B.Pharm, Pharm D

1. SUPPOSITORIES AND PESSARIES
NAGAM SANTHI PRIYA
Department of pharmaceutics

2. CONTENTS
Introduction
Classification of suppositories
Advantages & disadvantages
Ideal properties of suppositories
Formulation of suppositories
Preparation of suppositories
Evaluation & packing of suppositories
2

3. Introduction
• Suppositories are the solid dosage forms meant to be
inserted into the body cavities like rectum , urethra
and vagina ,where they melt or soften to release the
drugs and exert local or systemic effects.
3

4. 4
Anatomy and Physiology of Rectum
• The rectum is about 15
to 20 cm long.
• It hooks up with the
sigmoid colon to the
north and with the anal
canal to the south.
• It is a hollow organ with
a relatively flat wall
surface, without villi and
with only three major
folds, the rectal valves

5. 5
Anatomy and Physiology of Rectum
• The terminal 2 to 3 cm of
the rectum is called the
anal canal.
• The opening of the anal
canal to the exterior is
called the anus.
• The anus is controlled by
an internal sphincter of
smooth muscle and an
external sphincter of
skeletal muscle.

6. 6
Anatomy and Physiology of Rectum
• Under normal conditions, the rectum is empty
and filling provokes a defecation reflex which
under voluntary control.
• The transverse folds in rectum keep stool in
place until the person is ready to go to the
bathroom. Then, stool enters the lower
rectum, moves into the anal canal, and then
passes through the anus on its way out.
• Rectum contains about 2 to 3 ml of mucous,
which has a pH of 7.4 and little buffering
capacity.

7. 7
Absorption of drugs from the rectum
• Medicaments absorbed in the lower part of the
rectum are delivered directly into the systemic
circulation, thus avoiding any first-pass
metabolism.
• However, it has been found that suppositories
can settle high enough in the rectum to allow at
least some drug absorption into the superior
vein.
• Thus keeping the drug in the lower part of the
rectum would be advisable.

8. 8
Absorption of drugs from the rectum
• Insertion of a suppository into the rectum results in a
chain of effects leading to the bioavailability of the
drug.
• Depending on the character of the base, a
suppository will either dissolve in the rectal fluid or
melt on the mucous layer.
• Since the volume of rectal fluid is so small, complete
dissolution of the base require extra water.

9. 9
Absorption of drugs from the rectum
• Due to osmotic effects of the dissolved base,
water is attracted with a painful sensation for
the patient.
• Independent on the base type, dissolved
drugs in the suppository will diffuse out
towards the rectal membrane.
• The process of absorption will be passive
diffusion.

10. Classification Of Suppositories
• Rectal suppositories
• Vaginal suppositories ( PESSARIES )
• Urethral suppositories ( BOUGIES )
• Nasal suppositories
• Ear suppositories
10

11. VAGINAL SUPPOSITORY
• They are also called as PESSARIES.
• SHAPE : globular, oviform or cone-shaped.
• Used occasionally.
• Intended for local effects like contraceptives,
antiseptics in feminine hygiene
11

12. URETHRAL SUPPOSITORY
• Also called as BOUGIES .
• SHAPE – slender, pencil-shaped.
• Intended for anti-bacterial or as a local anesthetic
preparative for urethral examination.
• Occasionally used.
12

13. RECTAL SUPPOSITORY
• Intended for local action to relieve
constipation, irritation, itching and
inflammatory associated to hemorrhoids
13

14. Classification Of Suppositories Via
Position Of Action
LOCAL EFFECT :
• In case of pain, itching and hemorrhoid.
• Locally active drugs include astringents,
antiseptics, local anesthetics, vasoconstrictors,
anti-inflammatory,
soothing and protective agents and some laxatives.
SYSTEMIC EFFECT :
• Anti-asthmatics, anti rheumatics, anti-pyretic and
analgesics
14

15. ADVANTAGES
• EASILY ADMINSTERED to children, old
persons, to unconscious or sometimes to mentally
unstable persons who cannot swallow the drug.
• Convenient mode of administration for drugs
which irritate the GIT, causing vomiting and
destroyed in acidic ph of stomach and enzymes of
GIT.
• FASTER ONSET OF ACTION as compared to
oral administration because absorption of drug
through rectal mucosa directly reaches blood
15

16. DISADVANTAGES
• They are not acceptable by the patients.
• The manufacturing process is difficult.
• The drugs which cause irritation to the mucous
membrane cannot be administered as
suppositories.
• Most of the suppositories should be stored at
low temperature10-20°c in a refrigerator ,
other wise the base gets liquified.
16

17. IDEAL PROPERTIES OF SUPPOSITORY BASES
• It should melt at body temperature or dissolve
or disperse in body fluids.
• It should release any medicament easily.
• It should keep its shape when being handled.
• It should be non-toxic and non-irritant to the
mucous membrane.
• It should be stable on storage and also stable if
heated above its M.P.
17

18. IDEAL PROPERTIES OF SUPPOSITORY BASES
• It should be easily molded and should not
adhere to the mold.
• It should possess good wetting and
emulsifying properties.
• It should be able to incorporate a high
percentage of water.
• It should be chemically and physically stable
18

19. IDEAL PROPERTIES OF SUPPOSITORY BASES
If the base is fatty, it has the following
additional requirements:
• Acid value is below 0.2.
• Saponification value ranges from 200 to 245.
• Iodine value is less than 7.
• The interval between melting point and
solidification point is small.

20. 20
Specifications of suppository bases
1- Origin and chemical composition
The source of origin (i.e. entirely natural
or synthetic or modified natural).
Physical and chemical incompatibilities
with additives (i.e. preservatives,
antioxidants and emulsifiers)

21. 21
Specifications of suppository bases
2- Melting range
Since fats do not have sharp melting
point, their melting characteristics are
expressed as a range indicating the
temperature at which the fat start to
melt and the temperature at which it is
completely melted.

22. 22
Specifications of suppository bases
3- Solidification point
This value indicates the time required for base
solidification when it is chilled in the mold.
If the interval between the melting range and
solidification point is 10ºC or more, the time
required for solidification may have to be
shortened for a more efficient manufacturing
procedure by augmenting refrigeration.

23. 23
Specifications of suppository bases
4- Saponification value
The number of milligrams of potassium
hydroxide required to neutralize the free
acids and to saponify the esters
contained in 1 gm of fat is an indication
of the type of glyceride (mono- or tri-) as
well as the amount of glyceride present.

24. 24
Specifications of suppository bases
5- Iodine value
This value express the number of grams
of iodine that react with 100 gm of fat or
other unsaturated material.
The possibility of decomposition by
moisture, acids, and oxygen (leads to
rancidity in fats) increases with high
iodine values.

25. 25
Specifications of suppository bases
6- Water number
The amount of water in grams, which
can be incorporated in 100 gm of fat is
expressed by this value.
The water number can be increased by
addition of surface active agents.

26. 26
Specifications of suppository bases
7- Acid value
The number of milligrams of potassium hydroxide
required to neutralize the free acid in 1 gm of
substance is expressed by this value.
Low acid values or complete absence of acid are
important for good suppository bases.
Free acids complicate formulation work, because
they react with other ingredients and can also cause
irritation when in contact with mucous membranes.

27. Formulation of suppositories
1. Bases
2. Anti- oxidants
3. Emulsifying agents
4. Hardening agents
5. Preservatives
6. Thickening agents
7. Plasticizers
27

28. 1. Bases :They are of two types
a. Hydrophilic bases
i. water-dispersible bases:
 properties: These are mixtures of non-ionic surfactants
which are chemically related to polyethylene glycols.
 These are used alone or in combination with other types of
bases
 Cellulose derivatives like methylcellulose sodium carboxy
methylcellulose also come under this class.
Eg; polyoxyethylene sorbitan fatty acid (tween)
28
SUPPOSITORY BASES

29. TYPES OF BASES
OLEAGINOUS BASES :
1. Cocoa butter
2. Cocoa butter substitutes or synthetic fats
HYDROPHILIC BASES
1. Water soluble bases :
 Glycerogelatin
 Soap Glycerin
 Macrogol Bases
2.Water dispersible bases : Emulsifying bases

30. OLEAGINOUS BASES
1. Cocoa butter or theobroma oil is naturally occuring triglyceride
2. Solid fat
3. Melts at 30 - 35°c
4. Forms emollient oily liquid in the body cavities and allows drug release

31. Limitations of cocoa butter
• Undergoes rancidification
• Undergoes temperature dependent polymorphism
• Polymorphs of cocoa butter
• Cocoa Butter Slow Heating And Slow Cooling β ( 34-35°c)
α 20-22°c β‘ 24-28°c β ( 34-35°c)
• Cocoa Butter Over Heating And Rapid Cooling ɼ ( 15-18°c)
• Poorly miscible with body fluids , poor water holding capacity
• Certain drugs like volatile oils reduce its M.P-minimized by 4% bees wax and 20% spermaciti
• Lower contractibility – adhere to moulds
• Low solidification – sediments insoluble drug
• Disagreeble odor ,
• Leaks from the body cavities
• Melts in warm climates
• Leaks from body cavities

32. SYNTHETIC FATTY BASES
Hydrogenated vegetable oils
• Ex: coconut oil , palm kernal oil , cottonseed
oil, peanut oil , fractionated palm kernal oil
• Hydrogenation increases resistance to
rancidification and increases chemical
inertness

33. Merits over cocoa butter
1. Due to saturated nature these bases are less prone to rancidity
2. Donot exhibit polymorphism on heating
3. Exhibit good water absorption and emulsifying properties
4. Small melting range
5. Solidify rapidly in the mould
6. Shrink sufficiently making lubrication unnecessary
7. Melting points don’t effect drug release
8. Suppositories of these bases – WHITE,SMOOTH, ODORLESS

34. HYDROPHILIC BASES
• Drug release from these bases involves – DISSOLUTION OF
BASE
• Hydrophilic nature contributes to drug release and absorption
• Higher melting points – PREVENTS problems like
compounding , handling , storage

35. Water soluble bases
1. Glycero-gelatin
 This occurs as a gel .It is a mixture of gelatin, glycerol and water.
 According to B.P the composition of the base is gelatin-14%w/w ,glycerol-
70%w/w
 To get a stiff mass, the quantity of gelatin should be increased to32%w/w and
that of glycerol reduced to 40%w/w.
GELATIN GLYCERIN PHARMACOEPIA
14 70 B.P
16 70 I.P
20 70 U.S.P
32.5 40 B.P.C

36. GLYCERO-GELATIN SUPPOSITORIES
ADV:
• Laxative purpose
• Vaginal therapy
Limitations :
1. Glycerin is hygroscopic – cause mucosal irritation
2. Gelatin – incompatibile to drugs like tannic acid,ferric chloride
3. Preparation of base is time consuming
4. Tendency to stick to the mould

37. MACROGOL BASES
1. These are polyethylene glycols which range from liquids , semisolids ,waxy
solids as per molecular weight
2. Due to their hygroscopic nature PEG Bases dehydrate mucosa to produce
irritation
3. To reduce that discomfort they are dipped in water before insertion
4. Incorporation of 10-20% water in base also overcomes mucosal irritation
and facilitates addition of water soluble bases

38. Merits
1. Application in tropical climates
2. Good solvent properties
3. They become soft and release medicament slowly for
longer period of time
4. Highly viscous – no leakage of drugs
5. Suppositories - Attractive , clean , smooth surfaces
6. Donot hydrolyse , rancidify
7. Donot support microbial growth

39. Limitations
• Complexation of some drugs with macrogols
• Formation of brittle and granular
suppositories due to crystallization of
substances
• Incompatible with drugs like tannins , phenol
and plastic containers

40. PEG 6000 30% It is harder
It has higher melting point
It dissolves slowly
PEG 1540 70%
PEG 4000 60% 1. It has intermediate
characterisitics
2. It can be used as a
general purpose water
soluble suppository
base
PEG 1000 30%
PEG 400 10%
PEG1000 96% 1. It is low melting point
soft base
2. Dissolves readily
3. Requires refrigeration
during summer
months
PEG4000 4%

41. WATER DISPERSIBLE BASES
1. Include NON-IONIC SURFACTANTS like Tween , span
2. Act as self emulsifying agents in water forming soft , bulky , non irritant
emulsions
3. Promote drug release and drug absorption
Satisfy criteria like
 Temperature stability
 Non toxicity
 Non greasy
 Good moulding ability
 Drug compatibility
 Resistance to microbial growth
 Increased contact with mucous membrane

43. Anti-oxidants
• They protect the drug and the base from getting degraded due to oxidation.
• Examples :
i. Ethyl or propyl gallate
ii. Ascorbic acid and its esters
iii. Hydroquinone
iv. Tocopherols
43

44. Emulsifying agents
 They increase the water-absorbing capacity of fatty
bases. This makes it possible to include aqueous
solutions in the formulation.
 Examples : polysorbates (tween 61)
 Wool alcohol ,wool fat
Hardening agents:
 These are included in those formulations where the
melting point of the base is decreased by the drug.
44

45. 45
These agents bring the melting point to normal.
Examples : macrogols with high molecular weight.
Preservatives : They should be included in suppositories
which contain water soluble bases to prevent microbial
growth.
Examples :methyl paraben , propyl paraben
Thickening Agents: They increase the viscosity of molten
base and prevent sedimentation of suspended insoluble
solids.
Examples: Aluminium monostearate ,collodial silica
,magnesium stearate.

46. Plasticizers
• They impart plasticity to the fatty base and
makes it less brittle.
• Examples :
i. Castor oil
ii. Glycerine or propylene glycol
iii. Glycol
iv. Tween 80
v. Tween 85
46

47. Preparation of suppositories

48. PREPARATION METHODS
• Suppositories are prepared by four methods:-
1. HAND MOLDING METHOD
2. COMPRESSION MOLDING
METHOD
3. POUR MOLDING METHOD
4. AUTOMATIC MOLDING METHOD.

49. HAND MOLD SUPPOSITORIES
Mix measured quantity of medicinal substances with sufficient theobroma oil
Triturate soften with diluted alcohol and rub until smooth paste is formed
Add remaining qty of theobroma oil and add wool fat for consistency
Remove the mass from the mortar and pestle
Transfer to a piece of filter paper and keep in hands during the kneading and rolling procedure
Roll the mass by quick rotating movements of the hands and place on a pill tile
Rolling the mass on the tile with a flat board forms a cylindrical suppository
Cut into pieces by spatula
Give the shape by rolling one end on the tile with spatula
Pack in butter paper or in a proper container and store in a cool place

50.  Advantages:-
 Suitable for thermo labile ingredients.
 Economical for the manufacture of small number
of suppositories.
 Disadvantages:-
 No uniformity in shape & size of suppository.
HAND MOLD SUPPOSITORIES

51. COMPRESSION MOLD SUPPOSITORIES [ COLD COMPRESSION]
Mix theobroma oil and drug
Mixture is forced into a mold under pressure , using a wheel
operated press
Mold is removed , opened , replaced
On large scale , cold compression machines are hydraulically
operated by water – jacketed cooling and screw fed

52. Advantages:-
Suitable for thermo labile drugs.
No possibility of settling of the insoluble solids in
base.
Disadvantages:-
Rate of production is low so not suitable for large
scale.
Air get entrapped in the mass which leads to
oxidation of ingredients.
COMPRESSION MOLD SUPPOSITORIES [ COLD COMPRESSION]

53. FUSION OR MELT OR POUR MOLD
SUPPOSITORIES
Drug is dispersed or dissolved in a melted suppository base
Pour the mixture into a suppository molds and allow cooling
in ice bath
Finished suppositories are removed by opening the mold
Various types and sizes of molds are available for preparation
of suppositories . Molds are made of aluminium alloys , brass
or plastic and are available in 6 to several hundred cavities

54.  Incorporation of drug:
 Solid:-drug and additive powder mixed on warm tile
 Semisolid:-triturate the ingredients on warm tile with water.
this decrease the viscosity and give homogenous liquid.
 Liquid:-
 Volatile liquid:-they can be added to the molten base directly.
 Nonvolatile liquid:- same as semisolid.
FUSION OR MELT OR POUR MOLD SUPPOSITORIES

55. • All filling , ejection and mold cleaning
operations are fully automatic
• Output – 3500 to 6000 suppositories per hour
• Suppository mold is lubricated with brushing
or spraying and then filled to a slight excess
• Excess material is removed after the mass gets
solidified and collected for re – use
AUTOMATIC MOLD MACHINE

56. PACK AND LABEL
Packing of suppositories:-
It can be foiled in aluminum ,plastic, paper, tin strip.
Modern packing machine: nearly 8000 suppositories can
be wrapped per hour.
In packing molding : In this ,the suppository mass is directly
move into the series of molds which are made up of plastic.
After cooling , excess mass is trimmed of . By this technique
12,000 to 15,000 suppositories can be produce per hour.
Disposable molds:- They are suitable for tropical climate.
They are made up of plastic or aluminum .
Labeling:-
“store in a cool place.”
“Not to be taken orally.”

57. DISPLACEMENT VALUE
The volume of suppository from particular mold is
uniform but its weight will vary because the density of
medicament usually differ from the density of base .
To prepare product accurately , allowance must be
made for the change in density of mass due to added
medicament
The most convenient way of making this allowance is
to use the displacement value-“ THE NUMBER OF
PART BY THE WEIGHT OF MEDICAMENT THAT
DISPLACE THE ONE PART BY WEIGHT OF BASE”

58. Recent development(new trend in suppository)
Capsule suppositories
Coated suppositories
Layer suppositories
Tablet suppositories;
 Compressed tablet
 Effervescent base tablet

59. EVALUATION OF SUPPOSITORIES
Appearance
Uniformity of weight
Disintegration
Test for uniformity of drug content
Breaking test
Softening time
Test of melting range
 Test for Dissolution rate

60. APPEARANCE
• Odor
• Color
• Surface condition
• Shape
• They may contain several layers
• Instabilities are identified based on changes in
surface texture ,color,odor

61. WEIGHT VARIATION
• Weigh individually 20 suppositories
• Weigh 20 at a time
• Calculate average weight
• Limit: not more than 2 suppository differ from
the average weight by more than 5% and no
suppository differs from average weight by
more than 10%

62. HARDNESS or BREAKING TEST
1. PLACE THE SUPPOSITORY IN THE INSTRUMENT
2. ADD 600g, leave it for 1min
3. If not broken add 200 gm every 1minute untill
suppository is broken

63. MELTING RANGE TEST
• Macro-melting range is a measure of the time it
takes for the entire suppository to melt when
immersed in a constant-temperature (37ºC)
water bath.
• USP tablet disintegration apparatus is used
THE SUPPOSITORY IS CONSIDERED DISINTERGRATED if:
• It is completely dissolved
• Become soft “change in shape” with formation of
core which is not resistant to pressure with glass
rod

64. Disintegration
• For each 3 suppositories examine the state of
the sample
1. After 30minutes – fat-based suppository
2. After 60min – water –based suppository

65. Uniformity of mass
• Not more than 2 of the individual masses
should deviate from the average mass by
more than 5 % , and none by more than 10%

66. Softening time test
• u tube is partially immersed in a constant
bath and is maintained at a temperature
between 35 to 37 c
• There is a constriction in the tube in which the
suppository is kept and above is a glass rod is
kept
• Time taken for a glass rod to go through the
suppository and reach the constriction is
known as liquefaction time or softening time

67. Dissolution test
• Wire mesh basket or dialysis tubing is used for
invitro release from suppositories

68. Stability testing
• Cocoa butter suppositories on storage , BLOOM
i.e they form a white powdery deposit on the
surface
• This can be avoided by storing them at uniform
cool temperatures and by wrapping them in foils
• Fat based suppositories harden on storage [ shift
in melting range to become more stable
polymorphic form of base ]
• Softening time test and DC can be used to test
stability

69. Stability problems
RESPONSIBLE FACTORS :
• Water
• Incompatibilities
• Viscosity
• Blooming
• Hardening
• Rancidity and oxidation

70. Water
• Presence of water accelerates oxidation of fats
• Dissolved solids will crystallize if water
evaporates
• Liable to microbial growth
• Promotes interation of ingredients
• Glycerinated gelatin suppositories may lose
moisture in dry climates

71. Incompatibilities
• PEG bases : silver salts,tannic
acid,aminopyrine,quinine,ichthammolm,benz
ocaine,aspirin,camphor – crystallizes out and
leading to ointment like consistency
• Aspirin complexes with PEG but stable with
cocoa butter

72. Viscosity
• Not enough viscosity – settlement of
medicament in moulds leading to non uniform
drug content
• If viscosity changes occur they lead to changes
in suppositories during storage

73. Blooming
• White powdery deposit at the surface is
referred to as bloom
• It is avoided by wrapping of suppositories in
foils and storing them at low temperatures

74. Hardening
• This occours incase of oleogenous bases
• During their storage over a several months
results in elevated melting ponts (slow
crystallization) to more stable metamorphic
forms(Resulting in hard suppository)
• This is avoided by control of temperature
during manufacture and storage

75. Rancidity and oxidation
• Oleogenous bases under oxidation and
becomes rancid
• Use of antioxidants prevents this problem ex:
phenols,quinones,tocopherols,propyl gallate
and gallic acid,tannins and tannic acid,BHA
and BHT
• Suppositories may also interact with packing
materials and creates stabilty problems