DDS Lecture 1 Content

Drug

Drug

Any substance administered orally, parenterally, or topically with the purpose of altering body’s physiological processes through modifications of biochemical functions

Active Pharmaceutical Ingredient (API)

• Biochemically active component of the drug

• Seldom administered in the pure form, often combined with one or more inactive ingredients

Excipients

Inactive ingredients added to the API to stabilize the formulation, provide base of topical creams and ointments, ensure sterility of injectable products, or assist in the masking of unpleasant taste or smell

Over the Counter Drugs

• drug that can be dispensed without a prescription from a healthcare provider

• FDA approved, have come off patent and proven relatively safe over the years

Proper labeling for OTC drugs

• indication

• dose for various age groups

• side-effects

• warning

• expiration date

Prescription Drugs/Legend Drugs

• dispensed only with prescription

• carries Rx symbol

• divided into 5 drug schedules based on potential for physical and psychological abuse per Comprehensive Drug Abuse Prevention and Control Act 1970

Schedule I

• drugs with no currently accepted medical use and a high potential for abuse

• heroin, lysergic acid diethylamide (LSD), marijuana (cannabis), 3,4-methylenedioxymethamphetamine (ecstasy)

Schedule II

• drugs with a high poential for abuse, with use potentially leading to sever psychological or physical dependence

• dangerous

• Combination products with <15 mg hydrocodone per dosage unit (Vicodin), cocaine, methamphetamine, methadone, hydromorphone (Dilaudid), meperidine (Demerol), oxycodone (OcyContin), fentanyl, Dexedrine, Adderall, Ritalin

Schedule III

• drugs with moderate to low potential for physical and psychological dependence

• abuse potential less than I/II but more than IV

• products with <90 mg codeine per dosage unit (Tylenol with codeine), ketamine, anabolic steroids, testosterone

Schedule IV

• drugs with low potential for abuse and low risk of dependence

• Xanax, Soma, Darvon, Darvocet, Vallium, Ativan, Talwin, Ambien, Tramadol

Schedule V

• drugs with lower potential for abuse than Schedule IV and consist of preparations containing limited quantities of certain narcotics

• generally used for antidiarrheal, antitussive, analgesics

• cough preparations <200 mg codeine per 100 mL (Robitussin AC), Lomotil, Motofen, Lyrica, Parepextolin

Dietary Supplements

• Regulated by Dietary Supplement Health and Education Act (DSHEA) amendments of 1994

• Vitamines, minerals, herbs

• can act as weak drugs (side effects, adverse reactions, drug interactions)

• cannot make disease claims (cannot claim to prevent, treat, cure, mitigate, diagnose)

• must have disclaimer: this statement has not been evaluated by FDA

• manufacturers who meet USP criteria carry USP verified mark on label

New Drug Development/Approval Process

1. New chemical entity sourced from organic synthesis, molecular modification, or isolation from plants

2. Preclinical Studies

3. Investigational New Drug Applications (IND)

4. Clinical Trials

5. New Drug Application (NDA)

6. Postmarketing

Long, expensive process: takes 15-20 years, over few billion dollars

Pre-clinical studies

Studies

• chemistry

• physical properties

• biological properties

  • pharmacology (biological action of drug)

  • ADME

  • toxicology

• Pre-formulation

  • determines how drug can be formulated to deliver to humans

  • determined by chemistry, physical properties, ADME

• begins before clinical studies and continues during

• Long-term animal toxicity

• Product formulation

• Manufacturing and controls

• Package and label design

Investigational New Drug Application (IND)

submission and FDA review

Clinical Trials

Phase I, II, III

New Drug Application

• submission

• FDA review

• Pre-approval plant inspection

• FDA action

Post-marketing

• phase IV clinical studies

  • clinical pharmacology/toxiclogy

  • additional indeications

• adverse reaction reporting

• product defect reporting

• product line extension

Phase I Clinical Study

• 20-100 patients

• up to 1 year

• mainly to test safety

• 70% of drugs successfully tested

• most drugs given as injection

Phase II Clinical Trial

• 100-500 people

• lasts several months to 2 years

• tests mainly effectiveness and short-term safety

• 33% of drugs successfully tested

• drug mostly formulated parenterally (injection)

Phase III Clinical Trial

• 1000-5000 patients

• 1-4 years

• tests safety, effectiveness, dosage

• 25-30% of drugs successfully tested

• drug can be formulated in tablet form

Pharmacology

• includes biochemical and physiologic effect, mechanisms of action, absorption, distribution, metabolism, and excretion (ADME)

• in-vitro studies

• whole animal studies

ADME

• absorption, distribution, metabolism, excretion

• drug metabolism involves transformation of non-polar drug molecules to polar compounds

• animal studies are done to determine rate of drug absorption via different routes of administration, rate of drug distribution, chemistry and pharmacology of metabolites, rate, extent and routes of elimination

• because of polymorphism of enzymes, ADME will be slightly different for each person

Toxicology

• adverse or undesired effects of drugs

Types of toxicity studies

• acute or short-term toxicity studies

• subacute subchronic studies (longer than acute, shorter than chronic)

• carcinogenicity studies (done in animals, goes on label)

• reproduction studies (done on both genders of animals, see if there are effects on fetus, see if it causes hormonal imbalances)

• genotoxcity or mutagenicity studies (sees if drug has effect on DNA or cause mutation, most cancer drugs cause mutation but within acceptable limit)

Early Formulation Studies

• chemical and physical properties of a drug evaluated for the successful formulation and effective pharmaceutical product

• Pre-formulation studies

  • drug solubility (drug must be water soluble to be absorbed by body)

  • partition coefficient (how well drug will cross biological membrane)

  • dissolution rate (how fast drug will dissolve)

  • physical form

  • stability

• Formulation studies

  • dosage forms

  • excipients evaluation

National Drug Code

• unique number that appears on all drug labels

• 10 digits (DEA recommended update to 12 digits in June 2022, will change soon)

• Labeler code: 4-5 digits, indicates manufacturer

• Product code: 3-4 digits, indicates active ingredient, strength

• Package code: 1-2 digits, indicates packaging size type

• used for drug recalls by FDA

• minimizes medication errors in pharmacy

Sources of Drugs

• natural

• synthetic/semisynthetic

• biological/biotech

Natural Sources of Drugs

• microbial, plants, animal origin

• ex. penicillin, morphine, aspirin, insulin, human growth hormone

• drugs that were originally naturally sourced are now synthesized in lab to ensure purity, correct isomer, cost-effectiveness

Synthetic/Semisynthetic sources of drugs

• created artificially in lab through chemical synthesis

• derivatives of naturally occurring biomolecules

  • based off natural substrates

• toxicity and side effects can be modified by structural modifications

• majority of drugs sourced from synthetic sources (80-90%)

Biological/Biotech sources of drugs

• monoclonal antibodies produced by genetic engineering and hybridization

• small interfering RNA (RNAi)

• protein-based therapeutics

  • ex. insulin hormone

• many more approved in recent years

Applications of Drugs

• Therapeutic Agents

• Diagnostic Agents

Therapeutic Agents

• may be prophylactic (preventative)

• maintains health

• relieve symptoms

• reverse disease processes (chronic diseas

• anti-infective properties

• alters bodily functions in a desired way short-term or long term

• oral contraceptives

• most drugs classified in this category

Diagnostic Agents

• facilitates in understanding the nature and extent of disease condition

• utilizes radiopharmaceuticals

• application in imaging studies such as PET scan

Dosage form

• physical form of a drug formulation

• solid

• liquid

• Semisolids

• gas

Drug delivery system

• device used to deliver drug

• design feature of dosage form that affects delivery of drug (aspect of formulation that helps deliver drug)

• targeted delivery to desired site of action in body

• depends on:

  • type/amount of API

  • route of administration

  • purpose of therapy

  • duration of therapy

  • rate of administration

Drug Delivery Systems for Solid Dosage Forms

• tablets

• capsules

• powders

• granules

Drug delivery systems for liquid dosage form

• solutions

• emulsions

• suspensions

• oral or parenteral

drug delivery systems for semisolid dosage forms

• creams (emulsions)

• lotions (emulsions)

• gels

• ointments

• suppositories

• troches

• chapsticks

• topical or transdermal

Aerosol based drug deliver systems

• inhalational (through nose)

• oral

• topical

Nano-Drug Delivery Systems

• utilized to achieve targeted delivery of API

• can be used to improve pharmacokinetic properties

• can be used to decrease toxic response due to API

• small, encapsulated particles of drug

• ex. COVID vaccine

Implants

• drug delivery system

• compressed sterile solid containing purified API

• provides controlled drug delivery over a period of time

• usually biodegradable

Transdermal Drug Delivery Systems

• non-invasive mode of delivering drugs into blood stream

• bypasses oral route

• long duration of action

• less side-effects

• sustained drug delivery

• crosses dermal barrier into blood stream

United States Pharmacopiea

• describes drug substances and dosage forms

• contains drug monographs and general chapters

• published in combination with NF

• used when compounding

  • see solubility, stability, storage conditions of drugs

• official legal standards of drugs in US

National Formulary

• describes pharmaceutical ingredients

• published in combination with USP

• official legal standards of drugs

USP Chapter 795

• Pharmaceutical Compounding and Non-sterile preparations

• good compounding practices for preparation of non-sterile formulations for human/veterinary use

• compounding, compounder responsibilities, compounding processes, facilities, equipment, components, stability, beyond-use dating, packaging, documentation, quality control, patient counseling, personnel training, and compounding for animals

USP Chapter 797

• pharmaceutical compounding and sterile preparations

• guidance to prevent harm to patients as result of non-sterility, contamination, and poor quality ingredients

• responsibilities, training, evaluation of personnel/facilities, equipment requirements, SOPs, finished preparation release checks and test, risk levels, storage, beyond use date

USP Chapter 800

• hazardous drugs- handling in health care settings

• promotes patient, worker, and environmental safety/protection

• applied to all health care personnel who handle hazardous drug preparations and all entities that store, prepare, transport, or administer hazardous drugs

• 18 sections

• informational/definitions, responsibilities, protection, communication/training, processing concerns, cleaning/spill control, documentation and surveillance

• hazardous drugs based on NIOSH list of antineoplastic/other hazardous drugs in healthcare settings

USP chapter 1160

• pharmaceutical calculations in pharmacy practice

• general info to assist pharmacists and techs performing required calculations for compounding/dispensing

• covers most calculations pharmacist will require for practice

USP Chapter 1163

• quality assurance in pharmaceutical compounding

• various strategies to assure wuality of compounded preparation

• discusses training, standard operating procedures, documentation, verifications, analytical/chemical testing, physical testing, microbiological testing, cleaning/disinfecting/safety, packaging, outsourcing, responsibilites