DRUG DELIVERY

SYSTEMS
COVERAGE
• PRELIM- 100% prelim coverage
• MIDTERM- 90% Midterm coverage
• FINAL- 80% Final, 10%prelim, 10% midterm
DRUG
Development of The Practice
of Pharmacy
Papyrus Ebers
Papyrus Ebers
•a continuous scroll some 60 ft.
long and a foot wide dating back
the 16th century BC
Hippocrates
• Greek physician who is credited with the introduction of
scientific pharmacy and medicine.
• Known as the Father of Medicine
Theoprastus
• Greek physician and botanist who was the first to deal with
botany as an applied science of pharmacy.
• He is the Father of Botany
Dioscorides
• He contributed his work De Materia Medica which
led to the development of pharmaceutical botany
and the study of naturally occurring medicinal
plants (pharmacognosy).
*pharmakon – drug
* gnosis - knowledge
 Claudius Galen
• Greek pharmacist-physician who
attained roman citizenship.
• He originated so many preparations of
vegetable drugs by mixing and melting
the individual ingredients, which were
later referred to as Galenic Pharmacy.
Claudius Galen
• His most famous formula, cold cream, is called Galen’s Cerate
Emperor Frederick II
• Proclaimed a decree that would separate PHARMACY from
MEDICINE in 1240AD
Aureolus Philipus Theophrastus
Bombastus von Hohenheim
• also called Paracelsus
• a swiss physician and chemist who introduced chemical
science from the traditional botanical science
 Karl Wilhelm Scheele
• Swedish pharmacist who discovered the following
organic acids: lactic, tartaric, citric, oxalic.
• And also the arsenic acid, he identified glycerin, invented
new methods of preparing calomel and benzoic acid.
• Discovered OXYGEN a year before Priestly
Friedrich Serturner
• German pharmacist who isolated
morphine from opium
Pierre Robiquet

•isolated codeine from opium

Joseph Caventou and Joseph Pelletier
• isolated quinine and cinchonine from cinchona and;
• strychnine and brucine from nux vomica
Robiquet and Pelletier

• isolated caffeine
Philadelphia College of Pharmacy
•the first school of pharmacy
established in 1821
Drug Standards

• The scientific basis for drugs and drug

products developed.
• To ensure quality
Pharmacopeias/ Formularies
• Organized sets of
monograph or books
of these standards.
Official Compendia

•The term pharmacopeia comes

from the Greek word “pharmakon” (
drug) and “poiein” (make)
Official Compendia

•1778, the First American

Pharmacopoeia called “LITITZ
PHARMACOPOEIA” published in Lititz
Pennsylvania for use by the Military
Hospital of the US Army.
Official Compendia

•1864, the first British Pharmacopeia

(replacing London, Edinburgh, and
Dublin)
Official Compendia
• 1817, Dr. Lyman Spalding proposed the
creation of national pharmacopeia. He
was called “the father of USP”
Official Compendia

•1820, the first USP was published in

English and Latin
Official Compendia
• 1888, the first National Formulary was published under the title
“National Formulary of Unofficial Drugs”
• Then was later changed to “National Formulary” on June 30,
1906.
Official Compendia
• 1940, it was agreed upon that revision
shall be made every 5 years which was
used to be 10 years
Official Compendia

•July 1, 1980, the first combined

compendium (USP XX and NF XV)
was published
• the official compendium contains drug
monographs which assured availability
of quality drugs and pharmaceutical
products.

• USP-NF38
Monograph
1. Official title
2. Synonyms
3. Chemical formula
4. Purity rubric
5. Packaging and storage
6. Reference standards
7. Labeling
8. identification and preparation before use
9. Identification
10. Assay
11. Other references: USP DI, Homeopathic
Pharmacopeia of the United States (HPUS),
International Pharmacopeia, BP, EP, JP
• Quiz next meeting :
• Post quiz on development and practice of pharmacy
• PreQuiz on Chapter 1
Requirement:
• DDS notebook- project
 New Drug
Development
Process
 ADME

Efficacy

Safety

Toxicology
 Sources of New Drug
• Plant kingdom
• Animal sources
• Microbiological world
• Biological source
 Plant Source
• Rauwolfia serpentina
– (reserpine) tranquilizer and
hypotensive agent
• Vinca rosea (Periwinkle)
– For diabetes mellitus
• Vinblastin and Vincristine
– For cancer
• Pacific Yew Tree
– For ovarian cancer
 Animal Source
• Endocrine glands of cattle, sheep
and swine
–Thyroid extract, insulin and pituitary
hormone (replacement therapy)
• Pregnant mares
–Source of estrogens
 Microbiological Source
• penicillin, cephalosphorin,
tetracyclines,
aminoglycosides, lovastatin
 Biological source
• vaccines (living, attenuated
or killed microorganisms)
 Goal Drug
• Produce specifically the desired effect
• Administered by the most desired route
• Minimal dosage and dosage frequency
• Have optimal onset and duration of
activity
• Exhibit no side effects
• Would be eliminated completely and
without residual effect
 Discovery
• Synthesis, isolation, fermentation,
screening, SAR studies

Choosing a disease – focus is on the

financial return
Choosing a drug target – receptor,
enzymes and nucleic acid
DISCOVERING DRUG TARGETS
• Depend on finding the drug first
• Discovery of the chemical
messenger
• Genome projects
 Identifying a bioassay
• In vivo test – inducing a clinical
condition and treated with the
test drug
• In vitro test – drugs activity is
tested on isolated tissues, cells
or enzymes
 Lead Compound
• A prototype chemical compound
that has a fundamental desired
biologic or pharmacologic activity.
 Prodrugs
• A compound that requires
metabolic biotransformation
after administration to
produce the desired
pharmacologically active
compound.
Preclinical Studies
• chemical and physical
characterization
• pharmacology
• pharmacokinetics
• pharmacodynamics
• pharmaceutics
• analytical studies
• toxicology
 Preclinical Studies
• Pharmacology – the science of
the properties of the drugs and
its effects in the body

• Pharmacodynamics – the study

of the interaction of drugs with
cells
 Preclinical Studies
• Pharmacokinetics – the
handling of a drug within the
body, it includes the ADME
processes

• Toxicity testing – in vitro and in

vivo testing, determination of LD
50
 Preclinical Studies
• Pharmaceutics – the general
area of study concerned with
the formulation, manufacturing
stability and effectiveness of a
pharmaceutical dosage form
 Preformulation
• The characterization of the
physical and chemical
properties of the active drug
substance and dosage form.
• Performed during the
preclinical stage.
 File IND Application
• Patent the drug – an exclusive rights
to the use and profits of a novel
pharmaceutical for a limited term

Special consideration is given on

Orphan drugs
ORPHAN DRUG
• Orphan disease is defined as a rare disease or
condition that affects fewer than 200,000 people
in the United States (chronic lymphocytic
leukemia, Gaucher disease, cystic fibrosis, and
conditions related to AIDS)
ORPHAN DRUG
• The FDA provides support grants to conduct
clinical trials on safety and effectiveness.
Clinical Studies

Phas
Phas eV
Phas e IV
Phas e III
Phas e II
eI
 Phase I
• 20 – 100 healthy volunteer
• Tolerance and safety
• Toxicological studies
 Phase I
• Human pharmacology
• Structure-activity relationship
• Side effects associated with
increasing dose
• Evidence of effectiveness
 Phase I
• Data collected:
– Rate of absorption
– Concentration of drug in the blood over time
– Rate and mechanism of drug metabolism
and elimination
– Toxic effects
– Changes in physiologic processes from
baseline
 Phase II
• 100 – 300 first controlled studies on
patients
• Efficacy and therapeutic index
 Phase III
• 1000 – 3000 extended clinical trials
• dose, efficacy, toxicity and side
effects
• Performed with the final dosage
form developed in phase II
• Side effects are monitored
Clinical Research Phase Studies
 Phase 1
Patients: healthy volunteers.
Length of Study: Several months
Purpose: Safety and dosage
Percentage of Drugs that Move to the next Phase 70%
Phase 2
Patients: Up to several hundred people with the disease/condition.
Length of Study: Several months to 2 years
Purpose: Efficacy and side effects
Percentage of Drugs that Move to the Next Phase 33%
Phase 3
Patients: volunteers who have the disease or condition
Length of Study: 1 to 4 years
Purpose: Efficacy and monitoring of adverse reactions
Percentage of Drugs that Move to the Next Phase 25-30%
Submission of a New Drug Application

• Submitted to the FDA for review and

approval
• Product is effective by all
parameters
NEW DRUG Application (NDA)
• is submitted for review and approval after the completion of the
clinical trials and requirements have been met.
• Also, when the preclinical and clinical studies have proven the
IND’s effectiveness and safeness by all parameters
 ANDA
• ABBREVIATED NEW DRUG APPLICATION
• is one in which nonclinical laboratory studies and clinical investigations may
be omitted, except those pertaining to the drug’s bioavailability.
• These applications are usually filed for duplicates (generic copies) of drug
products previously approved
 Phase IV
• “Scaleup activities”
• Scaleup – increase in the batch size
from the clinical batch, submission
batch, or to the full-scale production
batch size, using the finished,
marketed product.
• *Postmarketing studies only
• Drug Approval for marketing
• Phase 4 or also known as post-marketing studies and
manufacturing scale-up activities take place
• Modification on drug formulation as obtained from
manufacturing scale-up and validation process may be
done
• Product development may continue.
 Phase V
• Drug product may be improved
• Additional clinical studies
Clinical Research Phase Studies
 Phase 1
Patients: healthy volunteers or people with the disease/condition.
Length of Study: Several months
Purpose: Safety and dosage
Percentage of Drugs that Move to the next Phase 70%
Phase 2
Patients: Up to several hundred people with the disease/condition.
Length of Study: Several months to 2 years
Purpose: Efficacy and side effects
Percentage of Drugs that Move to the Next Phase 33%
Phase 3
Patients: volunteers who have the disease or condition
Length of Study: 1 to 4 years
Purpose: Efficacy and monitoring of adverse reactions
Percentage of Drugs that Move to the Next Phase 25-30%
SNDA
• SUPPLEMENTAL NEW DRUG APPLICATION
• A file applied to make changes to the application of a new drug
• Some needs FDA approval others do not
Treatment IND
• Permits the use of an investigational drug in the
treatment of patients not enrolled in the clinical
study but who have a serious or immediately life
threatening disease for which there is no
satisfactory alternative therapy
“immediately life threatening”
• a stage of a disease in which there is a reasonable
likelihood that death will occur within a matter of
months or in which premature death is likely without
early treatment
(Advanced cases of AIDS, herpes simplex encephalitis,
advanced metastatic refractory cancers, bacterial
endocarditis, Alzheimer disease, advanced multiple
sclerosis, advanced Parkinson disease)
Drug Regulation and
Control
Federal Food, Drug and Cosmetics Act
1938
• Additional standards were set DUE TO SULFANILAMIDE INCIDENT
• Requires filing of a NDA
• Assures products are safe for human use
 Durham-Humphrey Amendment
1952
• Drug products were categorized into Rx and OTC
• Rx drugs may only be refilled upon consent of the prescriber

 “Rx Only”
 “Caution: Federal Law Prohibits Dispensing Without Prescription”
 Kefauver – Harris Amendment
• Initiated by the 1960 tragedy
• Thalidomide as OTC (sedative and tranquilizer)
• Enacted to ensure greater degree of safety for approved drugs
• Requires filing for IND
• Drugs safety and effectiveness
Comprehensive Drug Abuse
Prevention and Control Act of 1970

• Control on drugs of abuse

• Led by DEA in DOJ
• Classified the controlled substances
• Schedule I : no accepted medical use, high potential for
abuse
• Heroin, LSD, mescaline, marijuana
• Schedule II: accepted medical use, high potential for abuse –
may lead to psycho or physical abuse
• Morphine, cocaine, methamphetamine
• Schedule III: medical use, less potential for abuse
• Codeine, hydrocodone
• Schedule IV: accepted medical use, low potential for abuse
• Diphenoxin, diazepam
• Schedule V: accepted medical use, low potential for abuse
• Dihydrocodeine, diphenoxylate
Other Law
• Drug Listing Act
• Drug Price Competition and Patent Restoration Act
• Prescription Drug Marketing Act
• Dietary supplement Health and Education Act
• FDA Modernization Act
Drug Product Recall
• Class I – cause serious adverse effects or death
• Class II – cause temporary or medically reversible adverse
health consequences
• Class III – not likely to cause adverse health consequences
• Pre quiz on Dosage form
• Post quiz in NDDP
Solid Dosage Forms
Powders and Granules
• “powder” refers to a chemical or mixture that
is solid in physical state. chemicals that are
intended for internal ( ORAL ) or external (
TOPICAL ) use.
Advantages
• each dose can contain a different amount of
active drug
• can be administered easily to infants and
young children who cannot swallow tablets
or capsules
• drug will have a rapid onset of action since
disintegration is not required
Advantages
• drugs tend to most stable as a solid
• can be made into many different dosage
formulations (capsules, tablets, powders for
reconstitution, dusting powders, bulk
powders, powders for inhalation, etc.)
Disadvantages
• Patient misuse
• Limited only to good tasting drugs
• Difficulty in protecting from decomposition
specially for hygroscopic, deliquescent or
aromatic materials
• eutexia
Description of powder
• as fine particles
• are smooth to the touch and nonirritating to
the skin.
• generally range from 0.1 to 10 micron in size
Powder Fineness (USP24/NF 19)
Mesh Size Mesh Opening
Description Term
Number Size (μ)
Very Coarse >1000 2-10

Coarse 355-1000 20-40

Moderately 180-355 40-80

Coarse
Fine 125-180 80-120

Very Fine 90-125 120-200

Comminution Methods
• COMMINUTION
– is the mechanical process of reducing
the size of particles or aggregates.

.
Comminution Methods
1. Trituration
• is thecontinuous rubbing or grinding of the
powder in a mortar with a pestle. This method is
used when working with hard, fracturable
powders.
2. Pulverization by Intervention
is used with hard crystalline powders that do
, or gummy-type
not crush or triturate easily
substances
Comminution Methods
3. Levigation
• reduces the particle size by triturating it in a
mortar or spatulating it on an ointment slab or
pad with a small amount of a liquid (levigating
agent: glycerin and mineral oil) in which the solid
is not soluble.
• used most often when incorporating solid
ingredients into semisolids
• Ointments ,creams and suspensions
Methods on Blending
Powders
• 1. Spatulation
• mixing is with the aid of a spatula
• not suitable for large quantities of powders
• suitable for powders capable of forming eutectic
mixtures
Methods on Blending
Powders
2. Trituration
• for comminution and mixing as well
Methods on Blending
Powders
• 3. Geometric Dilution
• for potent substance mixed with large amounts
of diluents (to ensure uniform distribution of
potent drug)
Methods on Blending
Powders
• 4. Sifting
• Using sifters to produce light, fluffy powders
Methods on Blending
Powders
• Tumbling
• Large containers which rotates generally by a
motorized process
Types of powder papers:
Types of powder papers:
• Vegetable parchment – a thin, semi-opaque,
moisture resistant paper
• White bond - an opaque paper with no
moisture-resistant effect
• Glassine – a glazed, transparent, moisture
resistant paper.
• Waxed – transparent, water-proof paper
SHORT QUIZ 
Bulk Powders
• are _____________ and can be dosed with
acceptable accuracy and safety using
measuring devices such as theteaspoon,
cup, or insufflator
Classifications of Bulk
Powders
• 1. Oral powders
– Intended for __________ administration
Classifications of Bulk
Powders
• 2. Dentrifices
– contains, soap or detergent, mild
abrasives and anti-cariogenic agent
intended to be placed on wet
________________ to clean the teeth
Classifications of Bulk
Powders
• 3. Douche powders
– are used to prepare solutions that
cleanse the ____________
– very soluble and are intended to be
dissolved in water prior to use as
antiseptic for cleansing of body cavities.
– Most douche powders are used for their
hygienic effects, but a few contain
antibiotics
Classifications of Bulk
Powders
• 4. Dusting powders
– fine medicinal (bulk) powders intended to
be dusted on the ________by means of
_____________________containers.
Classifications of Bulk
Powders
• 5. Insufflations
– are ___________ fine powders to be
introduced into body cavities.
– All extemporaneously compounded
insufflations must be passed through a
________________________.
Classifications of Bulk
Powders
• 6. Triturations
– dilutions of potent powdered drugs
prepared by intimately mixing them with
a suitable diluent in
_____________dilutions with the aid of
_________________
Classifications of Bulk
Powders
• 7. Powder sprays
– In contrast to dusting powders, powders
dispensed under ______________ will
deliver targeted and uniform application
at the desired site.
– powders that are to be packaged as
powder sprays must not contain particles
greater than 50 microns
Dry Powder Devices
• 1. Diskhaler
• the drug is supplied in small blisters in a
_________, foil container. The ____________is
loaded in the device and punctured when
required for use
Dry Powder Devices
• 2. Rotahaler
• the drug is presented as __________and inserted
in the device. The device is twisted which splits
the capsule in two and the powders are inhaled
through the _____________
Divided Powders
• CHARTULAE; CHARTS; POWDER
PAPERS
• single doses of powdered medicinals
individually wrapped in cellophane, metallic foil,
or paper
• usually prepared by weighing or block and
divide method
Granules
• are particles ranging in size of ______________
• Granules generally are made by first blending the powders
together and then moistening the mixture to form a pasty mass.
The mass is passed through a sieve and then dried in air or in an
oven
Granules
• The most popular compounded granulation is the
Effervescent Powder (sometimes called ______________).
• These granulations are popular due to their taste and
psychological impression. When added to water, the granulation
effervesces ("fizzes") as _______________is liberated
Effervescent Powders
• citric acid monohydrate and tartaric acid
used in the ratio of 1:2
• Sodium bicarbonate reacts with both of the
acidsto produce ______________

• Citric acid alone – sticky

• Tartaric acid alone – friable and crumble
Effervescent Powders
• Prepared by two methods:
• Dry or Fusion Method
• Wet Method
Capsules
• are solid dosage forms in which one or more medicinal or inert
substances are enclosed within a _________________
Gelatin
• obtained by the partial hydrolysis of
collagen obtained from the skin, white
connective tissue, and bones of animals.
• Type A = pork skins by ________hydrolysis
• Type B = bone and animal skin by _________
hydrolysis
Hard Gelatin Capsules
• Dry Filled Capsules
• Empty hard capsule shells
are manufactured from a
mixture of gelatin, colorants,
and sometimes an
opacifying agent (titanium
dioxide); 0.15% sulfur
dioxide (USP) to prevent
decomposition of gelatin
during manufacture
Hard Gelatin Capsules
• Contains 12%-16% water,
varying with the storage
conditions.

• humidity is low  brittle

• humidity is high
 flaccid and shapeless
Capsule Sizes
CAPSULE SIZE RANGE OF POWDER CAPACITY
(MG)

No. 5 60-130
No. 4 95-260
No. 3 130-390
No. 2 195-520
No. 1 225-650
No. 0 325-910
No. 00 390-1300
No. 000 650-2000
Soft Gelatin Capsules
• Soft Elastic Capsules
• oblong, elliptical, or spherical in
shape, may be used to contain
liquids, suspensions, pasty
materials, dry powders,
or pelletized materials
Soft Gelatin Capsules
• prepared from gelatin shells to which glycerin or a
_______________(e.g., sorbitol) has been added (rendering them
elastic or shell like), these shells also contain preservatives (e.g.,
methyl and propyl parabens, sorbic acid) to prevent the growth
of fungi
Methods of Preparation:
• Plate Process
• Rotatory Die Process
• Developed by Robert Scherer
• Most common
• Reciprocating Die Process
 SGC can enclosed the ff liquids:
• Water immiscible, volatile and nonvolatile liquids such as
vegetable and aromatic oils, aromatic and aliphatic
hydrocarbons, chlorinated hydrocarbons, ethers, esters,
alcohol and organic acids.
• Water miscible, nonvolatile liquids such as polyethylene
glycols, and nonionic surface-active agents as ______________.
Specially-designed capsules
• Spansule
• Pulvule
• Kapseal
• Coni-snap
Test for Capsules
• Disintegration Test
• Dissolution Test
• Weight Variation Test
• Content Uniformity