Laboratory 4 - Sedimentation-Suspensions

A suspension is a heterogenous system containing dispersed solids of such size that they settle.  Whether a pharmaceutical suspension is to be taken orally, applied topically or injected, the dispersed phase should be uniformly distributed in order to ensure the administration of a uniform dose.  The rate of sedimentation or settling for a suspended phase depends on several factors which are under the control of the formultor or pharmacist.  Stokes developed an equation which relates the rate of sedimentation to the physical properties of the suspension.

dx/dt = [2r2(Rho1 - Rho2)g]/[9 X Viscosity]

where r is the radius of the dispersed particle, Rho1 is the density of the particles and Rho2 is the density of the medium, and g is the gravitational constant.

Although the Stokes equation does not consider all variables which affect a suspension, it gives an approximation of the rate of settling and an appreciation of the effect which controllable factors exert on the settling rate.  By reducing particle size, by increasing the viscosity, and by increasing the density of the external phase, we may retard settling.

Suspending agents are physiologically inert substances which increase viscosity when added to suspensions.  On prolonged standing suspensions tend to cake as some crystals knit together at point of contact at the bottom of the container.  Therefore, a second important function for suspending agents is to facilitate redistribution of a suspension on shaking.

Particles in suspension can come together to form either floccules or aggregates.  Floccules form when weak van der Walls forces are holding the particles together.  Foccules are easy to break apart.  If floccules sediment they trap solvent and are easier to resuspend than if the particles settle into a tighter aggregate without the traped solvent.  However, the large fluffy clumps that characterize a flocculated system settle rapidly.  It is the goal of a good formulator to develop a system which controls the rate of flocculation and sedimentation.

PROCEDURE:

Shake lotions, magmas and mixtures are traditionally classified as such for convenience but are all actually suspensions.  Depending on the properties of the ingredients, these products may or may not contain additional suspending agents. A lotion is a liquid preparation containing finely divided substances in suspension intended for external application. Calamine lotion is one of the most common.

The work should be divided between the members of your group in a fair and equable manner.

- Part A - Prepare 60 ml of calamine lotion using each of the formulars below.  Place each in a 2 ounce bottle and store for evaluation next week. Be sure and label the containers with your group designatoin and lab day(Monday, etc).

Formula I

Calamine                                                  8 g
Zinc Oxide                                               8 g
Polyethylene glycol 400                            8 g
Polyethylene glycol 400 monostearate       2 g
Water                                                    90ml
THIS MAKES A TOTAL OF 100 ml OF SUSPENSION

Heat the polyethylene glycol 400 monostearate to 700 C on a water bath.  Add the water previously heated to boiling to the PEG 400 Monostearate. Stir until the temperature drops to 400 C.  Mix the zinc oxide and the calamine in a motar and make a paste with the polyethylene 400.  Gradually add the cooled monostearate dispersion and continue to triturate until a uniform suspension is formed. DO NOT ADD VERY HOT LIQUIDS TO THE MOTAR _ IT WILL BREAK

Formula II

Calamine                                                    8 g
Zinc Oxide                                                  8 g
Glycerin                                                      2 ml
Bentonite Magma                                       25 ml
Calcium Hydroxide Solution q.s.                100 ml

Dilute the bentonite magma with an equal volume of calcium hydroxide solution.  Mix the powders in a motar with the glycerin and about 10 ml of the diluted bentonite magma until a smooth paste is formed.  Gradually incorporate the remainder of the diluted magma and enough calcium hydroxide solution to make 100ml.

Remember we are making only 60 ml of each not the 100 ml called for in the formula.
 

- Part - B Many lotions will require the addition of a suspending agent to slow settling.
Prepare the following formula first without any suspending agent(mixture 1) and than with 2 % methylcellulose 1500 as a suspending agent(mixture 2).  Pour them both into separate beakers and observe the differences and record your observations.

Sulfur                    2.5 g
Camphor               2.5 g
Alcohol                 20 ml
Rose water qs       60 ml

Camphor is difficult to work with as a powder.  Therefore dissolve the camphor in the alcohol first and then triturate that solution with the sulfur.  Gradually with trituration add the rose water.  When adding the methylcellulose powder mix it with the dry sulfur powder and prepare as before.

- Part C - Prepare 40 ml of an anionic flocculating agent which will be used in four of the five suspensions to be made in this part of the laboratory:

    Potassium dihydrogen phosphate               2 g
    Purified water qs                                    40ml

Assemble five 25 ml graduated cylinders and number them consecutively.  Add 2 g of bismuth subnitrate to each graduated cylinder.
    1)    To the first add sufficient water to make 25 ml of suspension.
    2)    To the second add 10 ml of the anionic flocculating agent solution and enough water to make 25 ml.
    3)    To the third add 10 ml of the anionic flocculating agent solution and sufficient 0.5% methylcellulose solution to make 25 ml.
    4)    To the fourth add 10 ml of the anionic flocculating agent solution and sufficient 1% methylcellulose solution to make 25 ml.
    5)    To the fifth and last add 10 ml of purified water and sufficient 0.5 % methylcellulose solution to make 25 ml.

Cover the graduated cylindars with parafilm.  Invert each several time to mix them well and measure and record the height of the suspension (in mls marked on the graduated cylindar) after 15 minutes, 60 minutes, and 120 minutes.  We will assume that the suspebsion starts at 25mls. right after you mix it.  Set aside for next week and measure the sediment again in next week's laboratory.

Because there is a limited number of 25 ml graduates only the odd numbered teams will save them for next week.  The even numbered teams will make thier own for the measurements made during lab but use the other teams results for the 7 day reading.

  .  Part D - Obtain four 100 ml graduated cylinders. This experiment will evaluate different suspending agents.
Using a motar and pestel prepare a suspension of:
    1)        5 gm of Calamine and no suspending agent;
    2)        5 gm of calamine and 2 grams of acacia,
    3)        5 gm of calamine and 2 g of sodium carboxymethylcellulose and
    4)        5 gm of calamine and 1 g of tragacanth.

Transfer the mixture to one of the graduate cylinders, rinse the morter with additional water and add that to the graduate.  Now qs to each mixture to100 ml.  Cover with parafilm and mix.  Record the appearance of the suspension and the volume of the sediment at 5 min, 15 min., 45 min. and 90 min.  Prepare a table with the results and plot the results.