T1 - Week 8 Flashcards
When is non aqueous vehicles used?
To dissolve drugs that are water-insoluble and drugs susceptible to hydrolysis
In order to use non-aqueous vehicles the drug must be?
- Nonirritating
- Nontoxic in the amounts administered
- Not sensitizing
- Pharmacologically inactive
What does it mean to be physicochemical?
- Stable at various pH ranges
- Maintain fluidity in a wide temperature range
- Have a high boiling point
- Miscible with body fluids
- Easy to purify
What are common non-aqueous solvents in parenteral?
- Fixed vegetable oils (non-volatile)
- Co-solvents
- Ethyl oleate, isopropyl myristate, dimethyl-acetamide
What are oils that can be used for non-aqueous vehicles?
Common: Corn, cottonseed, peanut, sesame
Less common: castor and olive
What are example co-solvents used for non-aqueous vehicles?
Alcohol, glycerin, propylene glycol, polyethylene glycol 400
What are the USP specifications for fixed vegetable oils?
- Must remain clear when cooled to 10C (50F)
- Most not contain mineral oil or paraffin
- Non toxic
- Labeled stating the specific oil
What occurs when oil is not clear?
Degradation leading to rancidity and production of free fatty acids
What type of excipient are added to parenterals?
- Antibacterial preservatives
- Buffers
- Solubilizers
- Antioxidants
- Adjuncts
What is USP requirement for multiple-does injectable containers?
Should contain preservative agents unless by a monograph or active ingredient is an antibacterial
What could be the effects of added substances?
- Toxic in large amounts
- Irritating when parenterally administered
What are the maximum limits of preservatives in parenteral?
- Agents containing mercury and cationic surface-active compounds, 0.01%
- Agents such as chlorobutanol, cresol, and phenol, 0.5%
- Antioxidants, sulfur dioxide, potassium or sodium salts of sulfite, bisulfite, metabisulfite, 0.2%
What is the purpose for replacing air with nitrogen?
To enhance the stability of the product by preventing a chemical reaction between oxygen and drug
What is sterilization?
Destruction of all living organisms and their spores or their complete removal from the preparation
What are the 5 methods of sterilizing products?
- Steam
- Dry heat
- Gas
- Ionizing radiation
- Filtration
How is a sterilization method selected?
Nature of preparation and its ingredients
Why would you use the steam sterilization?
- Most pharmaceutical products are affected by heat and dry heat requires a high temperature
- In the presence of moisture, bacteria coagulates and destroyed by low temps
How is steam sterilization preformed?
- Conducted in an autoclave that uses steam pressure
- Atmospheric conditions, the pressure is used to achieve high temperatures
- The temperature destroys the microorganisms not the pressure
What is the mechanisms of microbial destruction for steam sterilization?
Hot moisture causes denaturation and coagulation of organisms’ essential protein destroying the microbial cell
What is the important factor of the destruction of microorganisms in pharmaceutical products?
The time the heat in the steam takes to penetrate the product container, which is limited by exposure time
Describe the application of steam sterilization
- Materials not adversely affected by moisture but penetrable and can withstand the required temperatures
- Not useful for oils, fats, oleaginous preparations, and exposed powders the damaged by condensed moisture
What are example products that use steam sterilization?
- Aqueous solutions in sealed containers, such as ampules
- Bulk solutions, glassware, surgical dressings, and instruments
What is dry heat sterilization?
Carried out in thermo-regulated oven heated by gas or electricity
Why is dry heat less effective than moist heat for sterilization?
- Higher temperatures and longer periods for exposure are required
- Conducted 150°C to 170°C for not less than 2 hours
- Higher temperatures permit shorter exposure
- Lower temperatures require longer exposure times
What does dry heat sterilize?
- Substances not effectively sterilized by moist heat like fixed oils, glycerin, heat-stable powders
- Glassware and surgical instruments
What does gas sterilize?
- Heat and moisture sensitive materials
What are the 2 gases used for gas sterilization?
Ethylene oxide and propylene oxide gas
What happens when materials are introduced to gas sterilization?
It becomes highly flammable when mixed with air
How do you make a drug safe after gas sterilization?
Dilute with carbon dioxide or suitable fluorinated hydrocarbon
Why is ethylene oxide used for gas sterilization?
- Interferes with the metabolism of the bacterial cell
- Requires 4-16hrs of exposure
- Requires specialized equipment resembling an autoclave
How does exposure effect materials that tolerate moisture and temperature?
Increasing the relative humidity and exposure temperature enhances sterilization and reduce exposure to ethylene oxide
Describe the application of gas sterilization?
- Sterilizes medical and surgical supplies, appliances
- Sterilize heat-labile enzyme preparations and certain antibiotics
What is ionizing radiation sterilization?
Sterilization by gamma rays and cathode rays
Why does ionizing radiation have limited use?
- Requirement of highly specialized equipment
- Effects of irradiation on the products and their containers
What is filtration sterilization?
The physical removal of microorganisms by absorption on the porous filter medium or by a sieving mechanism
What can millipores filter?
- Thin, plastic polymer membrane of nitrate or acetate esters of cellulose
- Various pore sizes ranging 14-0.025 um
- Smallest is 40um
- RBC: 6.5um
- Smallest bacterium: 0.2um
- Poliovirus: 0.025um
What are the advantages of filtration?
- Speedy to filter smaller volume solutions
- Sterilizes thermo-labile materials
- Inexpensive equipment
What are the disadvantages of filtration?
- Fragile membrane
- Large volumes and viscous liquids require more time
What are methods of sterility testing?
- Membrane filtration
- Direct transfer (product immersion)
- Product flush
What is the prefer method of sterile testing?
Membrane filtration
What is direct transfer used for?
Testing medical devices sterility
What is a product flush used?
Hollow tubes
What is the incubation time for membrane filtration?
14 days
How is membrane filtration instigated?
- Microorganisms will collect onto surface of a sub-micron pore size filter
- Filter is segmented and transferred to the test the medium
What are the 2 mediums of the membrane filter?
- Fluid thioglycollate medium
- Soybean casein digest medium
What is the difference between FT and SCD medium?
FTM: supports growth of anaerobic and aerobic microorganism
SCDM: supports a range of aerobic bacteria and fungi
What is de-pyrogenization?
Oxidizing pyrogens that are eliminated as gases or nonvolatile solids
What is fractional distillation?
Pyrogens are separated from water
What are oxidizing agents of de-pyrogenization?
Potassium permanganate + small amount of barium hydroxide to impart alkalinity
How is the pyrogen test administered?
- Uses (3 or 8) healthy rabbits
- Baseline temperatures are recorded (difference not more than 1°C)
- Test product is injected into an ear vein of each of three rabbits and temp recorded at 30-minutes intervals for 1 - 3 hours
What are results of the pyrogen test?
- No rise in temp (0.5C-more) = No pyrogens
- Rise in temp (0.5C-more), test continues
- If not more than 3 of the 8 rabbits show rises in temp of 0.5°C or more and if the sum of the 8 individual maximum temp rises does not exceed 3.3°C, the material under examination meets the requirements for the absence of pyrogens
What is the endotoxin testing?
- Blood cells of horseshoe crab (Limulus polyphemus) contain an enzyme and protein system that coagulates in the presence of low levels of lipopolysaccharides
- This led to the development of the Limulus amebocyte lysate (LAL) test for the presence of bacterial endotoxins
- LAL test is more sensitive than the rabbit test
