liquid oral dosage forms Flashcards
why do oral solutions provide a faster therapeutic response?
the drug is immediately available for absorption as there is no dissolution process
how does bioavailability differ for oral solutions compared to solid dosage forms?
usually oral solutions have higher bioavailability as long as it does not precipitate in the gi tract. although sometimes the bioavailability may be the same just the rate of absorption would be quicker for solutions.
solutions are a homogenous system - what does this mean?
there is uniform distribution throughout the preparation, this means there will be no issues with dose variations due to phase separation on storage.
why do solutions generally cause less irritation?
solutions are immediately diluted by gastric contents hence there is reduced irritation where as excipients of solid dosage forms may cause irritation.
why do solutions have lower shelf life?
once solutions are opened they get exposed to microorganisms hence they will then have a lower shelf life.
what are some of the downsides of solutions?
drugs have poorer stability in aqueous solutions, can be difficult for patients to accurately dose, taste palatability issues, unsuitable for drugs that are chemicallly unstable in water, expensive to ship and bulky for patients to transport.
what happens if the aqueosu solubility of the drug is high at the selected ph of the formulation?
the drug can be readily incorporated into the vehicle
what if the aqueous solubility of the drug is moderate at the selected ph of the drug?
the solubility of the drug must be enhanced using cosolvents etc.
what if the aquous solubility of the drug is low at the selected ph of the formulation?
an alternative formulation should be used e.g. you could use a suspension rather than a solution.
what is used as the vehicle in solutions?
purified water (USP) as it is low cost and low toxicity however it would not be used for parenteral solutions
how is purified water prepared?
purified water can be prepared through distillation, ion exchange methods or reverse osmosis.
different entities can be added to improve the solubility of a drug within a formultion like cosolvents surfactants and complexation. what are some examples of cosolvents that may be used?
glycerol, alcohol usp, propylene glycol usp or polyethylene glycol.
why is a buffer added to solutions?
a buffer can be added to maintain a constant ph. the buffer used depends on the required ph, examples include acetates, citrates and phosphates - there is a limit of how much buffer can safely be added.
sweetening agents are used to increase palatability of solutions - what are some examples of these?
sucrose, liquid glucose, glycerol, sorbitol, saccharin sodium and aspartame.
what would be a low sugar sweetener and why would it be used?
we dont want to give high amounts of sugar to children or patients with diabetes mellitus hence we can use aspartame as the sweetener.
why are viscosity enhancing agents used?
viscosity enhancing agents can be added to solutions to increase the viscosity of the solution so that its easier to pour and get an accurate dose. drugs are also solubilised better is more viscous solutions.
what are some viscosity enhancing agents used in formulations?
cellulose derivaties like methyl cellulose (nonionic), sodium carboxymethylcellulose (anionic), sodium alginate (anion).
some formulations may not require viscosity enhancing agents, why is this?
certain liquid formulations dont need viscosity enhancers e.g. syrups as these have inherent viscosity due to the presence of sugar.
why are antioxidants added?
antioxidants are added to solution to increase the stability of drugs as they can be susceptible to chemical degradation by oxidation. you can get both water soluble and insoluble antioxidants that are only required in small concentrations.
how do antioxidants work?
antioxidants will get oxidiesd in preference to the drug, protecting the drug from decomposition.
the antioxidants are ether redox systems that exhibit more oxidative potential than the drugs - they inhibit free radical induced drug decomposition.
why are preservatives added?
preservatives are used to control microbial activity, they must cover a broad spectrum of antimicrobial activity (a few preservatives can be used in combination to acheive this), they must also be physically and chemically stable over the shelf life and have low toxicity.
what are some preservatives used in solutions?
benzoic acid and its salts, sorbic acid and its salts, alkyl esters of parahydroxybenzoic acid.
the correct form of preservative is required at a specific concentration to inhibit microbial growth - whats this called?
minimum inhibitory concentration
what might affect the concentration of preservative?
the presence of other excipients and the ph of the formulation.
factors that directly affect the efficacy of preservatives are the ph of the formulation, the presence of micelles and the presence of hydrophilic polymers.
how will changing the ph of formulation affect the preservative?
changing the ph will affect the fraction of unionised form of preservative which will affect its strength of action.
how dos preservatives work?
the unionised form of the preservative has antimicrobial properties - this diffuses across the outer membrane of the microorganism and into the cytoplasm. here the neural conditions allow the preservative to dissociate, the acidification of the cytoplasm therefore inhibits growth.
how can the fraction of acidic preservative at a particular ph be calculates?
using the henderson hasselbach equation, the fraction = 1/1+10^ph-pka
micelles improve the solubilisation of lipophilic drugs - how do they effect preservaties?
if the preservative is lipophilic it may enter the micelle hence it will be unaiavalable for antimicrobial action. this means the available concentration of preservative in solution decreases. the concentration of preservative must therefore be increased to obtain the correct free concentration so that its greater than the minimum inhibitory concentration.
how do hydrophilic polymers affect preservatives?
preservaties can chemically interact with the dissolved polymer hence decreasing the free concentration of the preservative, the concentration of preservative must therefore be increased.
why cant you use cationic hydrophilic polymers with acidic preservatives?
sometimes there is incompatibility with the preservative with hydrophilic polymers due to electrostatic interaction.
what are flavour adjuncts?
flavour adjuncts both add flavour and desensitise the taste receptors.
how are solutions prepared?
the solutes are dissolved into the solvent in a particular order and then filtered - in industry the vessels are thermostatically controlled so its done at an appropriate fixed temperature.
what are the 3 principal oral solutions?
solutions, syrups and elixirs
all components of the solution should be soluble - no signs of precipitation
why are oral solutions formulated over a broad ph?
they are developed over a broad ph range for resilience of the gi environment although the usual ph is 7
what are oral syrups?
oral syrups are aqueous solutions of sugar or sugar substitute. the drugs are directly incorporated into these systems or added as the syrup is being prepared.
how must the vehicle of syrups be chosen?
the syrup vehicle must be chosen appropriately based on physicochemical properties of the drug. e.g. using an acidic syrup may reduce the solubility of acidic drugs and they will therefore precipitate.
what are the components of syrups?
purified water and sugar - no viscosity agents or sweeteners are required and increasing the concentration of sucrose will mean theres lower water activity so no addition of preservative is required.
sugar free syrups can use glycogenetic for children and diabetic patients
flavours can be added - sometimes these may have therapeutic activity e.g. antacids contain mint due to the carminative properties of the ingredient.
what are oral elixirs?
oral elixirs are clear hydroalcoholic solutions, they have sufficient alcohol concentration to ensure all components remain in solution - its therefore unsuitable for children. if the alcohol concentration is greater than 12% preservatives are not required sue to its antimicrobial properties.
what are linctuses?
linctuses are viscous preparations in which the drug is dissolved in a vehicle composed of high sucrose, primarily used for treatment of a cough as it has soothing actions on the inflamed mucous membranes.
what are mouthwashes/ gargles used for?
mouthwashes and gargles may be usedfor treatment of infection and inflammation of the oral cavity.
what are suspensions?
a suspension is a dispersion in which the drug is dispersed in the system/vehicle not solubilised - this is used for drugs with low solubility.
the diameter of the disperse phase ranges from 0.5um to 100um - when the particle size is less than 0.5um it is colloidal.
whats the main issue with suspensions?
suspensions have low stability leading to sedimentation, particle particle interactions and caking (compaction)
what must we understand to understand the physical stability of suspensions?
the electrical properties of dispersed particles and the effect of distance of separation between particles on their subsequent interaction.
following dispersion within an aqueosu medium oarticles may aquire a charge, what may cause this?
ionisation of functional groups on the drug molecule or adsorption of ions to the surface of the particle may cause particles to aquire a charge following dispersion.
