A presentation on manufacturing and sterility test for ointments mainly for clinical pharmacy pharm D 4th year.

1. PRESENTED TO- PRESENTED BY-
DR. MEKHA MONSI KRISHNA MITTAL
ASSISTANT PROFESSOR
OINTMENTS

2. CONTENTS
1. INTRODUCTION
2. TYPES OF OINTMENTS
3. TYPES OF MEDICATED OINTMENTS
4. MEDICINAL USES OF OINTMENTS
5. TYPES OF OINTMENT BASES USED IN PREPARATION OF OINTMENTS:
6. METHODS OF PREPRATION OF OINTMENTS:
7. EVALUATION TESTS FOR OINTMENTS:
8. CHALLENGES IN OINTMENT MANUFACTURING

3. OINTMENTS
Any greasy or oily semi solid preparation, usually medicated, that
can be applied externally to the skin in order to heal, soothe or
protect it. It is a viscous semisolid preparation used topically on a
variety surfaces.
Drug ingredients can be dissolved, emulsified or suspended in the
ointment base. The word ointment comes from the latin ungere
meaning anoint with oil.

4. TYPES OF OINTMENTS
Medicated ointment
Non-medicated ointments
A) NON-MEDICATED OINTMENTS: These ointments do not contain any drugs. They are
useful as emollients, protectants. Example: Petroleum jelly.
B) MEDICATED OINTMENTS: These ointments contain drugs which show local or
systemic effects.

5. MEDICATED OINTMENTS ARE OF SEVERAL
SUB-TYPES:
• DERMATOLOGIC OINTMENTS
• OPHTHALMIC OINTMENTS
• RECTAL OINTMENTS
• VAGINAL OINTMENTS
• NASAL OINTMENTS

6. • DERMATOLOGIC OINTMENTS
These ointments are applied topically on the external skin. The
ointment is applied to the affected area as a thin layer and spread
evenly using gentle pressure with the fingertips. These are of three
types:
(1) Epidermic ointments: The drugs present in these type of ointments exert their
action on the epidermis of the skin. Example: Ketoconazole ointment.
(2) Endodermic ointments: The drugs present in these types of ointments exert their
action on the deeper layers of cutaneous tissue. Example: Demodex ointment.
(3) Diadermic ointments: The drugs present in these types of ointments enter into
the deeper layers of skin and finally in the systemic circulation and exert systemic
effects. Example: Nitroglycerine ointment.

7. • OPTHALMIC OINTMENTS
These are sterile preparations which are applied inside the lower eye lid. Only anhydrous bases
are used in their preparation. The ointment is applied as a narrow band of approximately 0.25
- 0.5 inch. Example: Sulfacetamide sodium ointment.
• RECTAL OINTMENTS
These are the ointments to be applied to the peri- anal or within the anal canal. The bases used
are combinations of PEG 300 and PEG 3350, cetyl alcohol and cetyl esters, wax, liquid
paraffin and white paraffin. Example: Benzocaine ointment.
• VAGINAL OINTMENTS
These ointments are applied to the vulvo-vaginal area or inside the vagina. As vagina is more
susceptible to infections, the ointment should be free from micro-organisms, moulds and yeasts.
Example: Candicidin ointment.
• NASAL OINTMENTS
These are used in the topical treatment of nasal mucosa. Drugs get absorbed into the general
circulation through the rich blood supply of the nasal lining. Example: lpratropium bromide
ointment.

8. MEDICINAL USES OF OINTMENTS
Ointments are used topically for several purposes, e.g., as protectants,
antiseptics, emollients, antipruritic, kerotolytics, and astringents.
In the case of a protective ointment, it serves to protect the skin against
moisture, air, sun rays and other external factors.
It is necessary that the ointment neither penetrates the human skin barriers
nor facilitates the absorption of substances through this barrier.
An antiseptic ointment is used to destroy or inhibit the growth of bacteria,
Frequently.
Bacterial infections are deeply seated; a base which has the capacity to either
penetrate or dissolve and release the medication effectively is therefore desired.
Ointments used for their emollient effect should be easy to apply, be non-greasy
and effectively penetrate the skin.

9. TYPES OF OINTMENT BASES USED IN
PREPARATION OF OINTMENTS:
There are five (5) classes or types of ointment bases which are differentiated
on the basis of their physical composition. These are
1. Oleaginous bases.
2. Absorption bases.
3. Water in oil emulsion bases.
4. Oil in water emulsion bases.
5. Water soluble or water miscible bases.

10. 1. OLEAGINOUS BASES:
These bases are fats, fixed oils, hydrocarbon or silicones.
They are anhydrous, greasy; non-washable does not absorb water and occlusive so it
increases the skin hydration by reducing the rate of loss of surface water.
They should not be applied to infected skin.
They are used as protectants, emollients, vehicles for hydrolysable drugs. Example: White
Petrolatum, White Ointment.

11. 2. ABSORPTION BASES:
Anhydrous but hydrophilic ointment bases, they can absorb several times their weight of
water to form water-in-oil emulsion.
They are non washable, not water soluble.
They used as protectants, emollients, vehicles for aqueous solutions, solids, and non-
hydrolysable drugs.
Example: Hydrophilic Petrolatum, Anhydrous Lanolin, AquabaseTM, Aquaphor®,
PolysorbR

12. 3. WATER IN OIL EMULSION BASES:
These are anhydrous, hydrophilic, absorbs water and non-water removable, with low
thermal conductivity and occlusive.
They have the same properties as the absorption bases.
They are used as emollients, cleansing creams, vehicles for solid, liquid, or non-
hydrolysable drugs.
Examples: Cold Cream type, Hydrous Lanolin, Rose Water Ointment, HydrocreamTM,
Eucerin®, Nivea®

13. 4. OIL IN WATER EMULSION BASES:
These bases are anhydrous, water soluble, absorb water and water washable.
They are either carbowaxes Polyethylene Glycols (PEGS) or hydrated gums (bentonite,
gelatin, cellulose derivatives).
They are used as drug vehicles.
Examples: PEG Ointment, PolybaseTM

14. 5. WATER SOLUBLE OR WATER MISCIBLE
BASES:
These bases are anhydrous, water soluble, absorb water and water washable.
They are either carbowaxes Polyethylene Glycols (PEGS) or hydrated gums (bentonite,
gelatin, cellulose derivatives).
They are used as drug vehicles.
Examples: PEG Ointment, PolybaseTM

15. METHODS OF PREPRATION OF OINTMENTS:
Ointments can be prepared by following methods
1. Levigation
2. Trituration
3. Fusion method
4. Emulsion method
5. Chemical reaction method

16. 1. LEVIGATION:
Finely powdered medicament is paced n a clean ointment slab or tile.
 Weigh the required quantities of ointment bases and keep it on different parts of slab.
Take a portion of base of about three times the volume of drug and levigate with the
help of ointment spatula until there is no solid particles found.
This can be checked by spreading as a thin layer on slab. Incorporate remaining quantity
of ointment base and levigate to get smooth ointment.
Examples: Sulphur ointment, boric acid ointment.

17. 2. TRITURATION:
This method is used for preparation of ointments in small scale industry.
It is used when base is soft in nature, medicament is a solid and insoluble in base in
small amount is incorporated in base.

18. 3. FUSION METHOD:
This method is used when an ointment containing a number of solid ingredients of
different melting points like bee's wax, steric acid and hard paraffin.
In small scale this method is carried out in porcelain dish which is heated on water
bath.
All the substance which have high melting point are melted in decreasing order of
melting point.
To above melted mass medicament is incorporated and is stirred. Example: cetrimide
ointment.

19. 4. EMULSION METHOD:
Oily substances are melted together in China dish at high temperature.
Water soluble substances are heated on water bath.
Suitable emulsifying agent is selected and is dissolved in aqueous or oily phases.
When both phases reach the same temperature then add the aqueous phase to oily
phase with stirring until a semi solid mass is formed.

20. 5. CHEMICAL REACTION METHOD:
In this type of method ointment is prepared by chemical reaction, medicament and
bases are made to react with each other to form ointment.
Example: Non- staining iodine ointment and strong mercuric nitrate ointment.

21. EVALUATION TESTS FOR OINTMENTS:
The different methods of evaluation of ointments are:-
1. Physical methods:
◦ Test of rate of absorption.
◦ Test of non-irritancy.
◦ Test of rate of penetration.
◦ Test of rate of drug release.
◦ Test of rheological properties.
◦ Test of content uniformity.
2. Microbiological methods:
◦ Test of microbial content.
◦ Test of preservative efficacy.

22. TEST OF RATE OFABSORPTION:
 Diadermic ointments are those from which the drug moves into deeper skin tissues
and finally into the systemic circulation.
Such ointments should be evaluated for the rate of absorption of drugs.
The ointment should be applied over a definite area of the skin by rubbing.
At regular intervals of time, serum and urine samples should be analysed for the
quantity of drug absorbed.
The rate of absorption i.e., the amount of drug absorbed per unit time should be more.

23. TEST OF NON-IRRITANCY:
The bases used in the formulation of ointments may cause irritation or allergic
reactions.
Non-irritancy of the preparation is evaluated by patch test. In this test 24 human
volunteers are selected.
Definite quantity of ointment is applied under occlusion daily on the back or volar
forearm for 21 days.
Daily the type of pharmacological action observed is noted.
No visible reaction or erythema or intense erythema with edema and vesicular erosion
should occur.

24. TEST OF RATE OF PENETRATION:
The rate of penetration of a semisolid dosage form is crucial in the onset and duration
of action of the drug.
Weighed quantity of the preparation should be applied over selected area of the skin for
a definite period of time.
Then the preparation left over is collected and weighed.
The difference between the initial and the final weights of the preparation gives the
amount of preparation penetrated through the skin and this when divided by the area
and time period of application gives the rate of penetration of the preparation.
The test should be repeated twice or thrice. This procedure is tedious and not followed
anymore.

25. TEST OF RATE OF DRUG RELEASE:
A clean test tube is taken and the internal surface is coated with the preparation as a
thin layer.
Saline or serum is poured into the test tube. After a certain period of time, the saline is
analyzed for the quantity of the drug.
The amount of drug when divided by the time period gives the rate of drug release.

26. TEST OF RHEOLOGICAL PROPERTIES:
The viscosity of the preparation should be such that the product can be easily removed
from the container and easily applied to the skin.
Using cone and plate viscometer the viscosity of the preparation is determined.

27. TEST OF CONTENT UNIFORMITY:
The net weight of contents of ten filled ointment containers is determined.
The results should match each other and with the labeled quantity.
 This test is also called minimum fill test.

28. MICROBIOLOGICAL METHODS
TEST OF MICROBIAL CONTENT:
Micro-organisms like pseudomonas aeruginosa and staphylococcus aureus may
contaminate the preparation and finally infect the skin.
So, ointments should be tested for the absence of such micro-organisms.
Solutions of different samples of the preparation are made.
Each sample is inoculated into separate volumes of 0.5 ml of rabbit's plasma under
aseptic conditions and incubated at 37 degrees C for 1-4 hours.
No formation of the clot in the incubated mass indicates the absence of the micro-
organisms.

29. TEST OF PRESERVATIVE EFFICACY
Using pour plate technique, the number of micro-organisms initially present in the
preparation is determined.
Solutions of different samples of the preparation are made and mixed with Tryptone
Azolectin (TAT) broth separately.
All cultures of the micro-organisms are added into each mixture, under aseptic
conditions.
All mixtures are incubated. The number of micro-organisms in each sample is counted
on 7th, 14th, 21st and 28th days of inoculation.

30. MICROBIAL LIMITS:
On 14th day, the number of vegetative cells should not be more than 0.1% of initial
concentration.
On 28th day, the number of organisms should be below or equal to initial
concentration.

31. CHALLENGES IN OINTMENT
MANUFACTURING
1. Formulation Stability:
◦ Balancing act between achieving desired consistency and preventing ingredient
separation.
2. Ingredient Compatibility:
◦ Addressing challenges arising from interactions between different active and
inactive ingredients.
3. Uniformity in Mixing:
◦ Ensuring homogeneous distribution of components for consistent product quality.
4. Microbial Control:
◦ Mitigating the risk of microbial contamination during the manufacturing process.

32. 5. Temperature Control:
◦ Overcoming challenges related to maintaining precise temperatures during heating and
cooling stages.
6. Packaging Integrity:
◦ Ensuring that packaging materials maintain integrity to preserve the ointment's stability.
7. Regulatory Compliance:
◦ Navigating complex regulatory requirements to meet quality standards.
8. Scaling Production:
◦ Adapting manufacturing processes when scaling up production volumes