Lecture 49: Liquid dosage forms suspensions and emulsions 2

what are the advantages of pharmaceutical oral suspensions?

• delivery system for low sol drugs

• avoid large volume of solvent

• avoid precipitation when storing when cosolvent is used

• taste masking

• difficulty swallowing solid forms

• controlled drug delivery

what are disadvantages of pharmaceutical oral suspensions?

• correct dose of drug?

• unstable, formulation to ensure stability over period of shelf life

• aesthetic suspension: difficult

• bulky so difficult for patient to carry

pharmacokinetics after administration of oral suspension:

what are some of the challenges with oral suspensions

• stability: can lead to sedimentation leading to particle particle interactions and caking

• need to know the particle size of the dispersed phase, excipients

• an alternative is producing solutions with solubilising agents

what are the key parameters which should be controlled?

• electrical properties of dispersed particles

• effect of distance of separation between particles on interaction(no interaction, agglomeration, floccules)

• viscosity

what are the 2 physical properties that need to be considered for the formulation?

Particle size: the larger the radius the more sedimentation. increasing stability by modifying rate of particle sed

• therefore particle size should be minimised. can be done by chemical methods(controlled precipitation) or physical methods(milling)

Wetting properties of drug:

• insoluble drug particles: hydrophobic and not easily wetted

• surface active agents: decrease interfacial tension

• particles poorly wetted: aggregation

what are the features of crystal growth?

• smaller particles dissolve better than large particles when dispersed in an aqueous vehicle

• an increase in storage temp caused smaller particles to dissolve in the vehicle

• crystallisation of dissolved drug may occur on surface of larger particles

• particles will have crystal growth around other particles when cold

• hydrophilic polymers decrease crystal growth by adsorbing on to suspended drug particles for protection

• crystal growth can be controlled by temperature cycling, monitor particle diameter and physical stability

what are the components of oral suspensions?

• Vehicle: purified water USP, buffers(citrate commonly used)

• excipients: they can physically stabilise suspensions, control rate of particle/ floccule sedimentation

what are the types of excipients and what do they do?

• electrolytes: they control flocculation by reducing zeta potential

• surface active agents:wetting, facilitating flocculation at conc less than 0.5% w/w

• non ionic preferred: polyethylene fatty acid sorbitan esters, lecithin

• ionic surfactants: greater toxicity

what are the types of excipients and what do they do? pt 2

Hydrophilic polymers: physical stability and affect flow properties

• they adsorb on to surface of suspended drug particles

• due to large MW, one section of polymer chain adsorb on to particles, the rest of the chain into an aqueous vehicle

• 2 polymer coated particles approach each other which prevents particles coming into close contact

• has the ability to stabilise suspensions: C, type of polymer

• increases viscosity which decreases sedimentation and increases physical stability giving it better flow properties making it easier to give to someone

what are the features of hydrophilic polymers in oral suspensions?

• they are cellulose derivatives, branched polymers, methycellulose, hydroxyethylcellulose or hydroxypropylmethylcellulose

• polyvinylpyrrolidone

• sodium aginate(ionic)

• acacia,tragacanth and xanthan gum: natural polysaccharide based polymers, low C

• hydrated silicates: for theological structuring, 5% swell in water leading to a vehicle with plastic flow

what are the other components of pharmaceutical oral suspensions ?

Preservatives:

• usually the external phase is water therefore there’s possible microbial growth

• highly pathogenic microorganisms (e coli) absent

• parables, organic acids such as benzoin acid

• interaction with hydrophilic polymers always required free C of preservatives available

Antioxidants: control degradation in preference of drug

sweetening agents/flavours: as for oral solutions

what are the features of direct incorporation?

the mixing rate is an important determinant

• if suspension is flocculated, high speed mixing is used

• if flocculation properties are poor, high speed mixing results in an increase in viscosity(it’s hard to mix homogeneously)

• the particle size of suspended drug may decrease using a ball mill. alternatively the particle size of the drug optimised by particle size reduction techniques

what is the precipitation method?

1. a drug is dissolved in vehicle prior to precipitation following addition of a counter ion(salt formed insoluble)

2. excipients dissolved in vehicle

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C

A , B, C