Saturday, 20 December 2014

Practical 4 - Friability

Objective:
To determine the ability of the tablet to withstand abrasion


Introduction:

Friability is the tendency for a tablet to chip, crumble or break following compression. This tendency is normally confined to uncoated tablets and surfaces during handling or subsequent storage. It can be caused by a number of factors including poor tablet design (too sharp edges), low moisture content, insufficient binder. It is then important that drug formulated to withstand such stress. The friability tester has now become an accepted standard throughout the pharmaceutical industry.


Apparatus:

      Drum of tablet abration
      Friability tester


Material:
      10 tablets


Procedure:

1.      10 tablets are selected and weighed.
2.      All tablets are put into the drum of tablet abration and friability tester. The rate of rotation is set to 100rpm, time is set to 10 minutes and the operation is set.
3.      At the end of operation, all the tablets are removed and they are ensured freedom from dust or powder (brush is used). The tablets are reweighed. The percentage loss of weight is determined.
4.      The compressed tablet should not lose more than 1% of its weight.




Results:

Weight of 10 tablets before testing
Weight of 10 tablets after testing
6.57g
6.48g
6.44g
6.50g
6.51g
6.40g
6.42g
6.55g
6.60g
6.39g
6.58g
6.57g
6.50g
6.48g
6.48g
6.54g
6.53g
6.45g
6.57g
6.44g

The column for weight of 10 tablets before and after the tablets are not directly indicated based on the column. The weight of 10 tablets is randomly recorded in the table.

Calculations:
Mean for 10 tablets before testing
(6.57+6.44+6.51+6.42+6.60+6.58+6.50+6.48+6.53+6.57) g / 10 = 6.52g

Mean for 10 tablets after testing
(6.48+6.50+6.40+6.55+6.39+6.57+6.48+6.54+6.45+6.44) g / 10 = 6.48g

Percentage loss of weight = (6.52 – 6.48) g / 6.52 g X 100%
                                          = 0.6%


Discussion:

Tablets are constantly subjected to mechanical shock and aberration during manufacturing, packaging and transportation process. Such stress can lead to capping, aberration, eve breakage of the tablets. So, in order to monitor the resistance of tablets to such stress, tablets are routinely subjected to friability test. While the basic design remains unchanged, considerable advances have been made in terms of reliability and ease of usage which have now been incorporated into current units.
Friability refers to ability of compressed tablet to avoid fracture and breakage during transport. It is closely related to hardness and is designed to evaluate ability of tablet to withstand aberration in packing, handling and shipping. Friability is usually is measured by the use of tumbler test. Friability tester has now become an accepted standard throughout the pharmaceutical industry for determining the resistance of uncoated tablets to the abrasion and shock experienced in manufacturing, packing and shipping operations. Tablets need to be hard enough such that they do not break up in the bottle but friable enough that they disintegrate in the gastrointestinal tract. Tablet hardness has been associated with property such as density and porosity. It is generally increase with normal storage of tablets depend on shape, chemical properties, binding agent and pressure applied during compression.


Conclusion:


The tablets examined have 0.6% percentage weight of loss which does not exceed the maximum requirement of less than 1%.

References:

  1. http://www.pharmacopeia.cn/v29240/usp29nf24s0_c1216.html
  2. http://jpdb.nihs.go.jp/jp14e/14data/Tablet_Friability_Test.pdf
  3. http://pharmlabs.unc.edu/labs/tablets/evaluation.htm

Practical 1 - Particle Size and Shape Analysis Using Microscope

Introduction:

Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye. It is an excellent technique to look directly at the particles. Microscopic method can observe shape of particles clearly in good dispersion. There are 3 types of microscope can be used that are light microscope, transmission electron microscope and scanning electron microscope for measuring different sizes of particles. In this experiment, light microscope is used.


Apparatus:

Light microscope
Weighing boat


Material:

Sand with various sizes of 150, 355, 500 and 850 micrometres


Procedure:

1.      A light microscope is prepared and set up on the table.
2.      Sand with different sizes of 150, 355, 500 and 850 micrometres are took in small quantity using weighing boat.
3.      150 micrometres sand are scattered evenly with suitable amount on the glass slide to prevent agglomeration of particles.
4.      The glass slide is covered with lens and observed under light microscope with x 10 magnification power.
5.      Then, the observation proceed to x 40 magnification power.
6.      Observations are drew out on a piece of paper.
7.      The experiment is repeated using 355, 500 and 850 micrometres sand.



Results:




Discussion:

Light microscopy involves passing visible light transmitted through or reflected from the sample through a single or multiple lenses to allow a magnified view of the sample. The resulting image can be detected directly by the eye, imaged on a photographic plate or captured digitally. The single lens with its attachments, or the system of lenses and imaging equipment, along with the appropriate lighting equipment, sample stage and support, makes up the basic light microscope. 2-D image obtained are generally assumed to be randomly oriented in 3-D. Using conventional light microscope, particle size analysis can carried out using projector screen with screen distance related to particle dimensions. Each sizes of sand are observed up to x 40 magnification because higher power causing a blur image. Both x 10 and x 40 images for each sizes of sand are drew and compared.


Questions:

1. Explain in brief the various statistical methods that you can use to measure the diameter of a particle.

            1.  Sieve method
      Carried out using dry powders, poor reproducibility for wet sieving
      Using sieve diameter, ds – particle dimension
      Lowest ds is 45 micrometres to maximum 1000 micrometres

2. Microscopic method
      Directly look at particles size and shape
      Equivalent diameters used are projected area diameter, projected perimeter diameter, Feret’s and Martin’s diameter
      2-D image obtained

3. Coulter counter
      Electrical stream sensing zone method
      Measures any particulate material that can be suspended in electrolyte
      Equivalent diameter : volume diameter

4. Laser light scattering method
      Interaction of light with particles
      Described using Fraunhofer or Mie theory
      Entire sample is measured and have high resolution

5. Sedimetation method
      Based on Stokes’s Law equation – expression of drag factor in a fluid, linked to the flow conditions
      Comparison of particles settling rate to a sphere at the same rate


2. State the best statistical method for each of the samples that you have analysed.

Microscopic method is used in experiment to examine sand of different sizes.
Projected perimeter diameter – based on circle having same perimeter as the particle
Projected area diameter – based on circle of equivalent area to that of projected image of solid particle
Feret’s diameter – mean distance between 2 parallel tangents to projeced particle perimeter
Martin’s diameter – mean chord length of the projected particle perimater (boundary separating equal particle areas)

Conclusion:
Microscopic method is the best statistical method in analysing particle’s diameter and size.

References:
1. Pharmaceutics, The science of dosage form design (2nd Edition) Michael E.Alton Edinburgh               London New York Philadophia St Louis Sydney Toronto 2002.
2. http://www.en.wikipedia.org
3. http://www.jenike .com
4. Physicochemical Principals of Pharmacy (2nd Edition) AT Florence and D.Attwood, The                     Macmillan Press Ltd.

Practical 1 - Powder flow (Angle of repose)

Introduction:
                Powder can be defined as solid particles that either have the same or different chemical composition. It is mainly used in production of tablet and capsule. Every powder has its own flowability. Flowability is the capability of a loose particulate solid to move by flow. Angle of repose is a term used to describe the maximum angle, measured upwards from the horizontal, at which a pile of a particular granular material will remain stable without any of the material sliding downward. It is useful in designing storage and transportation machinery for granular materials as it can give an engineer insight into the appropriate size and shape of such devices. The angle of repose for a particular powder can be used to determine the flowability and the flow characteristics of a powder. The value is in the range of 0° to 90°. There are various methods available to measure this value. In this experiment, we are given sand of various sizes and to determine the angle of repose and the factors that may influence it.


Objective:
1.       To determine the angle of repose of various sizes of powder.
2.       To determine the factors that may influence the angle of repose.


Apparatus:
1.       Cylinder
2.        Rubber stopper
3.        Newspaper
4.       Weigh balance
5.        Spatula
6.       Weighing boats


Materials:
1.       100g of 150 micron sand mixture
2.       100g of 355 micron sand mixture
3.       100g of 500 micron sand mixture
4.       100g of 850 micron sand mixture
5.       100g of various sizes sand mixture
6.       Magnesium stearate


Procedure:
1.       100g of 150 micron sand mixture is prepared.
2.       The sand is placed in a cylinder with a rubber base at the bottom.
3.       The cylinder is then removed and the sand is allowed to flow out and heap is formed.
4.       The height, slope and diameter of the heap is measured.
5.       The angle of repose is then calculated.
6.       The experiment is repeated using other sand or with addition of glidant (magnesium stearate).





Results:

1.      Sand without Glidant

Size of particles of sand (micron)
Height (cm)
Width (cm)
Angle of repose
150
2.2
2.4
42.510
355
2.1
2.4
41.190
500
1.9
2.4
38.370
850
1.8
2.4
36.870
Various Size
2.0
2.4
39.810


2.      Sand is mixed with Glidant

Size of particles of sand (micron)
Height (cm)
Width (cm)
Angle of repose
150
2.1
2.4
41.190
355
2.0
2.4
39.810
500
1.9
2.4
38.370
850
1.7
2.4
35.310
Various Size
1.9
2.4
38.370


Discussion:
In this experiment, we had measured an angle of repose of 150 mic, 355mic, 500mic, 850mic and various sizes of sands with and without the presence of glidant. Magnesium Sterate is used as a glidants.

The angle of repose (α) was calculated, from the following equation:


Height = height of the cone of sand

          The results show that with the addition of glidants, the angle of repose will increase. This is because a glidant is a substance that is added to a powder to improve its flow ability by reducing friction between particles. The magnesium compounds works by mopping up the excess moisture keeping the granules dry and free flowing. But there are several other factors that will affect the effectiveness of glidants. Firstly, the flow of the granules depends on the shape and size of the particles of the glidants and the granules. Secondly, a glidant will only work at a certain range of concentrations. Above a certain concentration, the glidant will in fact function to inhibit flow ability.



Conclusion:
The larger and more irregular the granular material grains, the higher the angle of repose.
The sands angle of repose decrease with the addition of glidants.


Questions:
1. What is the angle of repose for each materials?

Size of particles of sand (micron)
Angle of repose
(Without Glidant)
Angle of repose
(With Glidant)
150
42.510
41.190
355
41.190
39.810
500
38.370
38.370
850
36.870
35.310
Various Size
39.810
38.370


2. What other factor that will influence angle of repose for the materials?

       Firstly, internal factor that will influence angle of the repose of the sand that we use is the particle size, coarser particles have high angles of repose than fine particles. The next factor is the particle shape. Another factor is cohesiveness, fine particles may reveal cohesiveness owing to spherical particles having a greater tendency to roll. Water content also affects the cohesiveness of particles. If water is added to particles such as sand, water coating the grains would tend to bind them together by its surface tension, giving rise to greater internal cohesion, and therefore shear strength. Thus, moist sand has a much higher angle of repose than dry sand.
       Secondly, the external factors which is the presence of other components such as glidants. Next, the moisture of the sand. Angle of repose of loose dry powder increases by compacting as well as by introducing by moisture. Moist sand has a much higher angle of repose than dry sand. The last factors is the methods of measurement, Ledge and erater method give higher angle of repose than from the heap formation methods.


3. What other method can be used to calculate the angle of repose for the powder?
Ledge Method
Where the powder is initially charged into a rectangular box.A slot at the base of one vertical wall is closed by a board.The closure board is then removed to allow the material to flow slowly through the narrow slot.The angle with the horizontal plane of the surface of the powder equilibrium when the flow stops is calculated as the angle of repose.

Tilting box method
 This method is appropriate for fine-grained, non-cohesive materials, with individual particle size less than 10 mm. The material is placed within a box with a transparent side to observe the granular test material. It should initially be level and parallel to the base of the box. The box is slowly tilted at a rate of approximately 0.3 degrees/second. Tilting is stopped when the material begins to slide in bulk, and the angle of the tilt is measured.

Fixed funnel method
The material is poured through a funnel to form a cone. The tip of the funnel should be held close to the growing cone and slowly raised as the pile grows, to minimize the impact of falling particles. Stop pouring the material when the pile reaches a predetermined height or the base a predetermined width. Rather than attempt to measure the angle of the resulting cone directly, divide the height by half the width of the base of the cone. The inverse tangent of this ratio is the angle of repose.

Revolving /Rotating cylinder method
Where a sealed hollow cylinder half full of powder surface is rotated until the powder surface shows its maximum angle with the horizontal.The material is placed within a cylinder with at least one transparent face. The cylinder is rotated at a fixed speed and the observer watches the material moving within the rotating cylinder. The effect is similar to watching clothes tumble over one another in a slowly rotating clothes dryer. The granular material will assume a certain angle as it flows within the rotating cylinder. This method is recommended for obtaining the dynamic angle of repose, and may vary from the static angle of repose measured by other methods. When describing the angle of repose for a substance, always specify the method used.

Crater Method /Discharge Method
Where circular tube is placed vertically on a plate with an orifice in the center.The height of the remaining powder against the wall of the tube is measured at eight equidistant points around the circumference to determine the angle of repose.

Dynamic Angle of Repose
Determine in the apparatus consisting of a drum with a roughened internal surface that is half filled with powder and slowly rotated around its horizontal axis.Within a certain range of rotation speeds (usually from 2.5 to 6 rpm) the surface of the powder in the drum comes to a sufficient steady condition.The maximum angle of bed inclination just before slump occurs is designated as the dynamic angle of repose.


References: