Classes 1: August 16, 2021 b.

Inert Ingredients – Inactive ingredients that have little or

no physiologic or therapeutic effect. Only use to dilute/
Introduction to Pharmaceutical Dosage and Drug Delivery
stabilize drug product. (flavor, convenience (bulk))
Systems

Drug – defines as any substance taken into or applied to the

Dosage Forms (Physical Manifestation)
body for the purpose of altering the body’s biochemical
functions and thus its physiological processes.  Formulation containing a specific quantity of active
ingredient in combination with 1 or more excipients.
1. Pharmacological activity refers to therapeutic effect
2. An agent intended for use in the diagnosis, mitigation,  Refers to the physical manifestation of a drug that can be
treatment, cure, or prevention of diseases in humans used in a way:
or in other animals. (The uses) o Solid Dosage Forms
3. Facilitates examination in order to reach a conclusion/  Tablet, Powder, Capsules, Granules, Pellets
diagnosis (Bids), Lozenges, Implants, medical lollipops
1. Diagnosis o Liquid Dosage Forms
 Ex of radiopaque* / media contrast drugs:  syrups, suspensions, solutions, elixirs, topical
o Iodine 131 solutions, emulsions, tincture
o Compound Barium o Semi-solid Dosage Forms
2. Mitigation (the action of reducing severity/pain)  Suppositories, Transdermal, ointment, cream,
3. Treatment – lessen symptoms (Ex: Paracetamol) lotion, magma, gel
4. Cure – no more ill/ disease
5. Prevention – prevents disease/ ill (Ex: Vaccines, Drug Delivery Systems
Vitamins)
 Device used to deliver the drug
 Design feature of the dosage form that affects the
Sources of Drugs: delivery of the drug
1. Natural – naturally occurring biological products  Mean for transporting a drug to its site/s of action
made or taken from a single celled organism. within the body.
a. Plants extracts (Active metabolites)  The choice of delivery system depend on the following:
b. Animals (Heparin – Salmon, Beeswax – derma) o Active Ingredient to be delivered (physical-chemical
2. Synthetic – created artificially to exert a specific property – solubility, melting point, stability, etc)
pharmacologic effect (Ex; paracetamol) o Amount of active ingredient to be delivered (more or
a. Chemical Synthesis – made from chemicals/ raw less)
materials o Means or route that ingredient is to be delivered
b. Molecular Modification (can be Synthesized and (target organs: skin – transdermal)
semi) – insert/ remove structure (Cloned Sheep) o To what sites
 Biotechnology and Genetic engineering o At what rate – fast/ slow effect
 Stem Cell treatment o Over what period of time – prolonged effect
3. Synthesized – created artificially but are imitations of o For what purposes – internal or external
naturally occurring drugs (Ex: adrenaline/ Epinephrine  To facilitate safely the administration of drugs to their
– increase heart contraction) selected routes, appropriate dosage forms must be
4. Semi-synthetic – contains of natural and synthetic formulated and prepared.
molecules. Natural molecules are modified through
synthetic process.
a. By-products of microbial growth (Antibiotic) Drug References
 Penicillin (Alexander Flemming)  Scientific bases for drug products and uniform standard,
 Streptomycin to ensure the quality of product.
 Chloramphenicol  Sets of monographs and reference books containing the
 Vit. B 12/ Cyanocobalamin standardization test or assays to be used by those
involved in the production of drugs and pharmaceutical
Classes of Drugs products.
 Pharmacopeia – an organized sets of monographs or
Classified as: books that contains information to standardized drugs.
(“Pharmakon” = drug; “Poen” = to make)
a. Over-the-Counter (OTC) drugs – can be purchased/
o USP (United States Pharmacopeia) – Official Drugs
dispensed without prescription.
followed by the Philippines
 Ex: self-medication: Paracetamol, Vitamins,
o NF (National Formulary) – Unofficial drugs
Antihistamines
o USP-NF – was purchased by Laymans Palding in
b. Legend Drugs – prescription drugs. Can only be
order to unify the official compendia and providing
dispense with a prescription
the mechanism for a single national compendia.
 Ex: antibiotics, hypertensive, maintenance
o USP-NF Monographs – adopts standards for drug
 Legend = Rx
substances, pharmaceutical ingredients, and dosage
forms reflecting the best in the current practices of
Components of Drugs medicine and pharmacy and provide suitable tests
and assay procedures for demonstrating compliance
Drugs are products with a specific use in mind and contain with these standards.
many other components besides the active ingredient. o Purpose: object of a Pharmacopeia to select from
Components: among substances which possess medicinal power,
those, utility of which is most fully established and
a. Active Ingredients – biochemical reactive components best understood; and to form from them
causing therapeutic activity preparations and compositions, in which their
- Rarely given in pure/ undiluted/ uncut form. Always powers may be exerted to the greatest advantage.
given in 1 or more inert ingredients. o Components of a Monograph:
  name of product/ drug, empirical formula, patients or consumers must register with the FDA and
structural formula, definition, test used submit appropriate information for listing
(identification test), test and analysis 7. Drug Price Competition and Patent Term Restoration
Act of 1984 – This extends the effective patent life and
exclusive marketing period for innovative new drug
Drug Regulation and Control (US Standard) products, thereby encouraging pioneering research and
development.
1. Food and Drug Act of 1906 - first federal law in the 8. Dietary Supplement Health and Education Act of 1994
United States designed to regulate drug products – forbids manufacturers to labeling claims like. Ex: “No
manufactured and requires the manufacturing therapeutic effects”, “not intended to diagnose, treat,
company to produce products that comply with the cure, or prevent any disease.”
standard for strength, purity, and quality.
2. Federal Food, Drug and Cosmetic Act of 1983 –
created as the need for additional drug standard. Drug Product Recall
Also created the FDA in order to enforce the laws. If Drugs presents a threat or a potential threat to consumer
a. In the Philippines, equivalent to Food, Drug, and safety.
Cosmetic Act or R.A 3720 – ensure safety and
purity. Also created FDA Act of 2009 or R.A Class I: There is a reasonable probability that the use of or exposure to a
9711 violative product will cause serious adverse health consequences or
death.
b. Impact: prohibits the distribution and use of any Class II: The use of or exposure to a violative product may cause
new drug or drug product without the prior temporary or medically reversible adverse health consequences or the
filing of a New Drug Application (NDA) and probability of serious adverse health consequences is remote.
approval of the FDA Class III: The use of or exposure to a violative product is not likely to cause
3. Durham-Humphrey Amendment of 1951 - adverse health consequences.
established a legal distinction between prescription
and over-the-counter (OTC) or nonprescription
drugs. Contemporary Role of Pharmacist
4. Kefauver-Harris Amendment 1962 –manufacturers
 Pharmacist – member of health care team, will serve as
were now required to prove a drug both safe and
an expert source of drug information and participate in
effective before it would be granted FDA approval
the selection, monitoring, and assessment of drug
for marketing
therapy.
a. Thalidomide tragedy.
 Works:
5. Comprehensive Drug Abuse Prevention and Control
o Ambulatory Care Setting – community and hospital
Act of 1970 – served to consolidate and codify
control authority over drugs of abuse jobs
a. Equivalent to Comprehensive dangerous drugs o Institutional Setting – private institutions that
Act of 2002 or R.A 9165 exclusively dispense to their employees
o Industrial Setting – manufacturing companies
Schedule I: Drugs with no accepted medical use, or other substances o Government Services – FDA, DOH, PDEA, DOST
with a high potential for abuse (heroin, lysergic acid diethylamide (LSD),
mescaline, peyote, methaqualone, marijuana)
o Schools of Pharmacy – academic
Schedule II: lead to severe psychologic or physical dependence  Mission: Serve society as the profession responsible for
(morphine, cocaine, methamphetamine, amobarbital) the appropriate use of medications, devices, and
Schedule III: abused may lead to moderate psychologic or physical services to achieve optimal therapeutic outcomes.
dependence (codeine, hydrocodone)
Schedule IV: lead to limited physical dependence or psychologic
 Pharmaceutical Care:
dependence (difenoxin, diazepam, oxazepam) o “the care that a given patient requires and receives
Schedule V: lead to limited physical dependence or psychologic which assures rational drug usage”
dependence (dihydrocodeine, diphenoxylate) – Mikeal
o “Is a component of pharmacy practice which entails
4. FDA Pregnancy Categories - a classification of fetal risks the direct interaction of the pharmacist with the
due to pharmaceuticals patient for the purpose of caring for that patients
Category A - Adequate and well-controlled studies have failed to drug-related needs”
demonstrate a risk to the fetus in the first trimester of pregnancy and  Strand and others
there is no evidence of risk in later trimesters.
- Multivitamins, folic acid
Category B: failed to demonstrate a risk to the fetus, and there are no
adequate and well controlled studies in pregnant women
- Paracetamol, amoxicillin
Category C: shown an adverse effect on the fetus and there are no
adequate and well-controlled studies in humans, but potential benefits
may warrant use of the drug in pregnant women despite potential risks.
- Aspirin, antibiotics,
Category D: positive evidence of human fetal risk based on adverse
reaction data from investigational or marketing experience or studies in
humans, but potential benefits may warrant use of the drug in pregnant
women despite potential risks.
- ACE inhibitors
Category X: Studies in animals or humans have demonstrated fetal
abnormalities and/or there is positive evidence of human fetal risk based
on adverse reaction data from investigational or marketing experience,
and the risks involved in use of the drug in pregnant women clearly
outweigh potential benefits.
- Thalidomide, Statins

5. Black Box Warning - in prescription drug labeling is used

to call attention to adverse reaction/ effects
6. Drug Listing Act of 1972 - each firm that manufactures
or repackages drugs for ultimate sale or distribution to
 o Indications and contraindications
o Adverse effects
o Formulation composition
Classes 2: August 19, 2021
o Dosage and storage requirements
New Drug Development and Approval Process
Special Considerations – special regulations apply for the
New Drug – any drug that is not recognized as being safe and approval of certain new drugs to treat serious or life
effective in the conditions recommended for its use in the threatening illness (Ex: vaccine: EUA – Emergency Use
labeling among experts (Ipasa sa FDA) Authority)

- A drug need not new chemical entity to be considered - If there is no satisfactory approved drugs or treatment
new. alternatives for a serious medical conditions
- Circumstances:
Treatment Investigational New Drug (IND) – is the
o change in previously approached drug products
application being file to FDA to certain new drugs to treat
formulation or method manufacture serious life-threatening illness. (Urgent approval, Fast tract
o combination of two or more old drug or change in approval)
the usual proportions of drug (Ex: multivitamins, etc)
o New dosage schedule or regimen, route or - Placed on an accelerated or fast-track program for
administration, dosage form. approval
- New drug development (go to book for diagram) - Orphan Drug – pharmaceutical entities that remains
- Only when the preclinical studies demonstrate adequate commercially undeveloped but can treat serious, life-
safety and the new agent shows promise as a useful drug threatening illness
will the drug’s sponsor file an Investigational New Drug
(IND) Application with the FDA for initial testing in Abbreviated New Drug Application (ANDA) - is used to gain
humans. approval to market a duplicate of a product that is already
- After completion of the preclinical and clinical studies, approved and being marketed by the pioneer, or the original
the drug’s sponsor may file a New Drug Application sponsor of the drug. (Ex: Tylenol; Patency Law)
(NDA) seeking approval to market the new product. Supplemental New Drug Application (SNDA) – is filed or
submitted for approval if certain changes in a previously
approved NDA, such as labeling or a formulation changes (Ex:
Paracetamol, Biogesic)

Regulations for Specific Orphan Drugs – Antibiotics,

biologics, OTC and animal drugs, Medical devices may
require: (more common for veterinary drugs)

- INADA or NADA
- SNADA

Drug Discovery and Drug Design

Sources of New Drug – new drugs may be discovered from

natural, synthetic, synthesized, and semi-synthetic sources

Goal Drug – produced the specifically desired effect, be

administered by the most desired route at minimal dosage
and dosing frequency, have optimal onset and duration of
activity, exhibit no side effects and would be eliminated from
the body efficiently, completely, and without residual effects
(perfect drug)

Methods of Drug Discovery – most drugs are the results of

carefully designed: (3)

1. Research programs of screening or

(Preclinical trials: conducted in lab using animals) Random/ Untargeted Screening – Involves testing or
large numbers of synthetic organic compounds or
substances of natural origin for biologic activity (Ex: in
vitro or in vivo assays)
- Limitations: screening models are not sensitive enough
to reflect accurately the specific diseases against which
the agent
- Method: Bioassay (conducted to animals)
2. Molecular Modification – a chemical alteration of a
known and previously characterized organic compound
(lead compound) for the purpose of enhancing its
usefulness as a drug (ex: morphine – Codeine (CH3 is
taken out/ vaccines – 3D computers)
3. Mechanism-Based Drug Design – a molecular
Package Inserts - Is a summary of the entire drug modification to design a drug that interferes specifically
development process with the known or suspected biochemical pathway or
mechanism of a disease process (Pharmacology)
- Contains:  Lead Compound – is a prototype chemical compound
o Essential chemistry that has fundamental design biologic or pharmacologic
o Pharmacology activity.
o Toxicology
  May not possess all the feature desired, such as  Drug Stability - A drug substance administered by any
potency, absorbability, solubility, low toxicity, and so route must possess some aqueous solubility for systemic
forth. absorption and therapeutic response.
 Pro Drug – is a term used to describe a compound that  Partition Confident - a measure of its distribution in a
requires metabolic biotransformation after lipophilic hydrophilic phase system and indicates its
administration to produce the desired pharmacologically ability to penetrate biologic multiphase systems.
active compound (Enalaprelat, Acetaminophen)  Dissolution rate - The speed at which a drug substance
 Stability of the drug (Drug is inactive before dissolves in a medium is called its dissolution rate.
metabolism – active after)  Physical From - The crystal or amorphous forms and/or
the particle size of a powdered drug can affect the
dissolution rate, and thus the rate and extent of
Factors Considered to Design a Pro Drug: absorption, for a number of drugs.
1. Solubility – designed to possess solubility advantages  Stability - The chemical and physical stability of a drug
over the active drug, enabling the use of specifically substance alone, and when combined with formulation
desired dosage forms and routes of administration. components, is critical to preparing a successful
2. Absorption – the drug may be made more water or lipid pharmaceutical product.
soluble, as desired, to facilitate absorption via the
intended route of administration.
3. Bio stability – the design of a prodrug may protect the Phases of Clinical Investigation:
drug during its transport in the body.
Phase 1 – includes initial introduction of an investigational
4. Prolonged Release –it may provide prolonged drug
drug into humans
release and extended therapeutic activity.
- Objective: Assessing safety
Biological Characterization - prospective drug substances
- Subject: healthy human volunteer
must undergo preclinical testing for biologic activity to assess
- Outcome: determine the human pharmacology of the
their potential as useful therapeutic agent.
drug, SAR, side effects associated with increasing doses
- Studies, fall into general areas: and if possible early evidence of effectiveness
a. Pharmacology – is the science concerned with the drug, - Dosage form: capsules without excepients (undiluted,
their sources, appearances, chemistry, actions, and uses pure form)
- Subareas:
Phase 2 – Objective; controlled clinical studies to evaluate the
o Pharmacodynamics – the study of the biochemical
effectiveness of a drug in patients with the condition for
and physiologic effects of the drugs and their
which the drug is intended
mechanism of actions
o Pharmacokinetics – deals with absorption, - Subject: Informed patients (Placebo vs Medicine)
distribution, metabolism, biotransformation, and - Hundreds of patients, several months to 2 years
excretion (ADME) of drugs randomized trials (blinded studies: controlled group vs )
b. Drug Metabolism:
 the extent and rate of drug absorption from various Phase 3 – Objective: determine the usefulness of the drug in
routes of administration, including the one intended for an expanded patient base
human use
- Subject: several hundreds to thousands patients in
 the rate of distribution of the drug through the body and controlled and uncontrolled trials
the site or sites and duration of the drug’s residence - Lasts for several years
 the rate, primary and secondary sites, the mechanism of - 70-90% drugs successfully pass this test
the drug’s metabolism in the body, and the chemistry
and pharmacology of any metabolites Phase 4 – Often called: post marketing surveillance trials
 The proportion of administered dose eliminated from the
body and its rate and route of elimination. - Objectives: a. comparisons of the drug with the drug
c. Toxicology – deals with the adverse or undesired effects already marketed
of drugs a. Monitoring of long0term effectiveness and the
- Acute/ short term toxicity studies impact on patient’s quality of life
o Designed to determine the toxic effects of a test b. Determine of the cost-effectiveness of a drug
compound when administered in a single dose therapy
and/or in multiple doses over a short period, usually - Determine whether the drug can be removes from the
a single day. market
- Subacute or sub chronic studies - Subjects: general consumer
o designing an animal toxicology program,
relationships to projected human clinical studies for
safety must be considered (Ex: 2 weeks of daily
dosing)
- Carcinogenicity studies
o Usually chronic testing and is undertaken when the
compound has a shown promise as a drug to enter
human trials
- Reproduction Studies
o Reveal any effect to active ingredient to mammalian
reproduction
- Genotoxicity or mutagenicity Studies
o Determine whether the test compound can affect
the gene mutation (Assay: Salmonella Typhimurium)

Pre-formulation Studies: