DEVELOPMENT OF PHARMACEUTICAL PRODUCTS 2 (NFNF 2283)

UNIVERSITI KEBANGSAAN MALAYSIA

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

NAME :	1.	MOHD YADZLAN BIN YAHYA	A148257
	2.	MUHAMMAD NUR HAKIM BIN ZULKIFLI	A147672
	3.	PHYLICIA GAN YING HUI	A147533
	4. 5.	ONG YEE WEI SURUTHI A/P MOHHAN	A147638 A147962
LECTURER’S NAME	:	Prof. Madya Dr. HALIZA BINTI KATAS

SEMESTER II, SESSION 2015-2016

FACULTY OF PHARMACY

1.0 Introduction

Suppositories are solid dosage forms of various sizes, appearance and weights. Suppositories are one of the rectal preparations. Some other examples of rectal preparations may include foams and enemas. Suppositories are intended for administration by rectal route where they melt, soften or dissolve to exert their effect. They are capable of being easily inserted into the intended orifice without causing undue distention.

The suppository is usually composed of a medicament or drug incorporated in a suppository base. The suppositories may be made up of either oil-soluble or water-soluble base. The 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 is an example of base that possesses desirable properties to formulate a suppository. This is because they are non-irritating, chemically stable, miscible with both water and mucous secretions, do not melt at body temperature and at the same time able to provide sustained release of drug.

2.0 Objectives

    1.      To calibrate suppository moulds with PEG before preparing medicated suppositories.
    2.      To determine the effect of different compositions of PEG base on the physical characteristics of           suppositories.

3.0 Material and metodology

3.1 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

3.2 Materials

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

3.3 Methodology:

3.3.1 Calibration of Suppository Molds 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%	6 g
PEG 6000	40%	4 g

To calibrate the mold with PEG suppository base:

1. A clean and dry mold was taken. The mold was not lubricated. PEG 1000 was melt on a steam bath or hot plate, then, the heat was reduced and was mixed in the other PEG. 

2. The mixture was removed from the heat and allowed to cool before pouring into the mold. 
3. The cavities in the mold were overfilled and was let to stand at room temperature until solid.
4. The excess were carefully removed with a hot spatula; then the suppositories were removed from the mold. 
5. The suppositories were weighed and the total weight were recorded. The average suppository weight was calculated.

Mold #	6
Total weight for 6 suppositories =	6.1825 g
Average weight for one suppository =	1.0304 g

3.3.2 Preparation of paracetamol suppositories

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

               2.    The following paracetamol suppository (10 g) using the formulation below were prepared :

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. One type of PEG was melt on a hot plate, then, the heat was reduced and mixed in the other        PEG.

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

5. The cavities were overfilled in the mold and was let to stand at room temperature until               solid. 

6. Excess were removed carefully with a hot spatula; then the suppositories were removed             from the mold. 

7. The shape, texture and color of the suppositories were observed.

8. Each of the suppositories were inserted into a separate beaker containing distilled water (10        mL and pre-warmed at 37^oC) and then, the beaker was kept into a water bath (37^oC).

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

4.0 DISCUSSION:

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

Suppository moulds should be calibrated before preparing medicated suppository to ensure accurate dosing of the suppository produced. This is because error due to the slight differences among same type of moulds and among the cavities within a mold often occur. As each individual mold is capable to hold a specific volume in every openings, therefore calibration process of every suppository mould for the usual base is important to prepare medicated suppositories with accurate quantity of medicaments.

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

Suppository	PEG 1000 (g)	PEG 6000 (g)	Shape	Hardness	Greasiness	Color
I	9	0	Bullet	+	+++	Clear white
II	6	3	Bullet	++	++	Intense White
III	0	9	Bullet	+++	+	Intense White

Indicator:

+        Low

++      Medium

+++    High

All the suppositories are bullet-shaped because bullet-shaped mould is used to prepare the suppositories in this experiment. Different quantities of PEG 1000 and PEG 6000 will affect the physical characteristics of the suppositories such as in the form of hardness, colour and greasiness. In this experiment, the quantities of PEG 1000 decreases from suppository I to III while in the other hand, the quantitiy of PEG 6000 is increasing from suppository I to III. Formulation with the highest quantities of PEG 1000 take the longest time to solidify and therefore suppository I with the highest quantity of PEG 1000 take the longest time to be solidified in this experiment.. From suppositories I to III, the quantites of PEG 1000 is decreasing while the quantity of PEG 6000 is increasing. The hardness of the suppositories increases from I to III due to the reason that increasing quantity of PEG 6000 will increase the number of hydrogen bonds between the molecules which increase the hardness and strength of the suppositories formed. Besides, PEG 6000 affect the greasiness of the suppositories formed where the suppository with highest quantity of PEG 6000 appeared to be dry and less greasy.

Low molecular weight polyethylene glycol causes suppository formed to be more transparent and clear which is shown by the suppository I with greatest amount of PEG 1000 appeared to be the clearest suppository compared to suppository II and III. This is because low amount of PEG 6000 will causes the suppository to have less color intensity.

In a nutshell, PEG 1000 will increase the greasiness of the suppository. The higher the quantity of PEG 1000 in a formulation, the greasier the suppository. In the other hand, PEG 6000 will increase the hardness of the suppository. The greater the quantity of PEG 6000 in a formulation, the harder the suppository. As for suppository III, it has the highest quantity of PEG 6000 and the lowest quantity of PEG 1000, therefore suppository III is the hardest and the least greasy suppository among the suppositories produced in this experiment. The suppositories produced are in white colour because the active ingredient which is paracetamol used in this experiment is white in colour. The intensity of the colour of suppository depends on the quantity of PEG 1000 found in the formulation. The higher the quantity of PEG 1000, the more transparent it is. Suppository I appeared to be in clear white because it has the highest quantity of PEG 1000.  

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

The time required to melt the suppository against the amount of PEG  6000 in the formulation for the suppository I was 44.36 minutes, Suppository II was 42.44 minutes while Suppository III is 35.14 minutes. Based on the result, the Suppository I with zero gram of PEG 6000 required longer time to melt while Suppository III with 9 grams of PEG 6000 has shortest time to melt down. This shows that the higher the amount of PEG in the formulation of the suppository the shorter the time to melt down compared to the one with non-added PEG 6000 formulation. This is because the larger the molecular weight of the PEG, the harder the PEG is. That is why the Molecular weight affecting the time required for the suppository to melt down.

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

Paracetamol or Acetaminophen is one of drugs that have both antipyretic and analgesic properties. Analgesic is defined as an agent that relieves or reduces the sensation of pain by elevating the pain without disturbing consciousness. The antipyretic can be used as a drug that is responsible for lowering temperature of a feverish organism but has no effect on normal temperature states.

The Poly Ethylene Glycol or PEG is used in mixture of PEG to give satisfactory hardness and dissolution time of suppository and also act as an excipient which is lubricant for the suppository formulation. It also acts as a base for some cosmetic and suppository.

5.0 Conclusion

Calibration of suppository moulds with PEG before preparing medicated suppository is important in order to ensure accurate dosing of the suppository produced. Besides that, the different amount of combination of PEG 1000 and PEG 6000 in the suppository preparation affects the physical characteristics of suppositories such as the hardness, greasiness texture, shape of the suppository.

6.0 References

1. http://www.webmd.com/drugs/2/drug-56185/adult-suppositories-rectal/details 

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

Practical 4 : ASSESSMENT OF QUALITY OF TABLETS AND CAPSULES

PRACTICAL 4 : Experiment 1 - Uniformity of diameter, thickness and hardness
PRACTICAL 4 : Experiment 2 - Table friability
PRACTICAL 4 : Experiment 3 - Uniformity of weight of tablets and capsules
PRACTICAL 4 : Experiment 4 – Dosage performance tests
Practical 4 : Experiment 5 -Content of ibuprofen (assay)

Questions:
1. What are the objective of the tests for uniformity of diameter and uniformity of content?

The test for uniformity of diameter is done to determine the consistency in size and appearance of tablets, while the test for uniformity of content test is  done to ensure the consistency of dosage units, each unit in a given batch should contain the active drug within a narrow range around the label claim.

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

The test for diameter involves all the uncoated and coated tablets except for the enteric tablets, film-coated tablets and sugar-coated tablets. The test for content uniformity is required for all dosage forms.

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

    The reasons for the non-compliance may be due to the uneven feeding of granules into the die. Furthermore, it might be from the irregular movement of the lower punch. This may cause the variation in capacity of die space.

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

   Dissolution testing is used to formulate the drug dosage form and to develop quality control specifications for its manufacturing process This dissolution test ensures both batch to batch consistency and that the dissolution profiles remain similar to those of pivotal clinical trial batches. The test is used to identify any potential problem that may occur in the bioavailability of the product over a period of time Furthermore, dissolution test is used to obtain clinical results for the support of the product specification in the product quality control and to obtain information on the ability of test batches to dissolve in the bioequivalence studies. .

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

In USP, the dissolution procedure consists of three stages, in which the next stage is proceeded only if the previous stage is failed.

In BP, the test is carried out with 6 units of tablets or capsules and the result should be, for each unit tested, the amount dissolved is not less than 70% of the active ingredient within 45 minutes. If one unit fails to meet this requirement, a retest of another 6 units are carried out and the requirement is the same for all unit but one of the total units.

Practical 4 : Experiment 5 -Content of ibuprofen (assay)

Objectives :

To determine the actual content of Ibuprofen in Ibuprofen tablet.

Material:

 Ibuprofen powder, chloroform, ethanol (96%), phenolphthalein solution, 0.1M sodium hydroxide

Apparatus:

 filter paper, filter funnel, 100ml measuring cylinder, 100ml burette, 100ml beaker, hair dryer, conical flask

Procedure

1.      20 Ibuprofen tablets were weighed and crushed into powder using pestle and mortar.

2.      A quantity of powder was measured to contain exactly 0.5 g ibuprofen and then the powder was extracted with 20 ml chloroform for 15 minutes. The mixture was filtered by using filter paper.

3.      The residue washed with 3 . 10 ml chloroform and gently evaporate the combined filtrate just to dryness in a current of air. The residue was dissolved in 100 ml 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 the indicator. The content of ibuprofen was calculated if each ml of 0.1M sodium hydroxide is equivalent to 0.02063 g of C₁₃H₁₈O_2.

Result

Calculation for weight of tablet powder containing 0.5 g of ibuprofen;

Weight of powder of 20 tablet ibuprofen=7.840g

1 tablet= 200mg ibuprofen

             20 tablet= 20×200mg = 4000mg ibuprofen =4 g ibuprofen

    7.840g tablet powder = 4 g ibuprofen

        X g = 0.5 g ibuprofen

                         X =  (0.5 ×7.840)/4    = 0.98 g of tablet powder

Thus, 0.98g of tablet powder was weighted  and dissolved with 20ml chloroform.

Calculate the content of ibuprofen after titration;

           

Initial burette reading of 0.1M NaOH	100 ml
End point burette reading of 0.1M NaOH	79 ml
Volume of 0.1 M NaOH use	=100-79 =21 ml
The content of Ibuprofen in solution	NaOH + C13H18O2   C13H17ONa + H2O From equation, 1 mol of NaOH = 1 mol of C13H18O2 No. of mole of NaOH = MV = (0.1)(0.021) = 2.1x10-3 mol Hence,  2.1x10-3 mol of NaOH =  2.1x10-3 mol of C13H18O2 If each ml of NaOH is equivalent to 0.02063g of C13H18O2 21.0 ml x 0.02063 = 0.43323g of Ibuprofen Therefore, The content of Ibuprofen is 0.43323g.
Calculation for assay (standard deviation)	=(( Experimental value - Theoretical value )/(Theoretical value)) x 100% = ((0.43323-0.5 )/0.5) x 100 % = - 13.35% This means the experimental value is lower than the theoretical value by 13.35%.

Discussion

            In the theory, the amount of ibuprofen is 0.5g. Meanwhile in experiment, after calculation the amount of ibuprofen in the solution is 0.43323g. There is a small differences compare to the theoretical value with percentage of deviation is 13.35%. the resulted deviation may be due to a certain errors when we are conducting the experiment.

            One of the possible errors detected may due to the ibuprofen that we used for the experiment has expired, causing the loss of active ingredients in the tablets as the active ingredients might have decompose. Therefore, to increase the accuracy of the experiment, we should use ibuprofen tablets that are not expired.

            Others possible errors are, the active ingredient might be left behind a little because we may not rinse it correctly. Besides, the solution are not filtered through a sintered glass crucible but using filter paper and filter funnel. This will cause some of the powder that are not dissolved in the chloroform will pass through into the conical flask. Lastly, the error might happen due to the titration of the solution with sodium hydroxide. Lastly we might miss the actual end-point of the solution that turn the solution from colourless to pale pink in colour.

Conclusion

The content of Ibuprofen is 0.43323g which differ from the theoretical value by 13.35% due to many factors.