Medicinal Suspensions Flashcards
Why is deflocculation not desirable yet flocculation is in a pharmaceutical suspension?
Flocculation prevents caking whereas deflocculation increases the tendency to cake.
From consideration of Stokes Law, state TWO parameters that have a significant effect on the rate of sedimentation.
Diameter of sphere (size of suspended particle); viscosity of the continuous phase (inverse relationship); difference in densities between solid and liquid phases; acceleration due to gravity (normally constant).
Within a pharmaceutical context, why is the flocculated/deflocculated nature of suspended particles important?
Flocculated particles sediment quickly but are readily re-dispersed upon shaking, enabling a uniform dose of medicine to be administered.
Deflocculated particles remain in suspension much longer (than flocculated) but form a compacted sediment that is difficult to re-disperse upon shaking.
Cellulose ethers e.g. hydroxypropylmethylcellulose (Methocel E15), are useful viscosity enhancers in medicinal suspensions. Explain the reason for using the ‘hot/cold method’ when dissolving the solid polymer powders in water rather than simple dissolution in cold water.
These polymers have both hydrophilic and hydrophobic character (amphiphilic). The hydrophobic moieties i.e. methyl groups, are hydrophobic and less soluble in hot water than cold. Complete dispersion and wetting, using vigorous mixing in very hot water, causes individual particles to form a wetted suspension which can be quickly dissolved by the addition of cold water which lowers the temperature of the continuous phase (water) to below the ‘incipient gelation temperature’ (IGT) at which point dissolution/gelation instantly occurs. ‘Hydrophobic-hydrophobic attractions’ between methyl groups prevent dissolution from occurring in water heated to above the IGT.
If a suspension contains a dose of drug equivalent to 100 mg/5 mL, calculate the total quantity of drug in a bottle containing 100 mL.
100mg 5mL
x mg 100mL
x = 100 mg x 100 mL / 5 mL = 2,000 mg (2 g)
If the solubility of the drug in the vehicle is 10 mg/mL which is 100ml, calculate the total quantity of drug in suspension. Total drug is 2000mg?
Total drug = Drug in solution + Drug in suspension Drug in suspension = Total drug – Drug in solution
Total drug = 2,000 mg (from 5(a)).
Drug in solution = 10 mg/mL 1,000 mg/100 mL. Drug in suspension = 2,000 mg – 1,000 mg
= 1,000 mg (1 g)
What is a pharmaceutical suspension?
Dispersion of fine, insoluble, solid particles ( disperse phase) within a liquid (continuous phase or dispersion phase)
What is an oral suspension?
Denoting a drug to be taken by mouth e.g Calpol
What are the two types of solids within a disperse phase?
Solid particles ( of drug) with a mean size above 5 micrometers are normally referred to as ‘course suspensions’ - emulsions and suspensions
Solid particles (of drug) with a mean size below 1 micrometers are normally referred to as ‘colloidal dispersions’ - closer to the wavelength of light - blue light is scattered more than red. (usually blue coloured) - gels
What is the continuous phase?
Usually aqueous but can be organic or oil-based e.g magnesium hydroxide suspension (‘milk/cream of magnesia’) is an aqueous suspension of about 8% magnesium hydroxide available as ‘magnesium hydroxide mixture BP’ or ‘Liquid paraffin and magnesium hydroxide Oral emulsion BP’ is an aqueous suspension containing 6% magnesium hydroxide in 25% liquid paraffin (emulsion or suspension)
What are some properties of well - formulated suspensions?
-Disperse phase particles should be small, uniformly sized and not settle too rapidly,
-settled particles should not form a compact sediment which is difficult to disperse
-successive doses should contain the same amount of suspended solid and hence the same dose of drug,
-product should have an agreeable odour, colour, taste and texture ( not a ‘gritty’ feel),
-continuous phase should not support microbial growth on storage.
Why are suspensions used to patients? - Give an example
- Used where patients have trouble swallowing solid dosage forms
- Bitter/unpalatable taste of many drugs is less noticeable in the solid-state than the solution-state
- High surface area of fine suspensions is desirable for fast drug dissolution in the GI tract
- ## High surface area is required for the fast action of toxin adsorbing compounds (e.g Kaolin) or ‘antacids’ (e.g magnesium carbonate/ hydroxide)
What are the disadvantages of oral suspensions?
Sedimentation
Settling as a deflocculated sediment - slow sedimentation to forma. firm mass that is impossible/ extremely difficult to re-suspend - caking or claying
Settling as a flocculated sediment - fast sediment to form a ‘loose cake’ that can be re-suspended relatively easily
Both lead to inaccurate dosing and ‘inelegance’
Example of disadvantage of oral solutions?
Drug Stability
The presence of water - even with insoluble drugs can result in hydrolytic degradation with time e.g tetracycline antibiotics.
Dissolution of smaller particles that can subsequently re-crystallise on the surface of larger particles causing a shift in the mean particle size distribution - Ostwald Ripening (crystal ripening)
Example of advantage of oral solutions?
Oxytetracycline
some drugs hydrolyse in the presence of water (ie hydrolytic ally degrade) and loose their efficacy if prepared as solutions - in some cases it is possible to synthesise an insoluble derivative, it is possible to synthesise an insoluble derivative that can be formulated as an oral suspension. e.g oxytetracycline can be used as a mouthwash in cases of severe oral ulceration (e.g oral herpes).
However it hydrolyses in the presence of water. The insoluble calcium salt, does not hydrolyse quickly. A stable suspension can be made by suspending the calcium salt in a suitable aqueous vehicle. Alternatively an non aqueous continuous phase could be used but as this would normally be an oil therefore taste and mouth-feel can be a problem.
