Different effect of content of material towards the characteristics of suppository formulation

Aim : In this experiment, we will study about effect of different composition of base in suppository and the effect on rate of drug movement from suppositories  

Introduction

Suppository is a solid formulation  with variety size and shape. It is for rectal administration. A good suppositories must be easily melt or disintegrate after administration into the rectal. It will allow the movement of drug locally or systematically.

Drug should distribute in a suitable base of suppositories. A good base must not be a toxic, no irritation effect,no interaction with other drug and easy to be shaped according to the mould of suppositories  .A different composition of base will influence rate and limit of drug movement from suppositories

Apparatus :

Weighing machine

1 weighing boat

Spatula

50 ml beaker

500 ml beaker

Hotplate

5ml measuring cylinder

1set suppositories mould

Water bath (37 ⁰C)

2 long thread(to tie dialysis bag)

1 dialysis bag

1 glass rod

1 set pipette (5ml)and pipette bulb

1 plastic cuvet

UV spectrometer

Material

Paracetamol

Polyethylene glycol (PEG) 1000

Polyethylene glycol (PEG)6000

Procedure:

1.   A saturated stock of paracetamol (10g in 5 ml of distilled water) was prepared.
2. A suppositories paracetamol(10g ) was prepared according to this table

3. Suppository	Group	PEG 1000 (g)	PEG 6000 (g)	Paracetamol stock solution(g)	Total (g)
   1	1,5	9	0	1	10
   2	2,6	6	3	1	10
   3	3,7	3	6	1	10
   4	4,8	0	9	1	10

4. The suppositories were transferred in a suppository mould.
5. One suppository was inserted in a beaker containing distilled water (10ml,37 ⁰C) and the time taken of rate of dissolution was recorded.
6. One suppository was inserted in a dialysis bag and was inserted in a beaker (100ml) containing of distilled water (50ml) that was heated at 37 ⁰C.
7. For every 5 minuter,a sample of was drawn out by using a pipette and was transferred in a cuvet.Sample was stirred using a glass rod before drawn out.
8. The cuvet was examined by UV spectrometer for its wavelength in order to know how much UV absorption at 520nm.
9. The reading was recorded for 60 minutes.

Result and discussion

1) Difference between :

SHAPE, TEXTURE AND COLOUR OF SUPPOSITORIES

GROUP 1

SHAPE: Torpedo

TEXTURE: Smooth, hard, oily

COLOUR: Even white

GROUP 2

SHAPE: Torpedo

TEXTURE: Smooth, hard

COLOUR: Even white

GROUP 3

SHAPE: Torpedo

TEXTURE: Smooth, hard

COLOUR: Uneven white

GROUP 4

SHAPE: Torpedo

TEXTURE: Smooth, hard, oily

COLOUR: Uneven white

GROUP 5

SHAPE: Torpedo

TEXTURE: Smooth, hard, oily

COLOUR: Even white

GROUP 6

SHAPE: Torpedo

TEXTURE: Smooth, hard

COLOUR: Even white

GROUP 7

SHAPE: Torpedo

TEXTURE: Smooth, hard, sticky

COLOUR: Milky white

GROUP 8

SHAPE: Torpedo

TEXTURE: Smooth, hard

COLOUR: Uneven white

All groups obtained torpedo shape due to the usage of same moulds. Texture of the suppositories for all groups is generally smooth and hard. Some group obtained oily and sticky texture due to the use of oil to lubricate the mould to prevent suppositories sticking to the mould after cooling in refrigerator. Generally, all groups obtained white colour. However, there is even and uneven white were obtained as the result due to the different ways in handling the experiment.

2.Plot the graph of the time taken needed for suppository to melt versus PEG 6000 content in a formulation.Compare and discuss.

Suppositories A	9 gram PEG 1000	0 gram PEG 6000
Suppositories B	6 gram PEG 1000	3 gram PEG 6000
Suppositories C	3 gram PEG 1000	6 gram PEG 6000
Suppositories D	0 gram PEG 1000	9 gram PEG 6000

  From the result above shows that time taken for suppositories to be melt in 37 degree celcius.It state that  the time taken for suppositories to be melt  longer when use 9 gram of 6000 PEG.It is because melting proces depend on molecular weight of polyethylene glycol used as a coating for suppositories.

     If higher the molecular weight as higher/longer time taken for suppositories to be melt in body temperature.

   Limit test for have a better and best coating polymer for our active ingredient especially suppositories and enema are not too fragile and should be melt once in body temperature at 37 degree celcius.

      3) Plot a graph for Uv against time and give a comment
For procedure 8,

Time	UV Absorption
	0	5	10	15	20	25	30
UV absorption at 520 nm	0.015	0.088	0.028	0.202	0.100	0.069	0.048

.

           Based on the graph above, the release rate of paracetamol is not stable throughout the time. These was differ from theory that stated that the graph should be in sigmoid shape which indicates constant drug release rate until equilibrium is achieved. However, the graph still showing peak and trough throughout the experiment which indicates that the drug is not releasing at a constant rate for PEG 6000 formulation.

  

           There was several error that had been done during the experiment. Firstly, there was uneven heating of water bath which will lead to inconstant drug release rate from the suppository. Besides, the suppository we made may not be homogenously formed. This may cause the brittleness of PEG suppository or trapped air space in the suppository thus reducing the size and altering the drug release rate of drug from suppository dosage form. Futhermore, the distilled water in which the dialysis bag is exposed to may not be stirred evenly before it is taken to be tested on  UV spectrophotometer.

           In this experiment, paracetamol needs to pass through the dialysis bag before it can reach distilled water. Dialysis bag represents human biological membrane while the distilled water represents human blood plasma. The melting process,drug release and drug absorption processes occur in water bath at 37C, which represents human body temperature.

4) Plot a graph of UV absorption against time for formulation suppository that have different composition. Differentiate and discuss the result.

   

     In the experiment, dialysis tube had been use to determine the ability of the paracetamol of suppository to pass through the membrane and enter into the water. The amount of the sample that passed through the dialysis tube is measured by using the ultraviolet spectrophotometry. Dialysis tube indicates the human’s biological barrier. Based on the results, we can see that UV absorption at 520 nm is increasing with time for each of the suppositories. Increasing in UV absorption indicates that there is increasing in the numbers of particle of the suppositories diffuse through the dialysis tube membrane.

           Based on the graph above, the value that has been obtained is inaccurate because in this experiment, the suppository I which has highest drug release (given as the UV absorption) release the drug in a fluctuation trend.  Suppository I should be the highest among the four suppositories since it has the highest amount of the PEG 1000. The UV absorption will increase with time until it reaches a plateau stage where the entire drug has been released. Suppository II shows the higher rate of drug release than suppository III as it has higher composition of PEG 1000 and lower amount of PEG 6000 that slow the release rate of drug. This obeys to the theory.

            Water solubility of the drug suppository increases as the molecular weights of PEG decrease due to the water absorbing properties of PEG. Thus, the highest rate of release is expected for suppository I due to the lowest proportion or amount of PEG 6000 in the formulation In theory, the hardness of the polyethylene glycol will increase with increasing molecular weight. So, as the suppository becomes harder, it should required longer time to dissolve the drug and passing through the dialysis tube membrane. Polyethylene glycol with molecular weight from 600 to 1000 is presence in the semisolid form and molecular weight higher than 1000 is wax-like form. Therefore, suppository I should has the highest UV absorption.

            High proportion of high polyethylene glycol produce suppository which release drug slowly and also brittle. Suppository IV has the highest proportion of PEG 6000 which will produce the hard suppository that difficult to dissolve. Higher contents of PEG 6000 will give the slowest releasing rate of drug due to the strong hydrogen bond among molecules PEG 6000 with molecules Paracetamol.  It released the drug slowest. The result of the experiment can be considered same as the theory. In order to prepare less brittle suppository with release drug more readily, high molecular weight should be mixing with medium or low molecular weight of polyethylene glycol.

5) What is the function of every substance used in this suppository preparation? How can the different contents of PEG 1000 and PEG 6000 affect the physical characteristics of the formulation of a suppository and the rate of release of drug from it?

      Polyethylene Glycol (PEG) polymers are water soluble or water miscible type of bases. The PEG used in this experiment is PEG 1000 and PEG 6000. There are numerous active ingredients for example, Paracetamol in this experiment that can be dissolved in PEGs and still have a good bioavailability. They act as carrier bases, solubilisers and absorption improvers for the drugs. PEG such as PEG 1000 and PEG 6000 that is used in this experiment increases the effective dispersion and delivery of drugs through the rectal route by diffusing out from the PEG as PEG degrades. The drug will be released in the process of melting within the body. By choosing appropriate combinations of different PEGs, we can make sure that the drug is not too strongly sustained in the carrier bases and can be easily released. As a result, the rate of absorption through the rectal mucosa and bioavailability increases.

     
      Paracetamol that is used in the preparation of the suppository acts as the active ingredient. It is the main substance in the drug formulation which has the major role in contributing to the required drug therapeutic effects in the body.

     The desired solidity can be adjusted by choosing the molecular weight and suitable ratios. Higher proportions of high molecular weight polymers produce preparations which release the drug slowly and are also brittle. Less brittle products which release the drug more readily can be prepared by mixing high polymers with medium and low polymers. The PEG 1000 give very soft masses while PEG 6000 will give more solid products. The use of different contents of PEG 1000 and PEG 6000 results in different effects on the physical characteristics of the suppository produced and this will subsequently affect 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. This will result in the increase of the hardness of the suppository and also the difficulty of the drug released from the suppository. The production of whitish, very hard, less sticky and very rough suppository will be obtained. On the other hand, PEG 1000 produces whitish, very soft, most sticky, and very smooth suppository. Thus, suitable and appropriate combination ratio of PEG 1000 and PEG 6000 is important in the production of an optimum drug delivery with optimum bioavailability of drugs available to the body and also to avoid too hard or too soft suppository.
    
      Conclusion
    
      Polyethylene Glycol Polymers have received much attention as suppository bases in recent years because they possess many desirable properties. 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. Like glycerinated gelatin, they do not melt at body temperature, but dissolve to provide a more prolonged release than theobroma oil.

Certain polyethylene glycol 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.

Since the water miscible suppositories dissolve in body fluids and need not be formulated to melt at body temperature, they can be formulated with much higher melting points and thus may be safely stored at room temperature.

However,PEG content need to be accurately match if one of it over the supposely range it may cause the suppository form become more smoother or more harder.This will affect the drug release from suppository thus can't achieve theraputic effect.

Reference

https://www.inkling.com/read/contemporary-guide-pharmacy-practice-thompson-3rd/chapter-31/iii--selecting-the-suppository

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