Experiment 5 ; Content of Ibuprofen (assay)

Experiment 5

Title : 

Content of Ibuprofen (assay)

Objective : 

To identify the content of ibuprofen.

Experimental method :

1. 20 Ibuprofen tablets that are previously selected at random are weighed and are crushed to powder.

2. A quantity of powder containing 0.5g ibuprofen is extracted and mixed with 20ml
chloroform for 15 minutes and is filtered through a sintered glass crucible (BS Porosity No.1).

3. The residue is washed with 3x10ml chloroform and the combined filtrate is gently evaporated just to dryness in a current of air. The residue is dissolved in 100ml with ethanol (96%) that is previously neutralized to phenolphthalein solution.

4. The solution is titrated with 0.1M sodium hydroxide to end point with phenolphthalein solution as the indicator. The content of ibuprofen is calculated if each ml of 0.1M sodium hydroxide is equivalent to 0.02063g of C13H18O2.

Results and Calculation :

1 tablet of Ibuprofen     = 200mg
20 tablets of Ibuprofen = 20 x 200mg

                                    = 4000mg
                                    = 4g

Calculation to obtain 0.5g Ibuprofen

1 tablet contains 200mg of Ibuprofen with other excipient. Hence, 20 tablets contain 4000mg (4g) Ibuprofen.

Total weight of Ibuprofen powder which contains Ibuprofen and other excipient
= 8.2303g

End point of titration with NaOH = 26.3ml

                                       NaOH + C13H18O2 C13H17ONa + H2O

No. of mole of NaOH used in titration =MV/1000=(0.1 x 26.3)/1000=2.63 x 10^-3 mole

Based on the equation, 

                      1 mole of NaOH = 1mole of C13H18O2
      2.63 x 10-3 mole of NaOH = 2.63 x 10-3 moleof C13H18O2

If of NaOH is equivalent to 0.02063g of Ibuprofen,
Then, Ibuprofen contains in the solution for titration

= (2.63 x 10-3 mole )/(1 x 10-4 mole) x 0.02063g =0.5426g

the content of ibuprofen is 0.5426g

Discussion :

                      Based on the result, we can calculate the standard deviation of the experiment by using the formula below:

                          standard deviation= (Experimental value )/(Theoretical value)  ×100%

                                                     =⃒0.5426/0.5  ⃒×100%

                                                     = 108.52%

                            From the calculation, we obtained a standard deviation of 108.52%. The standard deviation is within 85% to 115% which is based on the range of the British Pharmacopoeia. Thus, the experimental value is considered comply the test. The resulted deviation may be due to several errors which occurred when the experiment was carried out. These errors affect the accuracy of the experiment data.
                           First and foremost, the ibuprofen that we used for the experiment may have expired, causing the loss of active ingredients in the tablets as the active ingredients might have decomposed. Therefore, to increase the accuracy of the experiment, we should use ibuprofen tablets that are not expired.
Besides, when we were crushing the tablets into the powder form, there may be loss of the active ingredients. This is because when we were using mortar and pestle to crush the tablets, some of them would drop out of the pestle, causing the loss of ingredients. Thus, to prevent this to happen, we should try to crush the tablet gently so that the loss of the active ingredient can be reduced.Only that, over-titration would have occurred when we were carrying out titration with the sodium hydroxide. This is due to the titration is too fast that we missed the volume of sodium hydroxide that caused the first change of colour in the solution. Thus, it would better that if we carry out titration slowly drop by drop, this will prevent us from missing the first end point of the titration.

Questions:

1. What are the objectives of the test for the uniformity of diameter and uniformity of content?

The test for the uniformity of diameter is to ensure the tablets produced are of the same and equal diameters. The test for the uniformity of content is to determine whether the individual contents are within limits set with reference to the average content of the sample. It is carried out based on the assay of the individual contents of active substances of a number of single doses.

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

The types of tablet that must be tested for uniformity of diameter include uncoated and coated tablets with the exception of enteric tablets, film-coated tablets and sugar-coated tablets. As for the uniformity of content, it is applicable for uncoated tablets, coated tablets, effervescent tablets, hard capsules, soft capsules, enteric-coated tablet or capsules and lastly modified-release tablet or capsules.

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

There are reasons for the non-compliance of the test of weight. One of them is due to the uneven feeding of granules into the die. Besides, the irregular movement of the lower punch will cause variation in capacity of die space.

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

Dissolution test is suitable to carry out batch to batch so that it can ensure the quality and consistency of each and every batch of the product. When the products that manufacturers produced are in a large scale, it is quite impossible to carry out dissolution test for each and every single product. Thus, if we carry out the dissolution test batch to batch, it can be considered as the simplest and fastest way to identify which product fail to pass the test.

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

There are significant difference between the USP and the British Pharmacopoeia. During the dissolution testing in that capsule products, especially those in hard capsules, float because of their fill density is less than 1g mL-1 is preferably to used Apparatus 1 as stated in the USP while the Apparatus 2 is preferably used for tablets. As for the British Pharmacopoeia, it authorize that the use of any product that floats and it has the most precise specification for one, which it is constructed from an acid-resistant metal wire 1mm in diameter and is described as being a metal cage, which the body are held together by double wires in the shape of a cross. It is constructed such that one of the endscan be opened to place the capsule inside and is closed with clasp. The British Pharmacopoeia simply states that for product that floats when using the Apparatus 2, a glass or metal helix should be used to keep the dosage horizontal at the bottom of the vessel.

Conclusion:

The ibuprofen content obtained from the experiment is 0.5426g, which contributes to the standard deviation of the experiment is 108.52%, complying the test of uniformity of content which is within 85% to 115%.

Practical 5; Analysis of Sizes and Shapes of Particles Using Microscope

Title:

Analysis of Sizes and Shapes of Particles Using Microscope

Introduction:

                     There are many ways to analyse the shapes and sizes of the particles. In many pharmaceutically relevant cases, particles deviate from circularity and sphericity. Thus, the use of a single equivalent diameter measurement may be inappropriate. It is more appropriate to use the concept of characterizing a particle using more than one dimension. For example, a powder consisting of monosized fibrous particles would appear to have a wider distribution according to statistical diameter measurement. Besides, the use of equivalent diameter may be misleading as the shape of particle may be acicular. Therefore, by returning to the concept of characterizing particle using more than one dimension, we can obtain the breadth of the fibre, di and the fibre length could be measured using the a projected circle circumscribed around the fibre, dc . The ratio of di / dc can be used as a simple shape factor to provide information about the circularity of a particle. The ratio of di / dc is 1 for a circle and diminish as the particle becomes more acicular.

                            To measure the particle size, we can use many different methods based on different criteria, which include size range of analysis, wet or dry methods, manual or automatic methods, and speed of analysis. The examples of the particle size analysis methods include sieve method, coulter counter, laser light scattering method, dynamic light scattering method, sedimentation method and lastly,microscope method. In this experiment, we will do the size and shape analysis using the microscope method, which is by observing the sand particles under the microscope.

Objective :

To observe and analyse the sizes and shapes of different types of sand samples by using a microscope.

Procedure:

By using the microscope, 5 samples of different sizes of sand are observed in terms of their sizes and shapes. First and foremost, a small amount of sand is put on the microscope slide. Then the microscope is transferred to the stage on the microscope. Then it is observed under the microscope. The samples observed are drawn. The steps are repeated in the other four samples of sand.

Observation:

Discussion :

                        Microscope method is an excellent technique in the development of analysing particle size and shape. We can directly look at the particles to determine the presence of agglomeration. This technique increase the manufacturing efficiency and improve product performance. By the way, use of microscopy and image analysis can be considered as the most reliable technique to characterize particle shape, size and volume distribution. From this practical, it is found that the overall shape of the sand is asymmetrical and oval. One of the methods used to measure a particle is the projected area diameter which is measured based on the equivalent area to that of projected image of that particle. Another method is the projected perimeter diameter which is based on the circle having the same perimeter as the particle. Both of the methods are non-dependent on the 3 dimensional shape of particle (orientation). They only consider the 2 dimensions of the particle, which is inaccurate for unsymmetrical particle. During the experiment, we put different types of sand on slide to be directly observed them using a light microscope. The specimen prepared for light microscopy must be adequately dispersed on the slide to avoid analysis of agglomerated particles. Principle of this measurement is that the size analysis is carried out on two-dimensional image of particles which are generally assumed to be randomly oriented in 3-dimensional and they are carried out accepting that they are viewed in their most stable orientation. Feret’s and Martin’s diameter that considering the orientation of the particles is one of the methods to measure the diameter of particle. Feret’s diameter is the mean distance between two parallel tangents to the projected particle perimeter while Martin’s diameter is the mean chord length of the projected particle perimeter. The best statistical method is Feret’s and Martin’s diameter because both of them use statistical diameter which are the average over many different orientations to produce a mean value for each particle diameter. Since we need to access the three-dimensional image of particle, we use the electron microscope that considering the orientation and shape of the image. However, microscope method is slow and need elaborate sample preparation.

Questions :

1. Explain briefly on the various statistical methods that can be used to measure

the diameter of a particle.

Most powders contain particles of a range of different equivalent diameters. To define a size distribution or compare the characteristics of two or more powders consisting of particles with different diameters, the size distribution can be broken down into size ranges and presented in the form of histogram. A histogram allows different particle size distributions to be compared. There are generally three methods used to measure the diameters of the particles. First, we can represent our data in a normally distribution which is fully symmetrical about the central value. The peak frequency value is known as the mode that separates the normal curve into two identical halves. Besides, there are also skewed distribution as a statistical method to measure the diameter of the particle as not all particle populations are characterized by normal distribution curve. There are two types of skewed curve, which are positively skewed and negatively skewed. Positively skewed curve is the curve such that the elongated tail towards higher size ranges while negatively skewed curve is the reverse case. In some size distribution, there may be more than one mode occurs. We can represent the data in a bimodal frequency distribution.

2. State the best scientific method for each sample that you used.

For 800 micrometer sand particles, sieve method is the best scientific method. The range of analysis for sieve method is within 45 to 1000 micrometer. Besides, sieve method is cheaper and readily usable for large particles. For other particles, microscope method is preferred due to their small size range. Besides, microscope method can be used to detect the presence of agglomeration and their two-dimensional images are analyzed according to the desired equivalent diameter which is Feret’s diameter,dF and Martin’s diameter,dm.


Conclusion:

In conclusion, microscope method is a size analysis method carried out on the two-dimensional images of particles which are generally assumed to be randomly oriented in three-dimensions but they must be in most stable orientation. It can be used to measure the 2-D images according to the desired equivalent diameters including projected area diameter, da; projected perimeter diameter, dp; Feret’s diameter, dF and Martin’s diameter, dM.

Practical 3 : Powder Flow

Title:

 Powder Flow

Objective:

To determine the flow rate of various sizes sand powder through the hopper

Introduction:

Measuring the ability and the time taken for a powder to flow through an orifice of known size is a useful method of quantifying powder flow.

At the same time, it is important to recognize that the ability of the powder to flow through the orifice can be affected by factors other than the characteristics of the powder itself. Such factors include the shape and material employed in the construction of the powder container, the diameter and height of the powder bed and the shape of the orifice concerned. The flow rate obtained in such a case however will depend on the geometrical parameters of the hopper, as well as the nature and size of the powder particles. Also, determining the flow rate through an orifice is useful only with free-flowing materials.

Procedure:

1.     5 different diameters of hoppers are taken.

2.     4 different properties and sizes of sand are taken.

3.     The orifice of the hoppers is closed and 100g of sands are put into it.

4.     The orifice of the hoppers is open and the sand flow through it.

5.     Time taken for the sand to flow through the orifice of the hopper completely is recorded.

6.     The experiment is repeated using different sizes of hoppers and sands.

Results:

Size of Sand (mic)	Diameter of the orifice (cm)	Diameter of hopper (cm)	Time taken for the sand to flow (s)
150	0.8	4.0	8.99
	1.4		3.55
	1.6		2.43
	0.8	6.0	7.83
	1.4		3.63
355	0.8	4.0	9.35
	1.4		3.61
	1.6		2.80
	0.8	6.0	11.9
	1.4		3.71
500	0.8	4.0	9.14
	1.4		4.44
	1.6		3.21
	0.8	6.0	8.78
	1.4		4.57
850	0.8	4.0	9.35
	1.4		4.37
	1.6		4.43
	0.8	6.0	11.40
	1.4		4.84
Various	0.8	4.0	10.01
	1.4		7.2
	1.6		4.1
	0.8	6.0	8.44
	1.4		5.81

Discussion:

Powder flowability is the ability of a powder to flow in a desired manner in specific equipment. Powders are probably the least predictable of all materials in relation to flowability because of the large number of factors that can change their rheological properties. Physical characteristics of the particles, like size, shape, angularity, surface texture, porosity and hardness will all affect flow properties. External factors such as humidity, conveying environment, vibration and perhaps most importantly, aeration, will compound the problem. The more common variables would include, firstly powder or particle variables, such as particle size, size distribution, shape and surface texture. Secondly is external factors will influence powder behaviour, for instances flow rate, compaction condition, vibration and container surface effects. From the experiment, the time taken for sand to flow is short when using large diameter of orifice and hopper. Furthermore, the smaller the size of the sand the shorter time taken for the powders to flow completely. However, when conducting the experiment, the time take for the sand to flow is not consistent as in theory. This error happened due to the hopper angle which made the sand stack there and did not flow smoothly. Other than that, shaking the hopper also will affect the sand flow as it increase the flow rate.

Conclusion:

       I.          The smaller the size of the sand the shorter time taken for the powders to flow completely

     II.          The bigger the diameter of the orifice, the shorter the time taken for the powders to flow

Question:

1.     What are the factors that affect the flow of powders?

The factors that may affect the flow rate of powders are size of the powders, diameter of the orifice, hopper wall angle and width of the hopper.

2.     Based on the experiments, which size of powders and diameter of hoppers that will give the best flow rate of powders?

The smallest size of the powders and the bigger diameters of orifice also the bigger width of the hopper will give the best flow rate of the powders.

3.     What are the methods that can be used to increase the flow rate of powders?

The methods used to increase the flow rate of the powders are shaking of the containers, increasing the hopper and orifice diameter and reduce cohesive strength of powder.

References:

http://jenike.com/bulkmaterialtesting/flow-properties/

http://www.freemantech.co.uk/en/powder-flow-and-powder-behavior.html

http://www.pharmacopeia.cn/v29240/usp29nf24s0_c1174.html

Practical 4 ; Angle of repose

Tittle :

Angle of repose

Aim :

To evaluate angle of repose and factors that influence angle of repose in certain material.

Introduction :

                      The angle of repose is the angle (relative to the horizontal base) of the conical pile produced when a granular material is poured onto a horizontal surface. It is related to the density, surface area and coefficient of friction of the material concerned.
                       Angles of repose have been used as indirect methods of quantifying powder flow-ability, because of their relationship with inter particulate cohesion. In general powders with angles of repose greater than 50 degree have unsatisfactory flow properties, whereas minimum angles close to 25 degree correspond to very good flow properties.

Apparatus and material :

Sand (size=150 mm, 355 mm,500 mm, 850 mm and mixed), Magnesium stearate,electronic beam balance,
hopper

Procedure :

1. 100 g 150 mm sand is weighted by using electronic beam balance.

weighting all the materials with care *,*

2. The hopper was filled with 100 g sand.
3. The hopper was pulled above and let sand flowed and heap or peak was forming.

See !! let the sand flowed and heap is forming ~~

4. Height, slope and peak diameter are measured.
5. The angle of repose is calculated.
6. Step 1 until step 5 are repeated by using 355 mm,500 mm,850 mm, mixed sand.
7. Step 1 until 5 are repeated with all the different size of sand by adding 1 % of magnesium stearate.

Result :

Diameter =48 cm

Table 4.1 : The height of different size sand

Table 4.2 : Angle of repose with or without magnesium stearate

Calculation :

Percentage difference :

Question :

1. What are the angle of repose of sand?

2. What are the factor affecting angle of repose? 

Factors that affecting angle of repose are :

a.Coefficients of friction between particles

b. Size of the particles

c.Moisture affects the angle of repose

3. What are the other methods that can be used to evaluate the angle of repose in certain materials?

The other method are :
a.Tilting box method
b.Fixed funnel method
c.Revolving cylinder method

Discussion :

                Based on table 4.2, the lowest angle of repose are 500 mm and 850 mm sand which is 8.29° meanwhile the highest angle of repose are 150 mm (16.92°).As Particle size increases the angle of repose is decreases. This is because, the smaller particles have dominant cohesive and adhesive forces as compared to particle weight whereas in bigger particles gravity plays a dominant role so less repose angle.

            The glidant are often used to decrease the frictional force and hence to increase the flowability. The angle of repose in general goes on decreasing with increasing concentration of the glidant. However, after a certain per cent, the change in the angle of repose may not be appreciable. The glidant increase the flow of material by reducing the friction between the particles.

            The angle of repose after adding glidant increase 1.5%. This is show that unsatisfactory flow properties. There are certain error maybe occur during weighting the sand and the glidant. The concentration of the glidant play important role. Beside that the efficiency of magnesium stearate decreases as the orifice size increases. The optimum glidant concentration is also dependent upon orifice size.Thus effecting our result.

Conclusion :

As a conclusion, the angle of repose depends on the coefficients of friction between particles,size of the particles and moisture affects the angle of repose.The smaller the particle size, the smaller the angle of repose. The addition of glidant will affect the angle of repose.

References :

1. Aulton's Pharmaceutics, The Design and Manufacture of Medicine, Third edition,Michael          E.Aulton,Churchchill Livingstone Elsevier:175-175

2. http://journal.scconline.org/pdf/cc1970/cc021n07/p00483-p00500.pdf

3. http://books.google.com.my/books?id=V3VIaBDTpJ8C&pg=PA159&dq=how+glidant+effect+angle+of+repose&hl=en&sa=X&ei=6MSCUqzHBIWmrQfctoDACA&redir_esc=y#v=onepage&q=how%20glidant%20effect%20angle%20of%20repose&f=false