Lec 7- Aseptics Flashcards
1
Q
Pharmaceutics
A
2
Q
Drug stability and incompatibility summary
A
- Instability
- Incompatibility
- Shelf life
3
Q
Drug stability and incompatibility
Instability
A
- The product is modified due to storage conditions (e.g. time, light, temperature, sorption). An unsuitable product is formed
- Degradation-
- Irreversible chemical reactions (oxidation, hydrolysis-degradation in presence of water, photolysis, trace metal catalysis)
- Result in different chemical entities
- May be inactive or toxic (treatment failure)
- May be slowed but not stopped-
4
Q
Drug stability and incompatibility
Incompatibility- Physicochemical
A
- Concentration-dependent precipitation or insolubility
- Calcium and phosphate precipitate very quickly
- If you put calcium in at the start and phosphate in at the end, the calcium ions have a chance to complex with other materials
- Preventable or reversible
- Acid-base reaction
- If changes are visible- termed, physical (visual) incompatibility
- The new product is unsuitable for the administration because
- ‘Active’ drug has been modified e.g. increase in toxicity or
- Physical changes have occurred e.g. change in solubility
5
Q
Drug stability and incompatibility
Shelf life
A
- Restrictions applied by drug instability or incompatibility
- Accelerated stability testing
- Sterility issues e.g. L-glutamine
- Usually much shorter once diluted for administered
- Colour changes may indicate degradation to coloured decomposition products e.g. browning reaction with lysine or basic amino acids. NOTE: Add just before administration (Same with glutamine)
- Time is taken to reduce the concentration of the drug to reduce by 10%
6
Q
Factors affecting incompatibility
Summary
A
- Saturation or solibility limits
- pH
- Drug-drug co-precipitation
- Choice of diluent or infusion fluids
- Temperature effects
- Concentration effects
- Sorption phenomena
- Leaching of plasticiers
- Photodegradation
- Salting out
7
Q
Factors affecting incompatibility in infusions
A
-
Saturation or solubility limits- drug will remain in solution as long as it’s concentration is below saturation solubility
- For syringe drivers this may be affected time and temperature
- Precipitation may not occur immediately
- Co-solvents sometimes used (e.g. etoposide)
- Calcium and phosphate ions; preparation care
8
Q
Factors affecting incompatibility in infusion
pH
A
- Some drugs (weak acids) are formulated at high pH to achieve solubility
- If pH is reduced by addition of a less alkaline solution, precipitation may result
- Extremes of pH may affect the degradation rate of some drugs, buffers may be included in the formulation improve stability. Check the likely impact of changes in pH on stability if mixing drugs
- E.g. Ciprofloxacin- basic drug soluble at acidic pH; Infusion contain lactic acid
9
Q
Factors affecting incompatibility in infusions
Drug-drug co-precipitation
A
- Usually by mixing organic anions with cations (herapin and aminoglycosides e.g. gentamicin)
- May depend on the concentration of the solution
- Never mix in an infusion
- Flush the infusion line between administration with NaCl 0.9% if given via line
10
Q
Sorption phenomena
A
- Patient given TPN, came in with nothing wrong with eyes
- Patient got night blindness
- This was because vitamin A adsorbed onto the tubing of the delivery system causing night blindness
11
Q
pH of sc injections
A
12
Q
Factors affecting incompatibility in infusions
Choosing correct diluent and infusion fluid
A
- Drugs which are relatively unstable in aqueous solution may have degradation accelerated depending on diluent and pH
- E.g. Erythromycin should be reconsituted in water, administration in NaCl 0.9% (not glucose 0.5% which has an acid pH)
- Ringers Lactate/Hartsman’s solution
- Should be used with care
13
Q
Temperature effects
A
- Each 10 degree temperature rise can increase rate of reaction 2-5x
- Increased rate of hydrolysis of beta-lactam anti-biotics at elevated temperatures
- Cold can also affect some molecules (ampicillin)
- Higher temperatures can evaporate solvents or concentrate the drug solution
14
Q
Concentration effects
A
- Increases in drug concentration may increase the rate of degradation
- May be more significant in syringe drivers where higher drug concentrations are usually present (central line administration)
15
Q
Solubility- temperature
A
- Temperature will have an effect on the solubility of the drug dependent upon weather the dissolution reaction is an endo or exothermic reaction
- If exothermic and we increase the temperature we slow down the reaction and decrease solubility (rate of dissolution)
