INTRODUCTION

The purpose of preservatives is to protect, by chemical means, products of various

types against contamination by micro-organisms and thus against deterioration in quality. In

principle, preservation is always required wherever water-containing organic products are

stored at normal or elevated temperatures This is because microorganisms require, in

particular, warmth, humidity and nutrients for growth. Preservatives are regulated and limits in

use concentration have to be respected.

In the last few months, a new type of natural preservative has appeared on the market.

Similar in look, feel and scent to an essential oil blend, and made by combining active fractions

of essential oils, this new preservative system seems to have the potential to address the

needs of those skin care manufacturers who want their products to be completely natural - yet,

being such a new product, some time might be required before its efficacy and possible

contraindications are proven once for all.

Among the synthetic preservatives available for handmade skin care products, paraben-

based systems seem to be particularly controversial. A large number of articles, books and so-

called "expert" opinions point to paraben-based preservative systems as being responsible for

the "skin unfriendliness" of many industrial products. However, in-depth medical and

scientifical researches show that paraben-based preservatives are by far less dangerous, both

for the skin, and for the environment, than most other types of preservatives, such as for

instance those that fall into the "formaldehyde donors"

GOOD PRESERVATIVE PROPERTIESTo overcome the broad spectrum of microbes,and at the same time, not to be harmful to

the skin and deleterious to other ingredients in a cosmetic product, it is critical to use right

preservative. The optimal preservative should have the following attributes:

• Broad spectrum activity (bacteriae &

• Be effective over the anticipated shelf

• Be preferably liquid and water soluble

• Be effective over a wide pH range

• Not be deactivated by other ingredients

• Be odorless, colourless, and safe

1

TYPES

PREFERRED SYNTHETIC PRESERVATIVES

• Parabens:

Methyl-, Ethyl-, Propyl-, Butylparaben

• Urea-Derivatives:

Imidazolidinyl Urea, Diazolidinyl Urea

• Isothiazolones:

Methylchloro-, Methyl-Isothiazolinone

• Halogen-Organic Actives:

Iodopropynyl Butylcarbamate, Methyldibromo Glutaronitrile

• Organic Acids & Others:

Sodium Benzoate, Chloracetamide, EDTA, Phenoxyethanol, Triclosan, DMDM-

Hydantoin, Quaternium-15

NATURAL PRESERVATIVES Extracts (Grapefruit Seed, Rosemary)

• Essential Oils (Tea Tree, Neem Seed,Thyme)

• Vitamins (Vitamin E, Vitamin C)

2

PRESERVATIVES IN COSMETICS

The reason given to add preservatives to a product is to stop the development of

invisible bacteria that can cause disease. Usually the development of harmful microorganisms

can be seen developing in a product. It will usually develop on the edge of the creams and will

gradually spreads throughout the surface of the product. It can take a month or two for it to

develop.

Often a natural product will better protect against contamination of microorganism as

bacteria can feed on the synthetic junk in synthetic products.

Preservative used in cosmetic can often be the most toxic as they are expected to last for a

long period of time on the shelf.

Preservative should be free of toxic effects and non-irritating on the skin, mucous

membranes and in the intestinal system.

Oil-in-Water products have been found to be more susceptible than water-in-oil

products. Usually the higher the water content of the product the more likely potential for

bacteria.

Most synthetic chemical preservatives are toxic and should be avoided. The artificial

preservatives are added for an economic reason so products can be made in mass quantity

and be warehoused for a long period of time. Parabens have been found as incompatible with

proteins and anionics.

Weakness Of Synthetic Chemical Preservatives

Just because there are such strong chemicals in a cosmetic that causes it to last on a

shelf for years does not mean that it is safe to use. Natural products may be used and

substances may be added to the products to extent its life but these additives may destroy all

the benefits (life-force) of the natural products.

Even though the chemicals may extent the shelf-life of a product that can not totally

keep a product from going bad so artificial fragrances and color are added to product to make

them appear fresh and to make it seem that they are not decaying.

Preservatives can be considered deadly because their purpose is to kill. If they are

synthetic then they can also have side-effect because of the chemicals that they are made of.

Also natural preservatives can be harmful too, especially if they are taken in excess. If a

natural preservative did not kill it would not be doing its job. For the most part natural

3

preservative are not as toxic as synthetic preservative. Ideally no preservatives should be used

but many products would not stay fresh even for s short time without them.

Supposed organic cosmetics are not good if they contain hexachlorophene, methyl,

propyl paraben and formaldehyde, so it is a good idea even to check organic cosmetics for

these substances.

Animal Testing of Preservatives

There can be a vast different in toxicity testing of preservative between human and

animal testing. For instance formaldehyde was found to be very toxic and for humans and no

so toxic when tested on animals. This is further proof that animal testing is ineffective.

The same people testing a preservative are also trying to sell the product.

A preservative like hexachlorophene may be found to be highly toxic, but then several similar

compounds can be made and then tested on animals and then declared to be safe.

Preservatives Absorbed From Cosmetic into the Body

Preservative are absorbed into the body and then can be spread around the body by

the blood and it has been found to accumulate in the stratum corneum. After a period of time a

rash may appear to found where it has accumulates. As the preservatives are poisonous they

can also kill beneficial bacteria on the ski

Natural Cosmetic Preservatives

Natural preservative are much safer because they have always existed in nature and

are known to the immune system of the body. Most preservatives derived from plants are safe

for humans. The main argument against natural preservative is that they are no powerful

enough, but it definitely does not mean that more is better.

An effective natural preservative is made from grapefruit seeds and the fruit.

Also large amount of vitamin C (ascorbic acid and vitamin E (tocopherols) is good for

preserving cosmetics. Citrus oils have antimicrobial activities. The chemical benzanthracene

found in lemon and lime oils have microbial properties.

Some companies making chemicals cosmetic use a citrus preservative so they can say

that don’t use artificial preservatives but the rest of the products contains artificial fragrances,

artificial FD & C color and synthetic ingredients, to make the customer feel safe, while there

are many harmful ingredients in the products.

4

Safe Amounts of Preservative in Cosmetics

It may be said that many potential toxic preservative are used in small quantities

therefore they are not harmful, which in of course not true. If a strong poison is used in any

amount it will have a toxic effect. Just because they don’t kill doesn’t mean they don’t harm

you.

Many times a food or cosmetic producer will instead of using an unsafe amount of one

preservative will use several different preservative in smaller amount to preserve a product.

5

EFFECT OF PRESERVATIVES ON AYURVEDIC MEDICINES (2006-

2007)

In this project, a study of microbial spoilage of ayurvedic medicines and its preservation

by using different preservatives is carried out. In the first part, a study of various contaminants

isolated from the spoiled ayurvedic products like kashayams and lehyas are carried out. The

study shows that major contamination is caused by fungus especially Aspergillus niger. The

contamination by bacteria is comparatively less. The identification of the contaminants helped

to study the sources of the contamination and the pathogenic action. This is turn will help to

prevent the spoilage by the application of different preservatives giving substantial

consideration to anti-fungal compounds. In the second part, the effect of different preservatives

in ayurvedic medicines is carried out. The study is carried out with chemical preservatives and

biochemical preservatives. It was found that a single preservative was not effective against all

contaminants hence a combination of preservatives must be used. The biochemical

preservatives proved to be at par with chemical preservatives even at lower concentrations.

Hence biochemical preservatives may be promising solution in the preservation of ayurvedic

medicines. The research field of preservatives for ayurvedic medicines is still novel. In this

project, the common contaminants of the ayurvedic medicines are identified and its

preservation techniques are studied. Some of the preservatives are found very effective for the

preservation of the ayurvedic medicines. Further study has to be carried out to find its

compatibility in ayurvedic medicines. Since there is a great variation in composition and pH of

different ayurvedic medicines the effectiveness of the preservatives has to be studied in every

medicine. Due to evolving nature of microorganisms antimicrobial effect against a broader

spectrum of micro-organisms has to be studied. Presently bio-preservatives are gaining

popularity over chemical preservatives due to its lack of side effects. Research in preservatives

has to be oriented to develop new bio-preservatives and has to get approved by FDA. The

compound showing the antimicrobial of the plant extracts are to be identified and applied to

ayurvedic medicines. This will make the ayurvedic medicines completely natural.

6

INCLUSION OF ANTIMICROBIAL PRESERVATIVES IN

IMMUNOLOGICAL VETERINARY MEDICINAL

1. INTRODUCTION

In this document, "preservative" means an antimicrobial preservative added to a

medicinal product to prevent spoilage or adverse effects arising from microbial contamination

during use. Trace quantities of antibodies or preservatives left over from production are not

The European Pharmacopoeia has adopted a monograph entitled "Efficacy of Antimicrobial

Preservation". The monograph lists a range of designated bacterial and fungal species to be

used in the efficacy test, these being supplemented, where appropriate, by other strains or

species which may represent likely contaminants to the preparation. The test protocols appear

to be designed for simplicity and reproducibility of results, rather than for reflecting the

complexity of naturally-occurring contamination situations. Thus, the range of designated

bacterial test species excludes anaerobes and spore-formers, for example, and the prescribed

strains do not have the penicillin and mercury resistance of those sometimes encountered i n

veterinary practice. The viral aspects of preservation have not been addressed in the

pharmacopoeia. Antimicrobial preservatives must not be used as a substitute for Good

Manufacturing Practice (GMP). Nevertheless, preservatives have traditionally been included

routinely by manufacturers in immunological products. However, in view of the desirability of

excluding potentially toxic excipients from medicinal products where possible, and the

emphasis on formulation, manufacturing methodology and GMP as a means of achieving an

acceptable product, preservatives would not seem to have a role in single dose sterile

products. In general, veterinary medicinal products are likely to be at risk from microbiological

contamination because of the circumstances under which they may be administered, and

those containing substantial amounts of biological macromolecules are particularly difficult to

preserve. For these reasons, and because of their limited stability following reconstitution

and/or removal from refrigeration, multidose parenteral immunological veterinary medicinal

products should be allocated an in use shelf life of no longer than one working day (8 to 10

hours). The exact proposed in use shelf life must be accompanied by a justification based on

appropriate stability and microbial safety data.

7

2. GUIDING PRINCIPLES

2.1 Immunological veterinary medicinal products in single dose containers shall normally not

contain a preservative. xceptions (e.g. where there is a practice of simultaneous manufacture

and marketing of both single dose and multidose presentations) shall be justified.

2.2 Multidose liquid preparations (including emulsions) must be protected from harmful

microbial contamination after first opening or broaching the container. One approach may be

the addition of a preservative at a concentration which has been demonstrated during product

development studies to be effective in combating the growth of

representative bacterial and fungal species. Any proposal to market a product in a multidose

container must be accompanied by a justification (including supporting data) vis-à-vis the non-

inclusion or inclusion, as appropriate, of a preservative. This justification may refer, for

example, to the delivery system(s) to be used to administer the product.

2.3 In selecting a preservative system the applicant should consider

– the effectiveness against potential microbial contaminants;

– possible interaction with the formulation or container (for example, thiomersal is ineffective in

sera, and can bind to SH groups and polymeric material);

– the potential pharmacological and toxicological effects on the target animal species, at the

dose rates appropriate to the veterinary medicinal product;

– any maximum residue limits which have been fixed for the preservative substance(s), if

appropriate;

– possible effects on testing of the immunological veterinary medicinal product, for example

tests on cell cultures or mammalian species.

2.4 Preservatives may not be added to products that are to be freeze-dried, though they may

be present in the diluent for reconstitution when the innocuousness of the preservative for the

lyophilised product has been proven, and where allowed by points 2.1 – 2.3 above.

2.5 The test procedures and microorganisms employed for demonstrating preservative efficacy

should be as outlined in the Ph. Eur. Monograph “Efficacy of Antimicrobial Preservation”. The

range of microorganisms chosen for the testing should reflect the potential risk. As the Ph. Eur.

allows some flexibility in the experimental conditions and range of microorganisms, the

materials and methods for testing should be described in appropriate detail by the applicant,

who must in particular validate the method to “ensure that any residual antimicrobial activity of

the product is eliminated by dilution, filtration or by the use of a specific inactivator” in the

8

recovery operation. The ideal acceptance criteria are the Ph. Eur. A-criteria. However, in view

of the short in use shelf-lives appropriate to multidose parenteral immunological veterinary

medicinal products (in general no longer than one working day or 8 to 10 hours as discussed in

the introduction), the sampling of inoculated products in the case of preservative efficacy

studies on these products should be at a minimum of three intervals covering the period of the

proposed in use shelf life. For example, samples might be collected at 0, 3, 6, and possibly 9

hours, to demonstrate the kinetics of the preservative efficacy. For bacteria, at least two log

reductions in viable count should ideally be achieved by six hours, with no increase thereafter,

and for fungi, no increase in viable count should occur over the sampling period.

2.6 The applicant is encouraged to provide additional evidence of microbiological safety,

for example by a multiple vial broaching test.

2.7 The finished product specification for any preparation containing a preservative should

include tests for both the identity and concentration of the preservative. In the case of

concentration, a specification within ±15% of label claim at time of release is acceptable.

2.8 For products containing a preservative, the maintenance of preservative efficacy

throughout the period of the shelf life should be demonstrated during the stability studies.

2.9 The name and concentration of any preservative present in an immunological veterinary

medicinal product should be stated on the labelling. Or, where this is not possible, in the

package insert text. In the case of multidose parenteral products, the i n use shelf life, justified

on the basis of development testing as outlined in 2.5 above, should also be stated on the

labelling, for example as "any product still extant more than x hours after first broaching the

seal should be discarded". The product literature for multidose parenteral products should in

addition include directions to use only sterile needles and syringes for administration and to

avoid the introduction of contamination during use.

Conclusions

When it comes to choosing the right preservative for your lovingly handmade skin care

treats, deciding whether you want to rely on a completely natural system or not is a matter of

personal choice, which requires a more thorough approach than just "following the trend", and

should never be taken lightly. In general, the safest and wisest option is to purchase

9

preservatives from reputable suppliers, who can offer advice on what to choose, why and how

to use it (and this, just as with any other ingredient, for that matter!)

As already mentioned, anti-oxidants and preservatives are not unavoidable in skin care

preparations; if you are making creams, lotions and balms for personal and family use, and if

you are prepared to take on full responsibility for possibly negative side effects, then you can

certainly avoid them completely, and be sure that your preparations are just as natural as

possible.

On the other hand, preservatives and anti-oxidants can hardly be avoided if you want to

sell your products. We have already hinted to the fact the debate on preservatives and anti-

oxidants, especially among those who aim for "natural cosmetics", is fierce - and hot are also

the discussions about synthetic fragrances versus essential oils, or natural soap versus Melt &

Pour bases. We believe that the only way to placate the altercations and give both

manufacturers and consumers the power to decide for themselves what is good for them, is to

fully understand the implications of using each ingredient, and commit ourselves to appropriate

"market niches" based on what we have responsibly and consciously chosen.

10

PRESERVATIVES USED IN LIQUIDS

Some Pharmaceutically used preservative in Liquids formulation

Si. No. Class Usual concentration (%)

A Acedic

1. Phenol 0.2-0.5

2. Chlorocresol 0.05-0.1

3. O-phenyl Phenol 0.005-0.01

4. Alkyl esters of parahydroxy benzoic acid 0.001-+0.2

5. Boric acid and its salts 0.1-0.3

6. Benzoic acids and its salts 0.5-1.0

7. Sorbic acids and its salts 0.05-0.2

B Neutral

1. Chlorbutanol 0.5

2. Benzyl alcohol 1.0

3. ß-phenylethyl alcohol 0.2-1.0

C Mercurial

1. Thiomerosal 0.001-0.1

2. Phenylmercuric acetate and nitrate 0.002-0.005

3. Nitromersol 0.001-0.1

D Quaternary Ammonium compound

1. Benzalkonium chloride 0.004-0.02

2. Cetylpyridinium chloride 0.01-0.02

11

Some Pharmaceutically preservative Description:

1. PHENYLMERCURIC ACETATE

Chemical Formula: C8H8HgO2

Other names: acetoxyphenylmercury, phenylmercury (II) acetate, phenylmercury

acetate

explanation: Phenylmercuric acetate is white to white-yellow crystalline powder

that is odorless. This phenyl mercury compound is used mainly as a fungicide, herbicide,

slimicide and bacteriocide. Phenylmercuric acid serves as a preservative in canned paint, eye

ointments and drops, injectable solutions, skin disinfectants and in cosmetics products such as

hair shampoos, mouthwashes and toothpastes. It is also used in contraceptive gels and foams.

Phenylmercuric acetate is prepared by interaction of benzene with mercuric acetate in glacial

acetic acid. Phenylmercuric acetate's former production and use as a fungicide and as a

mildew inhibitor in paints may have resulted in its direct release to the environment. This

substance is very toxic to aquatic organisms and may be hazardous to the environment.

Use: herbicide, fungicide

2. CHLOROBUTANOL

Chlorobutanol, or 1,1,1-trichloro-2-methyl-2-propanol, is a chemical preservative, sedative

hypnotic and weak local anaesthetic similar in nature to chloral hydrate.

Chemical synthesis

Chlorobutanol is formed by the simple nucleophilic addition of chloroform and acetone. The

reaction is base driven by potassium or sodium hydroxide.

12

3. NITROMERSOL

synthetic mercury-containing organic compound used as an antiseptic for the skin and

mucous membranes and as a disinfectant for sterilizing surgical instruments. It is related to

merbromin (Mercurochrome) and thimerosal (Merthiolate). Nitromersol disinfects by the action

of the mercury in the molecule, which disrupts the enzymatic metabolism of the

microorganism. It occurs as a yellowish powder or granules, soluble in alkaline solutions. It is

used as a 0.5 percent alcoholic tincture or as a 0.2 percent aqueous solution.

4. PROPIONIC ACID

Propionic acid (systematically named propanoic acid) is a naturally-occurring carboxylic

acid with chemical formula C H 3CH2COOH. In the pure state, it is a colorless, corrosive liquid

with a pungent odor. The anion CH3CH2COO− as well as the salts and esters of propionic acid

are known as propionates (or propanoates).

Properties

Propionic acid has physical properties intermediate between those of the smaller

carboxylic acids, formic and acetic acid, and the larger fatty acids. It is miscible with water, but

it can be removed from water by adding salt. As with acetic and formic acids, its vapor grossly

violates the ideal gas law because it does not consist of individual propionic acid molecules,

but instead of hydrogen bonded pairs of molecules. It also undergoes this pairing in the liquid

state.

Propionic acid displays the general properties of carboxylic acids, and, like most other

carboxylic acids, it can form amide, ester, anhydride, and chloride derivatives. It can undergo

13

alpha-halogenation with bromine in the presence of PBr3 as catalyst (the HVZ reaction) to

form CH3CHBrCOOH.

Production

In industry, propionic acid is main produced by the hydrocarboxylation of ethylene using

nickel carbonyl as the catalyst:[1]

RCH=CH2 + H2O + CO → CH3CH2CO2H

It is also produced by the aerobic oxidation of propionaldehyde. In the presence of cobalt or

manganese ions, this reaction proceeds rapidly at temperatures as mild as 40-50°C:

CH3CH2CHO + ½ O2 → CH3CH2COOH

Large amounts of propionic acid were once produced as a byproduct of acetic acid

manufacture. Current world's largest producer is BASF, with approximately 80 ktpa production

capacity.

Propionic acid is produced biologically as its coenzyme A ester, propionyl-CoA, from the

metabolic breakdown of fatty acids containing odd numbers of carbon atoms, and also it the

breakdown of some amino acids. Bacteria of the genus Propionibacterium produce propionic

acid as the end product of their anaerobic metabolism. This class of bacteria is commonly

found in the stomachs of ruminants and the sweat glands of humans, and their activity is

partially responsible for the odor of both Swiss cheese and sweat.

5. CETYLPYRIDINIUM CHLORIDE

Cetylpyridinium chloride (CPC) is a cationic quaternary ammonium compound in some

types of mouthwashes, toothpastes, lozenges, throat sprays, anti-sore throat sprays, breath

sprays, and nasal sprays. It is an antiseptic that kills bacteria and other microorganisms. It has

been shown to be effective in preventing dental plaque and reducing gingivitis.

IUPAC name 1-Hexadecylpyridinium chloride

14

Molecular formula C21H38NCl

Molar mass 339.986 g/mol

Melting point 77 °C, 350 K, 171 °F

Toxicology and pharmacology

IPR-RAT LDLO 15 mg kg-1

IVN-RAT LD50 30 mg kg-1

ORL-MUS LD50 108 mg kg-1

ORL-RBT LD50 400 mg kg-1

IVN-RBT LD50 36 mg kg-1

6. BENZOIC ACID

Benzoic acid, C7H6O2 (or C6H5COOH), is a colorless crystalline solid and the simplest

aromatic carboxylic acid. The name derived from gum benzoin, which was for a long time the

only source for benzoic acid. This weak acid and its salts are used as a food preservative.

Benzoic acid is an important precursor for the synthesis of many other organic substances.

Production

Industrial preparations

Benzoic acid is produced commercially by partial oxidation of toluene with oxygen. The

process is catalyzed by cobalt or manganese naphthenates. The process uses cheap raw

materials, proceeds in high yield, and is considered environmentally green.

U.S. production capacity is estimated to be 126,000 tonnes per year (139,000 tons), much of

which is consumed domestically to prepare other industrial chemicals.

15

Laboratory synthesis

Benzoic acid is cheap and readily available, so the laboratory synthesis of benzoic acid

is mainly practiced for its pedagogical value. It is a common undergraduate preparation.

For all syntheses, benzoic acid can be purified by recrystallization from water because of its

high solubility in hot water and poor solubility in cold water. The avoidance of organic solvents

for the recrystallization makes this experiment particularly safe. Other possible recrystallization

solvents include acetic acid (anhydrous or aqueous), benzene, petroleum ether, and a mixture

of ethanol and water.

By hydrolysis

Like any other nitrile or amide, benzonitrile and benzamide can be hydrolyzed to

benzoic acid or its conjugate base in acid or basic conditions.

From benzaldehyde

The base-induced disproportionation of benzaldehyde, the Cannizzaro reaction, affords

equal amounts of benzoate and benzyl alcohol; the latter can be removed by distillation.

From bromobenzene

Bromobenzene can be converted to benzoic acid by "carbonation" of the intermediate

phenylmagnesium bromide:

C6H5MgBr + CO2 → C6H5CO2MgBr

C6H5CO2MgBr + HCl → C6H5CO2H + MgBrCl

From benzyl alcohol

Benzyl alcohol is refluxed with potassium permanganate or other oxidizing reagents in

water. The mixture is hot filtered to remove manganese dioxide and then allowed to cool to

afford benzoic acid.

7. 4-HYDROXYBENZOIC ACID

4-Hydroxybenzoic acid, or p-hydroxybenzoic acid, is a phenolic derivative of benzoic

acid. It is a white crystalline solid that is slightly soluble in water and chloroform, but soluble to

extremely soluble in alcohols, ether, and acetone.

16

4-Hydroxybenzoic acid is primarily known as the basis for the preparation of its esters,

known as parabens, which are used as preservatives in cosmetics.

IUPAC name 4-Hydroxybenzoic acid

Other names p-Hydroxybenzoic acid, para-Hydroxybenzoic acid

Molecular formula C7H6O3

Molar mass 138.12074 g/mol

Density 1.46 g/cm³

Melting point 214-217 °C

8. SORBIC ACID

Sorbic acid, or 2,4-hexadienoic acid, is a natural organic compound used as a food

preservative. It has the chemical formula C6H8O2. It was first isolated from the unripe berries

of the Rowan (Sorbus aucuparia), hence its name.

Sorbic acid and its mineral salts, such as sodium sorbate, potassium sorbate and

calcium sorbate, are antimicrobial agents often used as preservatives in food and drinks to

prevent the growth of mold, yeast and fungi. In general the salts are preferred over the acid

form because they are more soluble in water. The optimal pH for the antimicrobial activity is

below pH 6.5 and sorbates are generally used at concentrations of 0.025% to 0.10%. Adding

17

sorbate salts to food will however raise the pH of the food slightly so the pH may need to be

adjusted to assure safety.

Sorbic acid is also used as a bio descaling agent.

Sorbic acid should not be confused with other chemically unrelated, but similarly named

food additives sorbitol, polysorbate, and ascorbic acid (Vitamin C).

The E numbers are:

E200 Sorbic acid

E201 Sodium sorbate

E202 Potassium sorbate

E203 Calcium sorbate

Some molds (notably some Trichoderma and Penicillium strains) and yeasts are able to

detoxify sorbates by decarboxylation, producing trans-1,3-pentadiene. The pentadiene

manifests as a typical odor of kerosene or petroleum. Other detoxification reactions include

reduction to 4-hexenol and 4-hexenoic acid

9. THIOMERSAL

Thiomersal (INN) (C9H9HgNaO2S), or sodium ethylmercurithiosalicylate, commonly

known in the United States as thimerosal, is an organomercury compound (approximately 49%

mercury by weight) used as an antiseptic and antifungal agent.

IUPAC name Ethyl(2-mercaptobenzoato-(2-)-O,S) mercurate(1-) sodium

Other names Mercury((o-carboxyphenyl)thio)ethyl sodium salt

Molecular formula C9H9HgNaO2S

Molar mass 404.81 g/mol

18

Appearance White or slightly yellow powder

Density 500 kg/m³

Melting point 232–233°C (decomposition)

Solubility in water 1000 g/l (20°C)

It was developed and registered under the trade name Merthiolate in 1928 by the

pharmaceutical corporation Eli Lilly and Company and has been used as a preservative in

vaccines, immunoglobulin preparations, skin test antigens, antivenins, ophthalmic and nasal

products.

Use

Thiomersal's main use is as an antiseptic and antifungal agent.

Toxicology

Thiomersal is very toxic by inhalation, ingestion, and in contact with skin (EC hazard

symbol T+), with a danger of cumulative effects. It is also very toxic to aquatic organisms and

may cause long-term adverse effects in aquatic environments (EC hazard symbol N). In the

body, it is metabolized or degraded to ethylmercury (C2H5Hg+) and thiosalicylate.

Few studies of the toxicity of thiomersal in humans have been performed. Animal

experiments suggest that thiomersal rapidly dissociates to release ethylmercury after injection;

that the disposition patterns of mercury are similar to those after exposure to equivalent doses

of ethylmercury chloride; and that the central nervous system and the kidneys are targets, with

lack of motor coordination being a common sign. Similar signs and symptoms have been

observed in accidental human poisonings. The mechanisms of toxic action are unknown. Fecal

excretion accounts for most of the elimination from the body. Ethylmercury clears from blood

with a half-time of about 18 days, and from the brain in about 14 days. Inorganic mercury

metabolized from ethylmercury has a much longer clearance, at least 120 days; it appears to

be much less toxic than the inorganic mercury produced from mercury vapor, for reasons not

yet understood

Allergies

19

Thiomersal is used in patch testing for people who have dermatitis, conjunctivitis, and

other potentially allergic reactions. A 2007 study in Norway found that 1.9% of adults had a

positive patch test reaction to thiomersal; a higher prevalence of contact allergy (up to 6.6%)

was observed in German populations. Thiomersal-sensitive individuals can receive

intramuscular rather than subcutaneous immunization, so contact allergy is usually clinically

irrelevant. Thiomersal allergy has decreased in Denmark, probably because of its exclusion

from vaccines there

10.BORIC ACID

Boric acid refers to 3 compounds; orthoboric acid (also called boracic acid, H3BO3 or

B2O3·3H2O), metaboric acid (HBO2 or B2O3·H2O), and tetraboric acid (also called pyroboric,

H4B4O7 or B2O3·H2O). Orthoboric acid dehydrates to form metaboric acid and tetraboric acid

above 170 C and 300C respectively. Orthoboric acid is derived from boric oxide in the form of

white, triclinic crystals. It is poorly soluble in cold water but dissolves readily in hot water, in

alcohol and glycerine. Metaboric acid is a white, cubic crystalls. It is soluble in water slightly.

Tetraboric acid is a white solid soluble in water. When tetraboric and metaboric acid are

dissolved, it reverts to orthoboric acid. The main uses of boric acid is to make borate salts such

as borax and other boron compounds. Boric acid is also used in heat resistant glass, in

fireproofing fabrics, in electroplating baths, in leather manufacturing, porcelain enamels and in

hardening steels. Boric acid has antiseptic and antiviral activity. Aqueous solutions have been

used as mouth-washes, eye-drops, skin lotions and cosmetics. Boric acid and its salts are

components of many commercial insecticides and wood preservatives.

FORMULA H3BO3 or B2O3·3H2O

MOL WT. 61.83

20

SYNONYMS Boracic Acid, Hydrogen Borate, Orthoboric Acid; Boracic

acid; Hydrogen orthoborate; Trihydroxyborane; Borsäure

(German); ácido bórico (Spanish); Acide borique (French);

PHYSICAL STATE white cystals

MELTING POINT 170 C

BOILING POINT 300 C

SPECIFIC GRAVITY 1.43 - 1.44

SOLUBILITY IN WATER 4 - 5 g/100 ml at 20 C

pH 5.2 (1% sol.)

Boric Acid is recognized for its application as a pH buffer and as a moderate antiseptic

agent and emulsifier. It is a component of ointments, mouth-washes, eye-drops, bath salts,

creams and shampoos. It can be used for skin cooking sensation due to good thermal

conductivity. It is also known boron compounds made with all 10B isotope selectively destroy

cancer cell.

In combination with its use as an insecticide it also prevents and destroys existing wet

and dry rot in timbers. It can be used in combination with an ethylene glycol carrier to treat

external wood against fungal and insect attack. It is possible to buy Borate impregnated rods

for insertion into wood via drill holes where damp and moisture is known to collect and sit. It is

available in a gel form and injectable paste form for treating rot affected wood without the need

to replace the timber. Borate based timber treatments which can be sprayed onto wood

surfaces or used as a bath to soak/dip them in are available. Surface treatments prevent slime,

mycelium and algae growth even in marine environments. There is a wide range of

manufacturers of wood preservers based on boric acid/borate mineral salts.

11.CHLOROCRESOL

Chemical Formula: C7H7ClO

Other names: p-chloro-m-cresol, parachlorometacresol, 4-Chloro-3-methylphenol

21

explanation: Chlorocresol is found as white or slightly pink dimorphous crystals

that have a phenolic odor. Chlorocresol is a man-made substance used as external germicide

or bactericide and as a preservative for cosmetics, glues, gums, paints, creams, lotions, inks,

textiles and leather goods. It is also used as a disinfectant and antifungal agent in eye drops,

and as a chemical intermediate in the manufacture of some pesticides. Chlorocresol is toxic to

wildlife, and water-dwelling organisms. This chemical is also an irritant to the skin and eyes. It

may be formed in waters which have undergone chlorination treatment. Chlorocresol may be

released in the environment from evaporation, waste releases, use and production.

Use: preservative, disinfectant, bactericide, antifungal

12.CPC (CETYLPYRIDINIUM CHLORIDE)

CPC (cetylpyridinium chloride) is a cationic surfactant with strong bactericidal and

resistance to fungi. CPC produced in Wako is crystal of high purity, colorless and odorless. It is

used as an antibacterial agent in toothpaste, mouthwash, pre-moistened wipe and lozenge. It

wins popularity in the fields of pharmaceuticals, cosmetics, toiletries and industrial use.

Chemical name Hexadecylpyridium Chloride , Monohydrate

Molecular weight 358.01

Appearance white crystalline powder

Melting point 80-84°C

Moisture absorption No hygroscopicity on the condition, RH=80%(25°C)

Solubility readily soluble in water, ethanol, or glycol.hardly soluble in acetone,

ether, or hydrocarbon

Toxicity oral (rabbit) LD50 400mg/kg skin (rabbit)LDo 2000mg/kg

22

13.PHENOXY-2-ETHANOL

It is a colourless oily liquid with a very low solubility in water (2.7wt%), soluble in ethanol,

neutral pH 7 (20g/lt. water 20°C) and specific gravity 1.109g/cm3 (20°C). It has a slight

aromatic odour.

14.FORMALDEHYDE

Formaldehyde (IUPAC name methanal) is a chemical compound with the formula

H2CO. It is the simplest aldehyde. Formaldehyde exists in several forms aside from H2CO: the

cyclic trimer trioxane and the polymer paraformaldehyde. It exists in water as the hydrate

H2C(OH)2. Aqueous solutions of formaldehyde are referred to as formalin. "100%" formalin

consists of a saturated solution of formaldehyde (roughly 40% by mass) in water, with a small

amount of stabilizer, usually methanol to limit oxidation and polymerization. It is produced on a

substantial scale of 6M tons/y. In view of its widespread use, toxicity, and volatilty, exposure to

formaldehyde is significant consideration for human health.

Synthesis and industrial production

Formaldehyde was first reported by the Russian chemist Aleksandr Butlerov (1828-1886), but

was conclusively identified by August Wilhelm von Hofmann.

23

Formaldehyde is produced industrially by the catalytic oxidation of methanol. The most

common catalysts are silver metal or a mixture of an iron and molybdenum or vanadium

oxides. In the more commonly used FORMOX process methanol and oxygen react at ca 250-

400 °C in presence of iron oxide in combination with molybdenum and/or vanadium to produce

formaldehyde according to the chemical equation:

2 CH3OH + O2 → 2 H2CO + 2 H2O

The silver-based catalyst is usually operated at a higher temperature, about 650 °C. Two

chemical reactions on it simultaneously produce formaldehyde: that shown above and the

dehydrogenation reaction:

CH3OH → H2CO + H2

Formalin can be produced on a smaller scale using a whole range of other methods including

conversion from ethanol instead of the normally-fed methanol feedstock. Such methods are of

less commercial importance.

In principle formaldehyde could be generated by oxidation of methane, but this route is not

industrially viable because the formaldehyde is more easily oxidized than methane.

15.GLUTARALDEHYDE

IUPAC name Pentane-1,5-dial

Other names Pentanedial, Glutural, Glutardialdehyde, Glutaric acid dialdehyde,

Glutaric aldehyde, Glutaric dialdehyde, 1,5-Pentanedial

Glutaraldehyde is a colorless liquid with a pungent odor used to sterilize medical and

dental equipment. It is also used for industrial water treatment and as a chemical preservative.

24

However, it is toxic, causing severe eye, nose, throat and lung irritation, along with headaches,

drowsiness and dizziness.

Glutaraldehyde is an oily liquid at room temperature (density 1.06 g/mL), and miscible

with water, alcohol, and benzene. It is used as a tissue fixative in electron microscopy. It is

employed as an embalming fluid, is a component of leather tanning solutions, and occurs as

an intermediate in the production of certain industrial chemicals. Glutaraldehyde is frequently

used in biochemistry applications as an amine-reactive homobifunctional crosslinker. The

oligomeric state of proteins can be examined through this application.

Monomeric glutaraldehyde can polymerize by aldol condensation reaction yielding alpha,beta-

unsaturated poly-glutaraldehyde. This reaction usually occurs at alkaline pH values.

Uses

A glutaraldehyde solution of 0.1% to 1.0% concentration may be used for system disinfection

and as a preservative for long term storage.

Glutaraldehyde is used in biological electron microscopy as a fixative. It kills cells

quickly by crosslinking their proteins and is usually employed alone or mixed with

formaldehyde as the first of two fixative processes to stabilize specimens such as bacteria,

plant material, and human cells. A second fixative procedure uses osmium tetroxide to

crosslink and stabilise cell and organelle membrane lipids. Fixation is usually followed by

dehydration of the tissue in ethanol or acetone, followed by embedment in an epoxy resin or

acrylic resin.

Glutaraldehyde is also used in SDS-PAGE to fix proteins and peptides prior to staining.

Typically, a gel is treated with a 5% solution for approximately one half hour, after which it

must be thoroughly washed to remove the yellow stain brought about by reacting with free tris.

A polymerized isomer of glutaraldehyde known as polycycloglutaracetal is a fertilizer for

aquatic plants. It is claimed that it provides a bioavailable source of carbon for higher plants

that is not available to algae. Though not marketed as such due to federal regulations, the

biocidal effect of glutaraldehyde kills most algae at concentrations of 0.5 - 5.0 ppm. These

levels are not harmful to most aquatic fauna and flora. Adverse reactions have been observed

by some aquarists at these concentrations in some aquatic mosses, liverworts, and vascular

plants.

25

16.PHENOL

Phenol, also known as carbolic acid, is a toxic, colourless crystalline solid with a sweet

tarry odor, commonly referred to as a "hospital smell". Its chemical formula is C6H5O H and its

structure is that of a hydroxyl group (-OH) bonded to a phenyl ring; it is thus an aromatic

compound.

Properties

Phenol has a limited solubility in water (8.3 g/100 ml). It is slightly acidic: The phenol

molecule has weak tendencies to lose the H+ ion from the hydroxyl group, resulting in the

highly water-soluble phenoxide anion C6H5O−. Compared to aliphatic alcohols, phenol shows

much higher acidity; it even reacts with aqueous NaOH to lose H+, whereas aliphatic alcohols

do not. One explanation for the increased acidity is resonance stabilization of the phenoxide

anion by the aromatic ring. In this way, the negative charge on oxygen is shared by the ortho

and para carbon atoms. In another explanation, increased acidity is the result of orbital overlap

between the oxygen's lone pairs and the aromatic system. In a third, the dominant effect is the

induction from the sp² hybridised carbons[clarify]; the comparatively more powerful inductive

withdrawal of electron density that is provided by the sp² system compared to an sp³ system

allows for great stabilization of the oxyanion. In making this conclusion, one can examine the

pKa of the enol of acetone, which is 10.9 in comparison to phenol with a pKa of 10.0.

It is a significant component in the aroma of Islay scotch whisky.

Industrial production

Phenol can be made from the partial oxidation of benzene, the reduction of benzoic

acid, by the cumene process, or by the Raschig process. It can also be found as a product of

coal oxidation.

Uses

26

Phenol has antiseptic properties, and was used by Sir Joseph Lister (1827-1912) in his

pioneering technique of antiseptic surgery, though the skin irritation caused by continual

exposure to phenol eventually led to the substitution of aseptic (germ-free) techniques in

surgery. Lister decided that the wounds themselves had to be thoroughly cleaned. He then

covered the wounds with a piece of "rag" or "lint" covered in carbolic acid. It is also the active

ingredient in some oral anesthetics such as Chloraseptic spray. Phenol was also the main

ingredient of the Carbolic Smoke Ball, a device marketed in London in the 19th century as

protecting the user against influenza and other ailments. In the early part of the 20th century, it

was used in the Battle Creek Sanitarium to discourage female masturbation by applying it to

the clitoris.

It is also used in the production of drugs (it is the starting material in the industrial

production of aspirin), herbicides, and synthetic resins (Bakelite, one of the first synthetic

resins to be manufactured, is a polymer of phenol with formaldehyde). Exposure of the skin to

concentrated phenol solutions causes chemical burns which may be severe; in laboratories

where it is used, it is usually recommended that polyethylene glycol solution is kept available

for washing off splashes. Washing with large amounts of plain water (most labs have a safety

shower or eye-wash) and removal of contaminated clothing are required, and immediate

hospital treatment for large splashes. This is particularly important if the phenol is mixed with

chloroform (a commonly-used mixture in molecular biology for DNA & RNA purification from

proteins).

Phenol is also used in the preparation of cosmetics including sunscreens, hair dyes,

and skin lightening preparations[8]. Compounds containing phenol moieties can be used to

prevent ultraviolet light-induced damage to hair and skin due to the UV-absorbing properties of

the aromatic ring of the phenol. These compounds also act as free radical scavengers and are

claimed without evidence to prevent premature aging and cancer caused by oxidative stress.

It is also used in cosmetic surgery as an exfoliant, to remove layers of dead skin. It is also

used in phenolization, a surgical procedure used to treat an ingrown nail, in which it is applied

to the toe to prevent regrowth of nails. 5% Phenol is sometimes injected near a sensory nerve

in order to temporarily (up to a year) stop it transmitting impulses in some intractable cases of

chronic neuropathic pain.

27

17.CRESOLS

Description Colorless in pure form; yellowish, brownishyellow, or pinkish liquid

Molecular formula C7H8O

Molecular weight 108.14 g/mol

Boiling point 191.0C (o-cresol)

202C (m-cresol)

201.9C (p-cresol)

Melting point 29.8C (o-cresol)

11.8C (m-cresol)

35.5C (p-cresol)

Solubility Soluble in 50 parts water; miscible with alcohol,

benzene, ether, glycerol, petroleum ether; soluble in

vegetable oils, glycol

Conversion factor 4.42 μg/m3 per ppb at 25ºC

Cresols are organic compounds which are methyl phenols . They are a widely occurring

natural and manufactured group of aromatic organic compounds which are categorized as

phenols (sometimes called phenolics). Depending on the temperature, cresols can be solid or

liquid because they have melting points not far from room temperature. Like other types of

phenols, they are slowly oxidized by long exposure to air and the impurities often give cresols

a yellowish to brownish red tint. Cresols have an odor characteristic to that of other simple

phenols, reminiscent to some of a "medicine" smell.

Applications

Cresols are used to dissolve other chemicals, as disinfectants and deodorizers, and to

make specific chemicals that kill insect pests.

Cresol solutions are used as household cleaners and disinfectants, perhaps most

famously under the trade name Lysol. In the past, cresol solutions have been used as

28

antiseptics in surgery, but they have been largely displaced in this role by less toxic

compounds. Lysol was also advertised as a disinfecting vaginal douche in mid-twentieth

century America.

Cresols are found in many foods and in wood and tobacco smoke, crude oil, coal tar,

and in brown mixtures such as creosote, cresolene and cresylic acids, which are wood

preservatives. Small organisms in soil and water produce cresols when they break down

materials in the environment.

18.CHLOROTHYMOL

CH3C6H2(OH)(C3H7)Cl White crystals melting at 59-61°C; soluble in benzene alcohol, insoluble

in water; used as a bactericide.

19. ;O-PHENYLPHENOL

Molecular formula C12H10O

Molar mass 170.21 g/mol

Density 1.293 g/cm³

Melting point 55.5-57.5 °C

Boiling point 280-284 °C

o-phenylphenol, is an organic compound that consists of two linked benzene rings and

a phenolic hydroxyl group. It is a white or buff-colored, flaky crystalline solid with a melting

29

point of about 57 °C. It is a biocide used as a preservative under the trade names Dowicide,

Torsite, Preventol, Nipacide and many others.

Uses

The primary use of 2-phenylphenol is as an agricultural fungicide. It is generally applied

post-harvest. It is a fungicide used for waxing citrus fruits. As a food additive, it has E number

E231.

It is also used for disinfection of seed boxes. It is a general surface disinfectant, used in

households, hospitals, nursing homes, farms, laundries, barber shops, and food processing

plants. It can be used on fibers and other materials. It is used to disinfect hospital and

veterinary equipment. Other uses are in rubber industry and as a laboratory reagent. It is also

used in the manufacture of other fungicides, dye stuffs, resins and rubber chemicals.

2-Phenylphenol is found in low concentrations in some household products such as spray

disinfectants and aerosol or spray underarm deodorants.

Eye contact can cause severe irritation and burns with possible eye damage. For some

individuals, 2-phenylphenol can also irritate the skin. It is one of the chemicals that the

Hyperactive Children's Support Group recommends be eliminated from the diet of children.

The sodium salt of orthophenyl phenol, sodium orthophenyl phenol, is a preservative, used to

treat the surface of citrus fruits to prolong shelf life. As a food additive, it has the E number

E232.

30

PRESERVATIVE FOR SEMISOLID

For semisolid products, any change in the preservative may affect the quality of the

product. If any quantitative or qualitative changes are made in the formulation, additional

testing should be performed. No in vitro release documentation or in vivo bioequivalence

documentation is needed for preservative changes.

Table: solubility of some preservative in g/100 ml. Solvent at 250 c.

Si.No. Preservatives Water Mineral oil Propylene glycol

1. Biothional 0.0004 1.0 0.5

2. Butyl-p hydroxybenzoate 0.02 Soluble 110

3. p-Chloro-m-xylenol 0.0025 Slightly soluble 1.5 in glycerine

4. Dehydroxy acetic acid 0.10 0.01 1.7

31

5. Ethyl paraben 0.075

6. Methyl-p - hydroxybenzoate 0.25 0.03 22

7. Propyl -p - hydroxybenzoate 0.06 26

8. Sorbic acid 0.2 5.5

1. DEHYDROACETIC ACID

IUPAC: 2-acetyl-5-methyl-3-oxopent-4-en-5-olide Or 3-acetyl-6-methylpyran-2,4-

dione

CAS: 3-acetyl-2-hydroxy-6-methyl-4H-pyran-4-one

Also 3-acetyl-4-hydroxy-6-methyl-2H-pyran-2-one

Also 3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione

Formula: C8H8O4

Dehydroacetic acid is a pyrone derivative used as a fungicide and bactericide. It is used

to reduce pickle bloating as a preservative for squash and strawberries.

The sodium salt, sodium dehydroacetate, is often used in place of dehydroacetic acid

because of its greater solubility in water.

2. ETHYLPARABEN

Ethyl para-hydroxybenzoate, also called ethylparaben is the ethyl ester of p-

hydroxybenzoic acid. Its formula is HO-C6H4-CO-O-CH2CH3.

It is used as a preservative. As a food additive, it has E number E214.

32

IUPAC name 4-hydroxybenzoic acid ethyl ester

Other names ethyl paraben, ethyl parahydroxybenzoate, ethyl p-

hydroxybenzoate

Molecular formula C9H10O3

Molar mass 166.174

Melting point 115–118 °C

Boiling point 298–299 °C

3. PRESERVATIVE A15

IUPAC name: Imidazolidinyl Urea

USP/NF name: Imidurea NF

Appearance: Fine white powder

Imidazolidinyl Urea is one of the widest used cosmetic preservatives and since 1977 is

the most frequently used in USA, after parabens.

Also listed in USP/NF with the name of Imidurea for use in topical pharmaceutical

products. Judged safe, non irritating and non sensitizer at normal levels of use by the expert

panel of the Cosmetic Ingredient Review (CIR).

Antimicrobial activity

Preservative A15 is highly effective against Gram-negative and Gram-positive bacteria.

Slightly active at use levels against yeasts and molds.

Properties and stability

33

Preservative A15 is very soluble in water and polar solvents, not soluble in oils and non polar

solvents. Stable and active in the pH range 3-9. Prolonged working temperature over 50°C

should be avoided. Compatible with cosmetic raw materials, including anionic, non-ionic and

cationic ingredients.

Applications

Preservative A15 is widely used in a broad range of cosmetic products. Due to its high

water solubility it is easily incorporated in acqueous formulations and emulsions. The many

cosmetic applications include:

− Hair care: shampoos, lotions, conditioners, gels, mousses.

− Body and face care: toners, lotions, creams, masks, wipe.

− Make up: foundations, eyeliners, mascaras, powders, wipe.

− Sun products: sunscreens, suntans, aftersuns.

− Bath products: shower gels, bubble baths, handcleaners, intimate, wipes.

− Baby care: shampoos, bath products, gels, lotions, creams, powders, wipes.

− Raw materials: surfactants, vegetal extracts.

− Topical pharmaceutical preparations.

Use levels

Preservative A15 is normally used at 0.2-0.4% in combination with antifungals. It is

synergistic with parabens, sorbic acid, dehydroacetic acid and chelating agents (EDTA).

Regulatory approval

USA and EU: allowed upto 0.6% without limitations.

Japan: allowed upto 0.3% in rinse off products with label.

34

MEASURES TO REDUCE PRESERVATIVES

Although preservative-related side-effects as skin irriations and allergies occur very rarely, use

of preservatives should not be excessive (do not use them at higher concentrations than

allowed by the FDA or other authorities). There are additional possibilities to avoid premature

spoilage of homemade cosmetics:

• Disinfect the working utensils and containers with isopropyl alcohol or by putting them in

boiling water for 20 minutes.

• Use sterilized (boiled for 20 minutes) and distilled water for your products

• Make your products in small batches only and not in family sizes that last forever

• Do not dip your fingers into your products (particularly creams). Use a spatula or spoon

• Store your products in the refrigerator and label the product with the date of production. Keep

products out of the sunlight and sunheat.

LOSS OF EFFECT OF PRESERVATIVES

35

Besides a gray-green layer of mold on the surface of a product, there are several other factors

indicating that a cosmetic product is severly contaminated with microbes:

• Loss of viscosity (product becomes thinner)

• Emulsion break (separation of water and oil)

• Cloudiness of previously clear products

• Loss or change of color or malodorousness

• Drop in pH (product becomes more acid)

In conclusion, it is strongly recommended to preserve your homemade products! Do not be

afraid of using synthetic preservatives. They are truly effective and safe. But do not forget to

work clean! If your product has spoiled though, throw it away. Adding preservatives will not

make it usable again.

PHARMACEUTICAL PRESERVATIVE EFFICACY TESTING

Pharmaceutical preparations with inadequate intrinsic anti-microbial activity are likely to

have anti-microbial preservatives added. These additives are designed to prevent proliferation

or limit contamination by micro-organisms. The preservative qualities of the preparation are

checked during development by performance of an Efficacy of Anti-microbial Preservation

Test.

During the development of pharmaceutical preparations, it is necessary to prove that

the anti-microbial activity of the preparation is adequate to prevent the problems that could

occur from microbial contamination or proliferation during storage.

The BP, EP and USP detail guidance on the performance and interpretation of

preservative efficacy testing.

Our in-house method, which is UKAS accredited , has been developed according to the

EP. We can, however, perform testing according to the BP or USP.

36

The types of preparations for testing range from powders through to liquids and include

topical creams, oral syrups and parenteral solutions.

Microbiological Assays

Bioassays are used for the analysis of certain antibiotics and vitamins by either

turbidimetric or agar diffusion techniques.

The turbidimetric assays have largely been developed in-house for vitamin analysis and

are applicable to a wide range of matrices, containing either supplemented or natural forms.

Products tested include foods, soft drinks, multi-vitamin tablets and pharmaceutical

preparations.

The agar diffusion technique is primarily for certain antibiotics used within the animal

health industry, although other standard procedures, listed within the various pharmacopoeias,

can be performed.

SURVEY REPORT

I have visited Anupam Biotech, Malanpur, Bhind,. Regarding to survey of preservative that are

used in the formulation.

Anti flam fort tablet(Analgesic)

Batch size 1 Lac.

Formula

Si. No. Ingredients Quantity

1 Diclofenac sodium 5 Kg.

2 Paracetamol 50 Kg.

3 Starch 6 Kg.

4 DCP 4 Kg.

5 PVPK-30 50 gm.

6 Starch paste 2 Kg.

7 MPS 20 gm.

8 Gelatin 600 gm.

37

9 Mg. Stearate 930 gm.

10 Talcum powder 600 gm.

11 SSG 600 gm.

12 Tartrazine 20 gm.

13 Brilliant blue 10 gm

Used Preservative:- MPS(Methyl paraben sulphate)

ANMOL 100mg. Tablet

Batch size 2lacs

Formula

Si.No. Ingredients Quantity

1 Paracetamol 21 Kg.

2 Starch 54 Kg.

3 Starch Paste 2 Kg.

4 Gelatin 400 gm.

5 M.P.S 200 gm.

6 P.P.S. 100 gm.

7 Telcum 300 gm.

8 Mg. Stearate 600 gm.

9 Ssg 1 Kg.

10 Citric Acid 200 gm.

11 Sodium Bicarbonate 200 gm.

Used Preservative:- (MPS)Methyl paraben sulphate, (PPS) Propyl paraben sulphate

E CONIN-P SUSPENSION

Batch size 200Lt.

Formula

Si. No. Ingredients Quantity

1 Paracetamol 108 Kg.

2 Nimesulide 5.25 Kg.

3 Mps 2 Kg.

38

4 Pps 400 gm.

5 Sodium Benzoate 80 gm.

6 Edta 500 gm.

7 Cmc 100 gm.

8 Xanthene Gum 1 Kg.

9 Citric Acid 200 mg.

10 Tween-80 200 gm.

11 Assence Mango Liquid 700 ml.

12 Sunset Yellow Color 20 gm.

13 Aspartames 200 gm.

14 Bromopal 20 gm

Used Preservative:- (MPS)Methyl paraben sulphate, (PPS) Propyl paraben sulphate, Sodium

Benzoate

APITO 200ml.

Formula

Si. No. Ingredients quantity

1 Sugar 50 Kg.

2 Sorbitol 10 Kg.

3 Cypro Heptadine 45 Kg.

4 Tri Choline 7 Kg.

5 Mps 200 gm.

6 Pps 40 gm.

7 Sodium Benzoate 200 gm

8 Edta 50 gm.

9 Bromopal 10 gm.

10 Citric Acid 200 gm.

11 Caramel Colour 2 Kg.

12 Respberry Essence 250 ml.

Used Preservative:- (MPS)Methyl paraben sulphate, (PPS) Propyl paraben sulphate, Sodium

39

Benzoate

FeZer-XT Iron syrup

Batch size 200 Lt

Formula

Si.No. Ingredients Quantity

1 Sugar 100 Kg.

2 Ferric ammonium citrate 4 Kg.

3 Vitamin B1 75 gm.

4 Vitamin B2 600 gm

5 Niacinnamide 25 gm

6 Vitamin B6 240 gm.

7 Vitamin B12 400 gm.

8 MPS 80 gm.

9 PPS 200 gm.

10 Sodium Benzoate 100 gm.

11 EDTA 20 gm.

12 Bromopal 100 gm.

13 Aspartam 200 gm.

14 Citric acid 500 gm.

15 Essence Mix. Fruit flavour 500 ml.

16 Caramel colour 5 Kg.

17 Sorbitol 20Kg.

Used Preservative:- (MPS)Methyl paraben sulphate, (PPS) Propyl paraben sulphate, Sodium

Benzoate

40

LITERATURE REVIEW

1. Preservative for emulsion and emulsion containing same

Abstract:A preservative for emulsion, comprising sorbic acid or a pharmaceutically acceptable salt

thereof, and, where necessary, sodium edetate and boric acid; an emulsion comprising sorbic

acid or a pharmaceutically acceptable salt thereof, and, where necessary, sodium edetate and

boric acid; an emulsion comprising the preservative; a method for preserving an emulsion

comprising adding sorbic acid or a pharmaceutically acceptable salt thereof, and, where

necessary, sodium edetate and boric acid, at a concentration pharmaceutically acceptable and

effective for the preservation of the emulsion; use of sorbic acid or a pharmaceutically

acceptable salt thereof for the production of an emulsion or preservative for emulsion; and the

use comprising adding, where necessary, sodium edetate and boric acid. The sorbic acid or a

pharmaceutically acceptable salt thereof and emulsions comprising them can impart superior

preservation capability to emulsions, such as water in oil (O/W) type emulsions, so that an

emulsion having high preservation property and less side effects is provided. The addition of

41

sodium edetate and boric acid provides an emulsion having a high pH with superior

preservation property even at low concentration of the preservative.

2. Physicochemical screening of antimicrobial agents as potential

preservatives for submicron emulsions.

Malgorzata Sznitowska, Stanislaw Janicki, Ewa A Dabrowska, Monika Gajewska

Department of Pharmaceutical Technology, Medical University of Gdansk, ul. Hallera 107,

Poland. msznito@farmacja.amg.gda.pl

Abstract:

Antimicrobial agents should be added to lecithin-stabilized submicron emulsions when

these preparations are non-sterile products or when packed in multidose containers. Eleven

antimicrobials were introduced to a standard submicron emulsion. The emulsions were

adjusted to pH 5.0 or 8.2 prior aseptic filtration or thermal sterilization, respectively. The

physicochemical stability of the preparations was observed during storage for 2 years at room

temperature. Parabens showed the best compatibility but satisfying stability was also observed

in emulsions containing phenylethanol, m-cresol and benzalkonium chloride. Partitioning

studies revealed poor correlation between aqueous solubility and content of the preservatives

in the aqueous phase of the emulsion. Only 1.2% of the total content of benzalkonium chloride

was found in this phase and incorporation of this compound into different microscopic

structures of the emulsion is proposed as a reason for such effect. Preliminary studies on the

efficacy of antimicrobial preservation was performed for emulsions containing parabens,

benzalkonium chloride or chlorocresol and the negative results bring conclusion that higher

concentration of antimicrobials or their combination may be required for efficient preservation

of submicron emulsions.

3. Partitioning of parabens between phases of submicron emulsions

stabilized with egg lecithin

Dorota Watrobska-Swietlikowska and Malgorzata Sznitowska

Department of Pharmaceutical Technology, Medical University of Gdansk, Hallera 107,

Gdansk 80-416, Poland

42

Abstract

Partitioning of methyl and propyl parabens (methyl and propyl hydroxybenzoate, paraben M

and P) between the major phases in the parenteral submicron emulsions was studied. The

investigated emulsions contained 10% or 20% soya-bean oil, 1.2% or 2.4% egg lecithin, 0.18%

or 0.36% paraben M and 0.02% or 0.04% paraben P. The aqueous phase was obtained by

ultracentrifugation, and subsequently, it was subjected to ultrafiltration, which procedure

allowed to distinguish between the fractions of free preservatives (Fw) and incorporated in the

liposomal or micellar region (Flm). The fractions present in the oily phase and in the interface

were calculated. Depending on the formulation, Fw was 17–31% and 2.3–6.0% for paraben M

and P, respectively. The Flm values were in a very narrow range, i.e. 3.0–6.0% for both

preservatives. Substantial accumulation, i.e. 38–58% was found in the interface and the

partitioning into this region was related to the oil/lecithin ratio rather than to lipophilicity of the

preservative

4. Interaction of parabens with nonionic macromolecules

Seymour M. Blaug, Sayed S. Ashan

State University of Iowa, College of Pharmacy, Iowa City

Abstract:

Methyl, ethyl, propyl, and butyl parabens interacted with various nonionic macromolecules

frequently found in cosmetic and pharmaceutical formulations. In general, the binding tendency

which the parabens exhibited for the various macromolecules increased with the molecular

weight of the paraben. Thus, the strongest complexing tendency was exhibited by

butylparaben, followed by propylparaben > ethylparaben > methylparaben. The hydrophile-

lipophile balance the macromolecules strongly influenced the binding tendency which the

parabens exhibited for them. The parabens interacted to a greater extent with polyoxyethylene

ester type macromolecules such as Tween 80 and Myrj 52 than with hydrophilic

macromolecules like polyethylene glycols 4000 and 6000 and polyethylene polypropylene

glycol.

5. PRESERVATIVE PROPERTIES OF OIL EMULSIONSL. S. Simonenko, I. S. Korsakova,

43

and Z. A. DudinaUDC 54-148:620.197

Abstract:

The preservative properties of oil emulsions are attracting more and more attention from

investigators owing to the combination of corrosion protection, detergency, cooling properties,

and other valuable properties.

For example, it is desirable to have a combination of good corrosion inhibition,

detergency, and preservative properties in detergents used in washing operations in

machinery construction. The use of such products makes it possible to combine processes in

which parts are washed and cleaned with preservation of these parts during the interim

between operations or during warehouse storage.

The preservative properties of the oil emulsions used as hydraulic fluids makes it possible to

preserve equipment during the time of operation and to protect it from corrosion when it is

disassembled and shipped to the ultimate user. The basic service properties of oil emulsions,

including the preservative properties, are determined primarily by the composition of the

material. However, knowledge of the basic relationships between preservative properties and

the application technology may result in considerably greater efficiency of use.

Here we are reporting on an investigation of the preservative properties of oil emulsions

under highhumidity and high-temperature conditions, in relation to the concentration of these

materials and the duration of the contact with the metal. In this study we used oil emulsions

prepared from the additives VNII NP-II7 and Vnitol, used at concentrations of 0.1-0.2% as

hydraulic and cooling fluids. Both additives are oil concentrates of corrosion inhibitors

(surfactants and other types}. These inhibitors act by forming on the metal surface a mu]iilayer,

water-displacing, hydrophobic film consisting of surfactants, oil base, and other corrosion

Inhibitors.

The protective properties of these emulsions were evaluated on the basis of the time to

the first appearance of visible corrosion damage on the surface of metal test specimens in a

corrosion test chamber operated at 100% relative humidity [4]. The protective layer was

applied to the metal specimens by immersing them in the test emulsion. In order to limit the

test period, most of the tests were run on gray cast iron, which is readily subject to corrosion.

On specimens of gray cast iron, St. 3, St. 45, and ShKh-15 steel* that had been prepared for

test but not treated with emulsion, uniform corrosion appeared within one day in the humidity

44

cabinet. Exposure of the specimens to water without added inhibitors increased the severity of

corrosion.

The tests on protective properties of the emulsions on gray cast iron AChS-I in

accordance with GOST 1585-70 at indicated that the Vnitol inhibitor emulsion was better than

the VNII NP-II7 additive. As the concentration was increased in either emulsion, the protective

properties became much better.

A similar effect was observed when the contact time between emulsion and metal was

increased. The Vnitol emulsion typically showed a sharp improvement in protective properties

with increasing concentration. Even at a concentration of 0.2% (at which the emulsion based

on VNII NP-II7 did not have any protective properties}, the Vnitol emulsion gave protection of

gray cast iron in the humid atmosphere for almost one week. When the concentration was

increased to 2%, with a l-h contact between the metal and emulsion, the protective life

increased to one month. The protective properties of the emulsion based on the additive VNII

NP-II7 were first manifested at a concentration of about 1.5%. In order to determine the

influence of temperature on the protective properties of the VNII NP-II7 and Vnitol emulsions,

tests were run in which the humidity cabinet was further heated to 50~ for 2 h each day. This

reduced the time to the appearance of initial corrosion quite considerably. The VNII NP-II 7

emulsion under these conditions, with a contact period between metal and emulsion of less

than 2 h, did not show any protective properties. When the contact time was increased to 3-4

h, initial corrosion appeared in 8-10 days. This soak time of 3-4 h corresponds to the end of

formation of a protective film on a metal surface. Further increase in the exposure time of the

metal to the emulsion did not give any further improvement in protection. Under these same

conditions, the protective properties of the Vnitol inhibitor emulsion were considerably betterl

when the metal was soaked for 2-4 days in the emulsion, the protective life was more than 3

months.

45

BIBLIOGRAPHY

1. www.wikipedia.org/ Benzalkonium chloride/html

2. www.wikipedia.org/ Cetylpyridinium chloride chloride/html

3. www.wikipedia.org/ Thiomersal /html

4. Drug information Online. Drugs.com (Revised 11/2006). Retrieved on 2007-10-08.

Drugs.com

5. World Health Organization, Care of the Umbilical Cord/annex,

http://www.who.int/reproductive-

6. U.S. EPA Reference Dose Tracking Report. U. S. Environmental Protection Agency,

Office of Pesticide Programs, U.S.Government Printing Office: Washington, DC, 1997.

7. Clarkson, T. W. Inorganic and Organometal Pesticides. In Handbook of Pesticide

Toxicology; Hayes, W. J. Jr., Laws,E. R. Jr., Eds.; Academic: San Diego, CA, 1991; Vol.

2, pp 497-583.

8. Basketter DA, Marriott M, Gilmour NJ, White IR (2004). "Strong irritants masquerading

as skin allergens: the case of benzalkonium chloride". Contact Derm. 50 (4): 213–7.

46

9. Graf P (2001). "Benzalkonium chloride as a preservative in nasal solutions: re-

examining the data". Respir Med 95 (9): 728–33.

10.Marple B, Roland P, Benninger M (2004). "Safety review of benzalkonium chloride used

as a preservative in intranasal solutions: an overview of conflicting data and opinions".

Otolaryngol Head Neck Surg 130 (1): 131–41.

47