This document provides an overview of suppositories including: - Definition: Suppositories are solid or semi-solid dosage forms meant to melt or dissolve in body cavities to deliver medication locally or systemically. - Types include rectal, vaginal, nasal, urethral, and ear suppositories. - Advantages include ease of administration to certain patients and targeted delivery to specific body cavities. Disadvantages include potential embarrassment and need for special storage conditions. - Common bases include fatty bases like cocoa butter and hydrophilic bases like gelatin that melt at body temperature to release the drug.

1. Pharmaceutics
B. Pharma
1st Semester
Unit -4
Chapter -1 Suppositories
Presented by – Nikita Gupta
(Assistant Professor )

2. Syllabus
• Suppositories: Definition
• Types
• Advantages
• Disadvantages
• Types of bases
• Methods of preparations
• Displacement value & its calculations
• Evaluation of suppositories.

3. Definition
Suppositories are solid or semisolid dosage form of medicament
for insertion into body cavity like rectum, vaginal, urethral tract
or nasal cavity.
They are designed to melt, disintegrate or dissolve at body
temperature and release the medicament for local, systemic or
mechanical action.

4. Type of suppositories :
(1) Rectal Suppositories:- These are meant for introduction into rectum
for their systemic effect. Generally made from Theobroma oil.
available in various size (weight about 1 to 2 g)
(2) Vaginal Suppositories: - These are meant for introduction in vagina
also known as pessaries (longer than suppositories) Vaginal
Suppositories may be conical, rod-shaped or wedge shaped (weight
about 4 to 8 g)
(3) Nasal Suppositories:- These are meant for introduction in nasal
cavity also known as nasal bougies These are thin and cylindrical
in shape always prepared with glycero-gelatin base. (9-10 cm long,
weight about 1 g)

5. (4) Urethral Suppositories - These are meant for introduction in
urethra also known as urethral bougies. These are thin, long and
cylindrical. (weight about 2 to 4g)
(5) Ear Cones: There are meant for introduction in ear also known
as aurinaria. These are thin, long and cylindrical in shape (Weight
about 1g)

6. Advantages
1)They can be easily administered to children, old persons and to
unconscious patients who can not swallow drug easily.
(2) These are inserted into body cavity to produce local effect.
3) These are inserted into rectum to promote evacuation of bowl.
(4) It is suitable for drugs which produce irritant effect in GIŤ.
(5) The drugs in suppositories are slowly absorbed → giving sustained
action.
(6) Suppositories are unit dosage form of drug.
(7) It avoid first pass effect.

7. Disadvantages
1. The irritant drugs can not be administered.
2. Suppositories cause embarrassment to patient.
3. Need special storage conditions (Low temp.) → 10-20°C.
4. These can not be prepared easily

8. Suppository Bases
The ideal suppository base should –
• Nontoxic and non irritating to mucous membranes.
• compatible with a variety of drugs.
• The base melts or dissolves in rectal fluids/body cavities.
• The base should be stable on storage
• It should not bind or otherwise interfere with the release or absorption
of drug substances.

10. Suppository bases are classified into two major categories
1. Fatty suppository bases
2. Hydrophilic suppository base
• Water-soluble/ water miscible bases
• Emulsifying base

11. S. No. Fatty base Properties
1.
Theobroma oil / coca
butter
– Most suitable for
rectal suppository
– Mixture of
Glyceryl ester of
different unsaturated
Fatty acids.
-MP range:
2.
Emulsified
Thepbroma oil
–
3. Hydrogenated oil
1. Fatty suppository bases

12. 2. Hydrophilic suppository base - Hydrophilic (Water-loving)
suppository base includes two categories –
A. Water-soluble Bases :- Water-soluble base favours more drug
release from suppository than Fatty/oil base.
Example - Glycero Gelatin base :- Gelatin + glycerine + water
BP: 14% w/w gelatin+ 70 % glycerine + water (q.s.)+ Drug
USP:- 20% w/w gelatin+ 70 % glycerine + water (q.s.) +Drug
PEG – Carbowaxes or macrogols & Polyglycols
B. Emulsifying Bases:– Synthetic bases.
Example – Witepsol, Massa estarinum, Massupol

13. Methods of preparations
1. Rolling method - It is an old method the suppository base is rolled
and desired shape is given by hand.
2. Hot procees or fusion method - The suppository base are method the
medicaments is incorporated filled in lubricant mould on colling
suppositories are formed.
3. Cold compression Suppository mould :- The ingredients are mixed
with an equal quantity of grated base add remaining quantity of base
and mixed Suppository mass is pulled in a cylinder. Cylinder is
closed and pressure is applied by Piston. When mould is filled
movable stop plate is removed. formed suppositories are ejected
(wipe off with clear cloth or filter paper). This method is useful for
thermolabile drugs.

14. Displacement value & its calculations
Displacement values - The volume of suppository for particular mould
is uniform but its weight will vary because of difference in dimity of
base and medicament used. for this displacement value of medicament
is taken in consideration.
Displacement value is defined as the quantity of drug which displace
one part of the base.
The displacement value of a given medicament can be determined by
the quantity of drug which displace one part the base.

15. The displacement value of a given medicament can be determined as-
1) Prepare and weight 6 suppositories containing base = a gm.
2) Prepare and weight 6 suppositories containing, say 40% drug = b g
3) Calculate amount of base in medicated suppositories 60 x b /100 =
c g
4) Calculate amount of drug in medicated suppositories = 40 x b
/100= d g
5) Calculate the amount of base displaced by dg d = (a-c) gm drug.
So, displacement value of drug : d = a-c

16. • Method of Preparation
• Thoroughly clean and lubricate the mould with suitable lubricant and
in inverted position on ice and drain required quantity of base is
added in Heat china dish (taking into account the displacement value
of medicament
• Stop heating when 2/3 of base melts and stir untill whole of the base
melts. (to avoid over heating)
• Place the weight quantity of medicament and about half of melted
base on a ointment tile. (mix throughly to get homogenous mass) and
transfer it in china dish.

17. • Warm the china dish on water bath for few seconds to get pourable
mass.
• Pour the melted mass into suppository mould placed over ice, fill
each mould to overflowing.
• Remove the excess mass with sharp knife or blade when the mass is
properly set.
• Keep the mould over, ice or in cool place for 10-15 min.
• Open the mould and remove the suppositories (Wipe off with clear
cloth or filter paper).
• Wrap the individual suppository in a wax paper.

18. Evaluation of suppositories
1.Uniformity of weight
2.Disintegration test
3.Content uniformity test
4.Melting point determination test
5.Liquefaction time (softening)
6.General appearance test
7.Assay of active contents
8.Test of drug uptake/ absorption in to blood steam

19. 1. Uniformity of Weight –
• Weigh 20 suppositories individually. Determine their average
weight.
• Not more than two of individual weights should deviate from the
average weight more than 5% and none deviates by more than 10%.
2. Disintegration Test -
It is the amount of dosage form that gets dissolved in body fluid in
unit time. It is a measure of the rate of drug release from the
suppository.

20. 3. Content Uniformity Test -
Take 10 suppositories; determine the active ingredients of each of
the 10 suppositories by using a suitable analytical method.
If not more than one of the individual values thus obtained is
outside the limit i.e.% of the average value and
none of them is outside the limit i.e. 25% of the average value.
Repeat the test by using another 20 suppositories taken at random.
If out of 30 suppositories not more than 3 individual values are
outside the limit 15% of the average values and none is
outside the limit 25% of the average value, then the test is ok,
otherwise failed

21. 4. Melting Point Determination Test -
Both micro melting range and micro melting range are determined as
follows:
(a) Macromelting range
It is a measure of the thermal stability of the suppository. It is the
time taken by the entire suppository to melt in a constant temperature
water bath. The test is conducted using the tablet disintegration
apparatus. The suppository is immersed in a constant water bath.
Finally, the melting range is recorded.
(b) Micromelting range
The melting range of the fatty base is measured in capillary tubes.

22. 5. Liquefaction time (softening)
Softening time is the time for which the suppository melts
completely at a definite temperature. This test measures the
softening time of suppositories which indicates the hardness of the
base.
6. General Appearance
All the suppositories should be uniform in size and shape. They
should have an elegant appearance. Individual suppositories should
be examined for cracks and pits due to the entrapment of air in the
molten mass.

23. 7. Assay of active content
Official limit for the active contents is 95- 105%
8. Test of drug uptake/ absorption in to blood steam
Both in-vitro and in-vivo tests should be conducted to assess the amount
of drug absorbed into the systemic circulation.
(a) In-Vitro test
The test conditions should be similar to those inside the human body.
The dissolution apparatus is used which consists of simulated gastric
and simulated intestinal fluids. A definite number of suppositories are
placed in the apparatus.

24. Aliquot portions of the dissolution medium are withdrawn at definite
intervals of time and drug uptake is measured using a U.V.
spectrophotometer.
(b) In-Vivo test
This test is carried on animals or human volunteers. The suppository
is placed in the intended body cavity. At regular intervals of time,
blood samples are collected and the amount of drug present is
determined

25. Pharmaceutics
Unit -4
Chapter – 2
Pharmaceutical incompatibilities
Presented by – Nikita Gupta

26. Syllabus
• Pharmaceutical incompatibilities
• Definition
• Classification
• Physical
• Chemical
• Therapeutic incompatibilities

27. Pharmaceutical incompatibilities -
It is defined as when two or more ingredients of a
prescription are mixed together, the undesired changes that
may takes place in the physical, chemical or therapeutic
properties of the medicament is termed as incompatibility.

28. 1. Physical Incompatibility - When two or more than two
substances are combined together, physical changes take place
and an unacceptable product is formed.
Physical incompatibility involves interaction between two or
more substance which leads to change in color, odor, taste,
viscosity & morphology.
These changes which occurs as a result of physical
incompatibility are usually visible and can be easily corrected
by applying the pharmaceutical skill to obtain a product of
uniform dosage.

29. ➢ Change the order or mixing of the prescription
➢ Emulsification
➢ Adding of suspending agent
➢ Change in the form of ingredients
➢ By adding, substitution or omission of therapeutically inactive
ingredient
❖ Examples of physical incompatibilities
➢ Immiscibility
➢ Insolubility
➢ Precipitation

30. Physical incompatibilities may be corrected by using any one or
more of the following method.
1. Immiscibility Oils and water immiscible with each other. They
can be made miscible with water by emulsification.
Example:
Castor oil.....15ml
Water.......60ml
Make an emulsion.
Note-In this prescription castor oil is immiscible with water. To
overcome this incompatibility an emulsifying agent is used to make a
good emulsion

32. 2. Insolubility -Insolubility means the inability of material to
dissolve in a particular system.
The major of incompatibilities are due to insolubility of the
inorganic as well as organic compounds in a particular solvent.
Example:
Ephedrine sulphate............0.25gm
Menthol..................0.02ml
Liquid paraffin (sufficient to make).............30ml
Note-The ephedrine sulphate is an alkaloidal salt and is not soluble
in liquid paraffin, but anhydrous ephedrine is soluble in it. Hence
ephedrine sulphate is substituted with anhydrous ephedrine to make
a clear solution.

33. 3. Precipitation :- A drug in solution may be precipitated, if the
solvent in which it is insoluble is added to the solution.
Example: The resins are insoluble in water. When the tincture
containing resins is added in water, resin agglomerates forming in
diffusible precipitates.
Note-This can be prevented by slowly adding the undiluted
tincture with vigorous stirring to the diluted suspension Or By
adding some suitable thickening agent.

34. 4. Liquefaction - When certain low melting point solids are mixed
together, a liquid or soft mass known as "eutectic mixture" is
produced.
This occurs due to the lowering of the melting point of mixture to
below room temperature and liberation of water of hydration.
The medicaments showing this type of behaviour are camphor,
menthol, thymol, phenol, chloral hydrate and aspirin.
Example –
Menthol...... Camphor........5g
Ammonium chloride.......30g
Light magnesium carbonate.......60g

35. In this prescription menthol, camphor and ammonia chloride get
liquefied on mixing with each other.
To dispense this prescription, menthol camphor and ammonium
chloride are triturated together to form liquid.
Add light magnesium carbonate and mix it thoroughly to make
free flowing powder.

36. 2. Chemical Incompatibilities - Chemical incompatibility may be
as a result of chemical interactions between the ingredients of a
prescription and a toxic or inactive product may be formed.
Chemical incompatibilities often occur due to
oxidation-reduction
Acid base hydrolysis
combination reaction.
Note- These reactions may be noticed by precipitation effervescences,
decomposition, color change or by explosion.

37. Types –
1-Tolerated: In tolerated incompatibilities, the chemical interaction can
be minimized by changing the order of mixing or mixing the solutions
in dilute forms but no alteration is made in the formulation.
2-Adjusted: In adjusted incompatibilities the chemical interaction can
be prevented by addition or substitution of one of the reacting
ingredients of a prescription with another of equal therapeutic value.
Example: Caffeine citrate can be substituted with caffeine in sodium
salicylate and caffeine citrate mixture.

38. Chemical Incompatibilities –
Intentional :- When the prescriber knowingly prescribes the
incompatibility drugs.
Unintentional :- When the prescriber prescribes the drugs without
knowing that there is incompatibility between the prescribed
drugs.

39. The precipitate form through the chemical incompatibility may be
diffusible or in diffusible.
The method A and B is followed in dispensing the prescription
yielding diffusible and in diffusible precipitates respectively.
Examples 1. Precipitate yielding Interactions :- The method is
followed when diffusible precipitates are formed in very small
quantity. Divide the vehicle into two equal portions. Dissolve one of
the reacting substances in one of the portion and the other in the other
portion. Mix the two portions by slowly adding one portion to the
other by rapid stirring.

40. 2. Soluble Iodides Incompatibilities - Iodides undergo oxidation
forming iodine which is an undesirable product.
Example :-
Oxidation of iodides (ferrous iodide) with potassium chlorate.
When soluble iodides react with potassium chloride, free iodine is
liberated.
To prevent the incompatibility, the two reacting substances must be
dispensed separately.

41. 3. Chemical incompatibility causing evolution of carbon dioxide -
Example :- Bismuth sub-nitrate when combined with sodium
bicarbonate in the presence of water, carbon dioxide gas is liberated
due to the following reaction.
2BIONO3 + 2NaHCO3(BIO)2CO3 + 2NaNO3 + CO2 + H2O
4. Incompatibility of emulsifying agents :- Emulsion prepared with
alkali metal, ammonia and triethanolamine soaps are incompatible with
salts producing polyvalent cations (Fe+3 cation, Ca+2 cation etc)
Due to double decomposition, a polyvalent soap is formed which
inverts the emulsion. An emulsion is "inverted" when the dispersed
phase becomes the continuous phase and vice versa).

42. 5. Colour Stability of Dyes :- The colour of the most of the dyes
used in pharmaceutical formulation is influenced by their
ionization which depends on pH of the solution. The
phenolphthalein dye is color less in acid solution but red in
alkaline mixture.

43. 3. Therapeutic incompatibility - It may be the result of
prescribing certain drugs to the patient with the intention to produce a
specific degree of action but the nature or the intensity of the action
produced is different from that intended by the prescriber.
Causes :- It may be due to the administration of –
➢ Overdose or improper dose of a single drug
➢ Improper Dosage form
➢ Contraindicated drug.

44. Example
Rx
Codeine phosphate............ 0.5 gm
Directions for Pharmacist :- Make powders.
Send such 10 powders.
1 dose to be taken at bed time
Note :- This is an example of over dosage. Probably, the physician
intended to write 5mg and yet prescribed 500mg of codeine
phosphate. The prescription must be referred back to prescriber.

45. ThankYou