EXPERIMENT 1: THE EFFECT OF DIFFERENT AMOUNT OF PEG ON THE PHYSICAL CHARACTERISTICS OF SUPPOSITORY

TITLE

The effect of different amount of PEG on the physical characteristics of suppository.

OBJECTIVE

• To calibrate suppository mould with PEG before preparing medicated suppositories.
• To determine the effect of different compositions of PEG based on the physical characteristics of suppositories.

DATE OF EXPERIMENT

7 March 2017

INTRODUCTION

Suppositories are solid dosage forms of various sizes, appearance (shapes) and weights intended for administration by rectal route where they melt, soften or dissolve to exert their effects. They are capable of being easily inserted into the intended orifice without causing undue distention.

The suppository usually composed of a medicament incorporated (dissolved or suspended) in a suppository base, this medicament may be intended for retention within the cavity for localized drug effect or to be absorbed for the exertion of systemic effect. For example, rectal localized action such as relief of constipation, pain, itching and inflammation associated with hemorrhoid conditions. Suppositories are indicated for systemic action in pediatric patients and in patients who cannot take or tolerate oral medication due to variety of reasons e.g. to relief nausea, vomiting and pain.

The drug must be spread in a suitable base of suppository. Ideal suppository bases should be easily formed by compression or molding; release any medicament readily; melt at body temperature or dissolve or disperse in body fluids; keep its shape when handled; compatible with the drugs, non-irritant and non-toxic.

Polyethylene glycol (PEG) polymers have received much attention as suppository bases in recent years because they possess many desirable properties. They are chemically stable, non-irritating, miscible with water and mucous secretions, and can be formulated, either by molding or compression, in a wide range of hardness and melting point. Moreover, they do not melt at body temperature, but dissolve to provide a prolonged release.

Certain PEG polymers may be used singly as suppository bases but, more commonly, formulas call for compounds of two or more molecular weights mixed in various proportions as needed to yield a finished product of satisfactory hardness and dissolution time.

APPARATUS

• Analytical balance                              
• 1 x Suppository mould set
• Water bath at 37oC                             
• 1 x Spatula
• Hotplate                                              
• 4 x Weighing boats
• 4 x 50 mL beaker                               
•  2 x Glass rod
• 1 x 5 mL pipette and pipette bulb
• 1 x 5 mL measuring cylinder

MATERIALS

• Polyethylene glycol (PEG) 1000        
• Distilled water
• Polyethylene glycol (PEG) 6000      
• Liquid paraffin
• Paracetamol

PROCEDURES

Calibration of Suppository Moulds with PEG Base

For this calibration exercise, 10 g is used with the following proportions of PEG 1000 and PEG 6000.

                       

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

To calibrate the mold with PEG suppository base:

• Clean and dry mould is used.

• PEG 1000 is melted on a steam bath or hot plate, then, the heat is reduced and it is mixed in the other PEG.

• The mixture is removed from the heat and it is allowed to cool before pouring into the mould.

• The cavities is overfilled in the mould and let stand it at room temperature until solid.

• Excess is carefully removed with a hot spatula; the suppositories is then removed from the mould.

• The suppositories is weighed and the total weight is recorded. The average suppository weight is calculated.

Preparation of paracetamol suppositories

• Saturated stock solution of paracetamol is prepared by adding 10 g of paracetamol in 5 mL distilled water.

• The following paracetamol suppository (10 g) is prepared using the formulation below:

• One type of PEG is melted on a steam bath or hot plate, then, the heat is reduced and it is mixed in the other PEG.

• The mixture is removed from the heat and it is allowed to cool before pouring into the mould.

• The cavities is overfilled in the mould and let it stand at room temperature until solid.

• Excess is carefully removed with a hot spatula; the suppositories is then removed from the mould.

• The shape, texture and color of the suppositories is observed.

• Each of the suppositories is put into a separate beaker containing distilled water (10 mL and prewarmed at 37o C) and then, the beaker is put into a water bath (37o C).

• The time for the suppositories to melt is recorded.

 RESULT

Total weight and average of suppository weight:

Mould #	1
Total weight for 6 suppositories	6.0708 g
Average weight for one suppositories	1.0118 g

Amount of PEG 6000 and the time taken for suppository to melt:

Suppository	I	II	III
PEG 1000(g)	9	6	0
PEG 6000(g)	0	3	9
Time (min)	3.55	5.55	9.30

DISCUSSION

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

Calibration is the comparison of measurement values delivered by a device under test with those of a calibration standard of known accuracy. It is very important to ensure the suppository mould being calibrated so that the medicated suppositories contain the proper amount of medication. This is because every mould is capable of holding a specific volume of materials in each of its openings. The difference in the density of the materials such as the base and the medication will lead to difference in weight of the resulting suppositories from the same mould. This means that the added medicinal agents will alter the density of the base and the weight of the resulting suppository will differ from that prepared with the base material alone. Hence, the suppository mould should be calibrated with a common base to calculate the average weight of suppository containing only the base produced from that mould.

Then, the weight of medication which is needed to make up a specific amount and displace the base within the medicated suppository can thus be calculated by using the calculated average weight and displacement value which is defined as the ratio between the weight of a medicament and the weight of the base of the same volume. Therefore, calibration is important to ensure the accuracy of dosing.

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

Suppository	Shape	Texture	Color
I	Irregular bullet	Smooth, firm and very tacky	Pure white
II	Bullet	Smooth, firm and tacky	White
III	Bullet	Ragged, firm and non-tacky	White

The physical appearance of each suppository differs from the other due to difference in proportion of polyethylene glycol (PEG) 1000 and PEG 6000 used in each suppository. In this experiment, all of the suppositories contain 10% of active ingredient namely Paracetamol where suppository I contains 90% of PEG 1000, suppository II contains 60% of PEG 1000 and 30% of PEG 6000 while suppository III contains 90% of PEG 6000.

In terms of shape, suppository I has an irregular shape compared to the bullet shape of suppository II and III. Theoretically, the suppositories should have bullet shape which is the same as that of the opening of the mould. However, the irregular shape of the suppository I might be due to its softness which makes it easier to deform.

     In terms of texture, from the observation, the hardness of the suppository increases as the amount and proportion of PEG 6000 increases. This might be due to the higher molecular weight of the PEG 6000 and more hydroxyl groups available to form hydrogen bonds among the molecules of PEG 6000 and paracetamol. As a result, the suppository with more PEG 6000 shows increased hardness which can be seen in suppository III which is the hardest one in this experiment. Besides, the greasy properties of the suppositories increases as the amount of PEG 1000 increases which is shown by the very sticky suppository I, sticky suppository II and non-sticky suppository III.  This might be due to the hydrophobic property of the PEG 1000. Hence, low amount of PEG 1000 and high amount of PEG 6000 cause the relative less sticky suppository.

Last but not least, in terms of colour, the active ingredient used in this experiment is Paracetamol which is white in colour and therefore the colour of the suppositories produce will be white but differ in the degree of cloudiness. The suppository with the highest amount of PEG 1000 will produce a more solid white compared to the others.

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

Based on the graph above, it shows that the time for the suppository to melt increase proportionally as the amount of PEG 6000 in a suppository formulation increases until 9g of PEG 6000.

    It can be said that the result can be correlate to the physiochemical properties of the bases used in the suppository.

Polyethylene glycol is a synthetic polyether that is readily available in a range of molecular weights.Polyethylene glycol (PEG) is a water soluble base that has highest water misciblity. PEG with higher molecular weight (PEG 6000) will exist in waxy solid form while PEG with lower molecular weight (PEG 1000) will exist as greasy semisolid. Thus, the combinations of these two bases will lead  to the different drug release rate and physicochemical properties.

The dissolution rate of the suppository and the time taken to melt the suppository is influenced by the PEG 6000 which is a lipophilic base in the suppository paracetamol .The increase in the content of PEG 6000 in the suppository makes it to become more insoluble in the water and and required more time to dissolve in water. The PEG 6000 has the lower tendency to absorb water compared to PEG 1000. Thus, the higher the content of PEG 6000 ,the more difficult the formulation of suppository to dissolve in the distilled water.

Describe function(s) of each ingredient used in the suppository formulation

PEG 1000 and PEG 6000 are the water-soluble carrier bases. As PEG degrades in our body after the rectal administration of Paracetamol, the drugs melt, diffuse out from PEG and dissolve in the body fluids. Different combination of PEGs will allow optimum drug release rate from the suppository meaning the drug is not too strongly sustained in the carrier bases and can be easily released. As a result, rate of absorption through the rectal mucosa and bioavailability increases.
     

Paracetamol is the active ingredient that will exert the therapeutic effects in the body.The use of different contents of PEG 1000 and PEG 6000 results in different effects on the physical characteristics, subsequently affecting the rate of drug released from the suppository. More hydrogen bonds are formed between the PEG 6000 molecules and drug molecules when the more PEG 6000 is used,resulting in the increase of the hardness of the suppository and also the difficulty of the drug released from the suppository.The production of dry, hard, smooth, coarse, tackier and clear white suppository can be manipulated.

Hence, it is important to choose the correct combination ratio of PEG 1000 and PEG 6000 to avoid the production of extremely hard or soft suppository and to ensure different approach of the drugs can be dispensed.

CONCLUSION

Calibrating suppository mould with PEG before preparing medicated suppositories is very important to make sure the proper amount of medication is available in the suppository. After calibrated with a common base, the average weight of suppository containing only the base produced from that mould is obtained. The average weight of suppository is useful in identifying the proportion between the weight of a medicament and the weight of the base of the same volume in the suppository. Thus, calibration is important to ensure the accuracy of dosing.



Different compositions of PEG base will give different effect on the physical characteristics of suppositories. Higher the amount of PEG 6000 will increases the hardness of the suppository. Besides, higher amount of PEG 1000 will increases the greasy properties of the suppositories. Lastly, the suppository with the highest amount of PEG 1000 will produce a more solid white compared to the others.

REFERENCES

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

LAB 3:ASSESSMENT OF QUALITY OF TABLETS AND CAPSULES

TITLE : ASSESSMENT OF QUALITY OF TABLETS AND CAPSULES

OBJECTIVE:

1. To determine the physical appearance

2. To measure the uniformity of diameter, thickness and hardness of tablets.

3. To determine the tablet friability.

4. To determine the uniformity of weight of tablets and capsules.

5. To discover the content of ibuprofen (assay).

Introduction :

Tablets and capsules are the example of the oral dosage form used. They must follow the pharmacopoeial standards which involve “added substances” that may influence toxicity, interference with analytical method and many more. The standards that exist in the British Pharmacopoeia and United Pharmacopoeia including the uniformity of diameter, weight, content of active ingredient, uniformity of content, disintegration and dissolution. Uniformity of diameter and weight of a tablet or capsule may increase the patient compliance because of the uniform size of appearance. The uniformity of active ingredient and content will make the dosage supplied to the patients is correct and preventing from overdose cases. Uniformity in disintegration and dissolution will make sure that each tablet and capsule will have similar reaction when metabolized in the body. However, there are also non-pharmacopoeial standards that are not included in the British Pharmacopoeia and United Pharmacopoeia, but they still influence the properties of the tablets and capsules. The non-pharmacopoeial standards involve hardness, friability and bioavailability of the tablets and capsules. 5 different experiments are carried out in order to achieve the 5 main objectives. 

EXPERIMENT 1: PHYSICAL APPEARANCE

EXPERIMENT 2: UNIFORMITY OF DIAMETER, THICKNESS AND HARDNESS

EXPERIMENT 3 TABLET FRIABILITY

EXPERIMENT 4: UNIFORMITY OF WEIGHT OF TABLETS AND CAPSULES

Experiment 5:Content of ibuprofen (ASSAY)

CONCLUSION:

The consistency and accuracy of content in a tablet or capsule can be tested by weighing the individual weight of sample tablet or capsule and compare with the average weight of sample tablet or capsule. 

The amount of active compound in the tablets must be accurate and consistent in order to have the therapeutic effect on the body. Tests are carried out to determine the amount of active compounds in the tablets before the batch of tablets being dispensed. If the average amount of active compound is not within the range, then the tablets cannot be dispensed.

REFERENCES:

•  United States Pharmacopeia, General Chapter. Disintegration (701).
• http://www.who.int/medicines/publications/pharmacopoeia/TabletFriability_QAS11-414_FINAL_MODIFIED_March2012.pdf
• https://www.academia.edu/4110379/Quality_Controlling_of_Tablets

QUESTIONS:

What are the objective of the tests for uniformity of diameter and uniformity of content?

The objectives of the tests for uniformity of content are to ensure that every dosage form contains equal amount of drug substance. This is to make sure that the therapeutic response can be achieved if the amount of drug substance (active ingredient) is optimum. The objective of this test is also to prevent the patients from overdose if the amount of drug substance (active ingredient) exceed in the capsules or tablets.

The objectives of the tests for uniformity of diameter are to increase the patient compliance by increasing the quality of product appearance. This uniformity also helps to prevent any confusion towards the patient about the dosage of the medications. 

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

All the uncoated and coated tablets must be tested for uniformity of diameter except for the enteric tablets, film-coated tablets and sugar-coated tablets while all types of tablets involve for uniformity of content tests.

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

Uniform weight and content of the tablets and capsules will ensure that patients take a precise pharmaceutical dose. This uniformity will also reduce the incidence of side effects of certain drugs, reducing medication costs, and making the swallowing of large tablets easier. These two tests also ensure the even distribution of ingredients in the drug because uneven distribution may alter the dose in each individual drug and therefore reach toxic range with the inability to reach the therapeutic range or exceed the therapeutic range.

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

The reasons for the noncompliance to test for the uniformity of weight are uneven die fill due to poor granulation flow properties, a wide variation in granules particle size which results in a variation in die fill density as a function of particle size distribution at different points in the production run, differences in lower punch length which results in different size die cavities, improper incorporation of glidant, this will reduce flow and lastly tablet machine  in mechanically poor condition or dirty which prevent free punch movement. All of the reasons above will cause weight variation and lead to non-compliance to test for uniformity of weight.

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

For the shapes, diameter and thickness it is to determine easiness of the drug to swallow and also to increase absorptions at certain area. Such as example, the flat tablets have greater adherence to the esophagus than capsule-shaped tablets. Patient compliance with medication regimens may be influenced by the size and shape of a tablet or capsule. While for taste and colour is due to enhance drug palatability. The will increase patients acceptance. So each drugs have its own purpose to give an effect to the patient.

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

The tests are used to determine the consistency in weight, size, and appearance of tablets in order 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 medication. Uniformity of content tests are used to determine the uniformity of active ingredients in the tablets or capsules and to ensure that uniform dosage is supplied to the patient. This is to prevent from overdose and underdose cases due to non-uniform amount of active ingredients.

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

Uniformity of diameter	Uniformity of content
Enteric coated tablets	Uncoated tablets
Film coated tablets	Compression coated tablets
Sugar coated tablets

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

The reasons of the noncompliance to the test for the uniformity of weight are due to degeneration ingredient of the drug, uneven feeding of granules into the die due to irregular movement of the lower punch that cause variation in capacity die space and also because of the packing geometry.