Section 4 - Preformulation/Flavouring Flashcards
What does flavour involve a combination of?
Taste, smell, touch, and sight
Where do taste sensations come from?
Taste buds located on all regions of the tongue
Does the tongue have specific zones for each flavour?
No
Where can taste occur?
On any part of the tongue and the mouth
What are the structures called that recognize taste?
Papille, located under the mucous membrane of the tongue
What happens when a chemical substance of a certain taste comes into contact with a sensory cell on the tongue?
It activates the sensory cell to transmit messenger substances, which in turn activate further nerve cells, which send impulses for a particular perception of flavour on to the brain
Which flavours are G protein-coupled receptors?
Sweet, bitter, and umami
What is the receptor for salty?
Sodium channel
What is the receptor for sour?
Unknown
What are the 5 basic tastes?
- Sweet
- Sour
- Salty
- Bitter
- Savoury
Flavour acceptance may be affected by ___
Age
What flavour do children typically like?
Fruit
What flavour do adults typically prefer?
Acidic
What flavour do the elderly typically prefer?
Mint
Which functional group is sweet taste associated with?
Hydroxyl
Which ion is associated with sour taste?
Hydrogen ions resulting from the dissociation of acids like citric acid
What is salty taste associated with?
Many inorganic salts
- Ex: sodium and potassium chloride, magnesium chloride, sulfate
Which functional groups are associated with bitterness?
Amine functional groups
Which molecules are associated with umami taste?
- Glutamic acid
- Aspartic acid
Is spicy a taste?
No, it is a pain signal sent via temperature and touch receptors on the tongue
Which flavours are effective in disguising dephenhydramine in a expectorant formulation?
Orange-mint
Which flavour is effective in disguising phenylephrine and chlorpheniramine?
Vanilla
Which flavour is effective in disguising adsorbents like kaolin and pectin?
Butterscotch
Which flavour is preferred in antacid preparation?
Mint
What are important characteristics for flavours used in formulation?
- Non-toxic
- Soluble
- Stable
- Compatible with the preparation
Is it better for a solution to be more or less viscous and why?
More b/c viscous materials give a better mouth-feel
What are 2 antibiotics that cause a metallic taste?
- Metronidazole
- Clarithromycin
What kind of taste can ACE inhibitors cause and why?
- Metallic, sweet, or salty
- Taste buds need zinc as a cofactor and ACE inhibitors can chelate zinc and prevent it from interacting w/ the taste bud receptors
Why do calcium channel blockers alter taste?
Inhibition of calcium channels right at the taste receptors
What happens to the number of taste buds as a person ages?
They decrease
Are flavouring agents potent?
Yes
What can be used to flavour water-containing solutions and suspensions?
- Water-soluble artificial flavours (1-4%)
- Concentrates (1-3%)
What can be used to help mask a bitter aftertaste?
Artificial marshmallow and vanilla flavourings
What is a flavour that can mask many bitter-tasting medications?
Chocolate
What is important to note about powdered flavours?
Usually require a higher concentration up to 5%
What are the normal concentrations of oil flavours?
0.1-1%
What are 2 common oil flavours used?
Peppermint and spearmint
What are commonly used artificial sweeting agents?
Stevia, aspartame, acesulfame, and saccharin
What is the normal concentration for stevia?
0.1-0.5%
What is the normal concentration for aspartame?
0.1%
What is the normal concentration for acesulfame?
0.1-0.5%
What is the normal concentration for saccharin?
0.1%
What is sodium chloride used for with respect to flavouring?
To reduce sourness and/or bitterness
What does citric acid do with respect to flavouring and what is the typical concentration that is used?
- Enhance fruit flavours
- 0.1%
What is sodium chloride used for with respect to flavouring and what is the typical concentration that is used?
- Adding salty tastes to medication for cats and dogs
- 1%
Which 2 flavourings should not be given to dogs and why?
- Chocolate and xylitol
- Toxicity
How can parents or caregivers help a child take a medication that tastes bad?
- Give a cold treat (slushy, ice pop, or ice chips) before or after the medication to numb the taste buds and minimize aftertaste
- Add sweeteners (chocolate or strawberry syrup) to the dose of liquid medication
- Give the child a lollipop after medication
What should be done to medications that are mixed with a food or flavouring agent AT HOME by the caregiver?
Must be given right away so that the effectiveness of the medication is not reduced
What is preformulation?
Gathering info regarding drug properties which may have a bearing on product formulation
What is the object of the first step of development of dosage forms?
Developing a stable, bioavailable product with good patient acceptance
What are organoleptic properties?
Description of drug substance including colour, odour, and taste
What can be done to fix an objectionable colour?
- Colouring agent
- Tablets may be coated
What can be done to fix an objectionable odour?
Coating or inclusion of an aromatic excipient
What can be done to fix an objectionable taste?
- Flavouring agent
- Coating
- Use of an insoluble salt form
What can be affected by the presence of trace amounts of metals?
Stability
What is micromeretics?
Particle size, shape, and surface area of drug material
What can micromeretics affect?
Physical and biopharmaceutical properties of finished dose form
___ plays a role in homogeneity of tablets
Particle size
____ and ____ will influence the flow and mixing efficiency of powders and granules
Size and shape
What effect does decreasing particle size have?
Will increase surface area which will be in contact with excipient and atmospheric moisture and oxygen
What problems can milling generate?
- Static electricity
- Agglomeration
- Polymorph formation
Product must dissolve in _______ prior to ______
- Gastrointestinal fluids
- Absorption
What effect does dissolution have on bioavailability?
Better dissolution means better bioavailability
What does it mean if a drug shows acid instability?
An oral dose form may not be possible unless a way can be found to protect the drug from gastric acidity
For HCl salts of oral products, what must you assess and why?
Assess common ion effect with chloride b/c gastric fluid has a high content of chloride ions
What happens if Kd is slower than Ka?
Absorption is rate-limited by dissolution and a change in Kd will affect absorption rate
What does a larger partition coefficient (logP) mean?
More affinity for organic phase
What can you conclude when logP = 1?
10 parts in organic to 1 part in water
What can you conclude when logP = 0?
1:1 organic:aqueous
Is a crystalline or amorphous structure more soluble?
Generally amorphous
Is a crystalline or amorphous structure more stable?
Crystalline
Does a crystalline or amorphous structure show better bioavailability?
Amorphous
For polymorphs, are all of the forms stable?
No, only one form is (generally in the solid state)
Can you decipher the forms of a polymorph once in solution?
No
What must a metastable polymorph exhibit to justify its use in a product?
Sufficient chemical and physical stability
What must you ensure when using a drug that is capable of forming polymorphs?
That processing does not cause a transition
What processes can cause polymorph transformation?
- Milling
- Granulation
- Drying
- Compression
What can granulation cause?
- Polymorph transformation
- Formation of solvates or hydrates
What can drying cause?
- Polymorph transformation
- Transformation to anhydrous crystalline or amorphous forms
Knowledge of _____ is needed to know which excipients may be needed and which are most effective
Stability
What are some stability studies for a tablet dose form?
- Solid state stability of drug alone (chemical and physical stability)
- Stability in the presence of potential excipients
- Stability of the drug in solution
What is the objective of stability studies at the preformulation stage?
To identify and therefore control or avoid situations where the stability of the active component may be compromised
Which properties of a drug influence stability?
- pKa
- Solubility
- Melting point
- Crystal habit and form
- Eq’m moisture content
What are the most common factors for instability?
- Light
- Heat
- Oxygen
- Moisture
What is the criteria for a stability prognosis to be good?
No change at 60 C after 30 days
Why are samples tested under increasing humidity at a constant temperature?
In the presence of moisture many drugs hydrolyze, react with excipients, or oxidize
What does density affect?
- Flow properties
- Blending of a drug if excipients have quite different densities (segregation may occur)
What is good flow essential for?
- Blending
- Granulation
- Compression
Should an excipient that increases or decreases flow properties be used?
Increases
What is the preferred angle of repose?
25-45
What type of compressibility is ideal?
- A powder which forms a hard uniform compact under moderate pressure
- Capping or chipping shouldn’t occur
