Microbial Spoilage in Pharmaceutical Industry

Detailed overview of Microbial Spoilage in Pharmaceutical Industry

1. UNIT V 5.1 Microbial Spoilage Presented by: Mohammad Abuzar( M. Pharm ) Assistant Professor School of Pharmacy AIKTC, New Panvel .

2. CONTENTS 2

3. 3 INTRODUCTION Spoilage Spoilage is a process where the product gets deteriorated to such an extent that it is considered as unfit for the human consumption It is a complex event, which may be combination of microbial and biochemical activities Spoilage process led to the addition of preservatives into the product to extend its shelf-life

4. 4 Microbial Spoilage Microbial Spoilage include the contamination of pharmaceutical products with the microbes which lead to spoilage of the product affecting drug safety and quality Microorganisms have the ability to degrade compounds at mild physicochemical conditions Mixture of microbial species are effective biodeteriogens The rate of degradation of materials varies from product to product

5. 5 The overall rate of deterioration of a pharmaceutical compound depends on: Its molecular structure The physicochemical properties of a particular environment Type & quantity of microbes present Whether the metabolites produced can serve as source of usable energy & precursor for biosynthesis

6. 6 Pharmaceutical ingredients susceptible to microbial attack are • Therapeutic agents • Surface active agents • Organic polymer: Starch, CMC, pectin -Agar –Polystyrene • Humectant: Glycerin, sorbitol • Oil & Fats • Organoleptic additives • Preservatives, disinfectants When used in concentration less than the effective concentration, Gram negative organisms can attack

7. 7 Factors affecting microbial spoilage 1. Types and size of contaminant inoculum 2. Nutritional factors 3. Moisture content: water activity (Aw) 4. Redox potential 5. Storage temperature 6. pH 7. Packaging design 8. Protection of microorganism’s products within pharmaceutical

8. 8 1. Types and Size of Contaminant Inoculum Formulators must consider the product's environment and usage. Low levels of contaminants may not always cause spoilage if they can't replicate. Inoculum size is not always a reliable spoilage indicator. Example: Low levels of aggressive Pseudomonas in weakly preserved solutions pose higher risks than high fungal/bacterial spores in tablets. Contaminants may have a lag period before causing spoilage. Preservation is essential to prevent growth during the product's shelf life.

9. 9 2.Nutritional Factors Many spoilage microorganisms can utilize components of medicines for growth. Crude vegetable/animal ingredients in formulations increase nutrition for microbes. Even demineralized water may contain enough nutrients for growth, especially for water-borne Gram-negative bacteria like Pseudomonas. 3.Moisture Content: Water Activity Microorganisms need water for growth. Solute-rich medicines (e.g., syrups) may appear wet, but microbes struggle due to competition for water with solutes. Higher solute concentration lowers water activity. Hygroscopic products need proper packaging to prevent moisture absorption and microbial growth. Surface moisture in viscous products can lead to yeast and fungal spoilage.

10. 10 4.Redox Potential Microbial growth is influenced by the oxidation-reduction balance. Viscous emulsions may have high redox potential due to oxygen solubility in fats and oils. 5.Storage Temperature Spoilage occurs between -20°C to 60°C. Deep freezing (-20°C or lower) minimizes contamination risk. Some products, like reconstituted suspensions, require cool storage. Water for Injections should be stored at 80°C or above.

11. 11 6.pH Extremes of pH prevent microbial growth. Bacterial spoilage is common near neutral pH; pseudomonas thrive in antacid mixtures and mouthwashes. Yeasts can raise pH, allowing bacterial growth. 7.Packaging Design Packaging must control contaminant entry during storage and use. Parenteral drugs require extra protection against contamination. Self-sealing closures and narrow-nozzle tubes are now used to minimize contamination risk. Water vapor-proof materials are essential for low Aw medicines.

12. 8.Microbial Protection in Products Some polymers and suspending agents can protect microbes from heat, desiccation, and preservatives, increasing their survival in products 12

13. 13 Sources and control of contamination During manufacturing Hospital manufacture Water Environment Packaging In use Human sources Environmental sources Equipment sources

14. Manufacturing: Microbiological Quality Factors Key Factors: Formulation components Manufacturing environment Manufacturing process Key Considerations: Quality must be built into every stage, not just inspected at the end. Raw materials (e.g., water, natural ingredients) should be microbiologically safe. Equipment must undergo preventive maintenance and cleaning to avoid cross-contamination. Clean premises with filtered air and trained, healthy staff are essential. Proper packaging is needed to prevent contamination during shelf life. 14

15. Hospital Manufacturing Increased contamination risk in hospital settings due to wet areas and contaminated cleaning equipment. Good manufacturing practices are crucial. Packaging & Water Cardboard, corks, and paper are unsuitable due to contamination risk. Reusable containers must be thoroughly cleaned. Treated water should be stored at >80°C and circulated to prevent bacterial biofilms. 15

16. In-Use Contamination Risks Human Sources: Patients may contaminate multi-dose products with skin flora. Hospitals face a higher risk of cross-contamination from multi-dose products. Environmental Sources: Airborne and waterborne contaminants may enter products if not properly handled. Equipment Sources: Use disposable applicators to prevent contamination. Hospital equipment needs proper maintenance and disinfection to avoid cross-infection. 16

17. Assessment of microbial contamination and spoilage Observable effects of microbial attack on pharmaceutical products are : Early indications of spoilage are organoleptic (smell & taste) Example: sour, fishy, bad eggs, bitter, earthy taste and smells Discoloration to products by microbial pigments Loss of viscosity due to depolymerization of thickening & suspending agent like acacia, carboxy methyl cellulose (CMC) resulting in sedimentation of suspended ingredients 17

18. Microbial polymerization of sugars and surfactant molecules can produce slimy, viscous, masses in syrups, shampoos and creams, fungal growth in creams produce 'gritty’ textures Acidic or basic microbial metabolites change pH of the formulation & enhance microbial growth Gaseous metabolites may be seen as trapped bubbles within viscous formulations When emulsions are attacked, it reduces the stability and accelerates creaming, coalescence and cracking of emulsion 18

19. The extent of microbial contamination Medicament-borne contamination have become very common these days A wide range of non- streile products were found to be contaminated with Bacillus subtilis, Staph. albus, yeasts and moulds , and large numbers of coliforms soon after manufacture Under Medicines Act 1968, pharmaceutical products made in industry were expected to conform microbiological and chemical quality specifications Higher rates of contamination are seen in products after opening and using Medicines used in hospitals are more likely to be contaminated than those used in the general community Medicines used in the home are not only less often contaminated but also contain lower levels of contaminants and fewer pathogenic organisms 19

20. Factors determining the extent of microbial contamination Type and degree of microbial contamination Resistance of the patient The route of administration 20

21. Type and degree of microbial contamination Microorganisms that contaminate medicines and cause disease in patients may be classified as true pathogens or opportunist pathogens Pathogenic organisms like Clostridium tetani and Salmonella spp. rarely occur in products, but when present cause serious problems Opportunist pathogens like Ps. aeruginosa, Klebsiella, Serratia require simple nutritional requirements when enable them to survive in a wide range of pharmaceuticals Opportunist pathogens can survive in disinfectants and antiseptic solutions that are normally used in the control of hospital cross-infection 21

22. Resistance of the patient A patient’s resistance is important in determining the outcome of a medicament-borne infection Hospital patients are more exposed and susceptible to infection than those treated in the general community Neonates, the elderly, diabetics and patients traumatized by surgery or accident may have impaired defence mechanisms People suffering from leukaemia and those treated with immunosuppressants are most vulnerable to infection The critical dose of microorganisms that will initiate an infection is largely unknown and varies between species but also within a species. Animal and human volunteer studies have indicated that the infecting dose reduces significantly in the presence of trauma or foreign bodies or if accompanied by a drug having a local vaso -constrictive action. 22

23. The route of administration Contaminated products injected directly into the bloodstream or instilled into the eye cause the most serious problems Injectable and ophthalmic solutions are often simple solutions and provide Gram-negative opportunist pathogens with sufficient nutrients to multiply during storage Contaminants in topical products may cause harm when deposited on broken skin Patients treated with topical steroids are also prone to local infections due to contaminations Eye when damaged through the improper use of contact lenses or scratched by fingernails or cosmetic applicators, infections due to ophthalmic preparations The acidity of the stomach provides a good barrier for contaminants ingested orally in medicines 23

24. 24 W.B. Hugo and A.D. Russel: Pharmaceutical Microbiology, Blackwell Scientific publications, Oxford London. Prescott and Dunn., Industrial Microbiology, 4th edition, CBS Publishers & Distributors, Delhi. Pelczar , Chan Kreig , Microbiology, Tata McGraw Hill edn . Malcolm Harris, Balliere Tindall and Cox: Pharmaceutical Microbiology. Rose: Industrial Microbiology. Probisher , Hinsdill et al: Fundamentals of Microbiology, 9th ed. Japan Cooper and Gunn’s: Tutorial Pharmacy, CBS Publisher and Distribution. Peppler : Microbial Technology. I.P., B.P., U.S.P.- latest editions. Ananthnarayan : Text Book of Microbiology, Orient-Longman, Chennai Edward: Fundamentals of Microbiology. 12. N.K.Jain : Pharmaceutical Microbiology, Vallabh Prakashan , Delhi REFERENCES

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