|Formulation in Pharmacy Practice 2nd Edition|
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.
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.
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.
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.
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 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.
Formulation in Pharmacy Practice