DDS-Formulation and Production of Sterile Dosage Forms Flashcards
What are the components of Parenterals - The Vehicle
- non-irritating
- non-toxic
- no pharmacologic activity
- no effect on the active ingredient
- physical properties: stability at various pH, temperatures, viscosity, miscibility with body fluid
What are the kinds of Vehicles that can be used for Parenteral
- aqueous vehicles
- water-miscible vehicles
- non-aqueous vehicles
What are the solutes for Parenterals
- antimicrobial agents (thimerosal 0.01%, benzethonium chloride 0.01%)
- buffers (citrates, acetates, and phosphates)
- antioxidants (sodium bisulfite 0.1%)
- other added substances (sodium benzoate)
General Manufacturing Process
- Procurement and selection of components and containers
- Product Preparation
- Quality Assurance
- Packaging and Labeling
What possibilities make all containers insoluble
- leaching
- permeation
- adsorption
What are the different options for container Selection
- glass
- plastic polymers
- rubber polymers
Types of plastic containers
polyethylene
polypropylene
polyvinyl chloride (PVC)
Different types of rubber containers
butyl
silicone
natural rubber
Industrial Preparation of Parenteral Products
compounding->filtration->filing/sealing->sterilizing
Methods of Sterilization
steam
dry heat
filtration
gas
ionizing radiation
Steam Sterilization
bacteria coagulate with moisture and are destroyed at lower temperatures in an autoclave. Bacteria with larger % of water are killed more easily than spores. usually method of choice. -Denaturing and coagulation of bacteria’s essential protein
Dry Heat
destruction done by dehydration in gas “ovens”. Less effective in killing than moist heat
Filtration
removal of adsorption via filter medium. Electric charge of microorganism, pH of solution, temperature (most membranes are nitrate or acetate esters of cellulose -highly polar with residual –OH groups)
Bubble Point Test
Used to filter integrity; minimum pressure required to force liquid out of the capillary space in the membrane; Smaller the pore size, higher bubble point –mfg gives standards for filter
Gas sterilization
Use of ethylene oxide or propylene oxide gas. Though to inhibit bacterial cell wall formation-extremely flammable when mixed with air. gen 4-16 hours.
Ionizing Radiation
Sterilization via gamma, cathode rays, or UV lamp. application is limited due to highly specialized equipment and the effects of radiation. thought to destroy vital chemicals and/or structures, such as chromosomal nucleoprotein
USP 797
2000 chapters that provide guidelines on the minimum practice and quality standards to which sterile preparations should be compounded. Enforced by state boards of pharmacy and FDA
Sources of ISO-Class 5
laminar airflow
compounding aseptic isolator
Laminar Flow Workbench
Horizontal and Vertical flow hood
-HEPA filter (high efficiency particular air): type of pleated mechanical air filter; Can remove at least 99.97% of dust, pollen, mold, bacteria, and any airborne; particles with a size of 0.3 microns
Proper Hygiene and Garbing
-remove personal outer garments
-remove cosmetics
-remove jewelry from hands, wrists, or any other visible body parts (no fake nails allowed)
-PPE in the proper order
Proper order of PPE
-shoe covers
-head and facial hair covers
-face masks/eye shields
-perform hand cleansing procedures
-non-shedding gown
Packaging
solutions ready for injection
dry soluble products ready to be combined with a solvent
-suspensions, emulsions ready for injection
-dry, insoluble products ready to be combined with a vehicle prior to use
-liquid concentrations ready for dilution
packaging for vials
single dose-no preservatives–drawn from only once with 6 hours expiration in ISO class 6
multi-dose-preservatives–drawn from more than once and expires 28 days after opening
Labeling
prep name; % of drug amount or drug/vol; amount of active ingredient; amount of solvent to add; ROA; storage conditions and exp; manufacturer and distributor; lot number
