QUESTIONS FOR ASSESSMENT OF QUALITY OF TABLETS AND CAPSULES

1) What are the objectives of the tests for uniformity of diameter and uniformity of content?

-The objectives of the tests for uniformity of diameter are to increase the patient compliance by increasing the quality of product appearance and also to prevent any confusion towards the patient about the dosage of the medications. The objectives of the tests for uniformity of content are to ensure uniform dosage supplied to the patient and prevent from overdose cases due to non-uniform amount of active ingredients in the capsules or tablets.

2) State the types of tablets and capsules that must be tested for the uniformity of diameter and uniformity of content.

- Uniformity of diameter was introduced by the BP in 1958 to remove doubt. Uniformity of diameter tests involves all the uncoated and coated tablets and it is not applicable for the enteric tablets, film-coated tablets and sugar-coated tablets. For uniformity of content tests, it involves all tablets.

3) Give reasons for the non-compliance to test for uniformity of weight.

-The reasons for non-compliance to test for uniformity of weight are uneven feeding of granules into the die and due to irregular movement of the lower punch that cause variation in capacity die space.

4)  Why does dissolution test suitable to be used for batch to batch quality control?

- Drug absorption from a solid dosage form after oral administration depends on the release of the drug substance from the drug product, the dissolution or solubilization of the drug under physiological conditions, and the permeability across the gastrointestinal tract. Because of the critical nature of the first two of these steps, in vitro dissolution may be relevant to the prediction of in vivo performance. Based on this general consideration, in vitro dissolution tests for immediate release solid oral dosage forms, such as tablets and capsules, are used to assess the batch to batch quality of a drug product.

5. Explain the difference found in the procedure for dissolution test in the United States Pharmacopoeia and the British Pharmacopoeia.

- In United States Pharmacopoiea (USP) only involved 4 types of apparatus which are basket type, paddle type, reciprocating cylinder, flow through cell types; whereas British Pharmacopoeia (BP) involves 3 apparatus which are basket type, paddle type, and flow through cell type. Besides that, for testing in conventional-released dosage forms, in USP the thermometer is removed after dissolution medium is equilibrate to 37°C °C, whereas in BP, the test may also be carried out with the thermometer in place, provided it is shown that results equivalent to those obtained without the thermometer are obtained. The difference in the procedure found in USP and BP could be due to the different standard of level of dissolution set by the regulation of different countries. Besides that, the linearity of the test conducted by both countries may be different

EXPERIMENT 1.1 : BALL MILLING

OBJECTIVES:

1. To determine the particle size distribution of the coarse salt. 

2. To observe the effect of speed and time in grinding the coarse salt.

INTRODUCTION :

Ball milling process is introduces as a process to reduce the particle size or in other grinding process. This process is used to grind materials to small fine particles and is widely use especially in the mineral dressing processes, paints and ceramics industries. The grinders that are used are from different materials including the ceramic balls, flint pebbles and stainless steel balls. 

This process works by the effective speed by which the balls rotating along with the cylindrical pot and an internal cascading effect of the balls reduce the materials size to small powders. 

 MATERIALS AND APPARATUS:

• 300.4179 g of coarse salt
• Steel ball
• Ball mill
• Sieve nest
• Weighing balance

PROCEDURE:

1) 313.980 of coarse salts were weighed

2) Different sizes of steel balls were inserted to the mill.

3) The weighed salts were inserted into the mill.

4) The milling process was initiated with the speed of 10 within 20 minutes.

5) The product obtained is then weighed again after the milling process ended.

6) The powder obtained was sieved using the sieving method with sieve nest. 

7) Results data was collected and a histogram was plotted.        

RESULTS:

DISCUSSION: 

         

Firstly, during weighing the course salts, we may observed the reading wrongly. We also may insert different size of steel ball into the cylindrical shell which may affect the reduction size as the larger size ball will crush the particulates better compare to the smaller ball size. Therefore, not all the coarse salts are reduced with same efficiency. We also may not adjust the speed relatively with the time causing the coarse salts not completely grind to even distribution of fines.

Other factors affecting the particles size reduction process are the size of grinding media. A smaller size would result in even smaller size of final product. Besides that,  the hardness of the grinding media, the stickiness of grinding media, the density of grinding media also effect the process. Other equipment that can be used to reduce the size particle is Hammer milling, fluid energy milling, and Colloid mill. 

All of this equipment used the mechanism of impact to reduce the size of particulate. In choosing the right equipment for size reduction process, one of the factor influences is the nature of the raw materials.  Most of the raw material must be dried before undergo the reduction process. Other than that, establishing the particle size required are also important to avoid undesired particle size formed due to incorrect choosing of right equipment. The product from the milling process is subjected for particle size analysis

QUESTIONS:

1) What are the factors that can influence the size reduction process of a ball mill?

• The number and size of the steel balls used in the milling process.
• The speed of the ball milling process.

2)What are the other equipment that can be used in size reduction of solid materials?

• Hammer milling, fluid energy milling, and colloid mill. 

3)What are the factors that need to be considered in choosing the suitable size reducing 

    equipment?

• The nature of the raw materials.

CONCLUSION : 

As the aim of this experiment is to study the effect of the various parameters on the performance of a ball mill. The factors studied are particle size,, time of grinding, and speed of the ball mill (rpm).  From the results, we can conclude that the amount of fine particles increase with the increase in time of grinding, speed (rpm) of the ball milling process. 

REFERENCES:

A ball mill for all grinding and milling needs. http://www.retsch.com/products/sumo/mixerball-millphp/ [24 November 2014]

Cao W. Synthesis of Nanomaterials by High Energy Ball Milling. http://www.understandingnano.com/nanomaterial-synthesis-ball-milling.html [25 November 2014]

EXPERIMENT 1.2 : SIEVING

OBJECTIVES:

1. To break the agglomerate
2. To determine the size of particles
3. To determine the  size distribution of the powder

INTRODUCTION:

Sieving is a process that is commonly used as the method of analysis because the equipment, analytical procedure and basic concepts are simple. It is used to sieve and sort a large quantity of particles into different size ranges and determine the particle size distribution based on the mass collected in each range. This method is simpler and more cost effective. However sieve analysis does not provide any particle shape information. In most cases, the analysis can be carried out in a dry state. There are some limitations of the sieving method, which is the need for an appreciable amount of sample, normally at least 25 microgram. Other than that is we could encounter difficulty in sieving oily or other cohesive powders or granules that tend to clog the sieve openings. 

METHODOLOGY:

i) Apparatus & materials:

• Microcrystalline cellulose (MCC)
• Lactose
• Sieve nest
• Spatula
• Weighing boat

ii) Procedure:

1. 100g of microcrystalline cellulose (MCC) was weighed using an electronic balance.
2. The sieve nest was prepared in descending order i.e largest diameter to smallest diameter, from top to bottom.
3. The MCC powder was placed at the uppermost sieve and the sieving process was allowed to proceed for 20 minutes. 
4. Upon completion, the powder collected at every sieve was weighed and the particle size distribution was plotted in the form of histogram.
5. The process was repeated using lactose.

RESULTS:

DISCUSSION:

Sieve analysis is used to obtained the particle size distribution of a solid material. This can be determined by the amount of powder retained  on the sieve nest of different size apertures.  Once the powder has been put on the uppermost sieve nest, the powder was then vibrated, thus allowing the powder particles to segregate onto different size sieves. Next, the powder that retained for each part was weighed in order to determine the particle size distribution.From the result obtained, it can be seen that the smaller the size aperture, the higher the amount of powders retained on the sieve nest. 

Based  on the two graphs, it shows that the size of microcrystalline cellulose (MCC) is much smaller than the lactose. This is because, more MCC is collected at the base collector as compared to lactose. The greater the amount of powder that passed through the 53µm sieve nest imply that the size of the powder is much smaller.

The size distribution of particles is very important in pharmaceutical preparation. This is due to the effect of the size itself to the absorption rate of certain medication at certain site in the body as well as their stability.

The size and the shape of the particle also play an important role in the flow rate of a formulation. The particle which is uniform in shape and more sphere has a better flow properties and vice versa.

QUESTIONS:

1) What is the average particle size for both  MCC and lactose?

• Based on the result of the experiment, the average particle size for both MCC and lactose is 200 µm and below. This is because most of  MCC and lactose powders were found in the sieve nest which the size of aperture is less than 200 µm.

2)What are the other methods can you use to determine the size of particle?

a) Microscope method either using light microscope, Transmission Electron Microscope (TEM)
    or Scanning Electron Microscope (SEM)

b) Laser light scattering method

c) Dynamic light scattering method

3)What are the importance of particle size in a pharmaceutical formulation?

• The particle size will affect the dissolution rate, absorption rate, content uniformity and stability of the medicine in the body.

CONCLUSION:

Based on the graphs, we can conclude that the particle size of MCC is smaller than lactose. This can be proved when the cumulative percentage retained for MCC is 99.6258% while for lactose is only 98.72%.

REFERENCES:

The Basic Principles of Sieve Analysis.
http://www.ninolab.se/fileadmin/Ninolab/pdf/retsch/documents/af_sieving_basics_2004_en.pdf [23 November 2014]

Particle size analysis-Sieving.
http://www.iso.org/iso/iso_catalogue/catalogue_ics/catalogue_ics_browse.htm?ICS1=19&ICS2=120 [23 November 2014]

Sieve Analysis Test. http://www.uta.edu/ce/geotech/lab/Main/sieve/index.htm [23 November 2014]

EXPERIMENT 1.3 : POWDER FLOW - HOPPER

OBJECTIVE:

To evaluate the powder flow of various sand with different particles size using hoppers with different dimension with different orifices. 

INTRODUCTION:

Powder that discharges freely from the hopper is said to undergo mass flow. This means that particles that first in will be the first to come out from the hopper. Powder that do not discharged freely, due to high adhesion or cohesion or hopper angles that are too shallow may undergo funnel flow. Particles which the last enter the hopper are the first to leave hopper forming ‘pipe’, ‘rat-hole’ or ‘funnel’.

In general, most powders will discharge by mass flow from hoppers with θ angles of about 20˚ , and by funnel flow from hoppers with angles of approximately 50˚.

METHODOLOGY:

i) Apparatus and Materials 

1. hopper with different sizes
2. stopwatch
3. different sand samples

ii) Procedures

       I.          Four to five of different sizes of hopper were prepared.

     II.         Various particle sizes of sand samples were prepared.

   III.         The hopper’s orifice was closed and 100g (or any suitable weights) of sand was placed inside
the hopper.

  IV.         The orifice was opened and the sand was allowed to flow out.

    V.          The time required for all the sand to flow out of the hopper completely was measured. The  hopper should not be shaken or tapped. The flow of sand was allowed to happen naturally.

  VI.         The above steps were repeated with different sand or hopper sizes.

RESULTS:

QUESTIONS:

1) What are the factors that influence the flow of a powder?

Factors that influence powder flow are particle shape or texture which need to be spherical. The surface texture must be smooth as rough texture will be more cohesive. Next is surface forces which is reduce the electrostatic forces by altering process condition that will reduce surface friction. Furthermore, moisture content also need to be low as moisture will increase bulk density and reduce porosity. Addition of glidants as flow activator also will influence powder flow as it will reduces adhesion and cohesion. Lastly, process condition of powder flow also influence powder flow.

2) Based on the experiment, which sand and hopper size resulted in the best powder flow?

Based on the experiment,  sand with 850 micrometer with hopper size of 16 mm resulted in best powder flow. This is because, bigger size of sand will show better flow rate than smaller size of sand

CONCLUSION:

The larger the diameter, the faster the powder will flow

Small size powder will have higher cohesion

The bigger the opening of hopper, the more easier the powder flow.

REFERENCES:

1. http://www.wiley.com/legacy/wileychi/rhodestechnology2e/hopper_flow.html

2. http://www.chemicalprocessing.com/assets/Media/MediaManager/fine-powder-flow.pdf

EXPERIMENT 1.4 : ANGLE OF REPOSE

OBJECTIVES:
1. To determine flow characteristics of a powder.
2. To determine the angle of repose and the factors that influence it.

INTRODUCTION:

The angle of repose of a granular material is the steepest angle of descent or dip of the slope relative to the horizontal plane when material on the slope face is on the verge of sliding. When bulk granular materials are poured onto a horizontal surface, a conical pile will form. The internal angle between the surface of the pile and the horizontal surface is known as the angle of repose and is related to the density, surface area , size and shapes of the particles, and the coefficient of friction of the material.

Angle of repose of a granular material is important in the design of equipment for the processing of particulate solids and also be used in determining whether  a slope of a stockpile or uncompact gravel bank will likely collapse or not. Thus, there are numerous methods for measuring angle of repose and each produces slightly different results.

METHODOLOGY:

i) Apparatus and Materials:

• sand
• cylinder
• ruler
• water

ii) Procedure :

1. 100g of sand is prepared and weighed by using weighing balance.

2. The sand is placed in the cylinder with the rubber base at the bottom.

3. The cylinder is removed and allowed the sand to flow out and form a heap.

4. The height, slope and diameter of the heap is measured.

5. The angle of repose is calculated.

6. The experiment is repeated by using other sand or with the addition of glidant/water. 

RESULTS:

DISCUSSION:

Angle of repose is one of the methods used to characterize the flow of a material. In this experiment, angle of repose for different sizes of sand and with the presence of a glidant is determined. The factors that affect the angle of repose are also studied.

From the result obtained, in the absence of glidant, the angle of repose decreases as the size of particles increases. This is because smaller particles have dominant cohesive and adhesive forces as compared to particle weight, whereas in bigger particles gravity plays a dominant role thus giving a smaller angle of repose. Studies have shown that angle of repose is also gravity-dependent. Cohesiveness of finer particles due to electrostatic forces causes difficulties in flowing thus forming a steeper pile which shown by the 150 micron sand having the highest angle (56.31°) compared to 500 and 850 micron sand. On the other hand we can see that mixture of various sizes of sand give a high angle of repose also (45.0°). When particles of different sizes and irregular shape are mixed together, the mechanical interlocking of particles increases and thereby increase the rolling friction. As a result a steeper pile with bigger angle of repose is formed.

When 10% concentration of magnesium stearate is added, the angle of repose increases. Magnesium stearate is used as a glidant. It may also act as a lubricant in reducing friction. Glidant functions in improving the flow of a material. From the result, 850 micron sand has a good flow. The addition of a glidant should decrease the angle of repose and enhances the flow of the materials. But however the addition of 10% magnesium stearate in this experiment produces a product of vice versa. This is because the rate of flow is improved by the addition of magnesium stearate up to a limiting concentration of glidant. Above a certain concentration (in this case 10%), the glidant will function to inhibit flowability. Thus, a glidant will only work at a certain range of concentrations. 

For a better result, it is advised to use a protractor instead of ruler as it reduces parallax error and it measures an accurate angle. The glidant and the sand should be mixed until an even distribution of mixture is obtained. This is to ensure that the glidant function effectively. Besides, the lifting velocity of the cylinder should just be moderate to avoid distraction to the material flow. For a clean and tidy working environment, a paper should be placed before starting the experiment so that the sand did not cluttered elsewhere. Experimenter must also wear goggle, mask and lab coat all the time to protect the eyes and nose from coming in contact with the sand.

QUESTIONS :

1.What are the angle of repose for the sands that you use?

For sands without magnesium stearate, the angle of repose of sand (150 µm) is 56.31˚, sand (355 µm) is 41.99˚, sand (500 µm) is 40.36˚, sand (850 µm) is 38.66˚ and variety of sands is 45.00˚. As for 100g of sands with 10% magnesium stearate, the angle of repose of sand (150 µm) is 57.99˚, sand (355 µm) is 45.00˚, sand (500 µm) is 45.00˚, sand (850 µm) is 43.53˚ and for variety of sands is 48.99˚ .

2. What are the factors that can influence the angle of repose of a powder?

One of the factors that influence the angle of repose is the moisture. Moisture will increases the angle of repose of sediments as a small amount of moisture between sand grains will bind them together due to cohesion. However, too moisture can result in particles moving freely over one another and therefore dramatically reduces the angle of repose.  For most dry sands, the angle of repose increases with decreasing grain size, but usually lies between about 40 and 45 ^o. Next is the shape and texture of the sand particles. Angle of repose is greater for particles that are irregular, flatter and more angular. Besides, the addition of glidant will decrease the angle of repose of the material by reducing the cohesion force between sand particles.

3. What other methods can you use to measure the angle of repose?

The other methods that can be used to measure angle of repose is tilting box method which is suitable for fine-grained, non-cohesive materials and contain individual particle size less than 10 mm. The material is placed within a box with a transparent side to observe the granular test material. The box is slowly tilted and is stopped when the material begins to slide in bulk. Then, the angle of tilt is measured. Besides, revolving cylinder method can also be used to measure angle of repose. The material is placed within a cylinder with at least one transparent face. The cylinder is rotated at a fixed speed and the observer observes the material moving within the rotating cylinder. The granular material will assume a certain angle as it flows within the rotating cylinder and the dynamic angle of repose is obtained.

CONCLUSION :

1. The angle of repose increases with decreasing particle size of sand materials.

2. The angle of repose increases after addition of 10% of glidant (magnesium stearate).

REFERENCES:

https://books.google.com.my/books?id=ZLI4i_iSfG8C&pg=PA16&lpg=PA16&dq=particle+size+analysis+ANGLE+OF+REPOSE&source=bl&ots=S1OOa_4Xri&sig=n3396yLA7vASfc1sqMoWjwoaReI&hl=en&sa=X&ei=2MGKVJeHI4iJuwS72YCgDQ&ved=0CEwQ6AEwBw#v=onepage&q=particle%20size%20analysis%20ANGLE%20OF%20REPOSE&f=false