The Pharmacist Semester 2 Flashcards
Give examples of semi solid preparations.
Ointments
Creams
Gels
Pastes
What is a transdermal formulation?
Absorbed through the skin to work systemically- more commonly as patches than semi solids.
What is a diadermal formulation?
Works in the dermis or lower with a local effect, useful for anti-inflammatories, anti-itching and local anaesthetics.
What is an epidermal formulation?
Works locally at the surface of the skin, useful in things such as lubrication, UV protection, emollients and antimicrobials.
What is a topical formulation?
An umbrella term for formulations used on the skin such as semi solids, eyedrops, rectal, vaginal or intra-nasal drugs- epidermal and endodermal, local effect.
What are the properties of creams?
Emulsions- contain oil Provide cooling effect on the skin Less greasy- patient friendly Less occlusive- good for macerated skin Require preservatives as they are hydrous- less stable
What are the properties of pastes?
Stiff preparation
Ointments with 30-70% of their mass being powder based
Precise localised treatment
Form thick, impermeable layer on the skin
Less spreadable than other semi solids
What are the properties of gels?
Made up of polymer and have high water content
Drug able to diffuse through gel to site of action
Leave little to no residue on skin
Require stabilisers
Explain the benefits of oily vehicles in semi solids.
Allow occlusive layer to form:
Mineral oils- limited penetration into skin
Vegetable oils- good penetration but can turn rancid
Synthetic oils- water repellent and occlusive
What is the benefit of water miscible vehicles in semi solids?
Added cooling effect and act as absorption promoters.
What do emulsifying agents do in semi solids?
Help oil and water to form a stable, uniform mixture and increase drug penetration.
Give examples of emulsifying agents.
Water in oil: bees wax, lanolin
Oil in water: waxes based on cetostearyl alcohol
Polyethylene glycols: macrogols/carbowaxes
Non-ionic surfactants: sorbitan
What is the role of humectants in semi solids?
Reduce the loss of water from creams and gels e.g. glycerol
What is the role of preservatives in semi solids?
Increase the stability of the preparation e.g. parabens and EDTA
What is the role of antioxidants in semi solids?
Preventing decomposition.
What three things most affect semi solid preparations?
Heat
Light
Micro organism growth
What should be considered when making packaging for semi solid preparations?
Assuring photo-stability.
The packaging should not interact with the formulation.
Give advantages and disadvantages of ointments and pastes.
Stable, occlusive, good for dry skin, less need for preservatives.
Greasy, slow absorption, high oil content preps can be flammable, not to be used on macerated skin.
Give advantages and disadvantages of creams and gels.
Non greasy, more patient friendly, rapid absorption, cooling effect, less additives in gels, can be used on macerated skin.
Susceptible to microbial contamination, require preservatives, less stable (short expiry), short duration of action.
What properties do aerosols for topical application have?
Drug is dispersed in solution/suspension.
Requires propellant such as HFAs, CFCs, butane.
To be stored below 25 degrees.
Aerosols must be shaken before use.
When making semi solids extemporaneously, how much excess should be made?
25%
What is trituration?
Method of incorporating liquids or powders into a semi solid base on a ceramic tile.
What is levigation?
Application of pressure to incorporate powder into a semi solid.
How long should extemporaneous records be kept for?
Legal requirement of a minimum of 5 years
What should an extemp record contain?
Formula and source Calculations and ingredients-checked Names and signatures of all involved with process Date prepared and supplied Expiry and batch no Details of patient and doctor Label
What is stability determined by?
Physical appearance Chemical changes Microbial Therapeutic effect Toxicology
What expiry date should be given if unavailable in the monograph?
Stable preparations (solid internals and externals)- 3 months Unstable preparations (liquids/semi solids)- can be 2-4 weeks
What are the most common preservatives used in aqueous liquids?
Chloroform water/spirit
What reasons are there for coating a tablet?
Protecting the drug
Masking taste/appearance
Easier to swallow
Altering release properties
What are the two types of capsule?
Hard gelatin
Soft gelatin
What do diluents/fillers do in solid dosage forms?
Add bulk e.g. lactose, mannitol
What do binders do in solid dosage forms?
Form granules e.g. gelatin, cellulose
What do lubricants do in solid dosage forms?
Improve flow properties e.g. magnesium/calcium stearate
What do colourants do in solid dosage forms?
For identifications/appearance e.g. E numbers
What excipients are present to give effervescent effect?
Reaction between carbonate and weak acid produces CO2 to break up tablet e.g. sodium carbonate and citric acid
What excipients are present specifically in chewable tablets/solids in liquid preparations?
Sweetners and flavouring
What are the three types of modified release tablets?
Delayed- releases after certain time frame
Enteric coated- pH dependent release
Extended- prolonged/suspended
What are the two most common methods for modified release tablets?
Matrix system- can be split
Reservoir/membrane system- cannot be split
What are the advantages of tablets and capsules?
Stable, accurate dosing, convenient for use, low cost, easy to make, taste can be masked, release can be modified, enteric coating available.
What are the disadvantages of tablets and capsules?
Slow onset of action, 1st pass metabolism, systemic action, side effects, often contain gelatine, difficulty swallowing.
What are the advantages of powders and granules?
Very stable, can be reconstituted to liquids, faster onset of action, accurate dosing in sachets, good for larges doses, easier for those with difficulty swallowing, release in granules can be modified.
When made extemporaneously what is the minimum weight of the contents of a capsule?
100mg- if below a diluent must be added.
What are the three methods for filling capsules?
Punch- pressing capsule into mixture
Capsule machines- use trays to hold capsules
Weighed aliquots- fill capsules individually
Define a solution.
A homogeneous picture of two or more components resulting in a one phase system.
What are the specialised aims of excipients in eye drops?
Tonicity- should be isotonic 0.9%
Viscosity- increasing can prolong contact with eye
pH- buffers to affect therapeutic activity, comfort, stability
Oxidation- antioxidants to protect
Preservatives- antibacterial affect
What is a suspension?
A mixture of 2 or more components resulting in a two phase system.
Dispersed and continuos phases.
What is a flocculated system?
Particles suspended form loose aggregates- sediment is fast forming but easy to re-disperse.
What is a deflocculated suspension?
Particles exist as separate entities- sediment is slow forming but difficult to re-disperse.
What is the role of a wetting agent in a suspension?
Reduce interfacial tension and clumping.
What are the three key components of an emulsion?
Continuous phase- vehicle
Discontinuous phase- dispersed
Stabilising agent- emulsifier/surfactant
How do emulsions, micro emulsions and nano emulsions differ?
Depends on particle size of dispersed phase:
Emulsions- 10-500µm
Microemulsions- 200nm-10µm
Nanoemulsions- <200µm
What is a colloid?
A mixture in which one substance of microscopically dispersed insoluble particles is suspended throughout another substance.
Where is an external formulation used?
Body surface or cavity
What two types of emulsion are there?
Oil in water
Water in oil
What is the maximum amount of an emulsion that the dispersed phase can be?
60%
What is cracking within an emulsion?
Water comes out of the dispersed phase of a water in oil emulsion and cannot be re-dispersed.
What is creaming within an emulsion?
Oil rises to the top or sinks to the bottom of an oil in water emulsion, shaking can however re-disperse.
What are the common features of an oil in water emulsion?
Less greasy
Less viscous
Rapid absorption/evapouration on skin
What are the common features of a water in oil emulsion?
Greasy by nature
More viscous and occlusive
Most commonly use liquid paraffin
How can cracking and creaming be prevented?
Retaining optimum size of dispersed phase
Stopping extremes of temperature
Using stabilisers to prevent coalescence
Preventing microbial contamination
What are the features of natural emulsifying agents?
Less stable than others Polysaccharides (o/w) Semi-synthesitic (o/w) Sterols (o/w) e.g. beeswax, wool fat
What are the types of synthetic surfactants as emulsifying agents?
Anionic- soaps (external o/w) such as sodium sterate
Cationing- antimicrobial (external o/w) such as cetrimide
Non-ionic such as glycerol or macrogol esters
What are the types of finely divided solids as emulsifying agents?
Wetted by oil (w/o) such as Plastibase
Wetted by water (o/w) such as bentonite, colloidal silicon dioxide
Form stable emulsions
What is the Hydrophillic-lipophillic balance of emulsions?
Each emulsifying agent is given a number from 1-20.
Low numbers mean w/o
High numbers mean o/w
What three ways are emulsifying agents chosen?
Route of administration
Active ingredient (interactions)
Allergenic potential
Why are antioxidants added to emulsions?
Oils are liable to oxidation
Why are preservatives added?
Water supports microbial growth
Examples include chloroform, benzoic acid, cetrimide
Give advantages of emulsions.
Delivery of oils and lipophillic drugs
Improved perception of a medicine
Improved medicine compliance
Used as soaps
Give limitations of emulsions.
Physiochemical stability Manufacturing difficulty Microbial stability Shake before use Flammable Allergies Storage conditions Bathroom slips
What are colloidons?
Form waterproof film on the skin
Contain solvents (evapouration causes drying), Proxylin (nitrocellulose produces the film), Camphor (makes the film waterproof), Plasticiser (makes film flexible)
Highly flammable
What are the features of transdermal drug delivery?
Delivered via patch on skin
Continuous release over a period of time
Rate of delivery slower than rate of absorption
Enters systemic circulation
What are the two methods of transdermal delivery?
Matrix
Rate limiting membrane
How do transdermal patches work?
Drug in solution or suspension, stored in matrix/reservoir.
Adhesive layer creates a diffusion gradient as well as adhering to skin.
Membrane is behind the adhesive layer.
What are the benefits of transdermal drug delivery?
Bypasses GIT Systemic effects No 1st pass metabolism Controlled and constant delivery rate Long duration of action
What are the features of injections?
Are solutions, suspensions or emulsions
For local or systemic use
Different injection routes include IM, IV and SC.
What excipients are present in injections?
Water for injection
Preservatives
Buffers
Tonicity adjusting agents
How does the stability of an injection vary?
Solution> suspension> emulsion
What methods of packaging are available for injections?
Single dose glass ampoules
Multi dose glass vials
Pre-filled syringes
Infusion bags
What are the advantages of injections?
Local or systemic
Used if oral route inappropriate
Avoids GIT and 1st pass metabolism
Rapid onset of action
What are the disadvantages of injections?
Invasive/painful
Risk of infection/embolism
Difficult to reverse effects
Difficult to administer, often require specialist training
What are the features of inhalers?
Designed to deliver drug directly to lungs- local and systemic
Many different types of device and combinations
How does particle size effect inhaler use?
<1micrometer results in exhalation of particle
>10micrometers results in particle remaining in oropharynx
Optimum size is 3-5 micrometers
How do Metered Dose Inhalers work?
Aerosol of drug in solution/suspension with propellant where actuation results in evapouration of propellant to form droplets for inhalation.
How do spacers benefit use of MDIs?
No coordination required, beneficial for children and elderly to ensure the receive full dose.
How do Breath Actuated MDIs work?
Inhaling triggers actuation of the device but correct inspiratory flow is required.
What excipients are present in MDIs?
Propellant such as CFC
Surfactants for wetting in suspension
Co-solvents to aid dissolution
How do Dry Powder Inhalers work?
Breath actuated, drug is a micronised powder for inhalation. Sharp deep breath results in powder being mobilised without the need for a propellant.
What excipients are present in DPIs?
Carrier such as lactose which remains in the mouth- can result in powder taste.
Pure drug- little or no taste residue.
How are MDIs packaged?
In canisters of: Tin plated steel Plastic coated glass Aluminium Container protects from oxidation and micro organisms making it very stable.
How are DPIs packaged?
Powder contained in: Preloaded chamber Foil blisters Hard gelatine capsules Susceptible to moisture degradation
What are the advantages of inhalers?
Can use small doses Reduce systemic side effects Fast onset of action Can use drugs with poor oral bioavailability MDIs are extremely cheap
What are the features of rectal drug delivery?
Used for local or systemic action
Local use- usually laxatives, haemorrhoids and inflammatory bowel deseases
Systemic use- for pain and seizures
Formulations include suppositories, creams, ointments, enemas
What are the features of suppositories?
Usually 1-4g in size
Drug contained within a vehicle
What are the characteristics of a good vehicle in a suppository?
Melt at body temperature of dissolve in rectal fluids Solidify quickly after melting Easily moulded and removed from molten Stable when molten Release active ingredient Non toxic and non irritant
Describe the features of fatty bases as vehicles in suppositories.
Melt at 37°C
Need to be stable on storage
Theobroma oil- replaced by new synthetic vehicles
Synthetic fats- hydrogenated vegetable oils
Describe the features of water soluble bases as vehicles in suppositories.
Mix of glycerol water and gelatine- dissolves in rectal fluids
Can cause irritation producing a laxative effect
Macrogols- dissolve in rectal fluids with no laxative effect
What other excipients are required for suppositories?
Viscosity enhancers such as colloidal silicone oxide create a gel like system for slower release of the drug
Lecithin- used when drug concentration is high to help flow properties
Surfactants- to create emulsion systems or act as wetting agents
What affects the stability of suppositories?
Heat- especially with fatty bases
Light
Moisture- water soluble bases can turn brittle and may need lubricating before administration
How should suppositories be stored?
Must protect against heat and moisture
Extemp products stored in glass jars
Foil or plastic sealed blisters
Blisters are packaged in cardboard boxes
What are enemas?
Oily or aqueous solutions administered rectally
What are the features of an enema?
Can be a foam in an aerosol canister with applicator
Local or systemic effect
Do not require melting or dissolution
Can have large volumes 100-200mL
Microenemas have small volumes 3-5mL
Contained in plastic bottles with specially designed nozzles.
What are the advantages of rectal drug delivery?
Oral route may not be available Drug may not be orally active Avoids 1st pass metabolism Rapid local action Avoids GIT absorption issues
What are the disadvantages of rectal drug delivery?
Not patient preference Slow and incomplete absorption Local irritation Difficult production Difficult administration Storage conditions
What are the features of vaginal drug delivery?
For both local and systemic use
Formulations include pessaries, tablets, capsules, creams, gels and foams
Most require an applicator
What are the features of pessaries?
Similar to rectal suppositories
Made with glycerol-gelatine bases
What are the features of vaginal tablets?
Require disintegrants due to low moisture content e.g. bicarbonate with an organic acid- fizzing
What are the features of vaginal capsules?
Meltable soft gelatine capsules filled with oils
E.g. gynodaktarin ovule
What are the features of vaginal creams/gels?
External and internal use
Prefilled applicator or tube available
What are the features of vaginal foams?
Aerosol canister for internal use
Come with applicators
What are the advantages of vaginal drug delivery?
Drug not orally active Better bioavailability for some drugs Avoid GIT absorption issues Avoids 1st pass metabolism Rapid local action Reduced systemic side effects
What are the disadvantages of vaginal drug delivery?
Not patient preference Local irritation Staining of underwear Difficult administration Difficult production Pregnancy and applicators Compatibility with condoms
