Formulation of suspension
The formulation of a suspension depends on whether the suspension is flocculated or deflocculated. Three approaches are commonly involved.
- Use of structured vehicle
- Use of controlled flocculation
- Combination of both of the methods
- Structured vehicles called also thickening or suspending agents.
- They are aqueous solutions of natural and synthetic gums.
- It is applicable only to deflocculated suspensions.
- E.g. methylcellulose, sodium carboxy methylcellulose, acacia, gelatin and tragacanth. These are used to increase the viscosity of the suspnsion.
- These structured vehicles entrapped the particle and reduces the sedimentation of particles.
- Thus, the use of deflocculated particles in a structure vehicle may form solid hard cake upon long storage.
- Too high viscosity is not desirable as:
- a) It causes difficulty in pouring and administration.
- b) It may affect drug absorption since they adsorb on the surface of particle and suppress the dissolution rate.
- Structured vehicle is not useful for Parenteral suspension because they may create problem in syringeability due to high viscosity.
Controlled flocculation of particles is obtained by adding flocculating agents, which are:
Flocculation in structured vehicles
Sometimes suspending agents can be added to the flocculated suspension to retard sedimentation
Examples of these agents are:Carboxymethylcellulose (CMC), Carbopol, Veegum, and bentonite
Ingredients for formulation of suspensions
|1.||API||Therapeutic active substance|
|2.||Wetting agents HLB= 7-9||Added to disperse solids in the continuous phase.|
Decrease interfacial tension between solid particles and liquid mediums.
E.g. Alcohol in tragacanth mucilage, Glycerin in sodium alginate.
|3.||Flocculating agents (Surfactant & Polymer)||To floc the drug particles; |
They lead to a decrease in repulsion potential and make particles come together to form loosely arranged floccules.
Act by reducing the surface tension. E.g. SLS, Tweens, Span, Carbowax.
|4.||Thickened & Suspending agents||Impart viscosity of the suspension |
a. Polysaccharide=> Natural- Acacia, Starch, Talc ; Synthetic- MC, b. HPMC
b. Inorganic agents=> Clay, AI(OH)3
c. Synthetic => Carbomer, Collodial SiO2
|5.||Buffer/ pH adjusting||To stabilize the suspension at the desired pH range|
|6.||Osmotic agent||To adjust osmotic pressure (Specially Parenteral preparation)|
|7.||Organoleptic additive||To impart desire color to improve elegance Coloring agent, sweetening agent, Flavoring agents|
|8.||Preservative||To prevent Microorganism growth Benzoic acid, Methylparaben, Benzoic acid, Sodium benzoate|
|9.||Protective Colloids||They are absorbed on insoluble particles and increase the strength of the hydration layer formed around suspended particles through hydrogen bonding and molecular interaction. E.g- Gelatin, natural gum and cellulosic derivatives.|
- Hydrophilic materials are easily wetted by water while hydrophobic materials are not.
- However hydrophobic materials are easily wetted by non-polar liquids.
- The extent of wetting by water is dependent on the hydrophillicity of the materials.
- If the material is more hydrophilic- less difficulty in wetting by water.
- The concentration used is less than 0.5 %.
- Suspending agent are also known as hydrophilic colloids which form colloidal dispersion with Water and increase the
viscosity of the continous phase.
Suspending agent form film around particle and decrease interparticle attraction.
- Most suspending agents perform two functions (i.e. besides acting as a suspending agent, they also imparts viscosity to the solution).
Evaluation of suspensions
- Two parameters are studied for determination of sedimentation.
- Sedimentation volume
- Degree of flocculation
- A most important parameter in the evaluation stability of the suspension.
- Sedimentation volume is a ratio of the ultimate volume of sediment (Vu) to the original volume of sediment (VO) before settling.
- The sedimentation volume gives only a qualitative account of flocculation.
Sedimentation Value: ‘F‘ has values ranging from less than one to greater than one
F= 1 (one)for Ideal suspension;
F=0 (Zero) Complete sedimentation, Totally unstable suspension
Practically, F should be near the value of one.
F>1: i.e Vu > Vo; Sediment volume is greater than the original volume due to the network of flocs formed in the suspension and so loose and fluffy sediment.
F=1: Vu = Vo; The system is in flocculated equilibrium and show no clear supernatant on standing.
F<1: Vu < Vo;
Degree of flocculation (β)
It is the ratio of the sedimentation volume of the flocculated suspension ,F , to the sedimentation volume of the deflocculated suspension, F∞.
The minimum value of β is 1,when flocculated suspension sedimentation volume is equal to the sedimentation volume of deflocculated suspension.
Settling of solid particles or floccules under gravitation force in liquid at bottom of the container.
The rate of sedimentation is governed by Stock’s Eq.
η= viscosity of external phase
g = gravity acceleration
- Limitation of Stoke’ s law
- Particle should be spherical but In suspension irregular
- Particle should settle freely & independently
- Applicatioble For Dilute Suspension: 0.5 to 2% solid w/v-Stokes law applicable
- For Concentration Suspension: 5 to 10% solid w/v- Hindrance occurs- Not Applicable
Stock’s law applicable to only Dilute deflocculated systems where particles settles independently.
How to prevent Sedimentation
-Suspending agents are used to prevent/slow the rate of sedimentation.
-Suspending agents decrease sedimentation by keeping solid particles in suspended in a liquid medium & impart viscosity to the liquid medium.
If a pharmaceutical suspension produces sediment upon storage, it is essential that it should be readily dispersible so that uniformity of dose is assured.
100mL suspension is placed in the graduate cylinder – allowed to settle. After that, the cylinder is rotated at 20 rpm through 360 & when the base of the cylinder is clear of sediment then the endpoint is noted.
Lower the no. of revolution or shorter time for redispersion- Faster dispersibility
Brownian movement: particle size of the suspension is about 2-5 m, they exhibit Brownian movement – No settling occurring.
If the Particle size of the suspension is about 2-5 micrometer, they exhibit Brownian movement – No settling occurring.
III. Rheological properties
- By “Brook field viscometer” with T-spindle- Behaviour of settling is evaluated &
- Consistency of suspension is evaluated by – cup & bob viscometer & Cone & plate viscometer
IV. Electrokinetics kinetic method
Determination of surface electric charge or Zeta potential of suspension is helpful to find out the stability of the suspension.
It can be determined by observing the movement of droplets under the influence of an electric current (electrophoretic mobility measurements), conjunction with photon correlation spectroscopy.
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