without a prescription
 Legend Drugs
 “Caution: Federal Law prohibits dispensing w/o
prescription“
 Refills have to be authorized
 Controlled or scheduled Drugs
 These drugs have potential for abuse
 DEA enforces these drugs
 Schedules I to V with decreasing levels of control

41. Controlled or scheduled drugs
 Schedule I
 Drugs with no accepted medical use and high potential
for abuse
 Heroin and LSD (Lysergic acid diethylamide)
 Schedule II
 Drugs with accepted medical use(s) but still have high
potential for abuse
 Causes severe psychological and physical dependence
 Amphetamine, morphine, oxycodone, and cocaine

42. Controlled or scheduled drugs
 Schedule III
 These substances have an abuse potential less than
those in Schedules I and II
 Cause moderate or low physical dependence or high
psychological dependence
 Anabolic steroids and products containing not more than
90 mg codeine in a dosage unit or products containing
less than 15 mg hydrocodone per dosage unit
 Any products containing amobarbitol, secobartibal or
ketamine

43. Controlled or scheduled drugs
 Schedule IV
 Less potential for abuse than I, II, and III
 Cause limited psychological and physical dependence
 Benzodiazepines and phenobarbital
 Schedule V
 Least potential for abuse
 In many states, you can get these drugs without a
prescription after signing a log book
 Certain anti-cough preparations containing not more
than 200 mg codeine in each 100 mL or 100 g
(promethazine or guaifenesin with codeine)

44. Reviews
Which of the following drug class has the
least potential for abuse.
o A. Schedule I
o B. Schedule II
o C. Schedule III
o D. Schedule IV
o C. Schedule V

45. Drug standards and
pharmacopeias
 Drugs and drug products must meet certain
requirements for purity, strength, labeling,
packaging and stability.
 We have monographs and reference books that
describe standards that manufacturers should
maintain when they prepare drug products
 Organized sets of monographs or books of these
standards are called pharmacopeias
 They are also called official compendia because
they are considered as legal standards

46. The United States Pharmacopeia
 The term pharmacopeia comes
from Greek ‘pharmacon’ meaning
drug and poiein = meaning make.
 The term pharmacopeia suggest
any recipe or formula or other
standards required to prepare a
drug
 First used in 1580 in Italy
 First United States Pharmacopeia
(USP) was published in 1820.
 Dr. Lyman Spalding, a physician
from New York, is recognized as
the Father of the United States
Pharmacopeia

47. The National Formulary
National Formulary (NF) was first published
in 1888
NF was first edited by pharmacists and
listed many drugs that USP did not list
In 1975 , USP and NF were merged into a
single book and first combined compendium
was published in 1980
USP contains information on drug
substances, but NF has information
regarding pharmaceutical ingredients

48. The United States Pharmacopeia
 The USP, a non-governmental agency, sets
standard for prescription and over-the-counter
medicines, dietary supplements, and other
healthcare products
 The USP helps healthcare providers reach the
standards.
 More than 130 countries recognize USP standards
 USP is a science-based public health organization,
not belongs to any agency of the US government

49. Other pharmacopeias
British Pharmacopeia
European Pharmacopeia
International pharmacopeia
Many countries have their own
pharmacopeias

50. USP MONOGRAPHS
• http://www.usp.org/USPNF/understanding
USPNF.html
http://www.usp.org/sites/default/files/usp_pd
f/EN/products/sample_monograph_35-30.pdf

51. Reviews
 Identify the correct statements
o A. USP is a reference book that establishes standards
to be used by the manufacturers to prepare drug
products
o B. USP is an independent, science-based public health
organization.
o C. Monographs of drug substances are in the USP
section and that of pharmaceutical ingredients are in NF
section
o D. USP is the only pharmacopoeia in the world
o E. USP is used only in the United States
o F. Monographs of USP mainly describes use of drugs