Published on March 24, 2009
STERILIZATION : STERILIZATION STERILIZATION : STERILIZATION STERILITY: Absence of life or absolute freedom from biological contamination. STERILIZATION: Inactivation or elimination of all viable organism and their spores. STERILIZATION : STERILIZATION DISINFECTANT: Substance used on non-living objects to render them non-infectious; kills vegetative bacteria, fungi, viruses but Not Spores. e.g. Formaldehyde STERILIZATION : STERILIZATION BACTERICIDE (GERMICIDE): Substance that kills vegetative bacteria and some spores BACTERIOSTAT: Substance which stops growth and multiplication of bacteria but does not necessarily kill them. Growth usually resumes when bacteriostat is removed. STERILIZATION : STERILIZATION ANTISEPTIC: Substance used to prevent multiplication of microorganism when applied to living systems. An antiseptic is bacteriostatic in action but not necessarily bacteriocidal. STERILIZATION : STERILIZATION VEGETATIVE CELL: Bacterial cell capable of multiplication (as oppose to spore form which cannot multiply). Less resistant than the spore form. SPORE: Body which some species of bacteria form within their cells which is considerably more resistant than the vegetative cell. STERILIZATION : STERILIZATION Methods: 1. Steam Sterilization 2. Dry heat sterilization 3. Filtration 4. Gas sterilization 5. Irradiation NOTE: End products must pass sterility tests. STERILIZATION : STERILIZATION DRY HEAT STERILIZATION: Equipment: Oven Method: Dry heat sterilization is carried out at 160 deg C. to 170 deg C. for 2 to 4 hrs. Application: Glassware Fixed oils Thermostable powders STERILIZATION : STERILIZATION Advantages & Disadvantages: Sterilization by means of heat requires higher temperatures and longer exposures than sterilization by steam. Heat transfer is slow, small volumes of oil and thin layers of powder should be used. STERILIZATION : STERILIZATION STEAM STERILIZATION: Equipment: Autoclave Method: In the presence of moisture, microorganisms are destroyed at a lower temperature than in dry heat. This is the method of choice when product can withstand such treatment. STERILIZATION : STERILIZATION 10 lb Pressure (115.5 deg. C)...30 minutes 15 lb Pressure (121.5 deg. C)...20 minutes 20 lb Pressure (126.5 deg. C)... 15 minutes STERILIZATION : STERILIZATION Application: 1. Solutions sealed in containers ampuls, vials 2. Bulk Solutions 3. Glassware 4. Surgical Dressing 5. Instruments STERILIZATION : STERILIZATION Advantages: Rapid, Inexpensive, Effective, Large volumes Disadvantages: 1. Cannot use for oily preparation (oil base ointment) 2. Cannot use for moisture sensitive preparations STERILIZATION : STERILIZATION FILTRATION: Physical removal of microorganisms by adsorption on the filter medium. Used for heat sensitive materials. STERILIZATION : STERILIZATION BACTERIAL FILTRATION: Equipment: 1. Porcelain filters 2. Siliceous earth filter 3. Sintered glass filters 4. Asbestos filters 5. Membrane filters STERILIZATION : STERILIZATION Method: Direct filtration 1. Positive pressure 2. Negative pressure Application: Thermolabile solutions of low viscosity. Advantages & Disadvantages: 1. Depend on filter media 2. Thermolabile solutions can be sterilized. STERILIZATION : STERILIZATION GASEOUS STERILIZATION Equipment: Special oven, for admission of gas and humidity & hermetic Method: Humidity of less than 20% RH Ethylene Oxide STERILIZATION : STERILIZATION Ethylene Oxide-Carbon dioxide Pressure 30 psi Temperature 20-55 deg. C Application: Thermolabile powder plastic\polymers ophthalmic prep. subcutaneous, vaginal inserts, plastic syringes, tubing sets STERILIZATION : STERILIZATION Advantages & Disadvantages: 1. Explosive hazard 2. Toxic 3. Not appropriate for solutions STERILIZATION : STERILIZATION RADIATION STERILIZATION Equipment: Ultraviolet Lamp Ionization (Beta Rays, Gamma Rays, X-Rays) Application: Thermolabile Drugs (Powdered) STERILIZATION : STERILIZATION Disadvantages: 1. Highly specialized equipment required 2. Effect of irradiation on products and their containers. STERILIZATION : STERILIZATION STERILITY TESTS (A) Microorganisms: USPXXll recommends the use of biological indicators. 1. For liquid preparations-add directly to the preparations. 2. For solid preparations or equipments- add the culture to strips of filter paper. STERILIZATION : STERILIZATION Different organisms for different methods of sterilization. The organisms that are resistant to a particular sterilization method should be chosen as the marker organism STERILIZATION : STERILIZATION Sterilization Method Marker organisms Steam sterilization Bacillus stearothermophyilus Dry-heat sterilization Bacillus subtilis Ethylene oxide Bacillus subtilis sterilization Ionizing radiation Bacillus pumilus sterilization STERILIZATION : STERILIZATION (B) Pyrogen and Pyrogen Testing Pyrogens are fever producing organic substances arising from microbial contamination. The causative material is thought to be a Lipopolysaccharide from the outer cell wall of the bacteria. This is Thermostable STERILIZATION : STERILIZATION TESTS: 1. RABBIT TESTS a) Render the syringes, needles and glassware free from Pyrogens by heating at 250 deg. C for not less than 30 minutes. b) Warm the product to be tested to 37 deg. ± 2 deg. C. c) Take three healthy rabbits STERILIZATION : STERILIZATION d) Inject into an ear vein of each of three rabbits 10 ml of the product per kg body weight. e) Record the temperature at 1,2,and 3 Hrs. STERILIZATION : STERILIZATION CASE I Results: (i) No rabbit shows an individual rise in temperature at 0.6 deg. C or more above its respective control temp. (ii) Sum of the three individual maximum temp. rises does not exceed 1.4 deg. C. Conclusion: The material meets the USP requirements for the absence of Pyrogen. STERILIZATION : STERILIZATION CASE II Results: (i) If any rabbits show a temp. rise of 0.6 deg.C or more or (ii) If sum of the temp. rises exceeds 1.4 deg. C Conclusion: Repeat the tests using five other rabbits. STERILIZATION : STERILIZATION Results: (i) If not more than three of the eight rabbits show individual rises in temp. of 0.6 deg. C or more (ii) If the sum of the eight temp. rises does not exceed 3.7 deg.C Conclusion: The material meets the USP requirements for the absence of Pyrogens. STERILIZATION : STERILIZATION 2) LAL TESTS: Limulus Amebocyte Lysate (LAL) Tests Extract from the blood cells of the Horse Shoe Crab (Limulus Polyphemus) contains an enzyme and protein that coagulates in the presence of low levels of Lipopolysaccharides. PARENTERAL DRUG DELIVERY : PARENTERAL DRUG DELIVERY Tarun K. Mandal, Ph.D. PARENTERALS : PARENTERALS PARENTERALS Injections: These are sterile, Pyrogen free preparations intended to be administered parenterally (outside alimentary tract). Parental Routes Of Administration PARENTERALS : PARENTERALS Most Common: 1. Subcutaneous (SC;SQ;Sub Q) 2. Intramuscular (IM) 3. Intravenous (IV) Others: 4. Intracisternal 5. Intradermal (ID) 6. Intraspinal 7. Intraarterial (IA) PARENTERALS : PARENTERALS PARENTERAL ROUTE IS USED FOR: 1) Rapid action 2) Oral route can not be used 3) Not effective except as injection PARENTERALS : PARENTERALS Official Types of Injections: 1. Solutions of Medicinal Example: Codeine Phosphate Injection Insulin Injection 2. Dry solids or liquid concentrate does not contain diluents etc. Example: Sterile Ampicillin Sodium PARENTERALS : PARENTERALS 3. If diluents present, referred to as.....for injection Example: Methicillin Sodium for injection 4. Suspensions "Sterile....Suspension" Example: Sterile Dexamethasone Acetate Suspension PARENTERALS : PARENTERALS 5. Dry solids, which upon the addition of suitable vehicles yield preparations containing in all respects to the requirements for sterile suspensions. Title: Sterile....for Suspension Example: Sterile Ampicillin for Suspension PARENTERALS : PARENTERALS The form into which a given drug is prepared for parenteral use by the manufacturer depends on the nature of the drug. 1. physicochemical characteristics 2. therapeutic consideration PARENTERALS : PARENTERALS Onset of Action\Duration 1. Chemical form of the drug 2. Physical state of the injection (a) Solution (b) Suspension 3. Vehicle used PARENTERALS : PARENTERALS Most rapid onset of action: Drugs that are very soluble in body fluids. Drugs in aqueous solutions > Drugs in oleaginous solution. Drugs in aqueous suspension > Drugs in oleaginous suspension. "Repository" or "Depot" Type injections - Long acting PARENTERALS : PARENTERALS Requirements: Solvents or vehicles used must meet special purity and other standards. Restrictions on buffers, stabilizers, antimicrobial preservative. Do not use coloring agents. Sterile and Pyrogen - Free. PARENTERALS : PARENTERALS Must meet compendial standards for particular matter. Must be prepared under aseptic conditions. Specific and high quality packaging. PARENTERALS : PARENTERALS Vehicles: Aqueous: Sterile water for injection. Nonaqueous: Fixed oils Glycerin PEG Alcohol PARENTERALS : PARENTERALS Restrictions on Fixed Oils: Remain clear when cooled to 10 deg. C. Not contain Paraffin or Mineral oil. Must meet the requirement of iodine number and Saponification number. PARENTERALS : PARENTERALS Iodine Number (Value): It represents the number of g of iodine absorbed, under the prescribed conditions, by 100g of the substance. Saponification Value (Number): It represents the number of mg of Potassium Hydroxide required to neutralize the free acids and saponify the esters contained in 1.0g of the substance. PARENTERALS : PARENTERALS Must specify the oil used e.g. corn oil, cottonseed oil, peanut oil, sesame oil. Must be free from rancidity. PARENTERALS : PARENTERALS Solvents used must be: Non-irritating Non-toxic Non-sensitizing No pharmacological activity of its own Not affect activity of medicinal PARENTERALS : PARENTERALS Added Substances -preservatives -buffers -antioxidants -solubilizers -thickeners -materials to adjust tonicity PARENTERALS : PARENTERALS Do Not Use Color Preservatives: Multidose containers must have preservatives unless prohibited by monograph. PARENTERALS : PARENTERALS ASEPTIC TECHNIQUE: An aseptic technique is one which is designed to prevent contamination of materials, instruments, utensils, containers, during handling. PARENTERALS : PARENTERALS Sources of Contamination -The Air -The Breath -The Skin -The Hair -Clothing -Working surfaces PARENTERALS : PARENTERALS Methods of minimization of contamination: apply common sense Airborne contamination--use laminar airflow Horizontal Vertical PARENTERALS : PARENTERALS HEPA filter (High efficiency particulate air filter) Contamination from the breath--use masks Contamination from the skin: Nails should be scrubbed Hands and forearms should be washed thoroughly with detergent solutions PARENTERALS : PARENTERALS Hair and Clothing: Always wear sterile gown over normal clothing Long hair should be tied back Wear a cotton cap Working surfaces: Clean the working surface with a bactericidal solution or ethyl alcohol PARENTERALS : PARENTERALS PACKAGING: 1) Single dose: Hermetic container holding a quantity of sterile drug intended for parenteral administration as a single dose. Example: ampuls sealed by fusion 2) Multiple dose: Hermetic container permits withdrawal of successive portions of the contents without changing the strength, quality, or purity of the remaining portion. PARENTERALS : PARENTERALS LABELING: Name of product % of drug or amount of drug in specified volume of amount of drug and volume of liquid to be added Manufacturer/Distributor Lot number Name and quantity of all added substances PARENTERALS : PARENTERALS Expiration date Veterinary product should be so labeled Must check each individual monogram for: Type of container Type of glass Package size Special storage instructions PARENTERALS : PARENTERALS LARGE VOLUME PARENTHERALS (LVP'S): Generally administered by intravenous infusion to replenish body fluids, electrolytes, or to provide nutrition--100ml-1L These solutions should not contain: *Bacteriostatic agents *Other pharmaceutical additives PARENTERALS : PARENTERALS BIOLOGICALS: -vaccines -toxins -toxoids -antitoxins -immune serums -blood derivatives -diagnostic aids PARENTERALS : PARENTERALS Storage: Refrigerator at 2 deg C to 8 deg C, avoid freezing These preparation should meet the std. of the bureau of biologies of the FDA. PARENTERALS : PARENTERALS IMMUNITY: Power of the body to resist and overcome infection. NATURAL OR NATIVE IMMUNITY: Individuals resistance to a particular toxic agent because of race, endocrine balance, etc. ACQUIRED IMMUNITY: Specific immunity that may be acquired (Active or Passive) PARENTERALS : PARENTERALS ACTIVE IMMUNITY: *Naturally acquired active immunity--occurs in response to an infection *Artificially acquired active immunity-- response to a specific vaccine or toxoid PASSIVE IMMUNITY: Introduce already formed antibodies into body to combat a specific antigen PARENTERALS : PARENTERALS VACCINES: Administered primarily for prophylactic action for the development of active acquired immunity. TOXOIDS: Toxins modified and detoxified by moderate heat and chemical treatment Example: Diphtheria, Tetanus PARENTERALS : PARENTERALS ANTITOXINS: Prepared from blood of animal immunized by repeated injections of bacterial toxins PARENTERALS : PARENTERALS ANTISERUMS: Prepared in same manner as antitoxins except that viruses or bacteria injected to produce antibodies. Produce passive immunity human immune serums and globulins. Serums containing specific antibodies obtained from blood of humans who have had the disease or have been immunized against it with a specific biologic product.