D1: Medicines: Their Structure, Ingredients and Design Flashcards
Drug
Pure active chemical
Medicine
Dosage form administered to the body
Dose
Amount of medicine.drug taken on one occasion
Frequency
How often the dose is taken
Local
Medicine that acts in the area where it is supplied
Systemic
Drug enters bloodstream and can act anywhere
Oral
Swallowed by mouth
Topical
Applied to a surface
Parenteral
Injected
What do Medicines contain
Drugs, excipients + structure
- drug = active substances
- medicine = non-active ingredients
Legal requirements of medicines and drugs by Human Medicines Regulations 2012
All medicines must have proven:
- efficacy = effective for the medical condition claimed
- safety = safe to use by patient
- quality = broadest sense
What does quality include
‘Dose uniformity’ = Accurate dose of drug every time
‘Patient acceptability’ = Pleasant and easy to use
‘Stability’ = A long shelf life
‘Directions’ = Clear instructions how to take it
Good medicine design is…
Tailored to the body site, is essential for patient safety and successful treatment
General design principles of Medicines
- Optimum drug release rate
- Stability to chemical, physical, and
microbial degradation so it has a long shelf life - High patient acceptability and ease of use
- Easy to manufacture as a quality product
- Uniformity – must give the same dose every time
Types of bulk powders
Oral bulk powders
Dusting powders
Powders for reconstitution
Types of single dose powders
Sachets + wrapped powders
Capsules - hard + soft
Tablets
Types of tablets
Dispersible Immediate release Delayed release Extended release Special routes
Dispersible tablet
Dissolve in water before taking, or on tongue with no water.
Most rapid drug release
Immediate release tablet
Disintegrates in stomach,rapidly releasing the drug. These are the ‘normal’ tablets we all take
Fast
Delayed release tablet
Releases whole dose further down the GI tract ‘Gastro-resistant’ or ‘Enteric coated’
Delayed. Whole dose released in the intestine.
Extended release tablet
Slow drug release over 8 to 24 hr
Prolonged action
Special route tablet
Sublingual = Under the tongue Vaginal = Body cavity
Excipients in bulk powders
Bulking agents - diluents Effervescent mixtures Flavouring, sweeteners, colours Granulating agents (binders) Flow aids
Example of bulking agents
Sugars, sorbitol, salts, talc
Example of Effervescent mixtures
Citric or other fruit acids with carbonates or bicarbonates. React to release CO2 in water.
Example of granulating agents
Polymers such as PVP and pregelled starch
Example of Flow aids
Colloidal silicon dioxide
Stability problems of powder medicines
1) Sensitivity to moisture
2) Flow
3) Mixing + separation
Why does powder unmix during movement
As they move, small particles fall through spaces between the big ones.
Separation due to size, shape, density differences.
• Vibration.
• Transport.
• Mixing & pouring.
‘Rolling plane surfaces’ within moving containers.
How do we prevent powder separation
Granulation
Granulation
Mix powders (drug, diluent, disintegrate) - Dry granulation = by roller compaction - Wet granulation = wet powder mixture with a solution of polymer 'binder' then sieve + dry Form granules
Granules
Particles glued together with water-soluble PVP
Advantage of granules
Structured mixture - permanent + cannot unmix
Large size - flows well into packing machines
Crunchy - compresses into tablets easily
Manufacturing tablets
Compression of granules or powder mixtures on a tablet press
- granules / powder mixture
- mix with a lubricant
- exact amounts
- compress on a tablet press machine
- incited tablets
- coating machines
- coated tablets
- packaged tablets
Ingredients in tablets + capsules
- Granuating agents (binders)
- Bulking agents
- compression aids
- lubricant
- disintegrants
- flow aid
- tablet coat
- capsule shell
Example of tablet coat
Polymers, colours, TiO2
Film coat
Example of capsule shell
Gelatin shell, colours, TiO2
Example of flow aid
Colloidal silicon dioxide
Helps granule/powder flow into tablet die for a more consistent fill
Example of disintegrants
Starch, Croscarmellose, Sodium starch glycollate, L-HPC
Swelling or wicking action
Breaks up tablet in water
Example of lubricant
Magnesium stearate
Help machine eject tablet
Example of compression aids
Microcrystalline cellulose
Deforms under pressure
Gives harder tablet
Example of Bulking agents
Sugar, lactose, dicalcium phosphate, mannitol, talc
Adds bulk
Example of granulating agents
Polymers such as PVP, pregelled starch
Binds powders together during wet granulation
How do tablets release drug into body
Disintegrant absorbs water + swells tablet
- Disintegration
- Dissolution (drug in solution)
- Absorption (across gut wall into bloodstream)
How do capsules release drug into body
Capsule shell (soluble polymer) dissolves
Powder contents are released + dissolve
( A disintegrate is sometimes used, if so disintegration is next)
Dissolution (drug in solution)
- Absorption (across gut wall into bloodstream)
Types of liquid medicines
Solutions
Suspensions
Emulsions
Solutions
All ingredients dissolved and therefore present as single molecules within the liquid ‘vehicle’.
Suspension
Insoluble solid particles dispersed in the liquid.
Emulsion
Insoluble liquid droplets dispersed in the liquid.
Excipient classes common in liquid medicines
- Vehicles
- Preservatives
- Stabilisers
- Colours
- Flavours
- Buffers
- Sweeteners
- Solubility enhancers
- Thickening agents
- Emulsifying agents
E number list
This lists excipients (‘Additives’) approved for foods in EC.
Vehicle
Main liquid ingredient
- Water
- Sweetening/flavouring vehicles
- Other liquids
Water used in medicines must be…
BP quality
Preservatives
Inhibit growth of dangerous microorganisms
- Prevent poor poisoning in oral liquids
- Prevent bottle contamination
- Prevent microbes degrading medicine
What other excipients can act/ aid as preservatives
Sulphite antioxidants
Glycerol, syrup, sorbitol in very high concentration
Alcohol > 10%
Disinfectants (hypochlorites)
Internal preservatives
Sorbates
Benzoates
Chloroform
Methyl, ethyl, propyl parahydroxybenzoate
External preservatives
Benzalkonium chloride Benzethonium chloride Thiomersal, Borates, Chlorocresol, Chlorbutanol Bronopol (Boots)
2 types of stabilisers
Antioxidants + chelating agents
Antioxidants
Reducing agents that react with dissolved oxygen?act as free radical scavengers
- prevent oxidation by being more easily oxidised than the drug / foodstuff they are protecting
Water-soluble antioxidants
Ascorbic acid (Vitamin C) Sulphur dioxide Sulphites
2 types of antioxidants
Water-soluble + oil-soluble
Oil-soluble antioxidants
Tocopherol (Vit E) Butylated hydroxyanisole (BHA) Butylated hydroxytoluene (BHT)
What formulations are oil-soluble antioxidants used in
Formulations that contain fatty ingredients (emulsions, creams, ointments, foods) to prevent fat oxidation ‘rancidity’.
Chelating agents
Molecules that complex with heavy metal ions in solution, reducing their ability to catalyse oxidation
Example of a chelating agent
Disodium Edetate (EDTA)
Clinical use of EDTA
- EDTA infusion to remove excess calcium (Ca2+) from the blood in hypercalcaemia arising from bone cancer.
- Radioactive 51Cr complex of EDTA is used to assess kidney
function - filtration rate.
Types of colour sources
Synthetic
Inorganic
Natural
Oral bulk powders
- Disperse spoonfuls of powder in water or milk
* A good way to give a large dose (grams) by mouth e.g. Indigestion remedies, bulk laxatives
Dusting powders
External skin diseases e.g. Athletes foot powders
Powders for reconstitution
Useful when drug is chemically unstable in water
• Powder dispersed in water before giving to patient e.g. Antibiotic syrups in a pharmacy; Freeze dried injections
• Make sure it all dissolves
Hard Capsules
Two part, hard polymer shell filled with a powder mixture
- Polymer is water-soluble = gelatin or methylcellulose-
- Easy to swallow
- Many different capsule sizes available
Soft Capsule
Flexible shell of plasticised polymer .
- Used for oils, liquids, pastes (A paste is a concentrated powder in a liquid)
What are Tablets?
Single dose of compressed powder
it contains:
- Printing/ Embossing
- Break line
- Coat
- Drug and excipients
Tablets differ in size, shape, colour etc; to aid identification and create a distinctive look (‘Market identity’).
Printing In edible ink or embossed (indentation)
Tablets can be uncoated, sugar coated or film coated.
- Film coat is the most common - thin layer of coloured or transparent polymer
Why are tablets so popular?
• Small, Portable • Convenient to take • Stable - no water present - coating blocks light - moisture proof packing
Sensitivity to moisture
HYGROSCOPIC - absorb moisture
DELEQUESCENT - absorb and dissolve in it (!) nasty mess
EFFLORESCENT – hydrate salts that lose water of hydration
CAKING - powder sticking together due to moisture
Flow
Critical for processing and packing.
• Depends on size, shape, moisture, surface charge etc.
• Large particles flow better.
• Add a flow aid if needed, or granulate
Mixing and separation
- How to get an even mix ?
- How to get small amounts evenly into a large bulk ?
- Mixing depends on size, density, shape, surface moisture, static.
- Unequal particles can separate.
- Fine powders (<10 microns) can agglomerate and don’t mix in
Solutions to mixing problem
- Granulation (Common in large scale manuf. Fixes powders in space)
- Ordered mixes
- Equalise particle sizes by grinding/sieving
- Mix equal amounts 50:50 = most efficient
- Geometric mixing (small scale technique)
Why is powder separation a big problem in factories
Powder mixes can unmix during movement
- As they move, small particles fall through spaces between the big ones
- Separation due to size, shape, density differences.
Describe Granulation
Granulation prevents separation
1) Mix Drug, diluents + disintegrants powders
2)
- By DRY GRANULATION - by roller compaction
- By WET GRANULATION - Wet the powder mixture with a solution of polymer ‘binder’
- – then sieve and dry
3) Granules are formed (particles are glued together with a water-soluble polymer e.g. PVP)
Advantages of Granules
Mixture now structured - permanent and cannot unmix
Large size - flows well into packing machines
Crunchy - compresses into tablets easily
Manufacture of Tablets
Compressing granules or powder mixtures on a tablet press
1) you mix granules/powder mixture with a lubricant (Mg Stearate)
2) Make exact amounts
3) Compress on a tablet compression machine
4) Uncoated tablets
5) Coating machines
6) Coated tablets
7) Tablets are packaged
Ingredients of tablets + capsules
Granulating agents (binders) Bulking agents (diluents) Compression aids Lubricant Disintegrants Flow aid Tablet coat Capsule shell
Function of granulation agent (+ example)
Binds powders together during wet granulation
- Polymers such as PVP, pre-gelled starch
Function of bulking agents (+ example)
Adds bulk
- sugar, lactose, dicalcium phosphate, mannitol, talc
Function of compression aids (+ example)
Deforms under pressure. Gives harder tablet.
- microcrystalline cellulose
Function of lubricant (+ example)
Helps machine eject tablet
- magnesium stearate
Function of disintegrants (+ example)
Swelling or wicking action. Breaks up tablet in water.
Starch, croscarmellose, Nastarch glycollate, L-HPC
Function of flow aid (+ example)
Helps granule or powder flow into tablet die for a more consistent fill.
Colloidal silicon dioxide
Function of tablet coat (+ example)
Film coat
Polymers, colours, TiO2
Example of capsule shell
Gelatin shell, colours, TiO2
Physical types of colours
Soluble dyes
Lakes
Soluble dyes
Water soluble.
Oil soluble
Soluble in polymers (plastics)
Extracts of natural materials
Lakes
Dyes adsorbed onto aluminium salts to make insoluble coloured powders
Powdered, dried foods - No toxicity testing needed
Why are colours attractive in medicine
Natural colours in foods are often good nutritionally
- Carotenoids are precursor of vitamin A; β-Carotene (orange) = Carotenoids widespread in fruit and vegetables
- Fruit colours are natural antioxidants or are involved in body metabolism; Anthocyanins (red, purple, blue) Blackcurrants, raspberries, blueberries are rich in these.
-
Why are colours coloured
Double bonds absorb UV and visible light as electrons in the π bond jump to higher energy orbitals
Colours are complex molecules with an
extensively linked (conjugated) network of double
bonds
Molecules with more conjugated double bonds, absorb UV and visible light at longer wavelengths, therefore coloured organic compounds have highly conjugated structures.
Issues with colours
Toxicity - colours are not essential
Azodyes - bronchoconstriction in asthmatics especially if aspirin intolerant.
Tartrazine - immunological sensitivity reactions.
Natural colours are often less chemically stable
than synthetics. Changing pH can change the colour (ionise)
Flavours
To taste (mask) drug
Traditional pharmacy flavourings
Oils Spirits & tinctures Concentrated waters Waters Syrups
Oils
Pure oil. Very concentrated
- e.g. Peppermint oil. Cinnamon oil.
Spirits + tinctures
Conc. oils/flavours in alcohol
- e.g. peppermint spirit
Concentrated waters
Conc. solution or emulsion in water
- e.g. Concentrated Peppermint water, Concentrated Chloroform water
Waters
Usually the most dilute form
- e.g. Peppermint water, Chloroform water
(often made from Double strength waters)
Syrups
A flavoured syrup
- e.g. Orange Syrup BP, Blackcurrant Syrup BP
What is the function of menthol, thymol and eucalyptol as a flavour/aroma?
Decongestant ( eg‘Vicks Vaporub’)
Mildly antiseptic
What is the function of chloroform as a flavour/aroma?
common flavour & preservative
What are the term used on labels when they don’t want
to disclose the flavouring or scenting agents?
Where is the word parfum usually used?
Aroma + Parfum
Parfum is usually used on cosmetics
Why is a bitterness flavour useful
What is the bitterest material in the world
Bitterness is useful as a WARNING and for AVERSION
Bitrex
What is the general use of bitrex
Prevent poorly sighted people, children and animals (wild and domestic ) eating or drinking dangerous things. Used in pesticides & herbicides, automotive, cleaning fluids, denatured alcohol
What is the pharmaceutical use of bitrex
- Surgical spirit
- Anti-nail biting liquids.
- Matching the bitterness of drugs in
clinical trial placebos. - Veterinary training products (e.g. dog chewing, tail biting)
What is bitrex composed of
Lidocaine (local anaesthetic) with an added benzyl group
Function of lidocaine
Local anaesthetic
Kills any sense of taste
Common feature of both lidocaine and bitrex
Both have profound but opposite effects on the
sensory nerves involved in taste.
Receptor agonists and
antagonists often have closely related chemical
structures.
Function of buffers
Stabilise pH
Mixtures of an acid and its salt (or a base + its salt)
What is pH
The concentration of H+ ions in solution
What is a pH range
Measures acidity or alkalinity in solution
Why is pH important to us as humans? + How do we prevent it from happening?
If the concentration of H+ ions is too high or low it damages our bodies : denatures our proteins, messes up all sorts of biochemical reactions, kills our cells etc.
We have detectors for pH on the tongue (sour taste)
and in the body (pain) e.g. bee stings are low pH.
Why is control of pH critical in medicines
1) Drug solubility - Some drugs only dissolve in a specific pH
2) Chemical stability - To prevent pH-sensitive ingredients changing/degrading
3) Effectiveness of critical excipients - benzoate preservatives effective pH 2-5
4) Prevent pH shift due to dissolving atmospheric CO2 - CO2 causes a shift to acid.
5) Prevent stinging (ouch!) - Eye/nose drops.
6) Prevent blood problems - Large volume injections.
7) Match flavour - e.g. Acid fruit flavours (lemon, strawberry)
How do buffers control pH ?
When H+ ions are added or removed they change the ratio of salt to acid and this keeps the pH the same.
- If you add acidic substances (adds H+ ions) = Buffer soaks up the H+ ions by converting salt to acid
- If you add basic substances (eg OH-) (removes H+ ions) = Buffer adds more H+ ions by converting acid to salt
The net result is H+ concentration in solution stays much the same.……..until you exceed the buffer capacity.
What is pKa
The pH at which [salt] and [acid] are present in equal molar concentrations.
Buffers are effective at pH values ±1 of their pKa.
Which pH is best for Ibuprofen oral liquid
Ibuprofen is a carboxylic acid - it ionises over pH 4-6
- At a low pH, ibuprofen (-COOH) will be poorly soluble + an aftertaste if a little dissolves
- At a higher pH, ibuprofen (-COO-NA+) will be soluble but tastes horrible
Types of sweeteners
Sugars Sugar alcohol Simple polyols Artificial sweeteners Miscellany
Examples of sugars
Sucrose, glucose, fructose
Examples of sugar alcohol
Sorbitol, maltitol, xylitol, mannitol
Examples of simple polyols
Glycerol
Examples of artificial sweeteners
Aspartame, Sucralose
Examples of miscellany
Starch hydrolysates (corn syrup)
Property + use of sucrose
Syrup BP Vehicle. Rots your teeth. (cariogenic)
66.7% sucrose, almost a saturated solution
Preserves by dehydration (like jam).
Properties + use of glycerol
Glycerol BP Vehicle. Dehydration preservative
Properties + use of sugar alcohol (Sorbitol)
Sorbitol BP = vehicle which is 70% sorbitol in water
- Diabetics usually OK. Metabolised more slowly than sugar so no sudden increases in blood sugar.
- Tooth decay avoided (non-cariogenic)
- Calories lower than sugars. Often used in ‘Sugar free’ products but they’re not calorie free !
Properties + use of synthetic/artificial sweeteners
Different taste. No calories or tooth decay.
Completely different ADME
Whats the function of Solubility enhancers
Improve drug solubility
Examples of solubility enhancers
Solubilisers, Cyclodextrins + Cosolvents
What are the function of cosolvents + give an example?
Salicylic acid 17%
Alcohol 18%
Ether 53%
- to aid solubility
Emulsions
Liquid medicines in which one insoluble liquid
is suspended as microscopic globules in another.
The two liquids don’t dissolve in each other
( ‘immiscible’).
Which medicines are usually emulsions?
Cream - Free-flowing liquids
Liquid emulsions - Semi solid, thick consistency,
(because disperse phase is often a wax)
What different types of emulsions are there?
o/w = oil in water (milky white)
w/o = water in oil (translucent)
w/o/w + o/w/o = multiple emulsions (droplets within droplets)
Types of oils
Fixed = Vegetable oils (Triglycerides)
Mineral = Liquid paraffin (Hydrocarbon)
Volatile = Oils from plants (various complex structures)
- volatile is used for aroma + flavouring (peppermint oil, lemon oil)
Types of instability emulsions suffer from
physical, chemical and microbiological instability.
Describe the physical instability of emulsions. Explain why it happens.
‘creaming and cracking’
(coalescence of droplets leading to growth and separation of the disperse phase)
- creaming = Disperse phase droplets
coalesce (increase in size) and collect near surface.
- cracking = Phase separation. Disperse
phase forms large globules or separate layer on surface
Why does ‘creaming and cracking’ happen
Emulsions are unstable…they want to separate because of:
1) droplet size = Smaller droplets = more stable.
Hand-made liquid emulsions Stable for 1 week ?
Commercial manufacture uses high shear mixers.
IV emulsion - Intralipid ® ~0.5 micron. Stable 2 years
2) Temperature = Warming or temperature fluctuation accelerates; Freezing/thawing causes rapid separation
3)Type = o/w more stable than w/o (Creams more stable than liquid emulsions)
4) Added ingredients = f interact with emulsifying agent, can destabilise.
Describe the chemical instability of emulsions. Explain why it happens.
Internal oil phases are sensitive to chemical degradation
- Internal phase has a HUGE SURFACE AREA = high surface area for oxygen + light-catalysed reactions so increased rate of fat oxidation (rancidity)
How do we prevent chemical degradation
Oil soluble antioxidant
- Tocopherols (Vit E)
- BHA (butylated hydroxyanisole)
- BHT (butylated hydroxytoluene)
Describe the microbiological instability of emulsions. Explain why it happens.
Emulsions can grow microorganisms
1) o/w = bugs grow well in the continuous water phase. Use oil droplets as food.
2) temperature = temperature dependent
3) preservatives = add for longer term stability
- – interact with emulsifier = destabilise emulsion
- –partition into the oil phase - ineffective
Use of oral liquid emulsions
Oral liquid emulsions used to administer oils by mouth
- more palatable = taste better
- easier to administer
- more digestable (oil as fine droplets has a high surface area so is digested faster by GI Lipases)
- more effective (liquid paraffin - not absorbed, more effective as a laxative as a emulsion
Use of topical emulsions
Topical emulsions - soothe inflamed skin + administer drugs topically
- hair lotions + shampoos
- skin infections ( emulsion bases to use as emollients + antipruritics)
- irritating skin conditions (drugs to treat fungal + parasite)
- topical lotions + creams (lice, dandruff)
What is a Suspensions
Liquid medicines in which insoluble solids (usually drug)
are dispersed as fine particles.
How does a suspension look under the microscope
Vehicle = liquid in which the particles are suspended
Suspended particles = disperse phase
What are the main problems of suspensions ?
Physical signs of instability are
- Separation = particles fall due to density differences (redisperse by shaking)
- Caking = high density sediment of particles (difficult to redisperse)
a UNIFORM suspension will allow the patient to get the same dose of drug every time they pour the medicine = patient gets better
with a SEPARATED/CAKED suspension, an early dose wont work. Later doses will overdose patient + they may need resuscitation.
How do we prevent these caking/separation ?
1) Shake it - if particles redisperse easily, you can pour accurate dose.
2) Thickening agents - 3 types (Entangling/gelling soluble polymers, colloidal polymers + minerals, colloidal silicon dioxide in an oil)
3) Flocculation - flocs are loose, weakly-bonded, particle aggregates (2 types)
- —adding a surfactant = absorbs + adds surface charge; add salt to adjust charge to get flocs
- — add soluble polymer which absorbs to the particle surface
Shake bottle; flocs break up on shaking + particles redisperse to uniform suspension; flocs re-form on standing to prevents caking
Function of thickening agents
Substance that increases the viscosity of a liquid without substantially changing its other properties.
Entanglement
Polymer chains are extremely long and will entangle each other. In dilute solution this increases the viscosity of the vehicle. Concentrated solutions are commonly called gels
Entanglement with junction zones
Bonds or ordered structures form between the chains. These ‘ junction zones’ act as molecular cross-links, making the gel stronger and more rubbery.
This structure is a ‘true’ gel to a polymer or food scientist.
Colloidal polymers/minerals
Very small plate-like particles finely dispersed in the liquid
They thicken by ‘charge dispersal’ = Particles are charged. Repulsion keeps particles at a distance from each other, so the whole liquid resists movement.
Examples = Carbomer (synthetic polymer), Bentonite (clay), ‘Veegum’ Aluminium mag. silicate
(mineral), Colloidal silicon dioxide.
Colloidal silicon dioxide
For gelling oil
Very small particles that form linked networks in the oil
Network breaks up when stirred (gel gets thinner)
Reforms on standing (gel thickens). This is called Shear thinning behaviour
e.g. xanthan gum
Properties + use of thickening agen
At low concentration = increase vehicle viscosity, keep drugs suspended + maintain dose uniformity in suspensions
At high conc = semi-solid gels; transparent gel base for pharmaceuticals + cosmetics
Thicken liquids for greater residence time at site of action (e.g. eyedrops, teething + mouth ulcer gels)
What are the different categories of thickening agents
Entanglement/gelling polymers + minerals
Colloidal soluble polymers
Colloidal silicon dioxide
What is a Cream
Creams are emulsions
in which one phase is a
semisolid/wax
Types of creams
o/w cream
w/o creams
O/W creams
Water is the continuous phase
- cream can mix with wound exudates
- feel cool as water phase evaporates
- allow wounds to dry
- used in acute conditions as not occlusive
- acceptable to patients
- less greasy /sticky than ointments
- rub-in well into the skin
W/O creams
Oil is the continuous phase:
- ‘Oily creams’
- Tend to be ‘occlusive’ (see ointments)
- Make dry skin more supple : ‘moisturising’.
- Protect against water : nappy rash, sun/sea
Use of Skin creams
- Common as cosmetics.
- Deliver a wide range of drugs to skin :
antibiotics, antivirals steroids,antifungals
Fungal infections of damp areas
eg miconazole creams for athletes foot,
sweat rash, jock itch, nail infections
Use of common creams for body cavities
Clotrimazole Combi-packs for vaginal thrush
- 10% cream for intravaginal use in an applicator
- 2% cream for outside
- 2% cream for partner
Rectal cream for haemorrhoids (piles)
e.g. Anusol cream – tube with long applicator
What is an ointment
Spreadable greasy semi-solids, which may contain:
- dispersed powders
- small amounts of aqueous liquids
The base (vehicle) is
- a mixture of waxes, fats and oils (triglycerides)
- usually hydrophobic (water repellent)
The base is a uniform mixture has the wax, fats + oils dissolve in each other when melted
What is a paste
Ointments with a high powder content
Name some ointment ingredients and how they differ
Hydrocarbons (Paraffins)
- unreactive
- different forms (smaller mw = liquids, longer mw = light paraffin)
Fatty alcohols, acids and esters
Uses of creams
Skin creams
Common creams for body cavities
Triglycerides
Triglycerides are esters of long chain fatty acids with glycerol.
- Common as animal and vegetable fats and oils
- Vegetable oils have more unsaturated bonds. (e.g. Sunflower oil is a ‘polyunsaturate’) => animal fats tend to be saturated
When unsaturated bonds oxidise and ester groups oxidise, it forms short-chain fatty acids which are very smelly.
- ‘RANCIDITY’ = degradation of fats & oils
Uses of ointments
Occlusives
Protectives and Emollients
Occlusives
Trap sweat and water vapour under the skin to increase
skin hydration
• Make dry skin more supple.
• Soften the Stratum Corneum.
• Used in Chronic dry skin disorders. eg eczema.
- prevents skin cracking
Protectives + emollients
Barrier to protect against water and wind
– Cracked lips = Lip Balm
– Nappy rash = Ointments, w/o creams
– Emollients = skin itching e.g. in eczema
Problems with ointments
- Greasy & messy
- Stains clothing and not easily removed from skin.
- Not for acute inflammation (oozing, red, infected) as these require:
- – Drying and cooling
- – o/w creams
- – Aqueous lotions
If you occlude a wound it : • Prevents drying • Raises skin temp • Bacteria grow • Difficult to clean the lesions
Structure of the nose
- olfactory area = area of smelling receptors
- turbinate bodies
- – Humidify and warm air to lungs.
- – Rippled - large surface area.
- – Lots of blood vessels near surface.
- mucosal surface
- – Mucus traps particles.
- – ‘Cilated’ epithelium - yellow area
- –‘Mucociliary clearance’ in 10-20 min
Structure of the eye
- eyelids + glands = eye creams + ointments
- cornea
- anterior chamber
- lens, iris, muscles
(cornea, anterior chamber + lens, iris + muscles use eyedrops) - posterior (back of the eye) = Systemic drugs or direct injection
What type of medicines do we use to deliver drugs to different parts of each organ?
Creams and ointments - For external parts
(Areas where the surface structure is skin)
Drops / nasal sprays - For areas they can access.
Drugs can be absorbed through thin membranes like the cornea but don’t expect them to penetrate deeply.
Systemic therapy - For areas drops can’t access.
Drugs by mouth or injection. Drug reaches the organ by
diffusing into tissues from the bloodstream.
What things do we need to consider when formulating liquids for use in these areas?
Isotonic with blood
pH adjusted
Irritancy tested
— Disease state can make eyes and nose extremely sensitive to stinging.
Low cilia toxicity - To be healthy, nose needs good muco-ciliary clearance
Vehicle - Prevents ‘Swimmers ear’
Polymer thickeners - Help retain drops at site. May be muco-adhesive
Preservatives - Prevents re-infection from the dropper tip.
Sterile (no microbes) - the dropper tip. Damaged eye has particularly poor immune defences against infection.
What types of injections are there ?
Large volume infusions
- 100ml to 3L bags
- Fluid replacement
- Parenteral nutrition emulsions
Small volume infusions
- single injections = Pre-filled syringes are supplied to wards
- multidose injections - reconstituted in pharmacy sterile unit
Main routes of injection
IV Intravenous = Vein IM Intramuscular = Muscle SC Subcutaneous = Under the skin ID Intradermal = Into the dermis IT Intrathecal = Spinal fluid
What things do we need to consider when formulating liquids for use as injections?
- Sterile (no microbes) = prevents infection
- No microbial waste products (Pyrogens) = prevents rise in body temperature
- IV particle free unless emulsion = prevents clotting
- Isotonic with blood = prevents stinging
- pH adjusted (pH 7.4 best) = blood is a good buffer
- Preservatives = Multidose injections
- Irritancy = Irritant drugs can cause tissue damage (necrosis) e.g. anticancer drugs
- Solubilisers, stabilisers, cosolvents = maintain drug solubility + stability
What problems do we have with the public perception of excipients ?
Excipients are known to the public as: • Additives • E-numbers • Artificial ingredients • Chemicals
They have had A Bad Press, Big-time !
• Lots of ‘Scare stories’ - Foods and medicines
• People are confused
• What is safe and what is not ?
How can the Pharmacist play a role in making the public accept excipients?
Advise the public when they are worried or misinformed
All excipients in medicines have a function
• Maintain chemical stability of the drug
• Prevent microbial growth in the medicines
• Ensure homogeneity - same dose everytime
They have been tested for toxicity.
Some people may react
Only a few excipients have been linked with adverse reactions
• But there are lots of scare stories.
• Which ones are true ?
What is emulsifierss ?
Prevent droplet coalescence
What molecular characteristic do all emulsifiers possess?
Hydrophobic tail (dissolves in oil) Hydrophilic head (dissolves in water)
These molecules locate at oil/water or air/water interfaces
What types of emulsifier are there ? Name an example of each type.
Anionic (negative) = Sodium dodecyl (lauryl) sulphate
Cationic (positive) = Cetrimide (CTAB)
Non-ionic = Cetostearyl alcohol
Explain the different ways emulsifiers can work
Surfactants • Accumulate at water oil interface. • Form an interfacial barrier. • But charged molecules repel. – only a thin layer • Not good for stabilising emulsion
Polymers and proteins
- Proteins have hydrophilic and hydrophobic areas and are amphiphilic.
- Adsorb at interface, meaning, they’re good emulsifying agents.
- They can bridge between droplets. OIL and therefore act as suspending/flocculating agent
Why does using a mixture of emulsifiers often result in a better emulsion than a single charged one ?
Mixed emulsifier surfactants
• Mix of hydrophilic + more lipophilic ampiphiles
• Denser interfacial film.
• Excellent for stablising emulsions.
• Widely used in creams (concentrated emulsions)
— e.g. emusifying wax BP (Sodium dodecyl sulphate (charged) with cetostearyl alcohol (non-ionic); Instant stable emulsions and creams (just add oil and water)
Name a natural emulsifier
Lecithin (egg yolk) - phospholipid
Whey proteins.- Milk is a stabilised emulsion
