Sterile dosage forms

Question 1

Sterile assurance level (SAL)

Answer 1

probability that a single unit subjected to sterilization remains non-sterile

Question 2

SAL of 10^-2

Answer 2

produce 100 units expect 1 to be non-sterile

Question 3

what is the value of SAL for GMP

Answer 3

10^-6

Question 4

what is the SAL for compounding

Answer 4

10^-3

Question 5

methods of sterilization (5)

Answer 5

steam
dry heat
gas 
radiation
filtration

Question 6

steam sterilization

• name of machine
• how work
• mechanism
• what does steam need touch

Answer 6

• autoclave
• water create steam in high pressure chamber (121degC for 15 minutes @~100kPa)
• superheated water transfers heat to microorganisms and kills via denaturation and coagulation of proteins
• steam needs come into contact with material you want to sterilize

Question 7

limitations of steam sterilization (autoclave)

• plastic
• chemicals (compounding consideration)
• typical use

Answer 7

plastic melts

chemicals break down
- cant be used for most compounded products

typically used to sterilize equipment
-ex. mops for clean room

Question 8

validation for steam sterilization (autoclave)

Answer 8

bacterial spore (typically bacillus)

Question 9

dry-heat sterilization/depyrogenation

• heat
• filter
• duration
• mechanism

Answer 9

heated to 200-250degC

HEPA filtered air

30-60min

dry heat dehydrates and burns (oxidizes) organisms

Question 10

validation of dry-heat sterilization/depyrogenation

Answer 10

3 log (or better) pyrogen reduction

Question 11

advantage of dry-heat sterilization/depyrogenation

Answer 11

use for powders and heat-stable items that are adversely affected by steam
-DOES NOT RUST METAL

Question 12

gas sterilization

• how work
• temperature
• gas concentration
• duration

Answer 12

pressure and vacuum chamber fills with gas

30-60degC

200-800 mg/I

several hours

Question 13

advantage of gas sterilization

Answer 13

materials that cannot withstand high temperature

-ex. disposable plastic syringe

Question 14

gas sterilization

• what gas
• what need gas to contact

Answer 14

gas such as ethylene oxide

must contact all surfaces

Question 15

mechanism of gas sterilization

Answer 15

alkylating agent interfering with cell metabolism

Question 16

disadvantages of gas sterilization

Answer 16

gas is flammable, toxic, and carcinogenic

Question 17

validation of gas sterilization

Answer 17

use biological indicator

- ex. bacillus atrophaeus

Question 18

types of ionizing radiation

Answer 18

radioisotope decay (gamma radiation)

electron-beam radiation (beta radiation)

Question 19

advantages of sterilization by ionizing radiation

Answer 19

low measurable residues

Question 20

purpose of sterilizing by ionizing radiation

Answer 20

products unable withstand heat sterilization

concerns about safety of ethylene oxide

Question 21

mechanism of sterilization by ionixing radiation

Answer 21

radiation ionizes water forming free radicals

free radicals react with organic cellular components (esp DNA)

leads to cell damage and death

Question 22

sterilization by filtration

-what is

Answer 22

physical removal of microorganisms

Question 23

sterilization by filtration advantages

Answer 23

• less equipment,

- heat/gas/radiation labile solutions

Question 24

sterilization by filtration

- what determines use

Answer 24

pore size determines use

range 10micrometer to ultra-filter (small molecules)

Question 25

parenteral definition - para - enteral

Answer 25

``` para = outside enteral = intestine ```

Question 26

where are parenterals given

Answer 26

preparations that are given outside the intestine | - parenterals intended for injection through sin or other external boundary tissue rather than through alimentary canal

Question 27

what are the "must"s of parenterals (5)

Answer 27

sterile no pyrogenic contamination no visible particulate matter stable compatible with diluents, delivery systems, other co-administered other drug products

Question 28

the should of paenterals

Answer 28

should be isotonic

Question 29

osmolarity - what is/ what measure - units

Answer 29

- osmolarity (osmotic concentration) is a measure of solute concentration units = osmoles of solute/L of solution

Question 30

osmolarity of 1 mole glucose

Answer 30

1 mol/L = 1osmole/L

Question 31

osmolarity of NaCl

Answer 31

1mol/L = 2osmole/L

Question 32

Question: what is osmotic concentration of normal saline? (0.9%w/vNaCl,M=58.5g/mol)

Answer 32

0.9% w/v = 0.9g/100mL = 9g/L Moles = mass/M, 9g/58.5g/mol = 0.154moles Since 1mole = 2 osmole/L , 0.154moles = 0.308osmol/L Answer = 0.308 osmol/L

Question 33

Tonicity - what is - is it unique to specific membs

Answer 33

measure of effective osmotic concentration across a semi permeable membrane property of solution in reference to a particular membrane (ex. RBC)

Question 34

does solute permeability affect tonicity

Answer 34

permeable solutions dont affect tonicity impermeable solutions do affect tonicity

Question 35

hypertonic solution

Answer 35

water flow out -> crenation | solute conc higher in solution

Question 36

hypotonic solution

Answer 36

water flow in -> lysis | solute conc higher in cell

Question 37

isotonic solution

Answer 37

no net movement of water

Question 38

storage and handling: expiration date - who sets - what ID - how det

Answer 38

- set by manufacturer ``` - ID time which conventionally manufactured drug prod expected maintain labelled: +identity + strength +quality + purity ``` determined based on product-specific studies

Question 39

storage and handling: BUD - what is - who assign - base BUD on what

Answer 39

date and time after which a cpd'd sterile preparation (CSP) cant be used and must be discareded assigned by pharmacy for a compounded preparation based on stability and sterility

Question 40

NAPRA BUD statement thing

Answer 40

date and time after which a compounded sterile preparation cannot be used and must be discareded because of a risk of loss of sterility administration of a compounded sterile preparation must begin before the BUD has passed

Question 41

USP797 (proposed revisions) for BUD

Answer 41

the date and time after which a CSP cannot be used bec its required characteristics (sterility, str, purity) cannot be ensured

Question 42

storage and handling: establishing BUD - what is critical factor - what is it based on

Answer 42

time is crit factor + more time = more risk of compromising stability/sterility based on shorter of stability and sterility

Question 43

watch video slide 7-11 and make cards fatass

Question 44

NAPRA: sterile unit

Answer 44

sterile unit: vial, ampoule, bag, drug, diluent 2 bag of solute represents 1 sterile unit 2 vials of cefazolin represents 2 sterile units 1 vial of sterile water for injection represents 1 sterile unit

Question 45

low contamination risk

Answer 45

final product compounded using up to 3 sterile units no ore than 2 septum punctures at the injection site for each sterile unic simple aseptic transfer technique drug prepared for one patient (patient-specific dose)

Question 46

medium contamination risk

Answer 46

final product compounded using 4 or more sterile units