Suspensions are heterogeneous systems consisting of two phases:
- The continuous or external phase, generally a liquid or semisolid.
- the dispersed or internal phase, made up of particulate matter (solid) that is essentially insoluble in, but dispersed throughout the continuous phase.
There are two types of suspension:
- flocculated
- deflocculated
At start up, we need to formulate a liquid dosage form but what about solution?
The choice of developing a solution or a suspension formulation is ultimately made based on the AQUEOUS SOLUBILITY of the drug.
- Poor aqueous solubility = suspension
Challenging stability issues like to get a sterile suspension for:
- parenteral
- ocular
- nebulized inhalation
Considerations in suspension formulation development:
- wetting
- particle interactions and behavior (sedimentation rate, crystal habit, crystal structure factors).
Suspension Formation:
1. Precipitation Methods:
- organic solvent precipitation.
- precipitation effected by changing the pH of the medium, eg. estradiol, insulin.
- double decomposition.
2. Dispersion methods (vehicle must be mutilated, solid phase easily wetted, dispersed).
Excipients used in suspension Formulation [for non-oral (sterile) dosage forms]:
1. Suspending agents:
- Methylcellulose
- Hydroxyethylcellulose
- Hydeoxypropylmethylcellulose
- Carboxymethylcellulose
- Sodium Carboxymethylcellulose
- Microcrystalline cellulose
- Gums & others (Xanthan gum, Bentonite, Carbomer, Carrageenan, Powdered cellulose, Gelatin).
2. Wetting agents, solubilizers:
- Lecithin
- Polyethylene glycol 300
- Polypropylene glycol
- Polysorbate 20,40,80
- Povidone
- Dimethylacetamide
- Dioctyl sodium sulfosuccinate
- Egg yolk phospholipid
- Ethyl alcohol
- Ethyl lactate
- Sodium deoxycholate
- Sorbitan monopalmitate
- Theophylline
3. OTHER sterile liquid dosage form excipients:
Isotonicity modifiers:
- Sodium chloride
- Sodium sulfate
- Mannitol
- Lactose
- Dextrose
- Glycerin
Buffers:
- Acetic acid, sodium acetate
- Benzoic acid and sodium benzoate
- Citric acid, sodium citrate
- Lactic acid, maleic acid
- Potassium phosphate
- Sodium phosphate monobasic, Sodium phosphate dibasic
- Sodium bicarbonate, Sodium carbonate
- Sodium tartrate
Antioxidants:
- Sodium metabisulfite
- Ascorbic acid
- Thiourea
- Tocopherol
Chelating agents (accelerate oxidation in presence of free radicals e.g. copper):
- EDTA
Vehicle
- Water for injection
Preservatives:
- Benzalkonium chloride 0.01% (eye drop, ignore in single dose)
- Benzyl alcohol (parenteral)
Read also:
- Sterility Testing in Pharmaceutical Industry
- Anti-oxidant and Its Impact on Pharmaceuticals
- Crystallization in Oral Liquid Dosage Form
