Exam Flashcards
Noyes Whitney equation
Dm/dt = D x S x (Cs-Cb/H)
Henderson hasselbach equation
Ph= pka + log10(A-/AH)
What class has the greatest bioavailability
Class 1 and class IV has the least
What is used to measure melting point
Heat flux DSC and Capillary melting tubes
What do we use to identify polymorphs
XRPD
What do we use to measure hygroscopicity
TGA, thermogravimetric analysis
What’s the Arrhenius plot used for in preformulation + equation
Rate of degradation - k = A x exp(-Ea/RT)
What’s used to check excipient drug compatibility
Heat flux DSC
Name some things we need to consider in powders
Particle size, surface area, particle shape, density - will effect the flowability, dissolution rate, excipient binding, dose uniformity,
How can we measure SA of a drug
BET theory uses a gas (nitrogen) to adsorb onto the surface of a molecule and pressure transducers sense the amount of gas adsorbed
S(BET) = (vm x s x N) / (V x m)
How to distinguish between crystalline and amorphous
Heat it up as crystalline structures will have a melting point and amorphous structures won’t and will just turn rubbery
What’s a meta stable polymorph
A polymorph that’s more soluble but LESS stable
Example of a drug that has polymorphs
Ritonavir used to treat HIV/AIDS has polymorphs that are more susceptible to moisture absorption- degradation- sub optimal dosing
Crystal lattice + water
Crystal lattice + any other solvent
1) hydrate
2) solvate
Does salt forms increase or decrease solubility
Increaseeee we want this and 50% of all drugs exist in salt forms
Do we want amorphous forms in drugs and why
Yes because they have increased surface energy which increases solubility
Milling causes the formation of what kind of particles
AMORPHOUS (greater surface energy, greater dissolution, greater hygroscopicity, decreased stability, reduced powder flow )
What’s cyromilling
Freezing material first before milling to increase brittleness
What’s the main environmental factor to consider when formulating drugs (milling)
Humidity - causes agglomeration, sticky particles that can stick to each other and the milling equipment
Give one main way to increase drug solubility
Decreasing particle size by milling particles
What’s is segregation and how to avoid it
Particles separating due to a number of different factors e.g. difference in size. Segregation can be avoided be ensuring particles are the same size,shape and density elf. By sieving the particles to separate them
What’s an ordered mix
Mcirconized particles adsorbed onto a larger carrier particle
Why don’t we want particles to be too small
Increased cohesion and aggregation leading to poor powder flow and mixing properties
What’s the other type of segregation
Ordered mix segregation - percolation, displacement and saturation
Why’s good powder flow important
Greater flowability = higher content, greater filling and therefore better weight uniformity
How does the following affect particle flow
A) decreasing particle size
B) irregular shaped particles
C) higher density particles
A) reduced powder flow due to increased cohesion
B) reduced powder flow
C) increased powder flow under gravity
What are the 3 ways to measure flowability of a powder
1) angle of repose - using tan = height/radius
2) carrs index = (tap density- bulk density)/tap density x 100
3) hausner ratio = tap density/bulk density
Why would we avoid wet granulation
If drug is heat sensitive - can change the drug structure to amorphous . Dry granulation is best for heat sensitive and moisture sensitive drugs
What do chelating agents do
E.g. EDTA - they form stable complexes with metal ions to prevent them from interfering with drug stability and interacting
Why do insoluble lubricants cause increased disintegration time
They from a hydrophobic layer around the tablet which reduces wetting of the tablet
Name some additional excipients added and their purpose
Colouring agents, taste masking additives, lubricants (reduce friction during tablet compresssion), antioxidations (e.g. absorbic acid prevents oxidation), glidants
What are the 3 types of degradation
Chemical, physical and microbial
Equation of half life for zero order and first order
Zero = t1/2 = [A]0/2k
First = t1/2= ln2/k
Equation for degradation/expiry of zero and first order
Zero = [A]0/20k
First = 0.051/k
What’s happened after pseudo zero order runs out
It becomes first order reaction
What other factors could affect stability of a drug
Isomerisation, polymerisation and oxidation
How can we avoid oxidation
Add chelating agents e.g. EDTA, add antioxidants e.g. absorbic acid, add free radical scavengers
How can we avoid photochemical effects
Place drug in a amber bottle, which absorbs UV rays, store in cool dark place or coat tablets with pigmented polymers
How can excipients affect stability
They can act as surface catalysts e.g. starch can absorb water initiating drug degradation
Give an example of physical degradation of a medicine
Salbutamol - if temperature is repeatedly increased and lowered the particle size will increase and the drug particles may therefore not be able to exit the inhaler and the pt won’t receive the intended appropriate dose
How can we make suspension and solutions more stable (2 ways)
By incorporating wetting agents e.g. surfactants, suspending agents e.g. potassium dihydrogen phosphate KH2PO4
Is flocculations good or bad and why
Good bc it means the particles form loose clumps which are easy to redisperse and prevents caking
What is zeta potential
To do with suspension - it describes the charge difference between the particle surface and the surrounding fluid. Higher zeta potential = strong electrostatic REPULSION = particles remain dispersed. It tells us how likely it is for particles in a suspension to aggregate
Particle aggregation leads to …
Caking (defloccuated)
What is creaming
Phase separation in a emulsion
What can prevent creaming of emulsion s
Hydrocolloid agents or add a surfactant
What’s coalescence
When droplets combine to make 1 big droplet in an emulsion - prevented using ionic surfactant
What’s the most dangerous type of degradation
Microbial bc it can have the most detrimental effects
Water exposure can lead to the growth of what bacteria
Pseudomonas
Air exposure can lead to the growth of what bacteria
Penicilium (so air in manufacturing spaces should be filtered)
What are the 3 types of coating
Sugar, film and enteric coating
What’s enteric coating
A film layer that prevents the drug from disintegrating in the stomach environment (low pHs)
How does sustained release film work
Resist dissolution at ALL PHS , dissolution is diffusion controlled
What software is used in 3D printing
CAD software
Where does the oral drug initially travel to
Hepatic vein where it undergoes first pass metabolism and most of the drug is broken down so it can be excreted
Name 2 quality control tests for solid dosage forms
Dissolution and uniformity of dose test
What are common manufacturing problems of solid dosage forms
Capping, chipping, sticking to equipment and mottling (uneven distribution of colour)
What’s the gingiva
Gum - keratinized epthethlia
What parts of the oral cavity is keratinized
Gingiva, tongue and hard palate
What area of the oral cavity has the thinnest epithelia (best for drug absorption)
The underside of the tongue and the floor of the mouth
What glands produce watery secretions
Parotid and submandibular glands
What glands produce thicker saliva
Sublingual and buccal
What’s xerostomia
Dry mouth, with more viscous saliva
Which route is faster buccal to sublingual
Sublingual bc there’s more blood vessels = greater blood supply to absorb the drug = faster onset of action (via diffusion)
What’s lyophilisation
Freeze drying of a drug - the drug is frozen then dried to allow sublimation to occur. This makes the drug more soluble due to the porous nature meaning the drug has an increased surface area = faster dissolution and greater onset of action e.g. naloxone used to treat opioid overdose ( we need this to have a rapid onset of action to reverse the effects of the opioids and potentially save a life)
Name a polymer that can be used for mucosal patches
Celluloses e.g. methyl cellulose
How can buccal patches have unidirectional and multidirectional release
If they have a impermeable backing they can only release the drug content in one direction = oral mucosa which is good for more controlled release
Advantage of a impermeable backing layer
Maximise drug concentration gradient bc the system is protected from saliva which will dilute and minimise the concentration gradient
What’s some disadvantages of buccal/sublingual delivery systems
High patient variability due difference in techniques and salivary production, compliance etc…
there’s short residence times bcs the drug will get washed away by saliva thus therapeutic effect may not be maintained,
they must have a neutral or pleasant taste to improve compliance ..
only drugs that are potent at low doses are suitable
Where does the drug taken rectally go to
Depends on which vein it gets absorbed by:
Superior haemorrhoidal vein = portal circulation = goes to the liver and MAY undergoes first pass metabolism
Middle haemorrhoidal and inferior haemorrhoidal vein = straight to the systemic circulation bypassing the first pass effect
What’s the difference between diffusion CR systems and dissolution based systems
With diffusion systems the drug should NOT be soluble in the matrix or the drug reservoir should be coated with an insoluble membrane e.g. polymer
Whereas dissolution systems have a slowly dissolving drug or slowly dissolving drug coating
How do osmotically controlled released systems work
Contains high conc of salts inside the drug and this causes water to move via osmosis into the drug and this caused the active drug to be displaced and move out of the drug through small holes
What are matrix formers
Used in controlled release formulations - they are polymers or waxes that suspend the drug as it slowly dissolves the drug is released
Types of hydrophilic matrix formers
Gelatin (has cross links) and HPMC ( no cross-links and is more viscous)
How Dow e know if a system is dissolution or diffusion controlled
If the matrix used is soluble = dissolution e.g. HPMC (can acc be used in both) and if the matrix is insoluble = diffusion controlled e.g. ethylcellulose
Why does MS Contin have a steady release profile
It’s release is independent of pH so it is steadily released throughout the GI tract
How does MS Contin work
Has HPMC as the matrix - water enter the drug and causes this matrix to swell and become gel-like = drug gradually diffuses out of the matrix overtime. As the gel erodes the drug is released via dissolution as well. So it is a dissolution and diffusion based system ;)
How do ion exchange systems work
Used in controlled release = relies on exchange of ions between drug and surrounding environment - drug is attached to a resin (can bind to ions). The exchange of ions results in drug being released (the resin is the part exchanging ions with the surroundings not the drug)
What’s a advantage of DPIs that MDIs don’t have
They’re CF free (don’t contribute to global warming)
How do DPIs work
Drug ADsorbed onto carrier molecule (lactose), inspiratory flow rate causes the drug to detach from the carrier and get inhaled
How can DPIs be made better
Make the carrier :
1) rounder and smaller
2) smoother
3) add force control agents
Is left or right bronchi wider
Right Sbnlh
How many divisions from trachea to alveoli
23
What are the 3 mechanisms of deposition
Inertial impaction, gravitational sedimentation and Brownian motion
What are the HFAs licensed for use in PMDs
HFA134a and HFA227 (they contribute to global warming tho)
Give an example of a surfactant and co-solvent used in PMDs
Oleic acid (to increase solubility) and ethanol
What’s a parenteral
Administration directly into the body (by passing the GI tract) through IV/injection
What’s the parenteral route that administers at 10-15degrees
Intradermal injection (ID)
What’s the parenteral route that administers at 45degrees
Subcutaneous injection
What’s the parenteral route that administers at 90 degrees
Intramuscular injection
Are intra spinal injections aqueous or oily
Aqueous ONLY (no oils or suspension)
What’s the intrathecal
Injection into the CSF so it diffuses into the brain used during chemotherapy
Why are chelating agents used
They extend the expiry date of drugs (they last longer)
What’s enteral route
Through the GI tract - opposite of parenteral route
Is buccal, sublingual and rectal considered enteral
Yes but they can be more specifically defined as oromucosal (through the mucous membrane)
What’s intra articular route
Injected into the joint - used to treat arthritis
Example of topical formulations
Nasal sprays, transdermal patches and creams
Controlled release vs sustained release
Controlled = zero order kinetics, release rate predetermined and drug remains at a steady level for longer
Sustained= NOT zero order (idk what order tho) aims to give a longer effect than immediate but shorter acting than controlled and Cp levels are not maintenance for long
What do polymers do in formulations
They can have different roles depending on formulation:
1) in gels and creams they act as thickening agents to increase viscosity
2) in solid dosage forms they can be used as protective films to prevent chemical degradation
3) used in controlled and sustained release to delay and prolong drug release e.g. HPMC and ethyl cellulose
If a drug has a logP of 3 what semi solid form would be most suitable
LogP=3 means the drug is lipophilic as it is above 0. We wouldn’t use a ointment because the drug would just dissolve in it and not penetrate the skin, pontentially cream but the drug may be trapped in a droplet or gel as the drug would be freely suspended and gels are best for hydrophobic drugs like this
What properties are ideal for a drug patch
Low molecular weight (large molecules can’t penetrate)
LogP of 1- 3 (balance of permeability and solubility)
Low melting point (greater solubility)
Short plasma half life (prevent accumulation = toxicity )
Low therapeutic level = potent drug as not much will be able to cross the skin
Pharmacokinetics vs pharmacodynamics
Cokinetics = ADME (what body does to the drug)
Codynamics = binding, action, therapeutic effects and side effects (what the drug does to the body)
What does a bioavailability of 1 mean
100% (only for IV)
Equation for F ( absolute bioavailability)
F = AUCev/AUCiv
What’s relative bioavailability + equation
Availability compared to another dosage form
RB = (AUCev/dose ev)/(AUCiv/dose iv). Or AUCa/AUCb where a = test and b= reference
What’s bioequivalance
Drugs that are pharmaceutical equivalents and have similar bioavailability (need to be 80-125% range within each other)
What effects bioavailability
Formulations, age, sex, weight, disease states, gastric emptying weight, food interactions, etc…
Name 3 test used by FDA to evidence bioavailability of 2 dosage forms
In vivo PK tests in humans
In vivo human test using urinary metabolites
In vivo test in animal correlated to in vivo PK tests in humans
What’s the pH of the intestine in a fasted vs fed state
Fasted = 6.5
Fed = 5
What dissolution testing apparatus would we use for micro particles or floating dosage forms
Basket apparatus
What dissolution testing apparatus would we use for sinking dosage forms (tablets and capsules)
Paddle apparatus
What dissolution testing apparatus would we use for flow through apparatus
Any but useful for modified release ones
What dissolution testing apparatus would we use for Franz cell system
Semi solids and patches (creams, ointments)
What’s the data analysis method for immediate release formulations
Noyes Whitney or Hixon & Crowell
What’s the data analysis method for controlled release/ monolithic release formulations
Higuichi model
What kind of reaction would usually occur in “sink condition”
Zero order reaction (dc/dt=constant - simple straight line graph unlike first order)
What does a angle of repose of less than 30 degrees tell us
Excellent powder flowability
What does a angle of repose of 31-35 degrees tell us
Good flowability
What does a angle of repose of 36-40 degrees tell us
Fair flowability
What does a angle of repose of greater than 40 degrees tell us
Poor flowability
How is dodge uniformity tested
Assay of drug API
