Chemical preservatives for semisolids must be carefully evaluated for their stability with regard to the other components of the formulation as well as to the container. Plastic containers may absorb the preservative and thereby decrease the quantity available for inhibiting or destroying the microorganism’s responsible for spoilage. Some preservatives may sting or irritate the mucous tissues of the eye or nasal passages. Methylparabens and propylparabens tend to be more irritating when applied in the nose than quaternary ammonium compounds or the phenylmercuric salts. Boric acid may be used in the ophthalmic preparations, but is omitted from products to be used in the nose because of possible toxic effects if absorbed in large quantities.

1. Prepared By:
Bipul Deka
Roll No: 05
B. Pharm 4th Year

2. *Topical bases often contain aqueous and oily phases, together with
carbohydrates and even proteins, and so bacteria and fungi readily
attack them.
*Conditions that lower immunity, such as injury, debilitating diseases or
drug therapy, may encourage organisms that are usually not highly
infectious to infect the host, i.e. to become opportunistic pathogens.
*In 1969, 33 samples of 169 cosmetics and topical drugs surveyed were
microbially contaminated, half with Gram-negative organisms which
were a health hazard.
*In the mid-1960s, an outbreak of serious eye infection was traced to an
antibiotic ophthalmic ointment contaminated with Pseudomonas.
*There are many potential sources of microbial contamination. It can
occur in raw material and in the manufacturing water, in processing and
filling equipment, in packing material, if there is poor plant hygiene or
an unclean environment, and if plant operatives fail to comply with
good manufacturing procedures.

3. *Chemical preservatives for semisolids must be carefully
evaluated for their stability with regard to the other
components of the formulation as well as to the container.
*Some preservatives may sting or irritate the mucous tissues of
the eye or nasal passages.
*Methylparabens and propylparabens tend to be more irritating
when applied in the nose than quaternary ammonium
compounds or the phenylmercuric salts.
*Boric acid may be used in the ophthalmic preparations, but is
omitted from products to be used in the nose because of
possible toxic effects if absorbed in large quantities.

4. *No interaction between the preservative with
*surfactants.
*Active substances
*other components of the vehicle.
*Sorption by polymeric packaging materials.
*The product storage temperature may change the
concentration of the unbound or free preservative in the
aqueous phase.
*Preservative action appears to depend on the concentration of
the free preservative in the aqueous phase. Surfactant
solubilized preservative may be bound within the micelles
which act as reservoirs of preservative in an actively preserved
system.

5. *The minimum inhibitory concentration of preservative may be
estimated by:-
*The use of parameters like
the oil/water partition coefficient,
concentration of surfactant,
oil/water phase ratio and
concentration of free preservative in the aqueous phase
*An ultra -centrifuge
*Direct analysis.
*Microbiologic quality guidelines have been established by The Cosmetic,
Toiletry and Fragrance Association.
 Baby Products-not more than 500 microorganisms per gram or milliliter.
 Products used about the eye.-nmt 500 microorganisms per gram or
milliliter.
 Oral Products.-nmt 1000 microorganisms per gram or milliliter.
 All other products.-nmt 1000 microorganisms per gram or milliliter.

6. *The container may contribute to contamination by harboring bacterial
spores, or by sorption or chemical interaction with the preservative,
which thereby lowers its concentration in the preparation.
*Plastic containers, rubber seals, and closures have been shown to react
with some preservatives.
*In the presence of 5%polysorbate 80, 80%of the total methylparaben
present in the aqueous phase is inactive. Such inactivation also occurs
with benzalkonium chloride, benzoic acid, cetylpyridinium chloride,
dehydroacetic acid,and sorbic acid.
*The partial inactivation of the preservative can be overcome by an
excess of the same preservative, by the substitution of a noncomplexing
preservative, or by the substitution of non complexing emulsifier system.
Macromolecule 2% w/v Unbound Methylparaben % Unbound Propyl Paraben %
Gelatin 92 89
Methylcellulose 91 87
Carbowax 4000 84 81
PVP 78 64
Myrj 52 55 16

7. *The preservative may partition between the oil and the aqueous phase,
and if the preservative is more soluble in one phase than another ,an
additional quantity of the preservative must be added so that both
phases are protected from microbal spoilage.
*Example: methylparaben and propylparaben are frequently used in
semisolids because of their better solubility in aqueous and oil phases,
respectively.
*The solubility of some commonly used preservatives.
*The paraben esters of p-hydroxybenzoic acid are still popoular as
preservatives because their toxicity is low they are odorless they do not
discolor, and they are nonirritating to the skin.
*Disadvantages:
*have low solubility in water
*less effective against gram-negative bacteria than molds and yeasts.
Preservative Water Mineral Oil Propylene Glycol
Bithional 0.0004 1.0 0.5
Butyl p-hydroxy Benzoate 0.02 Soluble 110
p-chloro-m-xylenol 0.0025 Slightly soluble 1.5
Dehydroacetic Acid 0.1 0.01 1.7
Ethyl Paraben 0.075

8. *Many semisolid preparations could deteriorate on storage because some
components oxidize when oxygen is present. This decomposition can be
particularly troublesome in emulsions, because emulsification may
introduce air into the product and because of the high interfacial contact
area between the phases.
*The ideal antioxidant would possess the following properties:
• Effective at low concentrations;
• It and its decomposition products should be non-toxic, non-irritant,
non-sensitizing, odourless and colourless;
• Stable and effective over a wide pH range;
• Neutral - should not react chemically with other ingredients;
• Non-volatile.

9. Thank You
1. The Theory and Practice of Industrial Pharmacy by Leon
Lachman and Herbert A. Lieberman
2. Ansel’s Pharmaceutical Dosage Forms and Drug Delivery
Systems Ninth Edition by Loyd V. Allen, Nicholas G.
Popovich, Howard C. Ansel
3. Handbook of Cosmetic Science and Technology by André O.
Barel, Marc Paye and Howard I. Maibach
Bibliography: