Name:
the agent)
Pharmaceutical Dosage
Chapter 2: New Drug Development and Approval Process
Chapter 5: Dosage Form Design: Biopharmaceutical
Pharmacokinetic Considerations
Acronyms
Clinical Drug Materials (CTM)
Dosage formulations used for clinical evaluation of a new
drug
Investigational New Drug (IND)
Protects the right and safety of the subjects
Ensures investigational plan is sound and designed to
achieve the stated objectives
New Drug Application (NDA)
Gains permission to market the drug product
Supplemental New Drug Application (SNDA)
Application by the sponsor of approved NDA to make
changes
Abbreviated New Drug Application (ANDA)
Non-clinical laboratory studies and clinical investigations
may be omitted except those pertaining to the drugs
bioavailability
Biologics License Application (BLA)
Manufacture of biologicals (blood products, vaccines, and
toxins)
International Conference on Harmonization (ICH)
Brings together regulatory requirements
Establishes (long range goal) a uniform set of standards for
drug registration within a geographic areas
Factors That Triggered Rapid Drug Development and Production in
the United States
Pharmaceutical industrys discovery of new drugs and
development into commercial products
Scientific and biomedical information generated worldwide
(research institutes, academic centers and industry)
Combined efforts in drug discovery and development
(chemists, biologists, molecular biologists,
pharmacologists, etc.)
Rapid growth of pharmaceutical industry during WWII
Development of other antibiotics
Postwar drug with the development of many new agents
Federal Food and Drug Cosmetic Act
New drug be approved by the Food and Drug
Administration (FDA) before legally introduced in
interstate commerce
Preformulation studies (physical and chemical properties of
Formulation studies follows develop initial feature of
proposed pharmaceutical product or dosage form
and
Drug Substance
Active ingredients or components that produce the
pharmacologic activity
Produced by:
Chemical synthesis
Recovery from a natural product
Recombinant DNA technology
Fermentation
Enzymatic reaction
Combination of these processes
Purification needed before use in a drug product
New Chemical Entity (NCE)
Drug substance with unknown clinical, toxicologic,
physical and chemical properties
Drug Product
Finished dosage form (containing the drug substances and
other excipients or inert substances)
Sources of New Drug
Variety of natural resources
Serendipity or result of tireless pursuit
Plant materials have served as reservoirs of
potential new drug
Conversion of botanic folklore remedies into
modern wonder drugs
Synthesis in the laboratory
Variety of Natural Resources
Reserpine (tranquilizer and hypotensive agent)
Medicinal chemical isolated by design from the
folklore remedy Rauwolfia serpentina
1
 Periwinkle or Vinca Rosea: for diabetes mellitus
Paclitaxel (taxol): for ovarian cancer
From an extract of the pacific yew tree
Other plant constituents (inactive or
therapeutically)
Chemically modified to yield important drug with
profound pharmacologic activity
Example: species of Dioscorea (Mexican yams)
Development of pharmaceutical products (result of genetic
engineering)
Submicroscopic manipulation of the double helix,
the spiral DNA chain of life
Two basic technologies that drive the
unimportant genetic field of drug development:
Recombinant DNA (rDNA)
Monoclonal antibody products (MoAB)
production

Rich in the chemical steroids structure:

cortisone and estrogens Similarities of Recombinant DNA and Monoclonal Antibody

Semi synthetically produced
Animals have served human in their search for new drugs:
Cattle, sheep and swine from the endocrine gland
Manipulate and produce proteins (building blocks of living
matter)
Production techniques influence cells in their ability to
produce proteins

Hormonal substances: thyroid extract,

insulin, and pituitary hormone
Differences of Recombinant DNA and Monoclonal Antibody
(replacement therapy in the human
body)
Recombinant
Pregnant mares (from urine)
More fundamental
Rich source of estrogen
Produce any protein
Production of various biological products
Gene splicing: genetic material transplanted from
Serums, antitoxins, and vaccines higher species (humans) which induce the lower
(lifesaving) organism (bacterium) to make proteins

Smallpox vaccine: pioneering work of Human insulin

Edward Jenner in England in 1796
Hepatitis B vaccine
o Cultures of renal monkey: poliomyelitis
vaccines Human growth
o Fluids of chicks embryo: mumps and
Interferon
influenza vaccines
MoAB
o Duck embryo: rubella (German
measles) vaccine
Conducted within cells of higher animals
o Skin of bovine calves inoculated with (including patient)
vaccinia virus: smallpox vaccines
Exploits cell to produce an antibody to combat
Synthesis in the laboratory or molecular manipulation the specific agent

Change natural chemical to different chemical Used in home pregnancy testing products
structure
In medicine: to stage and localize malignant cells
of cancer

Sources of New Drugs Future: combat disease (lupus erythematosus,

juvenile onset diabetes and myasthenia gravis)
2
 Absorption
Sources of New Drug
Prolonged release
Human gene therapy (promising new technology)

Prevent, treat, cure, diagnose, or mitigate human New Drug

disease, caused by genetic disorder
According to FDA:
First human gene therapy
Not recognized by experts as safe and effective
Treat adenosine deaminase (ADA)
deficiency (condition resulting in Change in previously approved drug products
abnormal functioning of the immune formulation or method of manufacture
system)
New combination of 2 or more old drugs or
change in proportions of drugs
Goal Drug
Proposed new use, new dosage regimen, new
route of administration or new dosage form
Produces:

Desired effect
Orphan Drug
Administered by the most desired route (orally)
at minimal dosage and dosing frequently Treatment IND are sought for to target small numbers of
patients with rare conditions or diseases (orphan diseases)
Optimal onset and duration of activity where there are no satisfactory alternative treatments.

Exhibit no side effects Orphan Disease: rare disease or condition affecting fewer
than 200,000 people
Eliminated from the body efficiently, completely,
and without residual effect Chronic lymphocytes
Gauchers disease

Lead Compound Leukemia

Prototype chemical compound Cystic fibrosis
Fundamental desired biologic or pharmacologic activity AIDS

Pharmacologic Profile
In vitro cultures of cells and enzyme systems
Prodrug In vivo animal models are used
Objective: to obtain basic information on the drugs effect
Metabolic biotransformation of compound after that may be used to predict safe and effective use in
administration to produce desired pharmacologically active humans
compound
Molecular Graphics
Inactive prodrug to active compound (enzymatic Use of computer graphics to present and manipulate the
biochemical cleavage) structure of the drug molecule to fit the stimulated
molecular structure of the receptor site
Example: enalapril (enalapril maleae, vasotec) bioactivated Complementary tool in drug molecule design
to enalaprilat (ACE inhibitor, for hypertension)
Methods of Drug Discovery
Random or non-targeted screening
Used for the following reasons:
Testing of large numbers of systematic organic
compound or substance of natural origin for
Solubility biologic activity

Biostability
3
 Detects unknown activity of test compound or
identifies compromising compounds to be studied
to determine specific activity
Ex. bioassays
Detects and evaluates biologic activity
Differentiates the effect and potency of test agent
compared with controls of known action or effect
Molecular modification
Chemical alteration of organic compound
frequently a lead compound to:
Enhance its usefulness as a drug
Enhancing specificity for a bodys
target site
Increasing potency
Improving rate and extent of absorption
Modifying time course in the body
Reducing toxicity
Change of physical or chemical
properties to provide desired pharmaceutical
features
Mechanism-based drug design
Drug design that interferes with the known or
suspected biochemical pathway of mechanism of
a disease process
Intention: interaction of a drug with:
Specific cell receptors
Enzyme systems
Metabolic processes of the pathogens or
tumor cells
Resulting in: blocking, disruption, reversal
of the disease process
Non Proprietary Names
For single agents
Proprietary or Trademark Names
Associated with a single chemical entity or with a mixture
of chemicals constituting a specific proprietary product
Pharmacology
Embraces:
Physical and chemical properties
Biochemical and physiological effects
Mechanisms of action, absorption, distribution,
biotransformation, excretion, therapeutic and
other uses of drugs
Concerned with drugs, their sources, appearance,
chemistry, action, and uses
Comes from the Latin word pharmaco (drugs) and
logos (study of)
Sub Area of Pharmacology
Pharmacodynamics
Study of the biochemical and physiological effect
of drugs and their mechanism of action
Pharmacokinetics
Deals with the absorption, distribution,
metabolism or biotransformation, and excretion
(ADME) of the drug
Clinical pharmacology
Applied pharmacologic principle to the study of
the effects and action of drugs in human
Todays Emphasis in Development of New Drugs
Identifying the cause and process of a disease
Designing drug molecules capable of interfering with that
process
Precise cause of each disease: not yet known
Known in most diseases arising from:
Biochemical imbalance abnormal proliferation of
cells
Endogenous deficiency
Exogenous chemical toxin or invasive pathogen
Quantity of Drug Will Influence its Effectivity
There is a relationship of drug molecules for interaction
and the capacity of the specific receptor site.
Following a dose of drug and its transit to the site of action:
Cells receptors may or may not become fully
saturated with interacting drug
Receptors fully saturated: effects of the specific
interaction are maximized
Additional drug present and not participating in
the interaction serve as a reservoir to replace drug
molecules that become releases from the complex
2 Drugs in a Biologic System
Compete for the same binding sites
Drug with stronger bonding attraction for the site prevails
Bound molecules of the more weakly bound drug
May be replaced from the binding site
Let free in the circulation as unbound drug
Biologic Characterization
Drug metabolism: series of animal studies of a proposed
drug ADME are undertaken to determine:
Extent and rate of drug absorption from various
routes of administration including human use
Rate of distribution of drug through the body and
the site or sites and the duration of drug residence
Rate, primary and secondary sites, and the
mechanism of the drug metabolism in the body
and the chemistry and pharmacology of any
metabolism
The proportion of administered dose eliminated
from the body and its rate and route of
elimination
Specific and Non-specific Enzymes
Participate in drug metabolism (liver, kidneys, lungs, and
GIT)
Drugs Following Oral Administration that Enter the Hepatic
Circulation after Absorption from GIT
Exposed to rapid drug metabolism
1st Pass Effect
Transit through the liver and exposure to the hepatic
enzyme system
To be avoided: other routes of administration (buccal and
rectal) may be used to absorb drug into the systemic
circulation through blood vessels other than hepatic
ADME Studies
4
 Performed through the collection and analysis of urine, Drug substance must possess some aqueous
blood and feces samples, and careful examination of animal solubility for system absorption and therapeutic
tissues and organs upon autopsy response.

Toxicology Poorly soluble compounds: incomplete erratic

Area of pharmacology that deals with the adverse or and/or slow absorption producing minimum
undesired effects of drugs response at desired dosage

Different Studies in Toxicological Profile Partition coefficient

Acute or short-term toxicity studies
Toxic effect of a test compound when Drug molecules must first cross a biologic
administered in single dose or in multiple dose over membrane of protein and lipid to produce a
short period, usually a single day pharmacologic response, which acts as a
Test compound administered at various dose lipophilic barrier to many drugs.
levels, with toxic signs observed
Doses are ranged to find dose not to produce Measure of its distribution in a lipophilic or
hydrophilic phase system, and is indicative of its
toxic effect, severe toxic effect, and intermediate toxic
ability to penetrate biologic multiphase system.
level
Subacute or subchronic studies
Dissolution rate
Considered: the relationship to projected human
clinical studies for safety
Animal toxicity studies (minimum of 2 weeks of daily Speed, rate, at which a drug substance dissolves
drug administration at 3 or more dosage levels to 2 in a medium
animal species) are required to support the initial
administration of a single dose in human clinical Provide indication of drugs absorption potential:
testing
Chronic toxicity studies Drug solubility
Drugs intended to be given to humans for a week or
more, animal studies of 90 to 180 days in length must Partition coefficient
demonstrate safety
For chronic human illness, long-term animal studies Physical form and particle size
for 1 year or longer
Carcinogenicity studies Affect drugs:
For limited number of rat and mouth strains: there is
reasonable information on spontaneous tumor Dissolution rate
incidence
Long term studies (18 to 24 months) with surviving Rate & extent of absorption
animals killed and studied at defined weeks during the
test period Stability
Component of chronic testing, undertaken when the
compound has shown sufficient promise as a drug to Tests: various temperatures, conditions of relative
enter human clinical trials humidity and environments of light, air and
Reproduction studies packaging
Reveals any effect of an active ingredient on
mammalian reproduction Critical in preparing a successful pharmaceutical
product, alone and when combined with
Evaluated for anatomical abnormalities, growth and
formulation components
development: maternal parent, fetus, neonates, and
weaning offspring
Drugs susceptible to:
Genetoxicity or mutagenecity studies
Determines whether test compound affects gene
Oxidative decomposition: add
mutation or cause chromosome or DNA damage
antioxidant stability agent
Used in assays to detect mutations: strains of
Salmonella typhimurium Hydrolysis: processing and packaging
required
Different Properties of Drug Substance Included in Pre-formulation
Studies Initial Product Formulation and Clinical Trial Materials (CTM)
Preformulation Studies
Product formulated (per formulation studies as basis) for
Drug Solubility the clinical studies and for the new drug with consideration
of:

Dose

5
 Dosage forms Patient observations, measurements and tests, etc.
Route of administration Pre- IND Meetings

Clinical supplies or clinical trial materials (CTM) FDA advises a sponsor relating to the preparation and
submission of IND on:
Includes:
Scientific
Proposed new drug
Technical
Placebos (non-medicated forms for
controlled studies) Formatting concerns

Drug products compared to new drug Includes:

(comparator drugs or drug products)
Advice on the adequacy of data to support an
Blinded Studies investigational plan
Controlled studies where 1 of the parties is not
knowledgeable of which product is being administered Design of a clinical trial or investigation
produces
Open Label
All parties are aware of the products administered. Data to meet requirements of the next step

Single Blind Studies Filing NDA to gain approval for marketing

Patient unaware of the:
Agent administered FDA Review of an IND Application
Placebo
Investigational drug The FDAs objective in reviewing IND:
Comparator drug
Protect the safety and right of human subjects
Double Blind Studies
Neither the patient nor the clinician is aware of the agent Ensure evaluation of the drugs safety and
administered. effectiveness

Parallel Designs Objections are best met by the accuracy and

completeness of the IND submission
Applicable to most clinical trials

Crossover Designs Design and conduct of the:

For comparing different treatments within individuals since Investigational plan
the following one treatment a patient is crossed over to a
different treatment Expertise
The Clinical Protocol
Diligence of the investigators
Part of the IND application FDA Drug Classification System
Submitted to ensure the appropriate design and conduct of
investigation Upon receipt and examination of IND or NDA application

Includes: FDA classifies the drug by:

Purpose and objectives Chemical type

Number of patients Therapeutic potential

Phases of Product Development of Drug Products Containing NCEs

Dosing plan
Preclinical stage
Investigational plan

Subject selection Animal pharmacology & toxicology data are

obtained.
Clinical procedures, laboratory tests
Determines the safety & efficacy of the drug
6
 Submission of investigational new drug (IND)
application for human testing to the FDA
Phase I
Initial introduction (clinical testing)
Subjects: healthy volunteers (20- 100)
Determines drug tolerance & toxicity (assessing
safety)
Phase II
Controlled clinical studies to several hundred
patients with the disease or condition are treated
Safety measured: determines the therapeutic
index (ratio of toxic dose to effective dose)
Final drug formulation developed bioequivalent
(same rate & extent of drug absorption to the
brand drug product) to the dosage form
Phase III
Several hundred to several thousand patients with
disease or condition treated for which the drug
was developed (controlled & uncontrolled trails)
Large scale, multicenter studies performed: to
determine safety and efficacy
Side effects are monitored.
Phase 3A
Completed studies sufficient for the NDA
Phase 3B
Additional studies are used to gather:
Supplemental information to
support certain labeling requests
Information on patients quality of
life issues
Product advantages over already
marketed competing drugs
Evidence in support of possible
additional drug indications
Other clues for prospective post
marketing studies
Phases of Clinical Investigation
Submission of a new drug application (NDA)
An NDA is submitted to the FDA for review &
approval when clinical trials are completed.
Phase IV
Continual clinical investigation
Manufacturing scale-up activities
Drug formulation modified slightly
To gather supplemental information (labeling,
product advantages, additional indications,
prospective post marketing studies)
Phase V
Product development continues after the FDAs
market approval of drug product
Drug product may be improved due to
equipment, regulatory, supply or market demands
Post Marketing Reporting of Adverse Drug Experiences
A drug sponsor is required to report to the FDA each
adverse drug experience that is both serious (life
threatening or fatal) and unexpected (not contained in the
approved drug product labeling) regardless of the source of
the information within 15 working days of receipt
information.
Drug Dosage and Terminology
Usual adult dose and starting dose for the patient
Amount of drug that produces the desired effect
in the majority of adult patient
Dosage regimen or schedule of dosage
Determined from:
Clinical investigation
Inherent duration of action
Pharmacokinetics
Characteristics of the dosage form
Units of activity
Derived from biological assay methods
Reflects drugs potency
Necessary when drugs (antibiotics & endocrine
products) suitable chemical assay methods are
unavailable
Minimum Effective Concentration (MEC)
7
 Drugs average blood serum concentration
Determines minimum concentration expected to
produce the drugs desired effects in a patient
Minimum Toxic Concentration (MTC)
Second level of serum concentration of drug
Above the average blood serum level producing
toxic effects
Negates desirable effects of the
compromising safety of the patient
ED 50 or Median Effective Dose
Produces the desired intensity of effect in 50% of
the individuals tested
Median Toxic Dose (MTD)
Produces a defined toxic effect in 50% of the
individuals tested
Therapeutic index
Relationship between drugs desired and
undesired effects
Ratio of drugs median toxic dose & median
effective dose, TD50/EF50
Terms
Maintenance dosage
Regularly schedule subsequent administration
Initial priming or loading dose required to attain
desired concentration of the drug in the blood of
tissues
Prophylactic dose
Protects the patient from contracting illness
Therapeutic dose
Administered to the patient after exposure or
contraction of the illness
Drug-drug interaction
Effect of drug modified by prior or concurrent
administration of another drug
Chemical or physical interaction between the
drugs or alteration of the absorption, distribution,
metabolism or excretion patterns of one of the
drugs
Include social agents (tobacco & alcohol)
affecting pharmacokinetics of a number of drugs
and alter drugs usual dose
Time and Conditions of Administration
Time drug is administered.
Influence dosage
Absorption more rapid
drug Stomach & upper portions of intestinal tract are
empty of food
Dosage Form and Route of Administration
IV or parenteral (injectable)
Drugs enter blood stream directly and completely
Required to achieve the same blood levels or
clinical effects
Oral
Rarely or if fully absorbed into the bloodstream
due to various physical, chemical and biologic
barriers to their absorption
Routes of Administration
Fundamental considerations in dosage form design:
Local effects
Direct application of the drug to desired site
of action (eye, nose, ears)
Systemic effects
Entrance of drug into circulatory system and
transport to cellular site of its action
Direct placement into the blood stream via
IV injection or absorbed into the venous
circulation following oral or other routes of
administration
Routes of Drug Administration
I. Oral Route
Most taken for systemic effects after absorption
from various surfaces along GIT
Most natural, uncomplicated, convenient and safe
means of administering drugs
Disadvantages:
Slow drug response
8
 Chance of irregular absorption of drugs Example: insulin
(constitutional make-up, amount or
type of food present within GIT) 2. Intramuscular injection

Destruction of certain acid reaction of Injected into the skeletal muscles-gluteal or

stomach or GIT enzymes lumbar muscles

II. Rectal Route Aqueous, oleaginous solution or suspension

Suppositories, solutions, or ointments Drugs injected: those irritating to subcutaneous

tissue
For systemic action preferred for drugs:
2 to 5mL
Destroyed or inactivated by the
stomach and intestine environments 3. Intravenous injection
Patient is unconscious or incapable of
swallowing Aqueous solution injected directly into the veins
of the forearm
Bypass the liver
Advantages:
Disadvantages: inconvenient; absorption is
Rate commensurate with efficiency, safety,
irregular & difficult to predict comfort to the patient

Desired duration of drug response

III. Parenteral Route
Useful in emergency situations where
immediate drug response is desired
Injected into the body using a fine needle at
various sites and depths
Administered: single, small-volume injection or
as large volume, slow IV drip fusion
Routes: subcutaneous, IM, IV, intracardiac and
intraspinal
IV fat emulsion-caloric source (receiving
parenteral nutrition)
Preferred for drugs:
4. Intradermal injection
Destroyed or inactivated in GIT
Administered into the corium of the skin (arm
Poorly absorbed to provide satisfactory and back)
response 10th of a mL in volume
Use: diagnostic measures
Rapid absorption is essential Example: tuberculin and allergy testing

Advantage: 5. Epicutaneous route

Applied topically to the skin (for action at site of
Treating patients who are uncooperative, application or systemic drug effects)
unconscious, unable to accept oral
medication Transdermal delivery systems
(adhesive disc/patch)
Disadvantage: Slowly releases medication for
percutaneous absorption
Once drug is injected, there is no retreat. Examples: nitroglycerin (antianginal),
nicotine (smoking cessation), estradiol
(estrogenic hormone), clonidine
(antihypertensive), scopolamine
1. Subcutaneous (hypodermic) injection (antinausea)
For local action:
Injected through layers of skin into the loose Prolonged local contact
subcutaneous tissue with minimal absorption
Antiseptics, antifungal
Aqueous solution or suspension (2mL or less) agents, anti-inflammatory
agents, local anesthetic

9
 agents, skin emollients and Indication and usage
protectants Contraindications
Creams, ointments, Warning
powders, aerosol sprays,
Precaution
lotions, solutions
Adverse reaction
6. Ocular, oral and nasal routes Drug abuse and dependence
For eye, ear and mucous membranes of the nose Over dosage
(not for systemic effect) Dosage and administration
Ophthalmic preparations: How supplied
Solutions, suspensions and ointments
Nasal preparations: Drug Product Labeling
Solutions or suspensions by drops as According to federal regulation, includes:
fine mist from a nasal spray container Label placed on an immediate container
Otic or ear preparations
Information on the packaging, in package insert and in
Viscid to soften ear wax, relieve company literature, advertising, and promotion
earache or combat an ear infection materials
7. Other routes
The package insert required to contain the summary
Lungs
information
Administered of gases and aerosol
sprays Completed New Drug Application
Should attain proper drug particle size Reviewed by the FDA, decides:
and ensure uniformity for consistent To allow the sponsor to market the drug
penetration
Drugs inserted into the: To disallow marketing
a) Vagina To require additional data before rendering a judgment
Tablet, suppositories, ointments, emulsion, FDA respond within 180 days (review clock) of receipt of
foams, gels, solutions an application
b) Urethra
Suppositories or solutions FDA Review and Action Letters
Approvable letter
Treatment IND or Treatment Protocol Specific additional data or other requested
Use of an investigational drug in the life-treating disease in material is submitted or specific conditions are
lieu of no satisfactory alternative therapy met
Makes promising new drug available to desperately ill Pertains to development or wording of the final
patient, early as possible in the drug development process product labeling
Approval letter
Withdrawal or Termination of an IND Approval of the application permitting marketing
By the sponsor any time ending all clinical investigation New approval letter
Stock of clinical supplies returned to the sponsor or One or more deficiencies
otherwise destroyed
If withdrawn because of safety reasons, must advice: FDA, ICH
IRB, and all investigators Harmonizing or bringing together regulatory requirements
FDA may terminate an IND for safety, efficiency, or with long-range goal of drug registration within these
regulatory compliance issue. geographic areas
Focused on 3 general areas:
The New Drug Application (NDA) Quality topics
Filed by the sponsor with the FDA if: Stability, light stability, analytical validation,
Three phases of clinical testing demonstrates impurities and biotechnology
sufficient drug safety and therapeutic Safety topics
effectiveness
Carcinogenicity, genotoxicity, toxicokinetics,
Preceded by pre-NDA meeting between the sponsor and reproduction toxicity and single and repeat dose
FDA to discuss: toxicity
The consent and format of the new-drug Efficacy topics
application
Population exposure, managing clinical trials,
clinical study reports, dose response, ethnic
Drug Product Labeling
factors, good clinical practices and geriatrics
Description of the product
Clinical pharmacology Routes of Drug Administration
10
Term Site Subcutaneous Beneath the skin

Oral Mouth Intramuscular Muscle

Peroral (per os) GIT via mouth Epicutaneous (topical) Skin surface

Sublingual Under the tongue Transdermal Skin surface

Parenteral Other than the GIT (by injection) Conjunctival Conjunctive

Intravenous Vein Intraocular Eye

Intraarterial Artery Intranasal Nose

Intracardiac Heart Aural Ear

Intraspinal or intrathecal Spine Intrarespiratory Lung

Intraosseous Bone Rectal Rectum

Intraarticular Joint Vaginal Vagina

Intrasynovial Joint fluid area

Intracutaneous, intradermal Skin Route of Administration and Delivery System of Primary Dosage
Forms

Oral Contact lens inserts

Ointments
Tablets Intraocular, intra-aural
Capsules
Solutions Solutions
Syrups Suspensions
Elixir Intranasal
Suspensions
Magmas Solutions
Gels Sprays
Powders Inhalants
Sublingual Ointments
Intrarespiratory
Tablets
Troches, lozenges Aerosols
Drops (solutions) Rectal
Parenteral
Solutions
Solutions Ointments
Suspensions Suppositories
Epicutaneous, transdermal Vaginal

Ointments Solutions
Creams Ointments
Infusion pumps Emulsion foams
Pasters Gels
Plasters Tablets
Powders Inserts, suppositories, sponge
Aerosols Urethral
Lotions
Transdermal patches, discs, solutions Solutions
Conjunctival Suppositories
Drug Class Examples

Some Drugs that Undergo Significant Liver Metabolism and Exhibit

Low Bioavailability when Administered by First-pass Routes

11
Analgesic Aspirin,
meperidine, pentazocine, propoxyphene

Antianginal Nitroglycerin

Antiarrhythmic Lidocaine

Beta-adrenergic blocker Labetolol, metoprolol,

propanolol

Calcium channel blocker Verapamil

Sympathomimetic amine Isoproterenol

Tricyclic antidepressant Desipramine, imipramine,

nortriptyline

12
13