unit 1

what two things can a medicine be?

licensed, unlicensed

can a prescriber still make and/or supply an unlicensed medicine?

yes

what do licensed medicines have that unlicensed don’t?

marketing authorisation number

what two ways can an unlicensed medicine be made?

by a manufacturer who holds a manufacturing specials license, under the supervision of a pharmacist

what is formulation science?

science of turning a drug into a medicine

what is the the active pharmaceutical ingredient

substance that has a direct effect in the diagnosis, cure and treatment of disease

what is an excipient

component other than the active substance which is present in a medicinal product

what 3 things does formulating/formulations improve?

patient compliance, API stability, pharmacokinetic profile

formulation cannot give a drug activity which it would not have but a poor formulation can affect?

activity

high drug-excipient interaction causes?

poor release

low drug-excipient interaction causes?

dump dosing

what are the two types of delivery routes?

invasive, non invasive

what is an invasive method?

a method drug delivery that accesses the target via physical trauma

what is non invasive?

a method of drug delivery that accesses the target without physical damage to tissue

what is a systemic delivery

drug enters circulation and is transported around the body

what is a local delivery

drug is administered at or close to target site

what is bioavailability

fraction of unchanged drug reaching the systemic circulation by any route

to get 100% bioavailability the entire dose of an orally delivered drug must:

• be completely — from the dosage form

• be fully — in the — fluids

• be — in the — fluids

• pass through the — — without being —

• pass through — with being —

released, dissolved, GI, stable, GI, GI barrier, metabolised, liver, metabolised

what shows the varying concentration of a drug in systemic circulation

pharmacokinetic profile

what is C_max

maximum concentration of the drug in the body following administration of a dose formulation

what is the aim of a dosage regimen?

maintain constant therapeutic plasma concentration for duration of therapy

what is a certain formulation that can be used to deliver and maintain consistent drug levels in the circulation (2 answers)

modified release tablets, transdermal patches

what is considered for preparations where they are not for immediate use (also important when water and/or natural products are present)

preservatives

what do preservatives need

high water solubility

COMMON EXCIPIENTS: Density Modifiers

the smaller the density difference between phases-

the less sedimentation will occur

COMMON EXCIPIENTS: do antioxidants prevent oxidation?

no

COMMON EXCIPIENTS: what is the function of buffers?

influence chemical stability, tonicity and physiological compatibility

COMMON EXCIPIENTS: what is the function of organoleptic substances?

mask flavour of drug

COMMON EXCIPIENTS: function of humectants

decrease evaporation of water

what is a solution

mixture of two or more components that form a single homogenous phase

what is the solvent

phase in which the distribution occurs

in liquid formulations the solvent is called the?

vehicle

in solid or semi solid formulations what is it called?

base

what is the solute

component which is dispersed as discrete molecules in the solvent

why do we use a solution?

• drug is already in its molecular form: — — of action

• drug does not require —: this allows rapid uptake following oral delivery

• their — nature means precise tailored doses can be delivered

• easy to —

rapid onset, dissolution, homogenous, swallow

DISADVANTAGES OF SOLUTIONS:

• some drugs are — when in solution and so would not be logistically feasible to make solutions using them

• not all drugs have adequate — — to make a suitably potent solution

• liquids are generally — and take up more space than equivalent solid oral dosage forms

• — of liquids is also more challenging

unstable, aqueous solubility, heavier, packaging

what is dissolution

transfer of molecules/ions from the solid state into solution

why does this happen?

the forces that bind adjacent molecules of the solute together are overcome by attractive forces of molecules of solvent

in dissolution, the liberated molecule of the solute becomes —, surrounded by solvent molecules in an arrangement known as a — —

solvated, solvation shell

what 3 things speed up dissolution

heat, kinetic energy, ultrasonication

what is solubility

extent to which dissolution proceeds under a given set of experimental conditions

AKA the amount of a substance that passes into solution when — is established between the — and — (undissolved) substance (forming a — solution)

equilibrium, solution, excess, saturated

what is miscibility

two components forming a solution are either both gases or both liquids

what is a saturated solution

solution in which no more solvent molecules are available to form solvation shells

what is the difference between solubility and dissolution?

solubility is the amount that can be dissolved and dissolution is how quickly solute enters solution

what does logP measure

how lipophilic or hydrophilic a drug molecule is

what is the equation for logP

solubility of drug in non aqueous medium/ solubility of drug in aqueous medium

can ionised drugs exist in isolation?

no

what do they need

counterion

what is an amorphous drug

drug in a random arrangement of molecules

what is the opposite of this?

crystalline drug

some drugs can form more than one crystalline arrangement- what is this described as?

polymorphic

why would more than one co-solvent be employed?

maximise drugs solubility and optimise efficacy and stability

the salt of a drug that is used can determine what?

formulation properties

what can addition of salt increase in a too lipophilic pure drug?

polarity

what is the function of buffers

maintain pH within a given range over a long period of time

what are semi synthetic polysaccharides made up of glucose molecules bound together in a cyclic “bottomless bucket” structure

cyclodextrins

what do cyclodextrins form?

guest host inclusion complexes

what does the inclusion complexation modify?

physical and chemical properties of the guest molecule

mainly by increasing?

aqueous solubility

what does it rely on?

dissociation at target membrane

what is the function of the formation of micelles/liposomes?

solubilise poorly soluble drugs

what are disperse systems?

systems that consist of 2 or more components in a heterogeneous mixture

what are the two different types of dispersion?

colloidal, coarse

which one has smaller particles?

colloidal

in colloidal dispersions, the particles are not visible to the naked eye- what do you require to see them?

electron microscopy

how are they distinguishable from solutions?

has an effect on light

colloidal dispersions differ from coarse dispersions in that their particles are small enough that — does not exert enough of an effect on them to cause them to settle. this means they can only be separated using —

gravity, ultracentrifugation

in colloidal dispersions the particles move by — — — and so will diffuse

random brownian motion

coarse dispersions are commonly referred to as?

suspensions

COARSE:

larger particles are liable to — due to gravitational forces which causes them to settle upon landing

— must be slow enough that a — dose can be obtained following shaking

sedimentation, sedimentation, homogenous

what type of drug may be formulated as a suspension?

drugs susceptible to aqueous degradation

advantages of disperse systems

done

disadvantages of disperse systems

done

oral medicines vs taste buds

done

PROPERTIES OF AN IDEAL DISPERSE SYSTEM MEDICINE:

• particles should be — — in the — phase

• particles must not — too rapidly

• sediment must be easily — —

• must easily flow out of the container

• particle size should be small and —

evenly distributed, continuous, sediment, re dispersed, uniform

what are the 3 classifications of colloidal systems

lyophobic, lyophilic, amphiphilic

which one is solvent hating

lyophobic

which one is solvent loving?

lyophilic

which one is both loving

amphiphilic

which system is the most thermodynamically unstable

lyophobic

what happens to the particles in lyophobic colloids

aggregate to lower their surface energy

in lyophilic colloids the particles have an affinity for the dispersant and this leads to —. this protective dispersant “coat” prevents — so the dispersion is inherently —

solvation, coagulation, stable

what is the critical micelle concentration?

molecules will arrange at the surface of the continuous phase until there is no space left

what happens after this point?

amphiphiles form micelles

what is a bilayer amphiphile structure?

liposomes

liposomes have a pocket of — phase within them which can be used to encapsulate — materials to control — and protect them from — degradation

— drugs can be dissolved within the middle of the micelle or the bilayer of the liposome and this is a means of utilising colloidal systems to solubilise poorly soluble drugs

continuous, lyophilic, delivery, enzymatic, lyophobic

what are association colloids?

micelles and liposomes constantly disassociate and reassociate with one another to form new structures

what is the name of the effect that occurs when light is shone through a colloidal dispersion?

tyndall effect

optical properties of colloids

done

tyndall effect

done

this light scattering property can be utilised to measure what within a disperse system?

particle size

suspensions are good for remaining oily globules after injection

this is a positive because it reduces — — in contact with physiological fluids and therefore slowing the rate of —

surface area, absorption

what is the definition of wetting?

ability of a solid particle to stay in contact with a liquid

what type of solid is more easily wetted?

diffusible solids

why are indiffusible solids not as easily wetted?

show some hydrophobicity

what do they need in addition to be wetted?

wetting agent

why are finely divided substances particularly difficult to wet?

presence of an absorbed layer of air around the particles

what is the function of a wetting agent?

decrease interfacial tension and help dispersion

interfacial tension slide

done