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

Introduction 

Suppositories are known as a solid dosage forms of various sizes, appearance and weights intended for administration by rectal route where they melt, soften or dissolve to exert their effect. Suppositories are adapted for introduction into the rectal, vaginal, or urethral route of the human body. In addition, a suppository may act as a protectant to the local tissues located near the point of insertion or as a carrier of therapeutic agents for systemic or local action. Suppositories used to relief constipation, pain, itching and inflammation associated with haemorrhoid conditions.

 Suppository bases that are usually used are cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, mixtures of polyethylene glycols of various molecular weights, and fatty acid esters of polyethylene glycol. The drug needs to be dispersed in a suitable suppository base. A good base should not be toxic, does not produce irritation, does not react with the drug, and easy to form into a suppository. Different base composition will affect the rate and release limit of a drug from suppository. Polyethylene glycol polymers are chemically stable, non-irritating and it is not melt in body temperature but it dissolves to provide a prolonged release. In this experiment, the effect of different base composition on the physical characteristics of the formed suppositories and its effect on the release of the drug from it are studied.

           

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

1. Polyethylene glycol (PEG) 1000
2. Polyethylene glycol (PEG) 6000
3. Paracetamol
4. Distilled water
5. Liquid paraffin

Apparatus

1. Analytical balance
2. Water bath at 37˚C
3. Hotplate
4. Beaker, pipette and pipette bulb
5. Measuring cylinder, suppository mould set
6. Spatula, weighing boats and glass rod

Procedure

Calibration of Suppository Moulds with PEG base

INGREDIENTS	PERCENTAGE
PEG 1000	60%
PEG 6000	40%

       table 1

1. 10 g of the following proportions of PEG 1000 and PEG 6000 was used for this calibration exercise. (refer to table 1 above)
2. A dry and clean mold was taken and the mold was not lubricated.
3. PEG 1000 was melted on a steam boat or hot plate and then the heat was reduce and mixed in   the other PEG.
4. Then,the mixture was removed from the heat and let it to cool before pouring into the mold.
5. The cavities in the mold was overfilled and let it at room temperature until it became solid.
6. The excess was then carefully removed with a hot spatula and then the suppositories also been   removed from the mold.
7.  The suppositories was then weighed and recorded.

Preparation of paracetamol suppositories

1. The saturated stock solution of paracetamol was prepared by adding 10 g of paracetamol in 5ml distilled water.
2. The paracetamol suppository was prepared using the formulation based on table 2 below.
3. One type of  PEG was melted on a steam bath or hot plate and the heat was reduced and it was mixed in the other PEG.
4.  The mixture was removed from the heat and it was allowed to cool before poured into the mold.
5. The cavities in the mold was overfill and let it to be cool and became solid
6. The excess was carefully removed with a hot spatula and then the suppositories also been removed from the mold.
7. The shape,texture and colour of the suppositories was observed.
8. Each suppositories was placed into a separate beaker containing distilled water(10 ml and prewarmed at 37˚C) and then the beaker was placed into a water bath.
9. The time for the suppositories to melt was recorded.

Suppository	PEG 1000(g)	PEG 6000(g)	Paracetamol Stock Solution	Total(g)
I	9	0	1	10
II	6	3	1	10
III	0	9	1	10

table 2

Result

Ingredients	Percentage	Weigh Basis
PEG 1000	60%	6.011 g
PEG 6000	40%	4.022g

                  

Weigh Basis of PEG 1000 and PEG 6000

Mold	6
Total weight for 6 suppositories	6.4235g
Average weight for one suppository	1.0706g

Total weight and average weight of suppositories

Suppositories	I	II	III
Shape	Bullet shape	Bullet shape	Bullet shape
Texture	Smooth but soft	Smooth and hard	Smooth and hard
Colour	Milky White	Milky White	Cloudy with slight transparency

The physical appearance of suppositories

Suppositories	I	II	III
Time taken (min)	41.17	40.11	42.15

Time taken for suppositories to melt in water bath (37 ̊ C)

Discussion

During the experiment, there are some errors occurred. The mold that is needed to fill in with suppositories is not lubricated with paraffin oil before the solution filled in the mold. Thus, some of the suppositories are broken and the experiment has to be redone. Next, when the amount of PEG 1000, PEG 6000 and paracetamol is measured, the accurate amount of substance measured is hard to obtain and this may lead to inaccuracy of result obtained. Besides, overheating of paracetamol and PEG also leads to inaccuracy of the result obtained.

Several precautions should be taken. Firstly, the mold should be lubricated with paraffin oil before filling in the solution to prevent it from breaking. Next, when measuring the weight of PEG 1000, PEG6000 and paracetamol, the reading should only be recorded after the weighing machine has shown the exact reading for a while. Then, when filling in the mold, make sure that there is no bubbles left inside the mold. When the suppositories are put inside the water bath, the temperature of the water bath should always be controlled at 37 ̊ C and the rate of dissolution of the suppositories should be observed carefully. 

Questions

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

• To know the average weight of a blank, base-only suppository for that mold
• Mould calibration weight used in the density displacement calculations
• To make sure that the mould produce an equal size and weight for each of the suppositories
• To determine whether the medicated suppositories have the same density as the base-only suppositories. If the drug powder had the same exact density as the suppository base, then the weight of powder would displace an equal weight of suppository base. However, if the density of the drug is greater than the base, the weight of drug powder will displace a proportionately smaller weight of base.

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

• The first medicated suppositories have a bullet shape, smooth but soft condition and Milky White in color. It is soft maybe due to the base that fully made up of the PEG1000 which is softer than PEG6000 and the color also very milky.
• The second one have bullet shape, smooth and hard condition and also Milky White in color. It is harder than the first one because it is added with small amount of PEG6000 but the color still milky.
• The third medicated suppositories have a bullet shape, smooth and hard condition and Cloudy in color with slightly transparent. It is hard and slightly transparent because it is fully made up of PEG6000 which have a hard characteristics than PEG1000 and the color is more transparent..

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.

Polyethylene Glycol have been used as suppository bases. The difference between PEG 1000 and PEG 6000 is that PEG 6000 has higher molecular weight and melting point due to longer polymer chain. Different molecular weights will contribute to differences in the solubility, freezing point, melting point, surface tension and so on.

A graph of time required to melt the suppository versus the amount of PEG 6000 in the formulation has been plotted. The suppository is placed in a beaker containing 10mL distilled water and the beaker was put into a water bath with temperature of 37^οC and the time needed to melt the whole suppository is recorded.

In this experiment, we examine the time needed for the suppository to melt with different composition of PEG 6000 in the formulation. When none amount of PEG 6000 is used, the time needed for the suppository to melt recorded is 41.7 minutes. Then, the time needed is 40.1 minutes of time when 3 g of PEG 6000 is added into the formulation. When 9 g of PEG 6000 is used, the time needed for the suppository to melt is 42.15 minutes. Based on this experiment, it shows that the time needed for the suppository to melt at constant 37^οC decreases when 3 g of PEG 6000 is added. Then, the time needed for the suppository to melt increases again when 9 g of PEG 6000 is added in the formulation. However, the time needed for the suppository to melt when 3 g of PEG 6000 is not too accurate. It should be increase as well compare to suppository without PEG 6000. This may be due to some errors when experiment is carried out. The water temperature may not reach 37^οC yet when the suppository is put in the water bath. Theoretically, increasing amount of PEG 6000 in the formulation requires larger amount of water to make the suppository soluble and this will takes longer time. This is because, the PEG 6000 has the lower tendency to absorb water compared to PEG 1000. Thus, the larger the amount of PEG 6000, the more difficult the formulation of suppository to dissolve in the distilled water with temperature of 37^οC.

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

Paracetamol is used as an active ingredients for suppositories. It is used for analgesic and anti-pyretic purposes. Polyethylene Glycol have been used as suppository bases. They are chemically stable, nonirritating, miscible with water and mucous secretions, and can be formulated, either by molding or compression, in a wide range of hardness and melting point. In this experiment, two different molecular weights of polyethylene glycol polymers in various proportions are used to yield a finished product of satisfactory hardness and dissolution. Next, distilled water is used as a solvent to incorporate a water-soluble substance in the suppository base. Meanwhile, liquid paraffin is used to lubricate the mold before the solution filled in it.

References

1. http://pskills.pharm.ku.edu/ios/html5/html5-compoundingvideos/html5-revised-lecture-video/Suppositories/Suppositories.pdf

ASSESSMENT OF QUALITY OF TABLETS AND CAPSULES

Date of experiment : 23^rd November 2015

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 number of procedures which apply specifically to tablets and capsules, and which are designed, not only to ensure that tablets or a capsuled 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 standard are found in British Pharmacopoeia and United Pharmacopoeia and include , uniformity of diameter , uniformity of weight(mass), content of active ingredients, 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.

There are 5 experiment  test involved with different objective each (follow the link below)

EXPERIMENT 1 : UNIFORMITY OF DIAMETER , THICKNESS AND HARDNESS

EXPERIMENT 2 : TABLET FRIABILITY

EXPERIMENT 3 : UNIFORMITY OF WEIGHT OF TABLETS AND CAPSULES

EXPERIMENT 4 : DOSAGE PERFORMANCE TESTS

EXPERIMENT 5 : CONTENT OF IBUPROFEN (assay)


Questions

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

          Content uniformity test is used to ensure that every tablet contains the amount of drug substance intended with little variation among tablets within a batch and to determine whether the individual contents are within limits set with reference to the average content of the sample.  Tablet diameter is an important quality control test for tablet packaging which affects packaging either in blister or plastic container .Tablet thickness is determine by the diameter of the tablet. Without proper normalisation of tablet hardness and compression force data, misleading conclusions may be drawn on formulation behaviour particularly when using different equipment for tableting. We have shown how important the tablet thickness and punch diameter is to normalise the tablet hardness and compression force data to give meaningful comparative data.

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

 For uniformity of diameter, all coated and uncoated tablets and all capsules intended for oral administration are applicable such as coated tablet, effervescence tablet and modified release tablet except enteric tablet, film-coated tablet and sugar-coated tablet. For the capsules, mostly capsules are applicable such as hard capsules, soft capsules, gastro-resistant capsules, modified-release capsules and cachets.

For uniformity of content, it was required for coated tablets, other than film-coated tablets containing 50 mg or more of an active ingredient that comprises 50% or more (by weight) of one tablet, , suspensions in single-unit containers or in soft capsules.

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

The reasons for the non-compliance to test for the uniformity of weight are because of the different amount of granules that put into the die maybe due to the uneven size of granules. Other than that, irregular movement of lower punch will cause variety in the capacity of die space. Next, this problem also can cause by the wrong measurement during weighing. Last but not least, the unwell mixed of the ingredients in blending stage can also cause the non-compliance.

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

Because the function of the dissolution test is to provide information of the bioavailability of active ingredient and the time release profile of drug into the body can be predicted. It is used for batch to batch quality control by ensuring the consistency of the scale up batch and production batch. This test also ensures that the dissolution profile is same as the pivotal clinical trial batch.

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

There are some differences between the USP and the British Pharmacopoeia. During the dissolution testing in that capsule product, 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 end scan 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.

In United States Pharmacopoeia, typical acceptance criteria for the amount of active ingredient dissolved, expressed as a percentage of the labelled content (Q), are in the range of 75% to 80% dissolved. In British Pharmacopoeia, the amount of active ingredient dissolves must not less than 70%. In US Pharmacopoeia, if the test failed, a retest may be carried out in three stages with different amount of tablets. In British Pharmacopoeia, if the test failed, a retest may be carried out using the same number of units of tablets 

Conclusion

The tablets and capsules are subjected to different type of tests in order to make sure they have the desired physical strength to overcome the mechanical shock during handling and packaging.The capsules or tablets produced must also give the best therapeutic effect and least side effect when administered into the body . The test must be done before it can be marketed and must follow the standard from Britsh Pharmacopoiea or Unites States Pharmacopoiea .

References

1.      Aulton, M.E. 2002. Pharmaceutics: The Science of Dosage form Design. Edinburgh Churchill Livingstone.

2.      Martin, A.N. 2006. Physical Pharmacy: Physical Chemistry Principles in Pharmaceutical Sciences. Ed. Ke-5. Philadelphia: Lea & Febiger.

3.      Michael E. Aulton. 2007. 3rd Edition Aulton’s Pharmaceutics : The Design And Manufacture of Medicines. Churchill Livingstone Elsevier.

4.      http://www.sciencedirect.com/science/article/pii/S1319016411000028