drug discovery and development

goal drug

- produces desired effect

- oral route e is the most desired route, so tablets are the number one choice, then capsules, etc

- rapid onset and minimal dosage with no toxicity

- eliminated efficiently and doesn't linger

drug source old

- plants

drug source new

animals and bacteria

- ex for animals: insulin from pig pancreas, estrogen from urine, vaccines and antitoxins from blood

- ex bacteria: inject human DNA in bacteria to code for insulin

genetic field of drug development

recombinant DNA (rDNA), monoclonal antibodies (Mab), human gene therapy

recombinant DNA (rDNA)

bacteria produce proteins (insulin)

monoclonal antibodies (Mab)

animal cells produce antibodies (HCG) human chorionic gonadotropin

human gene therapy

manipulation of genes by injecting DNA or virus as vector

United States Pharmacopeia (USP)

- a cookbook that says to measure active ingredient in the drug and +- 10% of accuracy of said value

- develops and publishes standards for drug substances, drug products, excipients, and dietary supplements

- considers purity

- USP DOES NOT ENFORCE, it is just a guide on how to make drugs

- FDA enforces standards and makes sure that these drugs follow USP cookbook standards

criteria of drug quality in USP

identity, strength, purity, quality

identity USP

meets the drug specifications as described in the USP monograph such as color, odor, physical form, etc

strength USP

contains the quantity of each active ingredient claimed on its label, within the applicable limits of its specifications

purity USP

free from extraneous substances

quality USP

maintains potency, therapeutic availability and appearance until used

pharmaceutics definition

area of pharmacy concerned with the design, manufacture, physical and biological evaluation of dosage forms and can be classified into technology and biopharmaceutics

pharmaceutical technology

- how to make the drugs and make sure it conforms with USP standards

- physiochemical properties of drugs

- additives/excipients

- formulation/design

- manufacture of dosage forms

biopharmaceutics

- see if it works RIGHT

- interaction of dosage forms with biological systems

Drug development timeline

takes about 10-15 years and $1-5 Billion to bring drug to market

- this is why drugs are expensive

Nutraceuticals

- vitamins, minerals, herbals, supplements

- so many brands

what to watch out for with nutraceuticals

- almost no research on molecules, preclinical or clinical studies done, meaning that they can't claim to cure or prevent specific diseases

- product variability of plant ID, growth, harvest, and storage conditions

- lack of practitioner or user education

- very limited certification of quality or content

- none of them meet standards of science and NOT FDA approved

- adulterants may be: drugs, mis-identified plants, heavy metals like lead and arsenic, prescription drugs, and pesticides

people most likely to use supplements

- disease where conventional therapy doesn't work and need to boost their immune system to be able to stay strong after treatments

- cancer, arthritis, chronic back pain, AIDS, GI problems/chronic renal failure, eating disorder, fatty liver disease, healthy people wanting to improve/maintain their health status

wrong labeling

- most label claims of common herbal remedy are false as research shows

- Ottawa, Canada issues health warning in Jan 2004

- many bottles were off by 400% of an active ingredient for drugs compared to what was on their label

- people should stick to one brand because plants from a different place can make the amount of active ingredient vary

Ginkgo case study

- Ginkgo used to be the treatment of everything

- placebo effect is what actually helped people with dementia not feel the effects for a bit, but there were no actual significant difference between a fake vs real Ginkgo drug

Nutraceuticals and FDA

- health group advocates wanted regulations on Nutraceuticals, but other groups did not because they didn't want the government telling them what vitamins they can and can't take

- in 1994, the Dietary Supplement Health and Education Act (DSHEA) was passed to expand Americans' access to natural health products and create a separate regulatory framework

- following USP standards for supplements is VOLUNTARY, so a lot of companies don't do this for cost cutting

- many vitamins have FDA approved prescription versions with higher doses for people who can't trust unregulated companies

USP Label on Nutraceuticals

- companies that chose to follow USP standards have a USP label

- healthier by comparison and have market advantage, because the USP label shows that what is on the label is in the bottle, which cannot be verified with vitamins and supplements that don't have the USP label on their product

- prenatal drugs used to not follow USP --> recommend USP grade items if someone asks

- nature made and Kirkland

drug manufacturing and compounding practices

way that we make drugs in a company/compounding lab

cGMP(current Good Manufacturing Practices)

- regulations established by the FDA to ensure minimum standards are met for drug product quality in the US

- they apply to both domestic and foreign manufacturers whose bulk components and finished pharmaceutical products are imported, distributed, or sold in this country

active ingredient

any component that is intended to furnish pharmacologic activity or other direct effect in the diagnosis, cure, treatment, or prevention of disease

batch

active ingredient goes into a big barrel and is shipped to the company (Ex: 50 kg = millions of medication)

- specific quantity of a drug of uniform specified quality produced according to a single manufacturing order during the same cycle of manufacture

lot

take part of that batch having uniform specified quality and distinctive identifying lot number

lot number

subsection of batch number or control number

- recalls a lot through lot number to save cost and identify the specific group of incorrectness

strength

The concentration of the drug substance per unit dose or volume

storage

- mostly room temperature

- suspensions or antibiotics in fridge

- when medication is yellow, brown, or orange, it is bad and you should throw it out

cGMP Compliant building and Facility

Each building's design, structure, space and placement of equipment must be such to enable thorough cleaning, inspection, and safe and effective use for the designated operations.

- includes water quality, security, materials used for floors, walls and ceilings, segregated quarantine areas for raw materials, etc

cGMP Requirements for Manufacturing in Pharmacies

- apply to pharmacies that manufacture, repack, relabel drugs and drugs products in a supplier function BEYOND the usual conduct of professional dispensing

- packaging and labeling guidelines are important

- FDA officers(of the law) can come whenever they want and open whatever they want and go anywhere

why is compounding needed?

- don't fit with commercially available dosages

- need different dosage form

- allergic to additive

- dosage form expires quickly so it must be made in front of the patient right before they take it

- children's and veterinary medications

- hospice

- physicians try products in innovative ways

containers

- container is "that which holds the article and is or maybe in direct contact with the article"

- different specifications required for parenteral, non-parenteral, pressurized and bulk containers and for those made of plastic, glass and metal

glass pros and cons

pros: cheap, heat resistant, transparent

cons: can break

plastic pros and cons

pros: flexible, many shapes

cons: chemical exchange with dosage form so risk of contamination!, shedding of microplastics, risk of incompatibility

*donated bodies with Parkinson's disease and dementia have spoonful's of microplastics

Glass Types

Type I: Highly resistant borosilicate glass THE BEST

Type II, III, NP not the best

Plastic use

use plastic with purpose

problems with plastic packaging

- permeability to atmospheric oxygen and moisture

- leaching of constituents of the container to the internal contents

- absorption of drugs from the contents to the container

- transmission of light through the container

- alteration of container upon storage

plastic additives

- added to alter container properties to reduce the problems that plastic packaging brings

- plasticizer to make plastic not break and make it flexible --> new car smell

- stabilizer/protectant

- antioxidants

- antistatic and antifungal agents

- colorant