preformulation

Question 1

what is pre-formulation

Answer 1

determination of physiochemical characteristics of a drug prior to formulation development- fundamental and derived

Question 2

derived characterisation data

Answer 2

particle size/morphology, powder flow, compression properties, excipient compatibility

Question 3

two fundamental properties that are mandatory

Answer 3

intrinsic solubility (C0) and dissociation constant (pKa)

These indicate the need and the possibility of making more soluble salts of the drug to improve absorption & bioavailability of poorly soluble drugs in solid dosage forms, e.g. tablets.

Question 4

solubility of drug

Answer 4

solubility and pKa- very important. aqueous solubility must be over 1%w/v at 37 degrees over pH 1-7 to avoid problems.
intrinsic solubility- saturation solubility of a compound
weakly basic drugs- solubility increases in acidic solution, weakly acidic drugs- solubility increases in alkali drugs

Question 5

what is IDR

Answer 5

intrinsic dissolution rate is the amount of drug that dissolves per unit time and surface area (mm/cm2.min)
IDR must be more than 1mg/cm2.min to ensure absorption is not dissolution rate limited, if less than this, it will be necessary to increase dissolution rare by salt formation or formulation techniques to improve solubility

Question 6

UV spectroscopy

Answer 6

simple analytical method, most drugs absorb light in UV wavelength (190-390), max absorbance occurs at lambda max.
extent of absorption can be measured to quantify drug concentration

excitation of the molecule in solution causes a loss in light energy (due to absorption) and the net change from the intensity of the incident light and the transmitted light can be measured
( measure difference in absorbance between reference (solvent) and drug (sample)
the amount of light absorbed is proportional to the concentration and the path length of solution through which the light source has passed.

Question 7

beer lambert equation

Answer 7

absorbance = log I0= epsilon (constant for molar absorptivity) x c x L
allows to determine concentration of a solution based on its absorbance
most useful- A=A1% 1cm x c x l
takes form of a straight line;
A=A 1% 1cm x c
y=mx + c

Question 8

what is thermal analysis

Answer 8

behaviour of drug and excipient heating 
measured by 4 techniques;
capillary melting- observation of melting in a capillary tube
hot stage microscopy
differential scanning calorimetry DSC
thermogravimetric analysis TGA

Question 9

differential scanning calorimetry (DSC)

Answer 9

only 2-5m pf sample required- very sensitive
sample and reference aluminium pans placed in DSC and heated/cooled
nitrogen atmosphere- inert atmosphere
instrument measures the amount of energy required to keep the sample at the same temperature as he reference i.e. measures the enthalpy of transition.
melting point measurement and other phase changes- primary diagnostic tool for asserting polymorphism
when no physical or chemical change is occurring within the sample then there is no need to input energy to maintain an isotherm. however, when phase changed occur energy is either given 0ut (exothermic- recrystallisation) or taken in by the sample (endothermic- melting) tis change in energy relative to reference is determined by attached software to produce a thermal scan

the greater the area of the peak, the more energy taken in/ given out during the transition

Question 10

thermogravimetric analysis (TGA)

Answer 10

used to measure the loss of mass on decomposition, solvent loss
helps to clarify DSC in terms of identifying peaks
sample placed on sample pan on balance
sample lowered into furnace, heated and change in mass recorded

Question 11

hot stage microscopy

Answer 11

complementary to both DSC and TGA. allows images to be taken of samples as they are heated/cooled. sample place on slided under microscope. heated/cooled to temperatures found for thermal events on DSC, TGA and picture taken to show physical change in sample

Question 12

excipient compatibility

Answer 12

formulation requires drug and excipients
thermal analysis- used to investigate and predict physiochemical interactions
initial screening tests to find suitable compatible excipients

Question 13

interpretation

thermal properties, interaction

Answer 13

thermal properties of a physical mixture- the sum of the individual components. scan compared with those of the drug and excipient alone
interaction- shown as changes in melting point, peak shape and area of transition. interaction suspected if scan shows new thermal events occurring or if events are lost, on mixing. new peals, gross broadening or elongation of peaks.
results must be interpreted cautiously n cases where the excipient concentration in product is low

Question 14

what type of experiments are better for room/body temperature

Answer 14

isothermal titration calorimetry rather than DSC as does not always show up interactions at these temps

Question 15

what is a polymer

Answer 15

a polymer is a natural or synthetic substance made up a of a series of monomers (at least 200)

Question 16

polymer properties-thermal

Answer 16

can be crystalline or amorphous or semi-crystalline
crystalline means that the structure allows them to have high degree of order

amorphous structure cannot back as closely together an are highly disordered

can be distinguished by their thermal properties. crystalline- sharp m.p.
amorphous have broad m.ps
both may have glass transition temps

Question 17

polymer properties- molecular weight

Answer 17

length of chains can be controlled during synthesis which can control molecular weight
however not possible to control length of chains absolutely
ideally want to control synthesis such that polydispersity is low
and so that average molecular weight can be quoted]

Question 18

polymer properties- viscosity/mechanical

Answer 18

the viscosity of a polymer is related to its molecular weight and structure
crystalline polymers due to their rigid structure tend to have high viscosities and are less flexible than amorphous materials

Question 19

polymers used in pharmacy

Answer 19

usually classified as water soluble or water insoluble
cellulose commonly used as backbone in polymers (pharmaceutical)
They can have a number of applications:
Binders in tablets
Emulsifiers/Surfactants to stabilise emulsions
Suspending agents in suspensions to keep the drug particles from sedimenting
Drug release controlling barriers/membranes/gels in order to modify the rate/place at which drugs are released in the body
Coating drugs in order to increase their dissolution rate in the body

Question 20

amphiphilic polymers

Answer 20

Amphiphilic polymers are copolymers of hydrophilic and hydrophobic polymers. This means that they have both hydrophilic and hydrophobic parts, i.e. like a surfactant.
Due to this they are also have surface activity (they reduce surface tension).
However their potentially most useful property is their very low CMC values. They are x100-1000 lower than with conventional surfactants and so micelles produced using them are more stable (less likely to be ‘diluted out’ in the body fluids) and potentially much more useful in drug delivery.