Suppository
A suppository is a type of dosage form in
which the drugs are delivered through body cavities. It is usually a
cone-shaped object or sometimes round that can be inserted into body cavities like
the rectum, urethra or vagina. (3)
Once inside the body cavity, the
suppository dissolves due to its solubility in aqueous environment or it melts in
the body cavity due to body temperature.
(3) Due to the two mechanism of drug release in suppositories we have
different bases which can be classified largely into the 1. Oleaginous bases 2.
Non- Oleaginous bases (water soluble) and also not very common 3. Emulsifying
bases. (4)(5)
Figure …..
Picture of all the suppository
bases used. PEG 4000, PEG 6000, WITEPSOL AND COCOA BUTTER
The oleaginous bases are
fatty bases that are solid at room temperature and melts at body temperature.
To fulfil the ideal properties of a fatty suppository base, the bases must be solid
or stable semi-solid at room temperature and able to melt at body temperature,
Theobroma oil, Palm kernel oil, cottonseed oil and cocoa butter are good
examples of Oleaginous bases. (4)(5)
Figure…..
Preparing cocoa butter suppository
FIGURE…..
OLEAGINOUS BASE
FIGURE….
FIGURE……
The aqueous bases are
soluble in aqueous environment and thus dissolve in body fluids. The
temperature at which the aqueous bases melts is usually higher than the normal
body temperature but it uses different mechanism of drug delivery. We have a
variety of aqueous bases ranging from the polyethylene glycols bases
(polyethylene glycol 4000, polyethylene glycol 6000), Soap glycerine and Glycero
– gelatine. (4)(5)
FIGURE….
PEG 4000
FIGURE….
PEG 6000
The emulsifying bases
essentially consist of the mono-, di- and tri-glycerides of the fatty acids,
examples include the Witepsol, Massa Esterinum, and Massupol. Most of the bases
have the advantages and address the short-comings of Oleaginous bases like cocoa
butter and it requires no lubrication. (4)
FIGURE…
PICTURE OF WITEPSOL IN MOLTEN
STATE
Suppositories
may not be the most appealing pharmaceutical dosage form or pleasant product to
use. But has proved to be of great importance by their use in cases where by
patients cannot swallow medications or there is a fear of adequate drug
delivery through the gut and stomach. (5)(6)
Examples of drugs available in suppository include drugs for motion
sickness, constipation, asthma, fever, Nausea, haemorrhoids, Anxiety, pain,
mental illness and some allergies to mention but few. (5)(6)(7)
FIGURE….
FIGURE…..
AVERAGE LENGTH OF
SUPPOSITORIES
FIGURE….
GELLY SEMI-SOLID TYPE
SUPPOSITORY
FIGURE….
PICTURES OF PACKAGED SUPPOSITORIES
FIGURE….
FIGURE….
FIGURE….
EXAMPLES OF COMMERCIAL
SUPPOSITORIES
RESULTS
TABLE ……
QUALITY CONTROL
APPEARANCE
APPEARA-NCE
PEG
4000
PEG
6000
WITEPSOL
COCOA
BUTTER
COLOUR
TRANSLUCENT
WHITE
TRANSLUCENT WHITE
WHITE
YELLOWISH CREAM
ODOUR
ODOURLESS
ODOURLESS
ODOUR-LESS
CHARACTE-RISTIC
ODOUR
SHAPE
BULLET
SHAPE
BULLET
SHAPE
BULLET
SHAPE
BULLET
SHAPE
SURFACE
SMOOTH
SMOOTH
SMOOTH
SMOOTH
Appearance: – The four different types of suppository prepared was
subjected to a suppository quality control, and under the appearance four major
things were checked. Which includes the Colour, the Odour, the surface
condition and also the shape.
The colour of
the polyethylene glycols changed from white to colourless when heated and to a
mild translucent white when cooled. The colour changes where same for the
polyethylene glycol 4000 and the polyethylene glycol 6000. For the Witepsol the
colour changes from white to colourless when heated and back to white when
cooled. The cocoa butter maintained a yellowish-cream colour from the solid
state to the melted and cooled phase, it was melted at a temperature below
35degrees so no drastic change in colour was observed during the phase changes.
Also, fissuring, the brilliance, sedimentation, cracks, pitting, axial cavity,
holes, dullness, exudation, air bubbles, mottling and dark regions, migration
of active pharmaceutical ingredients. where also checked. Longitudinal splitting of
the samples was done to observe the inside.
Weight uniformity/variation
TABLE …….
QUALITY CONTROL
WEIGHT UNIFORMITY
SAMPLES
WEIGHT
PEG 4000
(grams)
PEG 6000
(grams)
WITEPSOL
(grams)
COCOA BUTTER
(grams)
1ST SAMPLE
4.44
4.39
3.56
3.48
2ND SAMPLE
4.46
4.39
3.54
3.48
3RD SAMPLE
4.45
4.40
3.54
3.47
4TH SAMPLE
4.47
4.42
3.55
3.48
5TH
SAMPLE
4.43
4.41
3.54
3.48
AVERAGE WEIGHT
4.45
4.40
3.55
3.48
Weight uniformity test was not performed due to quantity of sample
used. 5 samples were made for each batch
Volume contraction is one
of the major challenges faced in making suppositories. Due to the high
expansion and contraction nature of most suppository bases, on solidification
the volume of the suppositories decreases and moves away from the mould. It has
the advantage of moving away from the mould, which facilitates easy removal
from the mould. It gives a lot of challenges especially the hole forming effect
at the open end of the suppository, which give rise to complications like
weight variations and an unacceptable appearance of the product.
This problem can actually
be addresses by pouring excess on top of the mould that has been heated to a
similar temperature, by over-filling the moulds and scraping off from the base
top of the mould which will thus remove the hole part or finally by allowing
the heated suppository to cool to a still pourable temperature and thus reduces
the overall contraction. (6)(7)
Figure….
Figure….
Figure….
First,
second and third picture showing the cooling stages (solidification)
Figure…..
Fourth picture
illustrating how the excess on top containing the hole should be removed
TABLE….
QUALITY CONTROL
MELTING TIME
SAMPLES
PEG 4000
(MINUTES)
PEG 6000
(MINUTES)
WITEPSOL
(MINUTES)
COCOA BUTTER (MINUTES)
1st SAMPLE
55:09:46
44:28:38
25:00:41
17:59:21
2nd SAMPLE
53:23:60
46:07:06
23:41:54
16:58:14
3rd SAMPLE
51:05:41
43:32:55
25:10:13
16:23:44
4th SAMPLE
52:33:43
41:42:21
27:43:15
17:11:44
AVERAGE
53:35
44:17
25:23
17:27
Melting
time is basically the time requires for a suppository to completely melt or
dissolves once inserted into the body cavity. The normal body temperature of 37oC
was
mimicked using a running water bath and the time it takes for the suppository
to completely dissolve or melt was observed and recorded. The experiment was
repeated four times to find the average melting time of the different sample
prepared.
