Pharmaceutical Microbiology Lecture 4 PDF

New Mansoura University Faculty of Pharmacy Pharm D program Pharmaceutical Microbiology PMB202 Dr. Dina Eid Professor of Microbiology and Immunology...

New Mansoura University Faculty of Pharmacy Pharm D program Pharmaceutical Microbiology PMB202 Dr. Dina Eid Professor of Microbiology and Immunology Lecture No. 4 Pharmaceutical Microbiology-PMB202  Lecture Key element Discuss the principles of source of contamination. Illustrate how to control microbial contamination in pharmaceutical product. Determine the most common preservatives. Apply evaluation method for the efficiency of preservative in pharmaceutical product. Pharmaceutical Microbiology-PMB202 Microbial contamination and preservation of pharmaceutical product  Introduction Many medicines contain a wide variety of ingredients, included to create formulations which are efficacious, stable and acceptable to patients Spoilage: is chemical and physicochemical degradation of pharmaceutical products rendering it unsuitable for use.  Such spoilage usually results in major financial problems for the manufacturer, either through direct loss of the faulty product or, possibly, expensive litigation with aggrieved users of the medicine Faculty of Pharmacy/Microbiology Department/ Clinical Pharmacy/ Level 3 Pharmaceutical microbiology  Types of spoilage 01 02 03 Chemical Physicochemical Biological (infection)  Types of spoilage 01 deterioration of chemical nature of drugs Chemical and excipients Potency of the drug may decrease or become inactive  Types of spoilage Viable Odour growth formation Foating layers, turbidity 02 Taste Physicochemical change Gas production Colouration / Decolouration  Types of spoilage Pharmaceutical products are susceptible to contamination by a variety of microorganisms. 03 Contaminants isolated from products such as Clostridium tetani Biological Ps. aeruginosa (infection) Salmonella species. The outcome of using contaminated product may vary from patient to patient , depending upon the type and degree of contamination and how the product is to be used.  Types of spoilage 03 Endotoxins can induce acute and often fatal febrile shock if they enter the bloodstream via contaminated Biological infusion fluids, even in nanogram quantities, (infection)  Sources of Contamination Quality must be built into the product at all stages of the manufacture process and not simply assessed at its end. A- In manufacture B- In use Pharmaceutical Microbiology-PMB202  Sources of contamination The microbiological quality of pharmaceutical products is influenced by the environment in which they are manufactured and by the materials used in their formulation. Water In manufacture Environment Packaging  Sources of contamination In Water Water for pharmaceutical manufacture requires manufacture treatment, usually by distillation, reverse osmosis or deionization. Water should be stored at a temperature above 80°C.  Sources of contamination In manufacture Environment Free-living opportunist pathogens, such as Ps. aeruginosa can normally be found in all wet sites, such as drains, sinks and taps. Cleaning equipment, such as mops, buckets, cloths and scrubbing machines, may be responsible for distributing these organisms  Sources of contamination In Packaging manufacture Packaging in hospitals is frequently re-used for economic reasons. Large numbers of containers may be returned to the pharmacy, bringing with them microbial contaminants introduced during use in the wards  Sources of contamination All multidose products are subject to contamination from a number of sources during use. Human sources In Use Environment sources Equipment sources  Sources of contamination In use Human During normal usage, the patient may contaminate his medicine with his own microbial flora; subsequent use of the product may result in self- infection. Topical products are considered to be most at risk. Opportunities for contamination may reduced by using disposable applicators for topical products.  Sources of contamination In use Human In hospitals, multidose products, once contaminated, may serve as a vehicle of cross- contamination or cross-infection between patients. e.g. Zinc-based products packed in large stock-pots and used in the treatment of bed-sores patients may become contaminated during use with organisms such as Staphylococcus aureus.  Sources of contamination In use Human In hospitals, nursing staff are potential source of contamination in hospitals During the course of their work, nurses‘ hands become contaminated with opportunist pathogens contaminants may subsequently be transferred to medicaments during administration.  Sources of contamination In use Environment Small numbers of airborne contaminants may settle out in products left open to the atmosphere. Such contaminants generally have simple nutritional requirements This problem is encountered particularly when the product is stored in warm place.  Sources of contamination In use Equipment Patient and nursing staff may use a range of applicators (sponges, brushes, spatulas) during medicament administration, particularly for topical products. If reused, these become easily contaminated and may be responsible for continuing contamination between fresh stocks of product. Disposable applicators or swabs should therefore always be used.  Microbial spoilage of pharmaceutical products The formulation of an effective medicine which is both stable and acceptable to the patient may necessitate: the use of a wide variety of ingredients in a complex physical state which could create conditions leading to the survival and replication of contaminant microorganisms  Microbial spoilage of pharmaceutical products Low levels of acutely 1 pathogenic microorganisms A medicine may be Spoiled considered High levels of opportunist product 2 pathogens microbiologically spoiled if: 3 Toxic microbial metabolites 4 Microbial growth resulting in physical or chemical deterioration of the product  Microbial spoilage of pharmaceutical products The ability of microorganisms to produce degradative spoilage in products depends on their ability to synthesize appropriate enzymes that varies from one species to another. Spoilage is usually observed as the result of general breakdown of the formulation such as: cracking or creaming of emulsions separation of suspended material viscosity changes  Microbial spoilage of pharmaceutical products Pharmaceutical ingredients subject to microbial attack Degradation of surfactant thickening and 01 Degradation of suspending preservatives agents 02 07 Utilization of 03 06 Breakdown of humectants and 04 05 active co-solvents ingredients Degradation of Degradation of sweetening, flavoring and oils and coloring agents emulsions  Microbial spoilage of pharmaceutical products 1- Degradation of surfactant Susceptibility to biodegradation depends on the chemical structure Anionic surfactants are generally stable due to the slightly alkaline pH of the formulations Non-ionic surfactants are readily metabolized by a wide variety of microorganisms. 26  Microbial spoilage of pharmaceutical products 2- Degradation of thickening and suspending agents A wide variety of are all biodegradable by extracellular enzymes such materials as Starch, Acacia, Dextran Agar is resistant to attack. Gelatin is hydrolyzed by a wide range of commonly occurring microorganisms. 27  Microbial spoilage of pharmaceutical products 3- Utilization of humectants and co-solvents Materials such as glycerol and sorbitol are included in some products to reduce water loss and are usually readily metabolized unless present in high concentrations 4-Degradation of sweetening, flavoring and colouring agents Sugars and other sweetening agents can act as substrates for microbial attack. Oral suspensions or emulsions containing sugars are liable to fermentation with production of gas and acid which may alter the stability of the formulation. 28  Microbial spoilage of pharmaceutical products 5- Degradation of oils and emulsions Microorganisms do not grow in a non-aqueous environment. in emulsions, they may grow in the aqueous phase Production of lipolytic enzymes which attack the triglyceride oil component at the oil-water interface. Ointments and oils are less prone to attack but spoilage may occur when these products contain traces of condensed water or are stored in a humid atmosphere. 29  Microbial spoilage of pharmaceutical products 6- Breakdown of active ingredients Degradation of antibiotics such as penicillin by beta-lactamases Microbial enzymes which degrade chloramphenicol, aspirin, phenacetin, paracetamol, alkaloids and steroid esters have been reported. 30 Thank you!