Random Shit u think is important for Pluta Lectures Flashcards
Dea Form 483
GMP (general manufacturing process) Law Penalty for improper manufacturing Comes before warning letter > decree/fine > DEBARRED
Pharmaceutical Compounding Process
- RX Receipt 2. Design Dosage Form 3. Infrastructure Review 4. RX Prep/label / documentation + final review 5. Dispencing & Counseling 6. Post Prep 7. Post dispensing & monitoring
USP 795
Pharmaceutical Compounding for NON-STERILE PREPARATIONS simple / moderate / complex
USP 797
Pharm Compounding - STERILE preps Low-risk CSP(compounded sterile product) Medium-Risk CSP High Risk CSP
What is included in a Material Record?
Ingredient Supplies ID# / Lot# Experiation Date Prepared by? Checked by?
Polar Solvents
WATER HIGH polarity/dielectric constant / dipole moment
Non-Polar Solvents
Mineral Oil Non-aqueous / non-polar / hydrophobic LOW polarity/dielectric constant/dipole moment
SEMI-Polar Solvents
Ethanol / Glycols Propylene Glycol / PEG Miscibile with both water and mineral oil INTERMEDIATE Polarity/dielectric constant / dipole moment
Solution + Surfactant
–> Micellar Dispersion
Solution + Insoluble Drug + Surfactant
-> Liposome
Solution + Oil + Surfactant
-> EMULSIOn
Solution + Insoluble Drug
= SUspension
Colloid
Insoluble ingredients w/ small particle size ex. Liposomes
Suspensions
Insoluble ingredients Ex. Pepto Bismol / Maalox / Calamine lotion
Emulsions
O/W or W/ O MAYONNAISE = O/W
Solution Product Components
- API
- Supporting INACTIVE Ingredients
- Cosolvent
- Inactive ingred. to STABILIZE API
- Buffer system / Chelant (EDTA)
- Antioxident
- Inactive ingred > Bioavailability
- Ingredients for application
- Inactive ingred for COMPLIANCE
- Viscosity / flavor / color / fragrance
Components in Syrups
API
Sweetener / Flavor / Color
Preservative
COomponents in Elixirs
API
ALCOHOL = cosolvent to dissolve drug
Flavor / Color
Preservative
Stokes Law
For SUSPENSIONS
The force of viscosity on a small sphere moving through a viscous fluid is given by
APplies to suspensions <2g solids/100ml
Suspension Dosage Forms
API
- Inactive excipients
- Suspending agent/gelling agent
- Viscosity enhancer
- Flocculating Agent
- ANti-microbial preservatives
- Buffer system
- WETTIN AGENT (surfactant/antifoaming)
- Sweetener/color / fragrance
Thixotrophy
Ability to of vehicle to maintain suspension after SHAKING
becomes LESS viscous after SHAKING
Viscosity Increasing Agents
Typically for SUSPENSIONS
-
Cellulosics
- methyl/hypro/HPMC/CMC/
-
Polymers
- PVP/carbomers/povidone
-
Natural Products
- bentonite/xanthangums
Brownian Motion
Applies to partcles <5 microns in size
for inhalation products <1 microns do not need suspending agent
Emulsion Product Components
- API
- Supporting Active Ingredients
- Oil to dissolve API
- Buffer / chelant / antioxidant
- Emulsifying Agent
- Aqueous Phase
- Salts/preservatives
- Flavor/color/fragrance
SEDDS
Self Emulsifying Drug Delivery System
-
Semipolar Solvents
- Ethanol/ PEG400 / propylene glycol
-
Surfactants
- Polysorbate 80
- Oils
- Corn/safflire
- Examples:
- Cyclosporin / ritonavir / tipranavir
Parenteral Products
STERILE / ABSENCE OF PYROGENS
minimal particulates / isotonicity
Adding Surfactant to Solution
Continuously
Micelle
Liposome
EMULSION
Anti Area
Iso Class 8 Area
for handwashing / garbing / component staging / high particulate activities done here
Iso Class 5
Where products are manufactured
ASEPTIC PROCESSING
CRITICAL AREA
lower the number = more clean
- CLASS 100 (WITHIN LAFW)
- THE HOOD
Sterilizing Grade Membrane Size
0.22 or 0.20 MICRON Pore Size
size that will ertain 100% pseudomonas dimunuta
Positive Pressure Room
Higher pressure room than the adjacent room
Net flow of air is OUT of the room
Negative Pressure Room
Lower pressure than adjacent room
Net flow of air is INTO THIS ROOM
typically the dirtier room (Iso Class 8)
Needles / Gauge
Gauge, HIGHER NUMBER = Smaller diameter
length / bevel
Sterile Filtration
Membrane filter for AIR
0.22 - 0.45 Micron filter for AIR
USP 800
compounding guidelines for
HAZARDOUS DRUGS
handling in healthcare settings
Two Primary Objectives
in STERILE Labs
-
No Contaimination of Preparation
- Sterility / pyrogenicity
- Particulate matter / stability
- Facility design / operation
- PERSONNEL TRAINING
-
No Human Inhalation / Contact of Drugs
- Garbing / gloves
- Drug Toxicity
ISO 7
Buffer Area
CLASS 10k (10,000)
between 8 and 5
Filter Straw VS Filter Needle
CHOOSE FILTER STRAW
b/c its a straw, you know you have to switch to a regular needle when transfering into the LVP
Coring
Damage to ubber closure with improper needle technique
prevented w/ anti-coring technique
45-60 degree into the bottle then go straight
LAFW Cleaning Direction
PERPENDICULAR TO AIRFLOW DIRECTION
Top –> Bottom
Back To Front
Heel Technique
Technique to remove needle guard from needle / syringe
help prevent needle sticks
Definition of Dispersions
ARE NOT SOLUTIONS
- Micelle solutions
- Colloids
- Suspensions
-
EMulsions
- BASED ON SIZE OF DISPERSED PHASE
Suspensions & Emulsions
COARSE Dispersions
Visible particles size >1 micron
IV Injection Sizes
Liposomes may be injected if small enough
EMULSIONS may be injected if small enough
IV FAT emulsion = 0.4 microns
Nanoparticles
Micronization
Particle size reduction to ~1micron particle size
- Done by:
- micropulverization
- fluid energy milling
- jet milling
Non-Newtonian Flow
Plastic
Pseudoplastic
Dilatant
- =non linear depends on shear rate
- RHEOLOGY (study of flow)
CAI
Compounding Aseptic Isolator
Aseptic Compounding device
AIR GOING INTO ISOLATER MUST PASS THROUGH HEPA FILTER
CACI
Compounding Aseptic Containment Isolator
Form of CAI
in which air exiting from CAI Passes through HEPA rententive filter
AUTOMATED
Isotonicity
Important Characteristic of STERILE DOSAGE FORMS
Sources of Contamination
Bacterial / Fungal / Particulate
MAINLY FROM PEOPLE
water / materials / packaging
Considerations for Facility Cleaning
NIH FDA 483
USP 797 Requirements
3 bucket system
KNOWLEDGE OF SITE FLORA
know what agents you need to use
Sterilization Methods
Thermal
Thermal = Moist Heat (STEAM)
Autoclave –> Protein Denaturation
121celcius for 15 min –> destroys bacteria & Spores
& Dry Heat
High temperature 160 celcius
Kills PYROGENS & microorganisms
1 hour dry heat = 15 min moist heat
Works with heat tolerant materials
Sterilization Methods
Non-Thermal
Radiation & FIltration
Gamma radiation cobalt 60
DNA DESTRUCTION
Drug solution filtration
AIR FILTRATION
Sterilization Methods
CHEMICALS
Gas & Liquid
Ethylene Oxide
use this when its the first time
Testing for Pyrogens
LAL = Limulus Amebocyte Test (horseshoe crab
MAT (monocyte activation test)
Rabbit pyrogen test
Prevention of Pyrogens
Difficult to remove
Removal for high temperature heat
IMPORTANT FOR PYROGENS
Sterile Products
Stability
-
Chemical
- Unstability in photo / hydrolysis / oxidation
- or deamination (PH)
-
Physical
- temperature / protein denaturing
- Aggregation / adsorption
-
Microbial
- PARTICULATES
- Biopharmaceutic/therapeutic
- TOXICITY
Chemical Stability
Also take account for INTERACTIONS w/ packaging
-
Degradation reactions
- Hydrolysis (pH)
- Oxidation
- PHOTO (light) amber glass
- Stress test
- deamination
Sterile Products
Compatability
W/ Bag (ns/d5w)
Administration set
filter
other drugs
Can be ADSORBED into the packaging etc
Sterile Products
Isotonicity
-
RBC
- Semipermiable
- WANT TO BE ISOTONIC
-
HYPERTONIC
- –> flows out of rbc
- Hypotonic
- –> flows IN
First Air
Unidirectional air that is exiting HEPA FILTER
essentiallly particle Free
Low Risk Level CSP
All activities with Class 100 (USP 5)
using sterile ingredients
LIMITED INGREDIENTS
FAST PROCEDURE
Simple LVP admixture
Medium Risk Level CSP
Multiple individual vials are COMBINED
Longer duration
transfers etc.
High Risk Level CSP
NON-STERILE INGREDIENTS
Powders etc
LONG PROCEDURES
poor air quality
no gowning
USP 828
RADIOPHARMACEUTICALS
compounded sterile products
USP 797
SOPS
Suggested Standard Operating Procedures
- Total of 23 WRITTEN & properly approved SOPs
Primary Engineering Control
PEC
LAF = LAMINAR AIR FLOW HOOD
ISO CLASS 5
Class 100
Site of compounding
USP 797
Personnel
Trained
Tested
& Recorded
Forms for the FDA to see if technicians were trained periodically
USP 797
Scope of Responsibilities
- Personnel training
- RX Prep
- CAREGIVER
- MONITORING
-
Dispensing & delivery
- tube systems
USP 800
-
Handling In Healthcare Settings
- HAZARDOUS DRUGS
-
ALL ABOUT YOU BEING PROTECTED
- nothing to do with the prep
- or technique
- Facility / Gowning / Equipment
USP 800
Gowning
DOUBLE GOWNING
- Has a hood, covers the face
- No exposed skin
- Double booties / double gloves
USP 800
Air Flow
Negative Air Flow (flow INTO this room) In Buffer room
Air goes into the room –> FILTERED OUT INTO ENVIRONMENT
DO NOT WANT the contaminated air to flow OUT into the rest of the building
ISO 7>7>5 > filtered out of building
USP 800
Hood Pressure
when we have a negative pressure room (chemo)
HOOD HAS POSITIVE PRESSURE
We want sterile air!!
DO NOT USE A CHEMICAL HOOD
USP 800
NIOSH
National Institute for OCCUPATIONAL SAFETY & HEALTH
- Defines Hazardous drugs (LIST)
- Carcinogens / teratogens etc
- ANTINEOPLASTIC –> target cancerous cells
- Defines Activites with these drugs
-
what can come in contact with the hazardous drugs
*
-
what can come in contact with the hazardous drugs
FDA
Insanitary Conditions
FDA 483
-
FDA AUDIT for Aseptic practices
- Watch the gowning
- Watch for sterilizaton / disinfection
- Every detail of what you’re doing
- WILL WATCH TECHNICIANS
FDA 503
A
Standard Pharmacy
Get an order and Fill for a PATIENT
controlled by state board (797 law requirements for some states)
FDA 503
B
Making something in advanced
–> SELLING IT
Like Mini Manufacturing
new equipment and have to SCALE UP things
Closed System Transfer Device
CSTD
-
Two Needles
- No contact with the air
- Exchanges Air & Drug
Administration Device
Very Important for STERILE COMPOUNDING
since everything is in packages
STERILE VS Non-STERILE
DIFFERENCES in Dosage forms
Most are THE SAME as in non-sterile
-
Main difference is:
- NO flavoring / colors / additives
- Buffers (mainain PH) / Preservatives
- Chelating Agents
Sterile Products
Special Specification
pH
Sterility
Particulates
Preservative Content
Potency
Water in Oil emulsion
Dry Gum
4-2-1 Method
Method to prepare W/O EMULSION
4 Parts Oil
2 Parts Water
1 Part Emulsifyer
-
Gum/emulsifyer is LEVIGATED w/ Oil
- thoroughly wet
-
Water is added
- until creamy white
- –> CRACKLING sound as it is titrated
Wet Gum
English Method
4:2:1 Ratio Still
BUT Emulsifying agent –> Water
Oil is then added LAST
