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Last Updated 8/19

Drug

Substance intended for use in the diagnosis, mitigation, treatment, cure, or prevention of disease in humans or other animals

Small Molecules Drugs

(includes most drugs) <900 daltons; compounds that are manufactured via chemical synthesis

Biologics (biopharmaceuticals, macromolecules)

Large molecules that are made in bacteria, plant, or animal cells using recombinant DNA tech

Prodrug

Inactive compound that becomes active in the body through enzymatic or biochemical transformation

Pharmaceutics

the science of designing dosage forms and drug delivery systems — turns an active ingredient into usable medicine

Dosage Form

the final physical form of the drug which may be used by the consumer without requiring any further manufacturing

Why is a dosage form needed?

• to admin an accurate dose that is convenient

• ensure patient compliance

• conceal unpleasant taste/odor

• Protect drug again decomposition from external environment

• control the release of drugs into the body

A finished dosage contains…

inactive and active ingredients

Active ingredients

substances that are responsible for pharmacological effects

Inactive ingredients

have well-define, non-therapeutic function in a drug product (contributes to texture, stability, taste, appearance)

Excipients

are intended to be inert and listed as inactive ingredients, but they can have risks/cause adverse events

Examples of excipients

fillers, thickeners, sweeteners, flavors, solvents, etc.

Why do you need to be careful when considering pediatric dosages?

Children are not born with fully functional organ and enzyme systems — Infants also have immature hepatic and renal function.

Compounding

Preparation, mixing, assembling, altering, packaging, and labeling of a dosage form by a licensed pharmacist

Manufacturing

Large scale production of dosage forms by pharm companies

Compounding is

tailored to the patient and regulated on the state level

Manufacturing involves

mass production and is regulated on the federal (FDA) level

Until the 20th century, pharmacy was compounding. The rise of commercial drug manufacturing caused a transition in pharmacists’ role from

compounding to dispensing

Reasons for renewed interest in compounding

• personalized therapy

• to recreate discontinued or unavailable medications

• improved access to supplies makes it easier to compound

• more information is available, making it easier to compound

The United States Pharmacopeia (USP) publishes

the USP-NF (United States Pharmacopeia, National Formulary)

The term pharmacopeia suggests

any recipe or formula or other standards required to prepare a drug

The Federal Food, Drug, and Cosmetic Act (FD&C) (1938) recognized the USP/NF as the

official compendia of drug standards

The USP is published

unnually

The USP/NF contains formulas, monographs, and reference books that

describe standards that manufacturers and pharmacists should maintain when they prepare drug products

A drug formulation or formula is a

recipe for preparation of a drug product

A drug formula includes

• name and quantities of ingredients (active and excipients)

• Mixing sequence and processing steps

(T/F) Other counties have their own pharmacopeias.

True

The drug approval process has 3 general steps. What are they?

1. Early discovery and pre-clinical development (tested on animals)

2. Clinical development studies (Phases 1, 2, and 3) (tested on humans)

3. Commercialization and post marketing surveillance (Phase 4)

Clinical Trial Phase 1 Includes

• administering the drug to a small amount of healthy volunteers

• Aims to learn side effects, dosing information, and administering the drug safely.

Clinical Trials Phase 2

• Tests hundreds of people with the disease

• aims to determine patient's’ response to drug

• If therapeutic response is evident, drug continues to phase 3

Clinical Trials Phase 3

• Enrolls a large number of participants to confirm effectiveness in larger studies

Post Marketing Surveillance (Phase 4)

• Tests an even larger population — rare adverse reactions are likely to be found after drug has been approved

• Drug may need to be furthered tested once FDA evaluates negative trends and implications (or may be taken off the market)

NEED TO ADD IND AND NDA PHASES OF DRUG DEVELOPMENT

Food and Drug Administration Act of 1997 (FDAMA) states that

[Section 503A] Drug products that are compounded by a pharmacist are entitled for exemptions from 3 key provisions of the Federal Food, Drug, and Cosmetic Act:

• FDA approval or drugs under new drug applications (NDAs) or abbreviated new drug applications (ANDAs)

• Labeling drugs with adequate directions for use

• Current Good Manufacturing Practices (cGMP) requirements

The following conditions must be satisfied for drug products compounded by a licensed pharmacist to be exempted:

1. The drug is compounded for an identified individual patient based on a valid prescription

2. The drug is being compounded by a licensed pharmacist

3. The drug is compounded in compliance with USP

4. The drug is NOT compounded in inordinate amounts any drug products that are essentially copies of commercially available drugs

Brand Product

• Innovator’s product

• Has exclusive patent (trademarked R)

Generic Product

• a copy of a innovator’s product (only can be made once patent expires due to Hatch-Waxman Act of 1984)

• Use non-proprietary (generic) names standardized by USAN + WHO

Generic Drug Development

• has the same active ingredients/strength/and dosage form

• Does NOT required preclinical trials

• Must show a bioequivalence study

• Has to be submitted to ANDA (abbreviated New Drug Application)

What Is Unbranded Generic?

• Generic that is sold after branded drug’s patent expired

• Needs to submit ANDA

What is Authorized Generic?

• The same thing as the brand name drug, and can be sold patent BEFORE patent expired (by the company who made the original)

• This is the original drug NDA

• Companies sell Authorized Generics to make more money

What is Branded Generic?

• A generic drug that has been given a market name

• Sold AFTER original patent expired

• Approved by FDA by ANDA

Dose

an amount of a drug that is enough to produce a therapeutic response without producing toxic effects

Strength

is the amount of active medicine in a single unit

What must be submitted before a drug can be tested in humans for the first time?

IND

IND:

Investigational New Drug Application; filed for first human test

NDA

New Drug Application; Filed once clinical phases are passed — drug is moved to the market

What is an Enteral dosage?

administered into the gastrointestinal tract (GIT)

• By mouth, stomach, or rectum

What is a Parenteral dosage?

given at sites that are outside of or beside the alimentary (GIT) tract

(aka anything that is not GIT)

Parenteral routes often include

needles and is also referred to as “injection-dependent routes”

Oral Route

• Drugs taken by mouth, and are absorbed in the GI tract.

• These drugs are mainly absorbed in the small intestine (due to large surface area + residence time)

• Major disadvantage is first pass metabolism

Disadvantages of Oral Route

• Not suitable for drugs that degrade in the GIT

• Interactions with food

• Unpleasant taste

• First pass metabolism reduced drug absorption

First Pass Metabolism

• Oral drugs enter the liver before entering systemic circulation

• Some drugs degrade in the liver (leads to low systemic availability)

Oral forms include

• tablet

• capsules

• solutions

• suspensions

• emulsions

Solutions

Drugs are dissolved in a vechicle to form a homogenous mixture

Suspensions

solid drug particles dispersed (suspended) in a suitable vechicle

Emulsions

drugs are present in a mixture of water and oil

Buccal and sublingual routes are NOT

oral routes

Where are drugs place for sublingual route?

Under the tongue

Where are drugs placed for buccal route?

Between the cheek and gums (gingivae) adjacent to teeth

What are advantages or buccal and sublingual routes?

• Avoids first pass metabolism + can be used in unconscious patients

• (however they taste bad + not good if drugs degrade in saliva)

Parenteral routes advantages

• Avoids first pass metabolism

• used in emergency situations/unconscious patients

Parenteral routes disadvantages

• Invasive

• Difficult to withdraw once it’s administered

• Must be sterile

Parenteral Routes include

• intradermal

• subcutaneous

• intramuscular

• intravenous

• intrathecal

• epidural

• intraarterial

Intradermal is injected into the

dermis (common site: anterior surface of forearm — TB test)

Subcutaneous is injected into the

subcutaneous tissue (fat layer under skin) (common site: thigh, lower abdomen, back of upper arm)

Intramuscular is injected into the

skeletal muscle, away from nerve and blood vessels (common site: buttocks, upper arms, lateral thighs)

Intravenous is injected into the

veins (ensures complete dose delivery (100% bioavailability)

Intrathecal is injected into the

subarachnoid space in spinal column (used for local pain)

Epidural is injected into the

epidural space near spinal column (local anesthetics for labor)

Intra-arterial is injected into

artery (used to create contrast for viewing an organ)

Intra-articular injection is injected into

directly into the joint

Drug Injection

liquid preparations (solitions)

Drug for injection

dry solids that, upon the addition of suitable vehicles, yield solutions

Drug Injectable Emulsion

liquid preparations of drug substances dissolved or dispersed in a suitable emulsion medium

Drug injectable suspension

liquid preparations of solids suspended in a suitable liquid medium (suspension)

Drug for injectable suspension

dry solids that, upon the addition of suitable vehicles, yield injectable suspensions (suspension)