1. THE FLOW PROPERTIES OF POWDERS AND GRANULESThe flow properties of powders and granules are of critical importance in the production of pharmaceutical dosage forms. It is recommended that pharmaceutical powders and granules be free flowing (i.e. of good, rapid and regular flowability) for the following reasons:1. Uniform feed from storage containers (as machine hoppers) into the tablet dies and capsule dosators, allowing uniform particle filling that maintains weight uniformity.2. Uneven Powder flow can result in excess entrapped air within powder which may cause capping or lamination of tablets.3. Uneven powder flow can result from the presence of excess fines that are suggested to increase particle - die wall friction and increase dust contamination risks during powder transfer and processing.Factors affecting powder Flowability1. Particle size. 2. Moisture content. 3. Particle shape. 4. Surface roughness (texture). 5.Particle density. 6. Surface forces, e.g. Hydrophobicity or electrostatic Charges.** To Predict the Flowability of a powder quantitatively the following indirect Parameters are to be measured : 1. Bulk density 2. Flow Rate. 3. Angle of repose. I- Determination of the Bulk density (gm/cm3): It is defined as the mass of a powder divided by the bulk volume.It depends on: particle size distribution, particle shape and the tendency of particles to adhere together.Procedure:1. Gently introduce an accurately weighed amount (5g) of each powder into a 10 ml graduated cylinder. 2. Record the volume (V0) of the powder and calculate "0 which is the initial bulk density before tapping. Wt. (g) 5 0 = --------- = ---------- g/cm3 Vol (cm3) V03. Drop and tap the cylinder carefully onto a hard surface from a height of 5 cm. until no further reduction in volume (Vf) is noticed (usually 40 50 times) and calculate f which is the final bulk density. 6. Calculate the Hausners ratio: Hausners ratio = loose bulk volume (V10) final bulk volume (Vf)Hausners ratio is related to inter-particle friction and so could be used to predict the powder flow properties.7. Calculate the percentage compressibility (Carr's Index): % compressibility (Carr's index) = f 10 x 100 fInterpretation of values:Carr's indexHausners ratioFlow behaviour

< 101 1.11Excellent

11 151.12 1.18Good

16 251.19 1.34Pass

26 311.35 1.45Poor

> 32> 1.46Very poor

You are supplied with different samples of powder mixtures . These are the recorded volumes. Calculate Hausners ratio and Carrs index, and then select the proper mixer used for the following samples.Sample. No.V10Vf0fHausners ratioCarrs index

A3.663.16

B7.016.91

C9.59.16

D5.664.83

E86

F5.55.33

II- Measurement of angle of repose:Angle of repose is the maximum angle possible between the surface of the pile (heap) of powder and the horizontal plane. It gives a measure of the frictional forces which oppose the flow of a loose powder.

Tan = H = 2H 0.5D D Where, is the angle of repose, H is the height of a heap of powder and D is diameter the powder.The rougher and more irregular surface granules, the higher will be the angle of repose. Factors affecting the angle of repose:Particle Size. Particle shape.Particle density. Presence of moisture.Techniques of measurement.* Relationship between angle of repose () & powder flowabilityAngle of repose ()Flow behaviour

< 25Excellent

26 - 30Good

31 - 40Pass

41 - 45Poor

> 46Very poor

Measurement of angle of repose using funnel and plate methodProcedure:1. Fix a funnel to a stand vertically above the center of a piece of paper so that the distance between the funnel tip and the paper is 5 cm.2. Allow 5 g of each sample to slide on the funnel wall slowly with a fixed rate by gentle tapping on the powder container so that the powder forms conical heap ( pile ) on the paper.3. Measure the diameter "D" of the bed in two planes at right angles taking the mean value. Also determine the bed height H" using a ruler. You are supplied with different samples of powder mixtures. These are the recorded diameters "D" andheight H. Calculate Tan and Angle of repose (), then select the best mixer used for the following samples. Exp. N0.H (cm)D (cm)Tan

Angle of repose ()

A0.64.6

B0.93.3

C1.94.4

D1.15.2

E0.53.3

Mean

Sample 2Exp. N0.H (cm)D (cm)Tan

Angle of repose ()

1

2

3

Mean

Which sample shows the lowest angle of repose and why?

2.IMPROVEMENT OF POWDER FLOWABILITYFlowability of powders could be improved by one or more of the following approaches:I. Alteration of particle size and size distribution by removal of fines or by granulation.II. Alteration of particle shape and texture by spray drying which produce spherical free flowing granules.III. Alteration of surface electrostatic forces by: A) Reduction of frictional forces between particles. B) Discharging the electrostatic charges in powder containers by connection to the earth.IV. Drying of powders and storage under low humidity to minimize moisture. V. Alteration of process condition by:1. Using of force feeders i.e. by fitting vibrating baffles at the base of the feeding hopper.2. Using of mechanically vibrated hoppers.VI. Addition of flow activators (glidants) e.g., talc, magnesium stearate or silicon dioxide.The use of glidants to improve powder flowability:Glidants may act through different mechanisms to improve powder flowability, including:1. Making the surface of the particles more smooth.2. Reducing electrostatic charge adhesion and cohesion.3. Reducing the moisture adsorbed on the particle surface.

Determination of the optimum glidant concentrationProcedure:1. Determine the "Angle of Repose" for the provided sample powder, without the addition of glidants, as mentioned previously.2. Mix well the powder with the glidant (1 %, w/w) and re-measure the angle of repose.3. Repeat the same experiment with the addition of (3 and 5%, w/w) of the glidant, respectively.4. Record your results in the following table:SampleDiameter (cm)Height (cm)Tan Angle of repose ()

no glidant

Mean

+ 1% glidant

Mean

+ 3% glidant

Mean

+ 5% glidant

Mean

Comment:

3. DETERMINATION OF THE MIXING EFFICIENCY OF A POWDER MIXTURE All dosage forms must be uniformly mixed to ensure that the proper dose of medication is given to the patient. Several mixing methods are used in small scale and large scale production. On the small scale, the following methods are used:1. Paper and spatula.2. Mortar and pestle.3. Wide mouthed bottle.Procedure:Determine the concentration and the percentage of sodium bicarbonate in the prepared samples after mixing with talc for 5 min.1. Using the mortar and pestle method, mix two samples of sodium bicarbonate (2 g each) with 8 and 18 g of talc, respectively. Repeat the mixing step with other samples adopting the paper and spatula method (Now you have 4 mixtures).2. For each mixture, take 2 samples each weighing 3 g.3. For each sample, add the weighed sample to a beaker containing 20 ml of water, stir with a glass rod for 3 min.4. Filter the previous dispersion using a wet filter paper.5. After complete filtration of the 20 ml, wash the residue on the filter paper with additional 10 ml of water and continue filtration till the final volume of filtrate be 30 ml.6. Take 10 ml of the filtrate, add 2 drops of m.o. indicator, mix well.7. Titrate against 0.5N HCl (F = 0.042) till the end point.

Calculations: Conc of sodium bicarbonate = ml of 0.5N HCl x F x 30 (g) 10 % of sodium bicarbonate = Conc of sodium bicarbonate X 100 (%) 3 8. Record your results in the following table.MethodMixturesml of 0.5N HClConcentration of Na Hco3Percentageof Na Hco3

Mortar and pestle methodMixture I

Mixture II

Paper and spatula methodMixture I

Mixture II

Which method provides higher mixing efficiency?