Performulation Flashcards
Factors affecting solubility
- temp
- pressure
- molecular structure of solute
- solvent characteristics
- crystal characteristic
- pH
- common ion effect
How is solubility affected in endothermic reaction
Temp increases so solubility increases (kinetic energy increase with temp)
What happens when pH increases with weak acids
Ionisation increases
What happens when pH increases with weak bases
Ionisation decreases
How soluble is Amorphous ?
Very soluble
How to assess solubility ?
XS solute in solvent to dissolve
Removed undissolved solid
Molecules with e- absorb light
Amount of light absorbed proportional to analytical conc.
What is surface tension depended on?
Temperature
Impurities (surfactants)
What to use to measure surface tension?
Wilhelmy plate
Du Noüy ring (interfacial tension too)
How does wetting happen?
Result of intermolecular interactions at the S-L interface
Surfactant ceutical uses?
- detergent
- emulsifying agent
- wetting agents
- foaming agent
- flocculating agent
- solubilising agent
What happens when the surfactant concentration too much?
No more surface for surfactant molecules to line thus form micelles
Critical micelle concentration
Surfactant conc. above micelles form
- in water, CMC decreases with increases molecular size of surfactant
- bulkier surfactant =less molecules fit in give SA so lower CMC
What administration can emulsions be given in?
Oral
Parenteral
Topical
Single emulsion
Liquid droplets (disperse phase) in another liquid (continuous phase)
Double emulsion
Primary emulsion droplets in another liquid
EG: O/W/O Emulsion
Most emulsifiers are?
Surfactants and therefore amphipilic
What to emulsifiers mediate?
Molecular interactions at the interface between disperse and continuous phase
Stable emulsions called?
Meta stable
Different types on emulsion instability?
Flocculation
Creaming
Sedimentation
Cracking
Flocculation
Electrical double layer around particles
Flocs May fuse = coalescence
How can floc interactions be altered
With additives
Sedimentation and creaming
Patrick’s sink in continuous phase under opposing forces
Sedimentation rate increases with?
- larger droplet size
- lowkey fluid viscosity
- greater density differences between droplet and continuous phase
If emulsifier is more soluble in water, what type of emulsion?
O/W emulsion
If emulsifier more soluble in oil, what type of emulsion?
W/O emulsion formed
What is crystalline structure?
Thermodynamically stable, sharp MPT
Polymorphism of same substance can differ in terms of:
MPT Density Chemical reactivity Mechanical properties Dissolution rate
Polymorphs absorption
Is different and bioavailability despite identical formulation
What undergoes glass transition?
Amphorous
Compaction cycle
1-filling in die cavity
2-compression -die volume decreases
3-ejection - tablet pushed (lubrication)
Compression results in:
Reduced porosity
Reduced bulk volume
Increases bulk density
Mechanical properties required for compaction
Plasticity - deformed particles when compressed = greater cohesion
Brittleness - particles fragment = increase SA and surface energy = greater cohesion
What is tensile strength
Stress needed to fracture tablet. Reflects strength of inter-particle bonding
If compaction pressure increases ?
Tensile strength increases
If tablets are flat it convex ?
Lower tensile strength
If the polymorph is stable?
Lower tensile strength
Driving forces
Gravitational force, mechanical agitation
Retardant forces
Cohesion /adhesion, friction, mechanical interlocking
What does adhesion attract
2 chemically different surfaces
What does cohesion attract?
Attractive forces between 2 chemically similar surfaces
Example of adhesion/cohesion forces?
- VDW
- electrostatic attraction
- capillarity forces (liquid bridges)
How do VDW forces increase?
With particle size and proximity
Dominant effect on fine particles over gravity
What do capillary forces do?
Adsorb moisture on particle surface, forming liquid bridges
What are the factors affecting particle size? (To favour flow)
Large particle size Spherical particle SA of particle = small High density Looser packing geometry Moderate moisture content
What happens when there too much moisture with particles?
They clump together
What is the angle of repose and how does it come about?
Cohesive powders flow less well and also pile up higher
=steeper slope, larger angle of repose = lower flowability
Product quality aims from mixing?
Uniformity of mass
Reproducibility
Therapeutic efficacy
Patient safety
What is a positive mixture ?
Approaches perfect mixture (eg: alcohol and water)
What is a negative mixture?
Energy input required to mix components and maintain mixture
(Eg:emulsion)
Neutral mixture ?
Energy input required to mix/segregate eg:powders/pastes
Random mixture?
Group of particles adjacent to one another
Free flowing primary particles
Ordered mixture (cohesive particles)?
Micronised particles adsorbed on surface of larger carrier particles
When is segregation likely?
Particle size non-uniform
Particle density non-uniform
Spherical shape (free flowing)
Demixing - percolation separation
Small particles fall through voids
Demixing - trajectory segregation
Larger particles go further as they have more mass
Demixing - elutriation segregation
‘Dusting out’ - fine particles settle on top after motion has stopped
How to minimise segregation ?
Select suitable particle size range
Select excipients to similar density
Reduce vibration
What is adsorption due to?
- physical bonding between adsorbent and adsorbate (weak VDW, H-bonds)
- chemical bonding called chemisorption (via strong covalent bonds)
Thin layer chromatography phases?
Stationary - silica (polar)
Mobile - liquid mixture of solvents
High performance liquid chromatography (HPLC) phases?
Mobile - runs through column of solid stationary phase at high pressure
Gas chromatography phases?
Mobil - has
Stationary - either liquid/solid
Alfa tor’s affecting adsorption
Temperature (increase temp, decrease adsorption)
Concentration
Nature of solvent
Solute
2nd solid present
pH - many materials ionisable/tendency to interact greatly if exist as polar ions
Example of good adsorbent and it’s use?
Activated charcoal for overdose/poisoning
-large SA (50-100g adult)
What is koalin drug?
Adsorb toxins and often used for mild diarrhoea
What is chemisorption?
When chemical bonding between adsorbent and adsorbate on the monolayer on the surface
-irreversible, only arise when chemical bonds
(Eg ammonia synthesis)
What is dissolution?
Transfer of molecules/ions from solid state into a solution (thermodynamically favourable)
What is solubility?
Capacity of absolute to dissolve in a solvent
Dissolution rate controlled by?
Speed of removal of particles from solid surface
Diffusion rate through boundary layer
Stirring/agitation decrease diffusion gradient
What happens when a drug has limited water solubility?
Dissolution is rate-limiting step to absorption
Why is dissolution testing carried out?
For quality control - consistency
Predictive testing - assess product stability
How much drug needs to dissolve in QC dissolution testing?
More than or equal to 80%
Dissolution testing apparatus
Basket
Paddle
Flow through cell
Reciprocating cylinder
Properties of dissolution medium
Mustn’t affect drug stability
Easy to prepare
Preferable inorganic
(Eg 0.1M HCL for weakly basic drugs)
Class I
Soluble at 250mL
More than 90% absorption
(Dissolution >85% in 30mins)
Class II
Not soluble in 250mL
Absorption >90%
Class III
Dose soluble in 250mL
Absorption <90%
Class IV
Not soluble in 250mL
Absorption <90%
Class I rate limiting step?
Gastric emptying
Class II rate limiting step?
Dissolution rate or solubility
Class III rate limiting step?
Membrane permeability + physiology
Class IV rate limiting step?
Various, including dissolution rate
