COD Lectures 1-6

What’s a monograph?

Standard that describes an item and provides the name, storage, package and labeling information.

What’s in the general notices?

definitions and explaination for accurate use

What’s freshly prepared?

made within 24hrs of issuing

What’s recently prepared?

Deterioration likely if stored for over 4 weeks @15-25C

What is PPM?

parts per million

weight in weight

Which appendix contains methods of sterile preparation?

Appendix 18

needles need to be sterile

1→ needle

8→ butt

\

How to sterilise aqueous preperations?

Steam sterilisation→ autoclave heating

What kind of water is water without specifications?

Potable water

What’s potable water?

Freshly drawn from public supply

Freshly boiled and cooled purified water

Which appendix has the test for efficacy of antimicrobial preservation?

16c

If a monograph already specifies a preservative, can you use another?

Yes, include on label!!

In which volume of BP are the appendices?

Volume 4

What’s in volume 3?

Formulated preperations

Which appendix has the dissolution test for tablets?

12d

What’s bioavailibility?

% of drug that enters systemic circulation

What are the most commonly used dosage forms?

tablets

oral liquids

capsules

Name an example of drug which is formulated with 95% excipient?

Digoxin

What is used to investigate the interactions between drug and excipients?

Thermal Analysis

DSC

List the routes that can be used for systemic delivery

* nasal
* buccal
* iv
* ip
* topical
* ia
* inhalation
* oral
* rectal
* im

Is the epidural systemic /local?

Local

stays in spinal cord

What are the disadvantages of the oral route?

Slow

First pass

GIT degredation

Can the rectal route be used for systemic?

Yes

but absorption really varies

Can suspensions be used in injections?

Yes, but they are slower than solutions

What can you use to alter absorbtion of injected drug?

Vasodilators/ vasoconstrictors

What’s the particle size that will reach the alveoli?

0\.5- 1 micrometers of diameter

Can insulin be administered via pulmonary route?

Yes!

How to increase nasal residence time?

Increase viscosity

How is the rate of uptake of dermal/buccal administration?

Poor

What’s the epithelia in the stomach/intestine?

Simple columnar

GIT is a simple column if you lay it out

What’s the epithelium in the buccal route?

Stratified squamous

What’s the epithelium in the vaginal?

Lick your inner cheek (buccal)

Same as eating her out!

Stratified Squamous

What’s the epithelium in the nasal route?

Pseudostratified columnar

long nose= columnar

Klown ma nos i pseu ci

What’s the epithelium in the alveoli?

Simple squamous

(absorbtion like the intestine)

What’s the epithelium in the bronchioles?

Simple cuiboidal

longer than alveoli- what happens when you elongate a cube- cuboid!

What’s the epithelium in the ocular route?

Stratified squamous

Does the pulmonary route have musous?

Only in the briochioles

\
not in alveoli! that would prevent O2 moving in

What’s special about stratified squamous?

They shed

so they are in skin shedding placesz

Do AQP facilitate the movement of drugs?

Not really

What’s the surface charge on most bio membranes?

Negative

Give me fick’s law?

dm/dt = DK/h (A\* Cg-Cb)

d=diffusivity

a= surface area

k= partition co-eff

What are sink conditions?

cg>>>>cb

What are the three simplied fick’s laws?

all under sink conditions!

dm/dt= Dk/h \* A *Cg = p* A * Cg= Ki*Cg*

Is facilitated diffusion needed for drug absorption?

* very minor role in drug absorption

What;’s the issue with facilitated diffusion?

* can become saturated
* competitive inhibition!

How are ACE inhibitors transported and why?

they resemble endogenous substances that bind to carrier and therefore can be transported via active transport

What other drugs can be actively transported?

Pencillin

Cephalosporin

Ace inhibitors

L-dope

(antivirals/ amino acid analogues)

What’s the F (bioavailibility) for Paracetamol?

iv= 100%

Oral= 62-89%

Rectal= 24-98%

Does the drug have to be in solution to be bioavailable?

Usually!

Name two drugs with a narrow therapeutic window

Digoxin

Warfarin

What thing is responsible for the apical efflux of drugs?

P-Glycoprotein

How is gastrin increased?

by the increase of peptides, amino acids, stomach digestion

Where is mucus secreted in the stomach?

surface mucosal cells

What’s the longest part of the GIT?

small intestine

How much of cardiac output goes to the intestine?

1/3 of cardiac output

How does the drug get from the small intestine to the liver?

hepatic portal vein

What is the long liist of things that affect oral bioavailibility?

1. git structure
2. aqueous boundary layer
3. metabolism
4. motility
5. fluid volume
6. food
7. absorbtion window
8. fluid flow


1. gender/race / age/ disease/ pharmacotherapy

What enzymes are in the lumen of the instestine?

proteolytic

How are the cells arranged of the mucosa?

with tight intracellular junctions

What’s on the brush border?

Enzymes

What’s the nature of the membrane?

Lipophillic

What does log p = -1 mean?

Polar compound

poor absorbtion

What’s the P in LogP

Conc of lipo/ Conc of aq

What does a high LogP mean in terms of secretion?

Slow secretion

will accumulate in adipose tissue as its reallll comfy there

Do ionised/unionised drugs pass better?

Unionised

What makes up the brush border?

Glucocalyx

What do the goblet cells secrete?

Mucus

What are mucins?

Protein core with a lot of carbohydrates

What do mucins resemble

A bottle/pipe brush cleaner

What are the carbohydrates on the protein chain in mucins?

N-acetylgalactosamine

N-acetylglucosamine

galactose

fucose

sialic acid

what charge are mucins?

Negatibve

Why are musins negatively charged?

Due to sialic acid

Why are mucins viscous

High molecular weight

with what goes the g-glycocalux co-operates?

Cytochrome p450 enzymes

* if drug fits pgp=drug leaves the cell via Pgb
* if drug fits pgp= drug will fit cyp450
* drug gets stuck in a cycle and gets metabolised by cyp enzyme

Whats the pH of the lumen?

6-7.5

What enzymes are in the lumen?

Proteases

Hydrolases

What’s pancreatic juice?

NaHCO3

Zymogens→ trypsin, chymotripsin

Amylase, lipase

What do trypsin, chymotripsin digets?

Proteins

What activates trypsin and chymotripsin?

Enterokinase

What’s bile made up of?

Bile aacids

Phospholipids

Cholesterol

Billirubin

Electrolytes

How does bile get recycled?

Enterohepatic recircultion

Name the things inside the gut that impact drug absorbtion.

buffers, food, fluid volumes, surfactants, microflora

Distinguish between particle size and molecular size?

Particle→ formulation characteristic

Molecular→ physchem property

What does the modified noyes-whitney equasion describe?

The physiochemical and physiological factors affecting drug absorbtion

Give the modified noyes-whitney equasion

* similar to fick’s law

DX/dT= (Cs=Xd/V) \*AD/h

What’s A

Phys/chem→Surface area

Physio→ Surfactants/ Bile

What’s D

Phys/chem→ Molecular size

Physio→ Viscosity

What’s h?

Phys/chem→

Physio→ Motility& flow rate

What’s Cs?

Phys/chem→ Hydrophilicity/ Crystal structure

Physio→pH/ buffer/ bile/ food

What’s Xd

Phys/chem→

Physio→ Permeability

What’s V

Phys/chem→

Physio→ Secretions

What’s the GRAS listing?

Toxicity listing

What are organoleptic properties?

Appeal to taste/smell

Can emulsions be supplied as a powder/granules?

nope

What’s the definition of oral suspensions?

API suspensed in a vehicle

→ easily redispersed

→ solids may slowly seoerate when left standing

How is the solute presented in a solution?

Molecular dispersion

NOT FINE PARTICLES

Why are solutions generally faster in terms of onset of action?

Even if they fall out of solution they’ll remain wetted and finely divided= good for re-dissolution

\
* wet
* fine
* not clumped

Are solutions homo/ heterogenous?

Homogenous

What oral formulation of aspirin will be more gentle on the stomach?

Solution

* tablets are highly localized (concentrated area of acid)

Why are solutions less stable?

High water content= microbial growth

=hydrolysis

therefore a shorter shelf life

What’s the solution to making solutions more stable?

formulate as granules/ sachets to be made up