Formulation in Pharmacy Practice   2nd Edition

VEHICLES
Suspending and Thickening Agents
 
HPMC Mucilage Carboxymethylcellulose
In this section some of the agents in use are briefly described but more information can be obtained from specialised texts.  It should be noted that in some formulations suspending agents may not be required, for example, when it is known that the drug is completely dissolved in the vehicle.  The use of syrup or glycerol as a simple suspending agent may be adequate in some circumstances.  The effectiveness of antimicrobial preservatives may be reduced by chemical degradation and binding interactions with macromolecules.  Mixture bases should not be stored for prolonged periods without appropriate testing to justify the shelf life.  In small-scale operations it is preferable to prepare the suspending agent at the time of dispensing.  The pH of the base must be compatible with the pH stability profile of the drug and the activity of the preservative system.

Carboxymethylcellulose (CMC)
This is usually available as the sodium salt.
CMC is used in concentrations of 1-2% w/v to give good suspending properties.  It has been reported that sodium carboxymethylcellulose solution has a pH of about 10 which may be incompatible with some acidic drugs.  However, to comply with the BP and USP a 1% solution is required to have a pH of 6.0 - 8.0 or 6.5 - 8.5 respectively.  Sodium carboxymethylcellulose is easily dispersed in water forming a colloidal solution.  CMC exhibits maximum viscosity at pH 7 - 9, and viscosity is markedly reduced below pH 4 and above pH 10.

Formula

Carboxymethylcellulose Suspension
(Australian Pharmaceutical Formulary and Handbook, 16th Ed.)
 
Carboxymethylcellulose 1.5  g
Ethanol mL
Compound hydroxybenzoate solution mL
Purified Water to   100  mL
 
CMC can be dispersed in cold water and allowed to hydrate and then heated to about 60°C.
Maximum gelling occurs in 1 - 2 hours.
Alternatively CMC can be mixed into a slurry with ethanol and then added to water.
 

Methylcellulose
The viscosity of methylcellulose solutions depends on the grade of methylcellulose used.  A 1% concentration is the most frequently employed.  Large amounts of electrolytes can cause precipitation of methylcellulose causing physical instability.
Methylcellulose hydrates and swells in hot water.  The usual method of preparation is to tritutrate at high shear with about 1/3 of the required amount of water at 80 - 90°C.  When dispersed, the rest of the water (as cold water or iced-water) is added with stiring.

Ora-Plus®, Ora-Sweet® and Ora-Sweet SF® (Paddock Laboratories http://www.paddocklabs.com)
Ora-Plus®, Ora-Sweet® and Ora-Sweet SF® are commercially manufactured products which have been used in many stability studies published in North America.
Ora-Plus® contains: purified water, microcrystalline cellulose, carboxymethylcellulose sodium, xanthan gum, flavouring, citric acid, sodium phosphate, simethicone, methylparaben, and potassium sorbate. pH 4.2.
Ora-Sweet® contains: purified water, sucrose, glycerin, sorbitol, flavouring, citric acid, sodium phosphate, methylparaben and potassium sorbate. pH 4.2
Ora-Sweet SF® contains: purified water, glycerin, sorbitol, sodium saccharin, xanthan gum, flavouring, citric acid, sodium citrate, methylparaben, propylparaben, potassium sorbate. pH 4.2.

Xanthan Gum
This preparation is used in some countries to prepare suspensions of crushed tablets.  As the preparation takes a while to dissolve, a 1% solution containing parabens can be prepared in advance and diluted to 0.5% with water when required.  Xanthan Gum has been successfully used in suspensions of many drugs including acetazolamide, allopurinol, diazepam and spironolactone.  However a small number of drugs (including tamoxifen, verapamil and amitriptyline) have been found to be incompatible.

Tragacanth
Tragacanth in the form of tragacanth mucilage or compound tragacanth powder has been widely used as a suspending agent.  Many commercial sources are heavily contaminated with microorganisms and tragacanth should never be used in preparations which do not contain an antimicrobial preservative.  Other agents are now considered to be superior to tragacanth.

HPMC 1% Mucilage
Formula reproduced with permission.  WA Hospitals Central Pharmaceutical Manufacturing Facility, Roberts Road, Subiaco, Western Australia 6008. 

Formula

HPMC 1% Mucilage
(Princess Margaret Hospital, Perth WA)
 
Hypromellose 4500 BP g
Methyl Hydroxybenzoate 400  mg
Propyl Hydroxybenzoate 100  mg
Water to   500  mL
 
Expiry:  Shelf life 2 years.
 
Storage:  Store below 30°C
 
Shake well before use
 


Formulation in Pharmacy Practice
2nd Edition