L47 - Liquid Dosage Forms - Solutions Flashcards
What are advantages of pharmaceutical oral solutions?
- easier to swallow (elders, infants)
- faster therapeutic response (immediately available for absorption)
- homogenous system (uniform distribituion, no dose variation bc of phase separation)
- reduced irritation (immediate dilution by gastric contents)
- taste-masking of bitter therapeutic agents
What are disadvantages of pharmaceutical oral solutions?
- manufacture, transport and administration problems
- growth of microorganisms
- poorer stability in aq sol than if solid dosage form
- shorter shelf live than solid dosage forms
- dose accuracy
- taste palatability issues
- unsuitable for chem unstable drugs in water
- expensive to ship, buly to carry
What are challenges of pharmaceutical oral solutions?
- homogeneity in formulation
- aq solubility of drug
What is it like when the aq solubility is high, moderate or low at the selected pH of the formulation?
- high - readily incorporated into vehicle
- moderate - solubility of drug enhance using co-solvents, related methods
- low - alternative dosage form used
What is purifies water USP like as a vehicle?
- low cost and toxicity
- drinking water not to be used (chem incompatibilities)
- preparation (distillation, ion exchange methods, reverse osmosis)
- solid residue - <1mg/100ml of evaporated sample
When should purified water USP not be used as a vehicle?
Parenteral formulations
How can you increase solubility of drug within formulation?
- co-solvents
- surface active agents and complexation
What are examples of co-solvents that increase solubility of drug within formulation?
- glycerol (glycerin, co-solvency due to 3-OH groups)
- alcohol USP (94.9, 96% v/v ethanol)
- propylene glycol USP
- polyethylene glycol (PEG, rep units of ethylene oxide)
What are examples of excipients in pharmaceutical oral solutions?
- buffers
- sweetening agents
- viscosity enhancing agents
What do sweetening agents do in pharmaceutical oral solutions?
Inc palatability of drug
What are examples of sweetening agnets in pharmaceutical oral solutions?
- sucrose
- liquid glucose
- glycerol
- sorbitol
- saccharin sodium
- aspartame
What are viscosity enhancing agnets in pharmaceutical oral solutions?
- non-ionic (cellulose devs, polyvinylpyrrolidone)
- ionic hydrophilic polymers ( sodium carboxymethylcellulose
- liquid formulations (no viscosity enhancing agents // syrup)
What do antioxidants do in pharmaceutical oral solutions?
- inc stability of drug (chem deg by ox)
- redox systems that exhibit inc in oxidative potential than drug/compounds that inhibit free rad induced drug decomp
What do antioxidants do in pharmaceutical oral solutions?
- oxidised in preference to drug - protects drug from decomp
- water soluble, water insoluble antioxidants, low C (<0.2% w/v)
What do preservatives do in pharmaceutical oral solutions?
Control the microbial bioburden of the formulation
What properties do preservatives have in pharmaceutical oral solutions?
- broad spec of antimicrobial activity
- chem, phy stable over shel life of product
- low toxicity
What are examples of preservatives used in pharmaceutical oral solutions?
- benzoic acid and salts (0.1-0.3)
- sorbic acid and salts (0.05-0.2)
- alkyl esters of parahydroxybenzoic acid - combo enhancement of the antimicrobial spec (0.001-0.2)
What is presevative efficacy like in oral solutions?
- correct form available at Creq to inhibit microbial growth (min inhibitory conc, MIC)
- conc may be affected by other excipient and formulation pH
What factors directly affect the efficacy of preservatives in oral solutions?
- pH of formulation
- presence of micelles
- presence of hydrophilic polymers
What is pH of formulation like?
- provides antimicrobial properties
- unionised form of HA diffuses across outer membrane into cytoplasm - neutral conditions enable dissociation, acidification of cytoplasm = inhibition of growth
- fraction of acidic preservative at a particular pH (form of HH eqn)
What is presence of micelles do to oral solutions?
- solubilisation of lipophilic drugs
- lipophilic properties from preservatives may partition into micelle, dec C available in sol
- eq
- inc Cpreservative, free C >/ MIC of preservative
What does the presene of hydrophilic polymers do to oral solutions?
- free Cpreservative - dec in hydrophilic polymers
- due to chem interaction - preservative with dissolved polymer
- problem sol - inc Cpresevative in formulation
What are the 4 basic taste sensations?
- salty
- sweet
- bitter
- sour
What are the salty tastes?
- butterscotch
- apricot
- peach
- vanilla
- wintergreen mint
What are the bitter tastes?
- cherry
- mint
- anise
What are the sweet tastes?
- vanilla
- fruit
- berry
What are the sour tastes?
- citrus flavs
- raspberry
What do flavours and colourants do in oral solutions?
- add flavour and desensitise taste receptors
- colour in combo with flavour
What is preparation and manufacturing like of oral solutions?
- dissolve solutes in solvent/mixture
- filtration system
- industrial scale - large mixing vessels with mech stirrers, vessels thermostatically controller, order of addition of components is fixed
What are the 3 principal types of solutions administered orally?
- oral solutions
- oral syrups
- oral elixirs
What are oral solutions like?
- systemic abs of drug
- formulated at proad pH range
- ~7.0 pH
- all components should be soluble, no evidence of precipitation
What are oral syrups like?
- highly conc, aq sol of sugar/sub
- unflavoured syrup - aq sol 85% sucrose
- drugs incorporated in, added as syrup prepared
- choice of syrup vehicle - physicochemical properties of drug
What are components of oral syrups?
- purified water
- sugar/sub - sweetness, high viscosity, inc Csucrose, no addition of preservaties
- no sucrose bases - sorbitol sol USP (64% w/w)
- sugar free for children and diabetic patients
- flavours - natural or synthethics
- colours
What are oral elixirs like?
- clear - hydroalcoholic sol
- Calcohol - ensure all other components remain (>10% v/v), other polyol cosolvents incorporated
- presence of alc - problem in paed formulations, adults who are avoiding
