solution formulation and partitioning Flashcards
do injections need to be sterile?
yes
what should the pH of an injection be
close to physiological pH and well controlled
why is range of pH used for injections then?
as physicological pH may not be optimum for drug solubility and a wide range can be tolerated so there is a range of 3-9
do orally administered solutions need to be sterile?
No but should be made in clean conditions
what is the most commonly used solvent?
water
why is water such a popular solvent 4 reasons
- physiologically compatible and palatable
- not toxic or irritant
- dissolves a wide range
- widely unavailable and inexpensive
what is potable water and what does it contain
water taken directly from tap, may contain mineral impurities aka hard water
what is water for preperation?
potable or purified water, freshly boiled and cool to destroy vegetative bacteria
why can you not use stored water
there may be microbial contamination
what is purified water?
potable water that has been distilled, ion exchanged or reverse osmosised
what is apyrogenic?
does not contain pyrogenic materials.
how is purified water stored and distributed
in conditions that prevent microbial growth and contamination
what is purified water used for?
for prep of medicines that mustbe sterile and apyrogenic
what is water for injection
water for the preperation of medicines for parenteral administraion when water is used as a vehicle and for dissolving or diluting substancees or preperations for parenteral administration
why are non-aq solvents used?
if the solute is not properly soluble or stable in water and needed for depot therapy
what are 4 examples of non-aqueus fixed oil solvents?
- almond oil (phenol injections)
- arachis oil (methyl salicylate liniment)
- castor oil (eye and ear drops)
- olive oil, sesame oil, soya oil
what are fixed oil solvents used for?
intramuscular injection (depot therapy), oral, external products
are fixed oil solvents volatile?
no
2 examples of alcohol non-aq solvents and where on the body they can be used?
isopropyl alcohol and Industrial methylated spirit (IMS) both can be used externally only as they are toxic
what is the non-aq solvent ethanol used for?
it is a co-solvent
- used external for cooling
- internal/ parenternally if very dilute
- There is also exicse duty which is an alcohol tax that must be payed
what is a tonicity modifier used for?
to make solutions isotonic with tissure fluid to avoid pain and irritation
what formulations are tonicity modifiers necessary for?
injections and a large amount for opthalmic solutions and mucuous mebrance solutions
examples of tonicity modifiers and what time they are added in a formulation?
nacl, kcl, mannitol and dextrose
- added at the end
3 benefit of a viscosity enhancing agent?
- allows aq based topical solutions to stay in place for longer
- allows soltuions to be measured accurately for a dose
- can inhance palatiblity of oral solutions
what solutions have increased viscosity without viscosity enhancer
syrups
examples of thickening agents
hydroxyethylcellulose and other cellulose derivatievs , xanthax gum, carbomer
what is the purpose of antioxidents?
to increase stability of oxidation susceptible ingredients
how do antioxidants work?
they have a higher oxidative potential than drug or they inhibit free radical-induced drug decompositions
examples of water soluble antioxidants used in aq solutions
sodium sulphite, sodium metabisulphite, sodium formaldehyde sulphoxylate, ascorbic acid
examples of water insokuble antioxidants in non-aq solutions
butylated hydroxytoluene (BHT), bytylated hydroxyanisole (BHA) and propyl gallate
where can contamination be introduced
-raw materials or during manufacture
what is most sucespitble to microbial growth?
water containing solution
what should preservatives target
- gram- and postivie and fungi be broad spectrum
2 characterisicts that preservatives should have?
chemically, physically stable over shelf life of product and low toxicity, odourless and stable
what are 5 examples of preservatives?
choloroform (0.25% v/v) phenoxyethanol para-hydroxybenzoates (parabens) ethanol chlorocresol (o.1% w/v) with chlorbutanol (0.5% w/v) sucrose solution in syrup
why is sucrose solution considered a preservative in syrup
as there is 67% w/w in the syrup and therefore there is not much free water available for microbial contamination
how many preservatives are used in a formulation?
usually 2 to increase the antimicrocial spectrum
what adsorbing and abosorping problems do preservatives have?
they stick onto plastics like pvc e.g bottles, syringes, infusions sets, contact lenses and rubber such as closures, bungs.
what is the salt form of para-hydroxybenzoate or parabens?
benzoic acid
how is benzoic acids efficacy affected by pH?
benzoic and sorbic acid that have pKa of roughly 4.2 so their ionisation and activity is pH dependant. They exist in unionised form that are more lipid soluble and more effective than than ionised forms in acidic solution
what other preservatives efficacy affected by pH?
phenolic (less pH dependant than benzioc) and parabens (slighlty affected)
what is sucrose widely used as?
a sweetner
5 properties of sucrose?
- very soluble
- stable at pH4-8
- pleasant texture
- masks salty and bitter taste
- smoothing effect on throat
disadvangtes of using sucrose as sweetner
- dental caries
- unsuitable for diabetics
4 sweetners that can be used for children and diabetes?
sorbitol, mannitol, xylitol and glycerol
3 examples of natural sweetners
treacle, honey, liquorice
what is the most widely used artifical sweetner?
saccharin sodium which leaves a metalic after taste
2 other examples of artifical sweetners
aspartame, sucralose
what masks salty tase?
butterscotch, apricot, peach, vanilla and wintergreen mint
what masks bitter taste?
cherry, mint,anise
what masks sweet taste
vanilla, fruit, berry
what mask sour taste?
citrus flavour, raspberry
what may synthetic dyes need protection from?
UV light, oxidising or reducing agents, surfactants, extreme pH
what is partitioning?
when chemicals added to one phase will partition into the other due to different solubilities an affinities of the molecules to the aqueous and lipid phase of the formulation.
what is the partition coefficient?
the measure of the lipophilicity of a drug and an indication of its ability to cross the cell membrane. It is defined as the ratio between un-ionized drug distributed between the organic and aqueous layers at equilibrium.
what is the equation for partition co-efficient?
Po/w = Co/Cw
what does everything stand for in the equation?
Po/w = oil-water partition coeffecient Co = equilibrium conc in oil Cw = equilibrium conc in water
