Up to the final Flashcards
Beyond use date
used for compounded prescriptions
Expiration dates
used by pharmaceutical manufacturers
<795>
non sterile compounding
<797>
sterile compounding
<1178>
good repackaging practices
use suitable containers with an equivalent closure system
label has appropriate storage conditions and BUD
include lot number
<1191>
stability considerations in dispensing practice
Stability
capacity of a drug product to remain within specifications established to ensure its identity, strength, potency, quality and purity
Signs of lack of stability
change in performance or appearance
efficacy failure
Assay
strength
indicates the amount of API in dosage form
Does stability apply to homeopathic drugs, allergenic extracts, and new drugs for investigational use?
no
What from the environment affects stability?
pH, temp, light, oxygen, CO2
How do drugs and excipients affect stability?
particle size
relative purity of excipients
How does microbial contamination affect stability?
API, excipients, processing
Trace metals and catalysts can affect?
stability
How do closure systems affect stability?
moisture in containers
Chemical stability
each active ingredient retains its chemical integrity and labeled potency within the specified limits
Physical stability
the original physical properties, including appearance, palatability, uniformity, dissolution, and suspendability, are retained
Microbiological Stability
Sterility or resistance to microbial growing is retained according to the specified requirements; retain effectiveness within the specified limits
Therapeutic Stability
therapeutic effect remains unchanged within shelf life
Toxicological stability
no significant increase in toxicity occurs
Common pathways for chemical degradation
hydrolysis, oxidation, photodegradation, dehydration, isomerization, decarboxylation
For official compounded preparations, use ingredients that meet requirements of ?
compendial monograph
USP or NF grade or what substances should be used for preparations?
Analytical Reagents
Certified American Chemical Society
Food Chemical Codex
Manufactured containers are labeled with the expiration date and?
batch control number
BUDs for compounded prescriptions are assigned based on?
Professional experience
careful interpretation of literature and laws
worksite policies and SOPs
NECC Case study
product caused fungal meningitis
resulted in a lot of deaths
14 people indicted
Drug Quality and Security Act
Amended FD&C Act to grant FDA more authority to regulate and monitor the manufacturing of compounded drugs
Compounded sterile preparations examples
injections, infusions
irrigations for internal body cavities
ophthalmic
preparations for pulmonary inhalation
baths/soaks for live organs and tissues
implants
Category 1 CSPs stored at CRT BUD
12 hours or less
Category 1 CSPs refrigerated BUD
24 hours or less
Category 2 CSPs stored at CRT BUD
more than 12 hours
Category 2 CSPs when refrigerated BUD
more than 24 hours
BUD is not to exceed
shortest expiration date or BUD of any components
Potassium Cyanide in Tylenol capsule is
hygroscopic, changes capsule appearance
Solid dosage forms instability signs
appearance of fog/liquid droplets
clumping of product
formation of crystals on outside of dosage form/on cap/vial
Sticking and Picking
removal of tablet surface material due to sticking to die wall or a punch face
Binding
improper tablet ejection due to the tablet sticking to the die
Double Impression
additional impression on tablet face due to the free rotation of the punches
Mottling
Unequal distribution of color on a tablet with light or dark areas
Chipping
breaking of tablet edges while tablet leaves the press or during subsequent handling
Cracking
small fine cracks on the upper and lower central tablet surface or very rarely on the sidewall
Capping
partial/complete separation of top or bottom crowns from main tablet body
Lamination
separation of a tablet into two or more distinct horizontal layers
Visual defects in tablets could be related to imperfections in?
tableting process
formulation design
machine
multiple factors
Lamination cause and remedy
caused by rapid decompression
fixed with reduced turrent speed
Capping cause and remedy
improper/deep concave tooling
use flat face punches
Picking cause and remedy
too much moisture in granulated materials
dry granules properly, adjust humidity conditions
Binding Cause and Remedy
insufficient or improper lubricant
fix by increasing amount/change lubricant type in formulation
signs of instability in hard and soft capsules
consistency, softening of capsule
cracking/drying of capsule
release of gas
distended seal
Signs of instability for uncoated tablets
excessive powder/pieces
from abraded, crushed/broken tabs
cracks/chips
swelling
mottling
discoloration
fusion of tablets
crystals
Signs of instability coated tablets
cracks
mottling
tackiness
crumpling
tablet-to-table color variation
abrasion/chipping on edges
signs of instability dry powders and granules
hard cakes
color change
unusual caking
fog/liquid droplets
odor
difficult with reconstitution
What is the optimal route of administration for first line drugs that treat asthma and COPD?
pulmonary
Salbumatol
used for symptomatic treatment of asthma and COPD
What are 200 million alveoli good for?
vast/large surface area for drug delivery/diffusion
What is the main function of the lung and respiratory system?
maintain normality of arterial blood gasses O2 and CO2
Advantage of pulmonary delivery of drugs
high drug concentrations directly to disease site
bypass first pass metabolism
achieve a superior therapeutic effect at a fraction of the dose
smaller diffusion barrier
What does MDI stand for
metered dose inhaler
Metered dose inhaler
aerosol/product that depends on the power of a propellant to dispense an API in the form of finely dispersed particles/droplets
pressurized container having a meter dose valve that allows an exact amount of the dose to be delivered
Advantages of aerosol application
portable
removes the dose from the device without contaminating the remaining drug dose
MDI protects drug against degradation by exposure to light, moisture, or O2 oxidation
container is tamper proof
Challenges of aerosol application
coordination of patient is difficult to ensure
deposition of drug to lower airways may be impeded by high volumes of mucus
Therapeutic benefit of inhalers depends on adequate and consistent drug deposition in?
the lower respiratory tract
Deposition is a function of
particle size
What is the main criterion by which pulmonary formulations are judged?
size of inhaled particles
Upper respiratory tract
nasal cavity, pharynx, larynx
lower respiratory tract
trachea, bronchus, bronchiole, alveoli
Inhaled particles 5-10 micrometers end up where?
in the trachea/bronchi regions
Inhaled particles greater than 10 micrometers end up?
in the oropharynx
Aerodynamic diameter
eliminates the effects of varying particle shapes/geometry and allows us to control for particle density
diameter of a spherical particle of unit density that possess the same gravitational settling velocity as the aerosol/any particle used for lung delivery
MMAD
in a log normal distribution of particles, the diameter at 50% of the particles by mass are larger and 50% are smaller
MMAD> 10 micrometers
trap in trachea
MMAD 10-1 micrometers
settle into bronchioles and alveoli
MMAD < 1 micrometers
easily exhaled
Bronchi and Trachea have ?
high air velocities and turbulence
inertial impaction
predominant mechanism of particle deposition in upper airways
gravitational sedimentation
predominant mechanisms for particles to transit towards the bronchioles
Solid dosage form BUD at CRT
180 days
Preserved Aqueous Dosage forms BUD at CRT
30
Non-preserved aqueous dosage forms BUD at refrigeration
14 days
Nonaqueous dosage forms BUD at CRT
90 days
What are the types of inhalers?
metered dose
dry powder
nebulizer
Purpose of propellant
provide driving pressure to force the therapeutic agent from the MDI to the upper respiratory tract
exhibit the required evaporation rate to facilitate particle delivery to the required site within the respiratory tract
dry powder inhalers
deliver API only when the patient inhales through them
no propellant
has a mechanical actuator to break an enclosure
Lactose is an inert…
carrier of API
nebulizers
takes a solution and turns it into ultra fine, micron-sized particles
may be single dose pump/continuous flow depending on treatment
droplets: 1-5 micrometers in size
