NFNF2283 : EFFECT OF DIFFERENT AMOUNT OF PEG ON THE PHYSICAL CHARACTERISTICS OF SUPPOSITORY

DATE: 7^TH MARCH 2017

TITLE: The Effect of Different Amount of PEG On The Physical Characteristics of Suppository

INTRODUCTION:

Suppository is another way to deliver a drug besides than oral or injections. It is a solid dosage form of various sizes, appearances and weight intended to be administered by rectal route where it will melt, soften or dissolve to produce its effects.

The suppository is usually composed of medicament that is dissolved or suspended in a suppository base. Suppository is intended for systemic action in paediatric patients and in patients who cannot swallow or tolerate oral medication due to a variety of reasons.

The base of the suppository must be suitable for the spread of drugs. Ideal suppository bases should be easily formed by compression or molding, can release any medicaments readily, able to melt at body temperature or can be dissolved or dispersed in body fluids, still in shape when handled, compatible with the drugs, non-irritant and non toxic.

For this experiment, we are using polyethylene glycol (PEG) polymers that have received much attention as suppository bases due to its desirable properties; chemically stable, non irritant, miscible in water and mucous secretions and can be formulated by either molding or compression in a wide range of hardness and melting point. In addition, they do not melt at body temperature but dissolve to provide a prolonged release.

Certain PEG polymers may be used as singly as suppository bases but commonly we use two or more molecular weights mixed in various proportions as needed to yield a finished product with satisfied hardness and dissolution time.

OBJECTIVES:

1.      To calibrate suppository mould with PEG before preparing medicated suppositories.

2.      To determine the effect of different compositions of PEG base on the physical characteristics of suppositories.

MATERIALS AND METHODOLOGY:

APPARATUS:

ü  Analytical balance

ü  Water bath at 37℃

ü  Hotplate

ü  4 x50mL beakers

ü  1 x 5mL pipette and pipette bulb

ü  1 x 5mL measuring cylinder

ü  1 x suppository mould set

ü  1 x spatula

ü  4 x weighing boats

ü  2 x glass rod
MATERIALS
ü  Polyethylene glycol 1000
ü  Polyethylene glycol 6000
ü  Paracetamol
ü  Distilled water
ü  Liquid paraffin

METHODOLOGY

1.      Calibration of suppository moulds with PEG base

For this calibration exercise, 10 g of the following proportions of PEG 1000 and PEG 6000 were used:

Ingredients	Percentage	Weight Basis
PEG 1000	60%	6g
PEG 6000	40%	4g

2.      To calibrate the mold with PEG suppository base:

1.      A clean and dry mold was taken and was lubricated with liquid paraffin.

2.      PEG 1000 was melted on a hot plate, then PEG 6000 was mixed into the hot plate after reducing the heat.

3.      The mixture was removed from the heat and was allowed to cool before pouring into the mold.

4.      The cavities was overfilled in the mold and let in room temperature until solid.

5.      The excess was carefully removed with a hot spatula and then the suppository was removed from the mold.

6.      The suppositories were weighed and the total weight was recorded. The average suppository weight was calculated.

RESULT

Mold #	1350
Total weight for 6 suppositories	6.1670 g
Average weight  for one suppository	1.028 g

3.      Preparation of paracetamol suppositories

1.      Saturated stock solution of paracetamol was prepared by adding 10g of paracetamol in 5 Ml distilled water.

2.      The paracetamol suppository (10g) was prepared using following formulation:

Suppository	PEG 1000 (g)	PEG 6000 (g)	Paracetamol stock solution (mL)	Total (g)
I	9	0	1	10
II	6	3	1	10
III	0	9	1	10

3.      PEG 1000 was melted on the hot plate, then the heat was reduced and mixed with PEG 6000.

4.      The mixture was removed from the heat and was allowed to cool before pouring into the mold.

5.      The cavities was overfilled in the mold and was let in the room temperature until it was solid.

6.      The excess was carefully removed with a hot spatula, the suppositories were removed from the mold.

7.      The shape, texture and colour of the suppositories was observed.

8.      Each of the suppositories was put into a separate beaker containing distilled water (10Ml and pre-warmed at 37℃).

9.      The time for the suppositories to melt was recorded.

DISCUSSION

1.Describe the importance of calibrating suppository mould before preparing medicated suppository.

It is important to calibrate the suppository mould before preparing the medicated suppository to ensure that the medicated suppository have the supposed amount of medicine. This is due to the ability of the medicinal substances to alter the density of the base material thus resulting in slight changes in the weight of the suppository when compared to the one without the medicine.

2.Compare the physical appearance of suppositories that are formed and discuss.

Suppositories	Observations	Shape	Texture	Colour
I		Bullet	Greasy, hard	White
II		Bullet	Greasy, hard	White
III		Bullet	Less greasy ,hard	Transparent white

All the suppositories are bullet-shaped as they are moulded in the same type of mould . Suppository I have PEG 1000 as its base whereas suppository III have PEG6000 as its base. Due to this factor, suppository I is more greasy than suppository III. Melting point for PEG 1000 is 37-40⁰c whereas melting point for PEG 6000 is 60-63⁰c.Melting point for PEG 1000 is lower than PEG 6000 because PEG 1000 have smaller molecular weight compare with PEG 6000. There is less hydrocarbon chain in PEG 1000 compare with PEG 6000 ,thus, less energy is needed to break the hydrocarbon chain. Hence, melting point of PEG 1000 is less than PEG 6000.

3. Plot a graph of time required to melt the suppository vs. the amount of PEG 6000 in the formulation. Compare and explain the results.

PEG 6000 amount (g)	0	3	9
Time (min)	4.58	6.63	8.20

 
   Polyethylene glycol (PEG) is a polyether compound that has a wide array of application ranging from industrial manufacturing to medicine. It is an inert, non-ionic and long-chain polymer which is commonly expressed as H−(O−CH2−CH2)n−OH. In this experiment, it is used as water soluble or water miscible bases for the manufacture of suppository. In this context, different molecular weights of PEG will contribute to differences in the physical parameters such as solubility, freezing point, melting point, surface tension and the time taken for the suppository to melt in our body.

From the aspect of physical characteristic, we observed that PEG 1000 with a lower molecular weight exist as a greasy semisolid while PEG 6000 with a higher molecular weight exist as a waxy solid. In this experiment, we are also required to examine the time needed for the suppository to melt with different composition of PEG 6000 in the formulation. Theoretically, the suppository with higher composition of PEG 6000 will take a longer time to melt compared to that with a lower composition of PEG 6000.  From the graph above, it show that the higher composition of PEG 6000 (9g) will take a longer time to melt as compared to the lower one which are 0g and 3g respectively. At first, the time required for suppository that consists of 0g of PEG to melt is 4 minutes and 35 seconds whereas the suppository consisting 3g of PEG 6000 takes 6 minutes and 38 seconds to melt. The time needed for the suppository consisting 9 g of PEG 6000 to melt is the longest, which is 8 minutes and 12 seconds. Thus, this experiment shows that the time needed for the suppository to melt increases with increasing amount of PEG 6000 in the formulation. This is due to the high composition of PEG 6000 which has lower water solubility as compared to PEG 1000, causing it to take longer time to melt. Thus, we can conclude that the suppository with higher amount of PEG 6000 should take longer time to melt in the body’s fluid as the suppositories in this experiment are melted at 37  in water bath which is similar to our body temperature.

4.Describe function(s) of each ingredients used in the suppository formulation.

The suppository contains of PEG 1000 and PEG 6000 as the base; chosen due to their stability chemically,  non-irriating and miscible with water and mucous secretion properties, paracetamol as the medicinal ingredient and water for the paracetamol stock solution.

CONCLUSION

1.    Calibration method was done by  using PEG 1000 and PEG 6000 in this experiment and the average weight of one suppository was 1.028 g.

2.   Different compositions of PEG bases gave different physical characteristics of the suppositories. Our hypothesis was, increase in PEG 6000 bases increases the hardness of the suppositories, thus increases the melting time. The hypothesis was accepted as seen in our results.

REFERENCE

1. http://pharmlabs.unc.edu/labs/suppository/bases.htm

2. https://www.slideshare.net/PHARMACISTS/suppository

3. https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=4&cad=rja&uact=8&ved=0ahUKEwiK0tWq19_SAhWIrI8KHc6XDToQFggrMAM&url=http%3A%2F%2Fwww2.syphu.edu.cn%2Fsyzx%2Fyjx%2Fmaterials%2Fjc_english%2F06.doc&usg=AFQjCNFGDH6W3hrSZkbkzLzrIbK897OiAA&sig2=cBIU9NbBeH07TVdTJoziiw&bvm=bv.149760088,d.c2I

EXPERIMENT 3 : ASSESSMENT OF QUALITY OF TABLETS AND CAPSULES

INTRODUCTION

           Like all other dosage forms, tablets and capsules are subjected to those pharmacopoeial standards which deal with “added substances” with respect to their toxicity, interference with analytical methods, etc. However, there are a number of procedures which apply specifically to tablets and capsules, and which are designed, not only to ensure that a tablet or a capsule exerts its full pharmacological actions, but also to determine the uniformity of the physical properties of the official tablet/capsule, irrespective of the manufacturer.

            Such standards are found in the British Pharmacopoeia and United Pharmacopoeia and include, uniformity of diameter, uniformity of weight (mass), content of active ingredient, uniformity of content, disintegration and dissolution. In addition there are a number of quality control procedures, which, though widely applied, are not defined by the pharmacopoeias (non-pharmacopoeial standards) such as thickness, hardness and friability.

           The following experiments demonstrate the application of a number of selected physical and dosage performance tests on samples of commercially available tablets and capsules. Students are required to refer to official pharmacopoeias for detailed description of other tests not carried out in this practical session. For this experiment, capsule and tablet are being used for the assessment of quality.

           For experiment 1, we will observe the physical appearance of the tablets and capsules. The physical characteristics of the samples are examined including the shape, colour, diameter, thickness, smell or special lines (marking). For experiment 2, uniformity of diameter, thickness and hardness are determined. This will actually influence the delivery of the drugs in body system.

          For example, a tablet should be hard enough to withstand the rough transportation process. However, it should not be too hard that it will not disintegrate or metabolise within our body. Next, tablet friability is checked in experiment 3. Friability is the tendency for a tablet to chip, crumble or break following compression. This is usually applied to uncoated tablets and surfaces during handling and storage processes. The result is inspected through the percentage loss of weight. 

           For experiment 4, the uniformity of weight of tablets and capsules are determined. If the deviation of weight of tablets exceeds the limit, it may be due to factors such as flowing properties of the powder, the speed of tableting machine, the pressure used in compression and the type of machines used in tableting. On the other hand, the deviation in capsule weight is normally caused by the defect of the capsule filling machine. Finally, the last experiment is about the content of ibuprofen. The content uniformity test is used to determine the potency and content of active ingredient in the ibuprofen powder. 

EXPERIMENT 1

Procedure:

1.      A tablet and a capsule is selected from the provided samples. Their shape, colour, diameter, thickness and/or other physical characteristics were examined.

Result:

Back                                                  Front 

Shape: Round with hexagon shape on it

Colour: White

Diameter: 1.3 cm

Thickness: 0.3 cm

Other physical characteristics: has a pale yellowish spot on the tablet.

Shape : Oval 

Colour : Red

Other physical characteristics : Has a strong odour, made of hard gelatin capsule, company logo and                                                      capsule weight are stamped on the capsule

EXPERIMENT 2

Procedure:

1.      10 tablets were selected. Tests for uniformity of diameter, thickness and hardness were carried out using Tablet Testing Instrument (PHARMATEST PTB 311).

Result:

Tablet	Diameter (mm)	Thickness (mm)	Hardness (N)
1	12.82	5.54	149.83
2	12.82	5.50	136.34
3	12.82	5.60	130.99
4	12.83	5.59	119.16
5	12.82	5.52	148.17
6	12.83	5.56	142.81
7	12.83	5.55	136.34
8	12.83	5.64	125.07
9	12.80	5.60	140.96
10	12.83	5.58	136.90

   

   Discussions:

      For this Experiment 2, it was stated that the deviation of individual unit from the mean diameter should not exceed ±5% for tablets with diameter of  less than 12.5 and ±3% for diameter of 12.5 mm or more.

    To know if we achieved this criteria, firstly we had to find the mean diameter of the 10 tablets.

Mean diameter = [ (12.82 X 4) + (12.83 X 5) + 12.80 ] / 10

                         = 12.82 mm

Secondly, we calculated the difference between the mean diameter with 12.5 mm

12.82-12.5 = 0.32

Thirdly, the difference of diameter is divided by the mean and we found out the percentage of the deviation:

[ 0.32 / 12.82 ] X 100% =2.50%

Therefore, the tablets did not exceed 3% deviation of individual unit from the mean diameter.

    While carrying the diameter, thickness and hardness tests, we were supposed to carry out properly by inserting the tablets properly in the Tablet Testing Instrument machine or else the tablets would not be tested properly, hence, error in results.

EXPERIMENT 3 : TABLET FRIABILITY

Procedure:

1.       10 tablets were selected and weighed all at once.

2.       All the tablets were put into the drum of the tablet abrasion and friability tester. The rate of rotation was set to 60 rpm and the machine was started to operate for 10 minutes.

3.       After 10 minutes, the machine was stopped and the tablets were removed and brushed free from dusts and powder. All tablets were weighed at once and the percentage loss of the weight was determined.

Result:

WEIGHT (g)			% Weight loss (g)
Before test	After test	Difference (before-after)
5.7988	5.5568	0.242	(0.242/5.7988) x 100     = 4.17%

Discussion:

                The friability test is conducted to determine the physical strength of the uncoated tablets towards the possible abrasion and collision that may occur in production state or everyday handling of the tablets. To mimic this possible condition, the friabilator machine was used with the rotation rate is set to 60 rpm for 10 minutes.

                Based on the result, the percentage weight loss of our tablets is 4.17% of their weight, which is not good. The ideal percentage weight loss should be less than 1% of their weight.

                There are several reasons that might be the cause of this situation. Firstly, the tablets might have expired or kept under poor condition. As the lab session will use the tablets from the same container, the previous students might have introduced the tablets to humidity due to inappropriate container capping. Next, the drum might have not be cleaned thoroughly resulting in some dust or any other sharp object left at the edge of it. When the test is conducted, the abrasion of the tablets with these things will cause the tablets to lose more of their weight. Lastly, the drum of the machine was installed in the wrong way such that the rotation will caused the tablets to be expelled from the machine. This happened while the machine is rotating at 60rpm and the expulsion might had caused some damages to the tablets even before we started with the test.

                    

EXPERIMENT 4

Procedure:

a) Tablets

1.20 tablets were selected at random and weighed .The average weight was determined.

2. The tablets were weighed individually and the weight of each tablet was determined. The percentage of deviation of the individual tablet from the average tablet was determined.

3. The deviation of individual weight from the average weight should not exceed the limits given below.

Average weight of tablet	Deviation (%)	Number of tablets
Less than 80 mg.	± 10.0	Minimum 18
	 ±20.0	Maximum 2
80 mg to 250 mg	 ±7.5	Minimum 18
	 ±15.0	Maximum 2
More than 250 mg.	 ±5.0	Minimum 18
	 ±10.0	Maximum 2

b) Capsules

1.      20 capsules are selected at random.

2.      One capsule is weighed. The capsule is opened and the contents are removed as completely as possible. The emptied shells are weighed. The net weight of its contents is determined, that is by subtracting the weight of the shells from the weight of the intact capsule.

3.      The procedure is repeated with other 19 capsules.

4.      The average net weight is determined from the sum of the individual net weights.

5.      The percentage deviation is determined from the average net weight for each capsule. The deviation of individual net weight should not exceed the limits given below:

Average net weight of capsule	Deviation (%)	Number of capsules
Less than 300 mg.	± 10.0	Minimum 18
	 ±20.0	Maximum 2
300 mg or more	 ±7.5	Minimum 18
	 ±15.0	Maximum 2

Result: 

a) Tablet: Paracetamol (500mg)

Weight (individual tablet)/g	Difference of individual tablet with the average weight of tablets/g	Percentage of deviation (%)
0.5762	0.0038	0.66
0.5617	-0.0107	-1.87
0.6120	0.0396	6.92
0.5707	-0.0017	-0.30
0.5589	-0.0135	-2.36
0.5572	-0.0152	-2.66
0.5670	-0.0054	-0.94
0.5717	-0.0007	-0.12
0.5751	0.0027	0.47
0.5669	-0.0055	-0.96
0.5693	-0.0031	-0.54
0.5801	0.0077	1.35
0.5708	-0.0016	-0.28
0.5709	-0.0015	-2.62
0.5893	0.0169	2.95
0.5746	0.0022	0.38
0.5714	-0.0001	-0.17
0.5632	-0.0092	-1.61
0.5714	-0.0001	-0.17
0.5692	-0.0032	-0.56

b) Amoxycillin capsules (250mg)

	Weight of capsule (g)	Weight of empty shell (g)	Net weight of content (g)	Deviation from average weight (g)	Percentage deviation (%)
1	0.3506	0.0638	0.2868	-0.0067	-2.28
2	0.3426	0.0653	0.2773	-0.0162	-5.52
3	0.3658	0.0622	0.3036	0.0101	3.44
4	0.3349	0.0614	0.2735	-0.0200	-6.81
5	0.3635	0.0630	0.3005	0.0070	2.39
6	0.3636	0.0638	0.2998	0.0063	2.15
7	0.3571	0.0627	0.2994	0.0009	0.31
8	0.3593	0.0635	0.2958	0.0023	0.78
9	0.3502	0.0644	0.2858	-0.0077	-2.62
10	0.3590	0.0633	0.2957	0.0022	0.75
11	0.3711	0.0618	0.3093	0.0158	5.38
12	0.3728	0.0617	0.3111	0.0176	6.00
13	0.3626	0.0638	0.2988	0.0053	1.81
14	0.3381	0.0631	0.2750	-0.0185	-6.30
15	0.3432	0.0641	0.2791	-0.0144	-4.91
16	0.3624	0.0623	0.3001	0.0066	2.25
17	0.3586	0.0643	0.2943	0.0008	0.27
18	0.3641	0.0636	0.3005	0.0070	2.29
19	0.3683	0.0630	0.3053	0.0103	3.51
20	0.3452	0.0620	0.2832	-0.0103	-3.51

Calculation:

Discussion:

The aim of measuring the uniformity weight of tablets is to ensure that weight of tablets in batch are in the acceptable limits and are marketable. The tablet which we are investigating is paracetamol (500mg).The average weight of the tablets is 0.5724 g .Thus, according to the tablet, the limits at the third column should be followed. From table 1, when the average weight of tablet is more than 250mg (0.250g), there must be a minimum of 18tablets having deviation ±5.0 %and maximum 2 tablets having deviation ±10.0%.Based on the results, 20 tablets tested follow the limits given .19 tablets are within the deviation of ±5.0%.Only one tablet is out of deviation ±5% but it does not reached the deviation ±10%.Hence, all the tested tablets have uniform weight and are acceptable.

The average net weight of content for capsule is less than 300mg, so the individual net weight of minimum 18 capsules should not exceed ±10% from its average net weight, and maximum 2 capsules should not exceed ±20% from its average net weight. From the result of experiment of 20 amoxycillin capsules (250mg), amoxicillin capsules pass the test of uniformity of weight of capsules. The highest percentage deviation of capsule is -6.81% which is still under the limit of ±10%. The high percentage deviation is due to the leftover of content inside the capsule that is unable to be removed completely. Therefore, the percentage deviation is not accurate as the capsule may not be completely empty when weighing. 20 capsules are tested to increase the accuracy of the test by finding their average weight.

EXPERIMENT 5

Procedures:

1. 20 Ibuprofen Tablets previously selected at random were weighed and powdered.

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

3. The residue was washed with 3 · 10ml chloroform and the combined filtrate was gently evaporated just to dryness in a current of air. The residue was dissolved in 100ml with ethanol (96%) previously neutralized to phenolphthalein solution.

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

Results:

Given 20tablets x 400mg = 8000mg

If 10.24g powder contains 8g ibuprofen and 0.5g ibuprofen is needed, then

Powder required =  (0.5 x 10.24) / 8

                               = 0.64g

In this experiment, each ml of 0.1M NaOH = 0.02063g of C13H18O2 and 19.7ml of NaOH is required to titrate the residue dissolved in 100ml of ethanol to its end point (phenolphthalein solution turns from colourless to pink), then

Ibuprofen content = (0.02063 x 19.7 ) / 1

                               = 0.4064g

Uniformity of content = 0.4064 X 100%

                                     = 81.28%

Discussion:

Uniformity of content refers to a method of pharmaceutical analysis to determine the actual content of tablets and capsules at which the tablets and capsules are randomly chosen.

Theoretically, the content of the ibuprofen in solution should be 0.5000 g. However, the experimental value of ibuprofen content in solution is 0.4064 g. This shows that the experimental value is actually lower than the theoretical value. The percentage deviation value calculated is 81.28%, which is not compliance with the experiment. In fact, the percentage deviation should be within 85%-115%, according to British Pharmacopeia. Any value outside the range of the standard is considered as a failed formulation in the B.P test for content of active ingredient. The experimental percentage deviation value is 3.72% lesser in order to achieve the compliance value. On top of that, 19.7 mL of 0.1 M sodium hydroxide is used in titration upon reaching the end point where the colourless solution turns pink. In fact, for the 0.5g content of tablets, the volume of 0.1 M sodium hydroxide solution expected should be 24.24 ml but not 19.7 mL of sodium hydroxide upon reaching the end point.

The deviations happened as there might be some errors happen during the experiment. One of the errors that might happen is when weighing the ibuprofen powder. The Ibuprofen might be weighed less or more during weighing session. Besides, the Ibuprofen powder may not transferred completely from one apparatus to another. Upon transferred, some of the Ibuprofen may remained in the weighing boat and conical flask, therefore there may be lesser Ibuprofen present in the solution. Thus, precautions step should be taken such as rinsing the apparatus thoroughly in order to ensure that there are no residues left in the apparatus. Another possible error is we used filter funnel and filter paper instead of sintered glass crucible to filter the solution. As a result, alteration of the powder uniformity might be happened. Incomplete drying of the solution can also be another source of error which leads to inaccurate results.

The determination end point of titration can be one of the sources of error during titration. Firstly, the amount of phenolphthalein added is small in quantity causing the colour change cannot be seen precisely. Next, the titration might be done too fast until we missed the end point where the colourless solution turns pink. In fact, the correct technique of titration is the titrate should be added drop by drop to the analyte in order to obtain an accurate result.

 QUESTIONS

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

The aim of tests for uniformity of diameter is to ensure the uniformity of the size and appearance of tablets. On the other hand, the objective of measuring the uniformity of content is to ensure the uniformity of the active ingredient in the tablets or capsules.

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

All the tablets and capsules including coated and uncoated tablet.

3.Why it is important that tablets and capsules have uniform weight and content?

The test for the uniformity of weight and content of tablets and capsules is to ensure the quality of tablets and capsules being marketed are under controlled. The importance of measuring the uniformity of content is to ensure that the active ingredient in the tablets or capsule is in a therapeutic range and do not cause any toxicity.

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

Firstly, there may be uneven feeding of granules into the die during tablet manufacturing at the tablet press. The powders may also not be mixed properly before the tablets are manufactured. The granules may be exposed to air during the compression process, where excess air is trapped inside the tablet causing uneven distribution of granules in the tablet. For capsules, they may not be filled completely or are overfilled. Distortion of the tablets and capsules due to heat, chemical or environment factors can also occur which causes loss of content. Human error is also possible where a mistake in procedure may happen due to fatigue or systematic error due to error in the apparatus.

5.Explain why is it beneficial for any tablets or capsules to have distinctive or identifying features.

It is easy for identification. The patients will be able to differentiate the tablets easily though its distinctive features such as colour and markings. Besides, the identifying features such as trademark markers can help a person to identify the pill. Some markers are codes which function as a legal requirement for pill identification. The distinctive features also give the tablets and capsules an attractive appearance, which will in turn help in improving patient compliance.