Seminar on Pharmaceutics IX

Topic: Preservation of

Semisolids

Prepared By:Bipul DekaRoll No: 05B. Pharm 4th Year

Introduction*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.

*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.

Preservation from Microbial Spoilage:

*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.

Parameters of a good preservative:

*The minimum inhibitory concentration of preservative may be estimated by:-

*The use of parameters likethe 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.

The minimum inhibitory concentration of preservative:

Role of Container as Sources Of Contamination:-

*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 89Methylcellulose 91 87Carbowax 4000 84 81PVP 78 64Myrj 52 55 16

*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 0.5Butyl p-hydroxy Benzoate 0.02 Soluble 110p-chloro-m-xylenol 0.0025 Slightly

soluble1.5

Dehydroacetic Acid 0.1 0.01 1.7Ethyl Paraben 0.075    

*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.

Antioxidants:

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: