Microbial Spoilage of Pharmaceutical Products

Microbial Hazards Microorganisms are everywhere -- they can be: Pathogens – cause disease Spoilers – cause the quality of food to deteriorate Beneficial – used for food production and present in and on the body

Infection eating products contaminated with pathogens Intoxication eating products contaminated with the toxins (poisons) formed by bacteria eating products contaminated with other biological or chemical toxins (poisons) Toxin-mediated infection eating products contaminated with pathogens that grow in the body and form toxins (poisons)

A spoiled product may be described as one that has been rendered unfit for use Microbial spoilage can be caused by bacteria, yeasts or fungi which are all extremely versatile in their metabolic activities

An elegant & efficacious medicine which is both stable & acceptable by the patient may be contaminated & spoiled due to growth of microbes which can enter the product during its manufacture or during its use by the patient or medical staff. Such as using of creams ointments ,tooth pastes etc. Such spoilage may cause financial problems to the manufacturer and will cause damage to the user.

Microbial spoilage includes Survival of low level of acutely pathogenic microorganisms or higher level of opportunistic pathogens The presence of toxic microbial metabolites Microbial growth and initiation of chemical and physico-chemical deterioration of the formulation

Factors Effecting Microbial growth molecular structure of pharmaceutical products. the physicochemical properties of a particular environment. the type & quantity of microbe present. whether the metabolites produced can serve as source of usable energy & hence the creation of more microorganism. some naturally occurring ingredients are particularly sensitive to microbial attack.

Pharmaceutical ingredients susceptible to microbial attack 1. Organic polymer 2. Surface active agent 3. Therapeutic agent 4. Fats and oils 5. Sweetening agents 6. Preservative and disinfectant.

Pharmaceutical ingredients susceptible to microbial attack 1. Therapeutic agents Spoilage converts active drug constituents to less potent or chemically inactive forms variety of microorganisms can metabolize a wide assortment of drugs, resulting in loss of activity Eg: the metabolism of atropine in eye drops contaminating fungi

Medicines under threat alkaloids (morphine, strychnine, atropine), analgesics (aspirin, paracetamol), thalidomide, barbiturates, steroid esters and mandelic acid can be metabolized and serve as substrates for growth

2.Surface-active agents Anionic surfactants, such as the alkali metal and amine soaps of fatty acids, are generally stable due to the slightly alkaline pH of the formulations, although readily degraded once diluted into sewage

Non-ionic surfactants, such as alkylpolyoxyethylene alcohol emulsifiers, are readily metabolized by a wide variety of microorganisms. Increasing chain lengths and branching again decrease ease of attack The cationic surfactants used as antiseptics and preservatives in pharmaceutical applications are usually only slowly degraded at high dilution in sewage

3. Organic polymers: Many of the thickening & suspending agents used in pharmaceutical formulations are subject to microbial depolymerization by specific classes of extracellular enzymes yielding nutritive fragments & monomers. These include amlyses( starches),pectinases( pectins)) & proteases( protein) .

4. Fats and Oils: While the microbial metabolism of pharmaceutical hydrocarbon oils is rarely reported 5. Sweetening, flavoring and coloring agents. Many of the sugars and other sweetening agents used in pharmacy are ready substrates for microbial growth. a variety of coloring agents and flavoring agents frequently supported the growth of Pseudomonas spp., including Ps. aeruginosa

Factors affecting microbial spoilage of pharmaceutical products. Nutritional factors: The simple nutritional requirements & metabolic adaptability of many common spoilage microorganisms enable them to utilize many formulation components as substrates for biosynthesis & growth.

Moisture contents: water activity (Aw): Microorganisms require readily accessible water in appreciable quantities for growth.

Redox potential : Microbial growth in an environment is influenced by its oxidation-reduction balance as they require compatible terminal electron acceptor for their respiratory pathways to function.

Storage temperature: Spoilage of pharmaceuticals could occur potentially over the range of –20c to 60c. Reconstituted syrup & multidose eye drop packs are instructed to store at 8-12c to reduce the risk of growth inadvertently introduced during use.

PH: Extremes of pH prevent microbial attack. Above pH 8 spoilage is rare. In products with low pH levels e.g. flavored syrups with a pH 3-4 mould or yeast attack is more likely. Yeast can metabolize organic acids & raise the pH where secondary bacterial growth can occur

Packaging design: Packaging can have a major influence on microbial stability of some formulations in controlling the entry of contaminants during both storage & use.

Effect of spoilage Microbial Spoilage Toxin production taints: taste, appearance, odour degradation products degradation substrates  microbial infection Toxin production formulation breakdown  viscosity changes separation of suspended material  turbidity fermentation reservoir of infection