PHARMACEUTICS 21 | LECTURE

CHAPTER 1: INTRODUCTION TO DRUGS & PHARMACY

1ST SEMESTER | S.Y. 2022 – 2023
LECTURER: IVORY DIANE C. AMANCIO

WHEN DO WE NEED TO USE DRUG for MEDICATION? AYURVEDA

➢ For treatment of a certain disease.
➢ For prevention of diseases
➢ Use in the diagnosis for disease
FOOD DRUG AND COSMETIC ACT OF 1938
➢ A drug is defined as an agent intended for use in the
diagnosis, mitigation, treatment, cure, or
prevention of disease in humans or in other animals.
DIVERSITY OF DRUGS
➢ This quality enables their selective use in the
treatment of a range of common conditions
involving every body organs, tissues, and cell.
DRUGS ARE SELECTIVE
➢ Mydriatic - ex. Oxytocin
➢ Sleep Hormone – ex. Melatonin
➢ Antidepressants – ex. SNRIs
➢ Miotics (parasympathomemetics) – ex. Pilocarpine
DRUG DISCOVERY AND DEVELOPMENT
HERITAGE OF PHARMACY
TRADITIONAL MEDICINE
➢ Drug existed along with human existence
(vegetation and minerals)
➢ The instinct to survive from a disease led to their
discovery throughout the ages
➢ Includes spiritual therapies, manual techniques and
exercises and applied singularly or in combination to
treat, diagnose and prevent illnesses or maintain
well-being
➢ Examples:
o bathing wounds to cool water
o Use of fresh leaf for soothing pain
o Decoction of fresh leaves to relieve cough
➢ traditional Hindu system of medicine, which is
based on the idea of balance in bodily systems
and uses diet, herbal treatment, and yogic
breathing.
NATUROPATHY
➢ system of alternative medicine based on the
theory that diseases can be successfully treated
or prevented without the use of drugs, by
techniques such as control of diet, exercise, and
massage.
HOMEOPATHY
➢ the treatment of disease by minute doses of
natural substances that in a healthy person would
produce symptoms of disease.
THE FIRST APOTHECARY
APOTHECARY
➢ is the art of preparing medicinal material from
plants.
QUALIFICATIONS:
➢ Who have Knowledge of the healing qualities of
plants and been gathered through experience or
handed down by word of mouth.
➢ Must have a connection with the world of spirits
and thus perform as intermediates between the
seen and the unseen.

SPIRITUAL INCANTATIONS
SHAMANISM
➢ conducted by a Shaman
➢ The goal of this is usually to direct these spirits or
spiritual energies into the physical world, for healing
or some other purpose SUCCESS OF THERAPY:
➢ Depends on compassion of a god, the observance of
TRADITIONAL ALTERNATIVE MEDICINE ceremonies, the absence of evil spirits and the
healing intent of the dispenser
ACUPUNCTURE
➢ involves pricking the skin or tissues with
needles, used to alleviate pain and to treat
various physical, mental, and emotional
conditions.
 EARLY DRUGS DIOSCORIDES
GEORGE EBERS ➢ Greek Physician and Botanist
➢ discovered an Egyptian papyri, whose contents ➢ First to deal botany as an applied science of Pharmacy
concerned with medical matters in 1875.
MATERIA MEDICA
EBERS PAPYRUS ➢ Study of naturally occurring, medicinal plants
➢ is a scroll 20,23 meters in length and contains ➢ Known as Pharmacognosy today
108 columns of text. I is dated at the reign of ➢ the area of identifying and collecting natural drug
Amenophis (1536 B.C.) products, the methods of their proper storage and the
➢ 800 +drug formulas means of detecting adulterant or contaminants
➢ 700+ drug mentioned
MASTER FORMULA: PHARMACOGNOSY EXTRACTION METHODS
Botanical Agents Binder: Acacia MACERATION
Emulsifying/Stabilizing agent: Castor Bean (we make ➢ is an extractive technique that is conducted at room
castor oil) temperature. It consists of immersing a plant in a liquid
Aromatic flavor: Fennel (water, oil, alcohol, etc.)
Minerals: Iron Oxide, Sodium Carbonate, Sodium
Chloride, Sulfur
Vehicles: Beer, Milk, Honey, Wine

ANIMAL EXCREMENTS

PERCOLATION
➢ comes from the Latin word percolare, which means "to
➢ The History channel lists human and animal strain through."
➢ happens when liquid is strained through a filter, like
excrement as a favorite of ancient Egyptian
doctors for both diseases and injuries, and it when someone makes coffee.
wasn’t necessarily a bad thing.
➢ “Donkey, dog, gazelle and fly dung were all
celebrated for their healing properties and their
ability to ward off bad spirits. While these
repugnant remedies may have occasionally led
to tetanus and other infections, they probably
weren’t entirely ineffective — research shows
the microflora found in some types of animal CLAUDIUS GALEN
dung contain antibiotic substances.” ➢ Greek Pharmacist
➢ And the BBC notes that the ancient Egyptians ➢ Create perfect system of physiology, pathology and
used crocodile dung as a form of contraception, treatment.
among the various materials they tried. ➢ His medical writings includes descriptions of
numerous drugs of natural origin with drug formulas
INTRODUCTION OF SCIENTIFIC VIEW POINT and methods of compounding.
➢ Notable individuals that contributes a
revolutionary influence in the Development of GALENIC PHARMACY
Pharmacy and Medicine: ➢ Preparations o vegetable drugs by mixing or melting
HIPPOCRATES the individual ingredients.
➢ Greek Physician ➢ Galenical (dosage forms)
➢ Introduce scientific pharmacy and Medicine
➢ Gives description to hundreds of drugs

PHARMAKON
➢ Came to mean purifying remedy for GOOD
ONLY, transcending the previous connotation of
a charm or drug for good or for evil purposes
 PARACELSUS
➢ Aureolus Theophrastus Bombastus von Hohenheim
(1493-1541)
➢ Swiss Physician and Chemist
➢ Transformation of Pharmacy profession based
primarily on Botanical Science to one based on
Chemical Science.
➢ He believed that it was possible to prepare a
specific medicinal agent to combat each specific
disease and introduced a host of chemical
substance to internal therapy
DRUG STANDARDS
PHARMACOPEIA OR FORMULARIES
PHARMACOPEIA
➢ An organized sets of monographs or books
containing standards in the production of drugs
and Pharmaceutical Products
➢ Pharmakon (drug) ; Poiein (make)
➢ Means any recipe or formula or other standards
required to make or prepare a drug.
USP AND NF MONOGRAPHS
1852
o American Pharmaceutical Association (APhA)
made the 3rd revision of the USP as a therapeutic
guide to medical profession ; and was restricted
to drugs with established therapeutic merit.
1888
o National Formulary of Unofficial Preparations
June 30,1906
o National Formulary signed by president Theodore
Roosvelt that USP and NF are two legal standards
for medicinal and Pharmaceutical Substances.
➢ Law required that whenever the designation of
USP and NF was used or implied on drug labeling,
product must conform to the Physical and
Chemical standards set forth in the compendium
monograph
➢ To avoid being deemed adulterated, drugs must
comply with compendial standards for strength,
quality or purity, unless to show respects in which
the drug differs. To avoid being deemed
misbranded, drugs recognized in the USP-NF also
must comply with compendial standards for
packaging and…
NEW DRUG APPROVAL PROCESS AND CLINICAL
TRIAL DESIGN
STEPS IN DRUG DEVELOPMENT PROCESS:
➢ Discovery and Development
➢ Preclinical Research
➢ Clinical Research
➢ FDA review, FDA post Marketing
➢ Safety Monitoring
STEP 1: DRUG DISCOVERY AND DEVELOPMENT
➢ Pharmaceutical companies generally begin the
discovery process by targeting a broad category
(cancer, cardiovascular disease) or a specific disease
state (breast cancer or hypertension)
➢ A chemical with potential therapeutic benefits, known
as the LEAD COMPOUND, must first be identified.
➢ A lead compound may be found in chemical libraries.
➢ Libraries can be searched for possible leads through
high throughput screening methods.
➢ The associated database that stores the library's
information can also provide useful information.
PROCESS OF LEAD COMPOUND
RANDOM SCREENING
➢ involves no intellectualization; all compounds are
tested in the bioassay without regard to their
structures.
➢ Thousands of new organic compounds are synthesized
and subjected to pharmacological screening
COMBINATORIAL CHEMISTRY
➢ is a laboratory technique in which millions of
molecular constructions can be synthesized and tested
for biological activity.
➢ Traditional Organic Synthesis:
A + B -> C
A (5 components) + B (10 components ) -> 50
PRIVILEGED MOTIFS
➢ Structures that might have significance for new
therapeutic agents.
LITERATURE AND PATENTS
➢ only 12% of drugs entering clinical trials result in an
approved medicine. Unlocking the power of patent
data is a smart, cost-effective way to help mitigate this
risk.
LIGAND BASED DRUG DESIGN
➢ is an approach used in the absence of the receptor
3D information and it relies on knowledge of
molecules that bind to the biological target of
interest.
 ENDOGENOUS LIGANDS
➢ are those that are produced in the body, not those
introduced into the body, such as certain drugs.
CHEMOGENOMICS
➢ is a new strategy in drug discovery which, in
principle, searches for all molecules that are
capable of interacting with any biological target.
STEP 2: PRECLINICAL TESTING
1. DISCOVERY TESTING
➢ Specifics of Compound’s properties are determined
such as:
o Mechanism of action of the drug in animal
models
o Duration of action
o Structure-activity relationships
o Compound specificity
2. CHEMICAL SYNTHESIS
➢ Adequate levels of new chemical compounds must
be produced at HIGH LEVEL of PURITY.
➢ Impurities present at concentration greater than
0.1% must be characterized and tested for toxicity.
3. FORMULATION DEVELOPMENT AND STABILITY
TESTING
➢ Physicochemical properties is determined
➢ DRUG DELIVERY SYSTEM in human is developed
during this pre-clinical testing phase
➢ Possible side effects and toxicities are noted
➢ Often times the most appropriate animal model to
predict human response is not known; thus toxicity
studies are conducted in two animal species;
rodent and non-rodent to obtain a comprehensive
view of toxicity
4. ANIMAL SAFETY TESTING
➢ To ensure limited toxicities to lead agent.
➢ Animals should be given the new drug product
must be of the same route as intended for humans.
➢ Certain dosage forms maybe difficult to administer
to animals (buccal, nasal, aerosol)
➢ Dosing studies are conducted: the highest no-effect
dose is determined.
➢ Plasma concentration of the drug are followed.
➢ Noted toxicities are correlated to the dose and/or
blood concentrations
PRECLINICAL STUDY
➢ Each year not less than 10 novel drugs are being
approved by the Center for Drug Evaluation and
Research (CDER, US-FDA).
➢ Even before it can be subjected to clinical trials,
preclinical studies are performed.
➢ only 12% of drugs entering clinical trials result in an
approved medicine.
➢ “Testing the newly discovered compound in animals
with the objective of gaining information regarding the
various aspects of the compound with respect to the
biological systems so that the same can be
extrapolated for the use of that compound in humans”
➢ Also called Translational research.
➢ It refers to the process of applying knowledge from
basic biology and clinical trials to techniques and tools
that address critical medical needs.
SCOPE OF PRECLINICAL STUDIES
1. Pharmacology - Therapeutic Activity
2. Toxicity - Hazardous acute effects
3. Pharmacokinetics - Toxic Dose
4. Scale up production - ADME of Lead compound
5. Compound’s stability - Genotoxicity
6. Development of formulation – Animal studies
MODELS FOR PRECLINICAL STUDIES
INVITRO
➢ In vitro studies are a relatively fast, simple, and cost-
efficient way of preclinical testing.
➢ it utilizes cell, tissue, and organ cultures, or focus on
particular cell components such as proteins or other
biological macromolecules.
CELL CULTURE
➢ refers to the process of cultivating cells and tissues
outside the body of an organism in an environment,
which stimulates the in vivo conditions such as
temperature, nutrition and protection from
microorganisms
IN VIVO (LIFE)
➢ More commonly used; gold-standard method of
conducting toxicity studies.
➢ It considers the complete organism based on various
animal models.
➢ The choice of appropriate animal models depends on
several criteria and requires understanding of species-
specific physiology and similarity with regard to the
target organ, metabolic pathways as well as financial,
regulatory, and ethical considerations.
➢ Similarities of conditions between human and certain
animal makes it preferable and useful during conduct
of drug research:
o High percentage of similarity in DNA of humans
o Shorter life cycle allowing a continued study of the
whole lifespan
o Environment conditions are easily controlled
 ANIMAL MODEL FOR NEUROLOGICAL ACTIVITIES
DRUG DISCOVERIES THAT INVOLVED USE OF
ANIMALS
STEP 3: CLINICAL TRIAL
➢ Documents may be submitted as hardcopy or
electronic le based-on preference of FDA and
ERB/ERC.
➢ Amendments, notifications and other reports to be
submitted to the FDA will be coursed through the
same process. Any amendment to the protocol and
accompanying documents will have to be approved by
the FDA in close coordination with the ERB/ERCs.
➢ All clinical trials are required to be uploaded in the
Philippine Clinical Trial Registry.
➢ It is the responsibility of the study sponsor to upload
information related to the clinical trial it is conducting
to the Registry
PHASE OF CLINICAL TRIAL
➢ PHASE 0 (MICRODOSING)
➢ PHASE 1
➢ PHASE III
o Phase IIIa
o Phase IIIb
➢ PHASE IV (CONTINUED CLINICAL TRIAL)
PHASE 0 (MICRODOSING)
➢ Phase 0 trials are the first clinical trials done among
people
➢ Its aim is to learn how a drug is processed in the
body and how it affects the body.
➢ In these trials, a very small dose of drug is given to
about 10 to 15 people.
PHASE 1
➢ Phase 1 administers the drug to healthy volunteers,
in some protocols, patients
➢ Phase 1 trial aim to assess the safety of the drug.
➢ The drug will be tested in a small group of 15-30
patients
➢ Starting dose is very low (1/10th of the highest no
effect dose observed during animal studies). If a
drug is found to be safe enough, it can be tested in a
phase II clinical trial
PHASE III
➢ Phase III trials enroll 100 or more patients
comparing a new drug to the standard of- care drug.
➢ These trials assess the side effects of each drug and
which drug works better.
➢ Evaluates the benefit-risk relationship of the new
drug and to file a complete NDA
PHASE IIIA
➢ data presents sufficient evidence to file NDA but the
studies are continued
PHASE IIIB
➢ presents additional information that may support
certain labeling requests, provide information on
patients’ quality of life issues, reveal product
advantages over already marketed competing drugs,
provide evidence in support of possible additional
drug indications, or provide other clues for
prospective post marketing studies (Phase 4)
PHASE IV (CONTINUED CLINICAL TRIAL)
➢ New drug receives approval from the FDA
➢ The drug is tested in several hundreds or thousands
of patients that allows for better research on short-
lived and long-lasting side effects and safety.
➢ Some rare side effects may only be found in large
groups of people
 INVESTIGATION NEW DRUG APPLICATION FDA APPROVAL
(IND APPLICATION)
➢ Must be filed by FDA and approved prior to
administering New Drug to Humans.
➢ IND must include the following:
o Preclinical Animal Data
o Names and Locators of the investigators who will be
performing the planned clinical trials
o Data from clinical trials conducted in other countries if
applicable
➢ The FDA has 30 days from receipt of IND if the
proposed clinical trial should proceed.
➢ The administration of drugs to humans at the earliest
time possible saves valuable resources, as highly toxic
compounds can be eliminated while lead agents and
alternative compounds are developed. ➢ If a developer disagrees with an FDA decision, there
➢ Additional preclinical studies are conducted during are mechanisms for a formal appeal.
clinical testing to support larger trials and eventually
the marketing of the drug product. VARIATION FOR NDA APPLICATION
➢ Formulation development continues throughout the TOXICITY
development process and the data gained from both ➢ If the toxicity of a new drug is too high in human or
animal and human allow for optimization of the Drug animal patients, the drug may be rejected due to
Delivery System. safety concerns about its use following manufacture

NEW DRUG APPLICATION EFFICACY

➢ Once phase 3 trials have been completed, all ➢ If a new drug’s efficacy is not high enough or evidence
preclinical and clinical data are compiled and is inconclusive, the FDA may reject it.
submitted to FDA for review.
➢ The NDA process is the last hurdle prior to approval
and marketing.
➢ The FDA also reviews the proposed packaging and
product inserts.
➢ Regulation guidelines include:
o Safety and efficacy of drug treatments
o Components of drug products
o Description of methods and controls used in the
manufacturing of active ingredients
o Proposed labeling.

GOALS OF NEW DRUG APPLICATION: PHARMACOKINETIC PROPERTIES OR BIOAVAILABILITY

➢ The drug is safe and effective as a treatment for the
condition it has been developed for
➢ The drug’s therapeutic benefits outweigh the risks.
➢ The drug’s labeling is fit-for-purpose and whether all
required details are included.
➢ PK properties or poor bioavailability due to low
aqueous solubility, or high first-pass metabolism, may
also cause a drug to fail FDA review.
➢ PK causes of drug failure include inadequate action
duration and unanticipated human drug interactions.

➢ The methods used to manufacture the drug and

measures to ensure the drug's quality are satisfactory.
 INADEQUATE DRUG PERFORMANCE
➢ If the new drug performs the desired function, but only
at a shallow level, the FDA may reject the application
in favor of a formulation that performs better
SURROGATE OR INTERMEDIATE OUTCOMES
➢ involve things that do not directly involve patients'
well-being
➢ should ideally be proven to correlate with patient-
oriented outcomes
INTERNATIONAL NONPROPRIETARY NAMES (INN)
➢ facilitate the identification of pharmaceutical
substances or active pharmaceutical ingredients.
MANDATE
➢ WHO has a constitutional mandate to "develop,
establish and promote international standards
with respect to biological, pharmaceutical and
similar products".
➢ The World Health Organization collaborates closely
with INN experts and national nomenclature
committees to select a single name of worldwide
acceptability for each active substance that is to be
marketed as a pharmaceutical.

NEW DRUG
BRAND NAME
➢ a drug that has not been declared safe and effective by
➢ (Proprietary or trademark names)
qualified experts under the conditions prescribed,
➢ a name developed by the company requesting
recommended, or suggested on the label and that may
approval for the drug and identifies it as the
be a new chemical formula or an established drug
exclusive property of that company
prescribed for use in a new way.
➢ Generic and trade names must be unique to
➢ not recognized as being safe and effective in the
prevent one drug from being mistaken for another
conditions recommended for its use among experts
when drugs are prescribed and prescriptions are
who are qualified by scientific training and experience
dispensed. The FDA must agree to every proposed
(FDA Definition)
trade name to prevent this confusion
DRUG NOMENCLATURE
EMPIRICAL NOMENCLATURE
➢ a representation of an organic compound when it is
first synthesized from a natural source
(Amoxicillin=C16H19N3O5 S.3H2O)
➢ simplest ratio of elements in a compound rather than
the total number of atoms in the molecule
GENERIC NAME
➢ (chemical’s nonproprietary name) indicates the
common name of the drug.

UNITED STATES ADOPTED NAMES (USAN) COUNCILS

➢ The organization is responsible for designing
appropriate nonproprietary names.
1964
➢ American Pharmacist Association (APA) joined the
organization

1967
➢ FDA was invited to be part of the organization
 PRE-FORMULATION STUDIES
REASONS FOR DOSAGE FORMS DESIGN
➢ To protect the drug substances from the
destructive influences of atmospheric oxygen or
humidity (ex. Coated tablets, sealed ampules)
➢ To protect the drug substance from the destructive
influence of gastric acid after oral administration
(ex. Enteric coated tablet)
➢ To conceal the bitter, salty, or offensive taste or
odor of a drug substance (ex. Capsules, coated
tablets, flavored syrups)
➢ To provide for insertion of a drug into one of the
body’s orifices (ex. rectal or vaginal suppositories)
➢ To provide for placement of drugs directly in the
bloodstream or body tissues (ex. injections)
➢ To provide for optimal drug action through
inhalation therapy (ex. inhalants and inhalation
aerosols)
➢ To provide liquid preparations of substances that
are either insoluble or unstable in the desired
vehicle (ex. Suspension)
➢ To provide clear liquid dosage forms of substances
(ex. syrups, and suspensions)
➢ To provide optimal drug action from topical
administration sites (ex. ointments, creams,
transdermal patches, and ophthalmic, ear, and
nasal preparations)
PHYSICAL DESCRIPTION
➢ Chemical Properties: structure, form, and reactivity
➢ Physical Properties: particle size, crystalline
structure, melting point, solubility, stability
(temperature and photosensitivity)
➢ Biological Properties: bioavailability &
Effectiveness
MICROSCOPIC EXAMINATION
➢ It gives an indication of particle size and size of the
raw material along with the crystal structure.
➢ SPHERICAL and OVAL POWDERS flow more easily
than needle-shaped powders & make processing
easier.
MELTING POINT DEPRESSION
MELTING POINT OR FREEZING POINT
➢ of a pure crystalline solid is defined as the
temperature at which the pure liquid and solid exist
in equilibrium
➢ An Altered peak or a peak at a different
temperature may indicate an adulterated or impure
drug
PARTICLE SIZE
➢ It is essential to establish how the particle size of
the drug substance affects the drug formulation
and efficacy.
SOLUBILITY
➢ An important physicochemical property that a
drug substance should somehow possess for
therapeutic efficacy.
SOLUBILITY AND PARTICLE SIZE
➢ Basically, particle size affects the solubility of a
drug substance.
➢ The reduction of particles size will result in the
enhancement of drug solubility
SOLUBILITY AND pH
➢ Adjustment of the pH of the solvent can enhance
solubility.
pH (power of Hydrogen)
➢ is a measure of acidity
DISSOLUTION
➢ limiting steps for absorption
DISSOLUTION RATE
➢ the time it takes for the drug to dissolve in the
fluids at the absorption site which is the first
limiting step in absorption.
(water-soluble salt = increases dissolution rate)
MEMBRANE PERMEABILITY
➢ The assessment of the passage of drug molecules
across biologic membranes to produce a biologic
response. (ex. drugs that cross the blood-brain
barrier)
PARTITION COEFFICIENT
➢ The oil-water partition coefficient is a measure of
lipophilic or hydrophilic character resulting in an
appropriate selection of solvent to stabilize the
drug.

THE PHASE RULE

PHASE DIAGRAMS
➢ are often constructed to provide a visual picture of
the existence and extent of the presence of solid
and liquid phases in binary, ternary, and other
mixtures.
BIOPHARMACEUTICS AND PHARMACOKINETICS
CONSIDERATIONS
BIOPHARMACEUTICS
➢ Relates between the physiochemical properties of a
drug in dosage form and the pharmacology,
toxicology, or clinical response observed after its
administration
➢ Provides the scientific basis for drug product design
and drug product development
PHARMACOKINETICS
➢ Refer to the absorption, distribution, metabolism,
and elimination (ADME; sometimes LADME where L
is Liberation) of the drug
➢ Some drugs can alter the ADME of another; thus
Pharmacokinetics is also referred to as the study of
drug interaction
PRINCIPLES OF DRUG ABSORPTION
➢ Before an administered drug can arrive at its site of
action in effective concentrations, it must surmount
a number of barriers
➢ Drugs taken by mouth must transverse the
gastrointestinal membranes gain entrance to the
general circulation.
BARRIERS
➢ Succession of biologic membranes such as those of
the Gastrointestinal epithelium, Lungs, Blood, and
Brain.
DISSOLUTION AND DRUG ABSORPTION
FACTORS AFFECTING DRUG DISSOLUTION
THE pH OF THE ENVIRONMENT
➢ like dissolves like principle
AGING
➢ elderly decreases physiological functions; (gastric
acidity, number of absorptive cells, intestinal blood
flow, rate of gastric emptying time, intestinal
motility).
DISSOLUTION
➢ the rate-limiting step for drug absorption
FACTORS AFFECTING GASTRIC EMPTYING TIME
GASTRIC EMPTYING TIME
➢ Stomach (2-4 hours);
➢ Small intestine (4-10 hours)
o Anticholinergics (Dicyclomine HCl, Amitriptyline
HCl, Loperamide)
o Laxatives
o Food
TRANSPORT MECHANISM FOR DRUG DISTRIBUTION
➢ Movement of a substance across a cell membrane
from an area of low concentration to an area of high
concentration
o Requires the use of carries
o Requires energy (ATP)
PUMPS
➢ Proteins that use active transport to move particles
between the interior and exterior of the cell
➢ Example: Na+/K+ pump
o Used to move sodium and potassium ions
across nerve membranes
PASSIVE DIFFUSION
➢ Used to describe the passage of the drug molecules
through a membrane that does not actively
participate in the process (higher-lower conc.)
ACTIVE TRANSPORT
➢ Specialized transport denotes a process with the
additional feature of the solute or drug being moved
across the membrane against the concentration
gradient (lower-higher concentration)
➢ Ex. Vitamins (thiamine)
FACILITATED DIFFUSION
➢ Specialized transport mechanism that requires a
carrier for transport
➢ Ex. Sugars and amino acids
BIOAVAILABILITY AND BIOEQUIVALENCE
BIOAVAILABILITY
➢ Describes the rate and extent to which an active drug
ingredient or therapeutic moiety is absorbed from a
drug product and becomes available at the site of
action
BIOEQUIVALENCE
➢ Refers to the comparison of bioavailability of different
formulations, drug products or batches of the same
drug product.
FACTORS AFFECTING BIOAVAILABILITY
SURFACE AREA
➢ When a particle is broken up, the total surface area is
increased
➢ to increase surface area manufacturer uses:
o MICRONIZED POWERS for Solid Dosage forms (5um
and smaller)
o BLENDING OF THE WATER-SOLUBLE POLYMER
(polyethylene glycol PEG) for poorly-water soluble
powders
o MICRONIZED DRUGS for ophthalmic preparation and
topical preparation for better absorption and less
skin irritation.
 FACTORS AFFECTING BIOAVAILABILITY
SALT FORM
➢ The dissolution rate of a salt form of a drug is
generally quite different from that of the parent
compound (strong acids and bases)
➢ The salts of weak organic acids and weak organic
bases are dissolved more readily than respective
free acids and bases
o Sodium and potassium salts of weak organic
acids
o Hydrochloride salts of weak organic bases
➢ Weak acids are un-ionized in the stomach and
absorbed fairly well from this site;
➢ Whereas weak bases are highly ionized in the
stomach and not significantly absorbed in the gastric
surface
o Ex: DEXTROMETHORPHAN HBr
o PHENYLEPHINE HCl
LIQUID DOSAGE FORMS
➢ Suspensions, Syrups, Solutions, Magmas, Elixirs, Gels
ORAL PREPARATIONS
➢ ADVANTAGES:
o Convenience of administration (esp. tablets)
o Elimination of discomfort with injections
o Prevention of formation of high toxic drug
concentrations
➢ DISADVANTAGES:
o Reduced and erratic bioavailability due to
incomplete absorption/drug interaction
o GI discomfort

ROUTES OF ADMINISTRATION
➢ One of the fundamental considerations in dosage
forms.
➢ 2 CATEGORIES:

LOCAL
➢ Achieved by direct application of the drug to the
desired site of action
o Epicutaneous (topical)
o Transdermal
o Conjunctival
o Intraocular
o Intranasal
o Aural
o Respiratory
o Rectal
o Vaginal

SYSTEMIC
➢ Entrance of drug into the circulatory system and
transport to the cellular site of its action
o Oral (Per os)
o Sublingual
o Parenteral
▪ Intravenous
▪ Intra-arterial
▪ Intracardiac
▪ Intraspinal or Intrathecal
▪ Intraosseous
▪ Intra-articular
▪ Intrasynovial
▪ Intracutaneous or Intradermal
▪ Subcutaneous
▪ Intramuscular

ORAL DOSAGE FORMS

SOLID DOSAGE FORMS
➢ Powder/Granules, Capsules, Tablets,
Troches/Lozenges