Formulation of injections

Question 1

Parenteral

Answer 1

• injection through skin or mucous membranes
• sterile drug, solution, suspension packaged by hypodermic injection

SVP - airtight sealed in a container less than 100mL
LVP - more than 100mL

Question 2

Reasons for use of inj

Answer 2

Systematic delivery when other routes not available
Direct control ie anaphylaxis
correct rapid electrolyte imbalance
target specific areas
local action (local anaesthetics)
minimise systemic side effects
unconscious patients
uncooperative/ uncontrollable patients

Question 3

Formulation Issues

Answer 3

Volume of injection
Solvents
Selection of Vehicle
Types of vehicle
Excipients:
- Buffers
- Antioxidants
-Preservatives
Tonicity

Question 4

Volume of injection

Answer 4

• IV large volume 1-100ml

- IM 3ml, SC 2ml

Question 5

Solvents

Answer 5

• IV, Intraspinal –> dilute aqueous
• IM, SC –>aqueous, oily, suspension
  Desired properties:
• inert
• non-toxic
• fluid at body temp
• miscible with body fluids
• can be sterilised

Question 6

Selection of vehicle

Answer 6

Solubility increase with use of colsolvents, complexing agents, pH manipulation

Question 7

Types of vehicles

Answer 7

Aqueous based e.g. WFI
Water miscible solvents
- glycerol, ethyl alcohol, propylene glycol, glycol 300 400
- inert, mix with body fluids, maybe irritating and toxic

Question 8

Buffers

Answer 8

Solubiltiy
Stability
Issues:
- isotonicity
- buffer capacity
- pH change

Question 9

Antioxidants

Answer 9

autoxidation
pH effects: increase pH increase oxidation
chelating agents: catalyse oxidation

Question 10

Preservatives:

Answer 10

Multi-dose containers
loss into rubber closure
partitioning into non-aq phase

Question 11

Tonicity

Answer 11

isotonic: same osmotic pressure as blood plasma otherwise painful

Question 12

Suspension

Answer 12

crystal growth, easily resuspendable, particle size
Limitations:
- microbiological purity
- range of ingredients allowed
- mechanical flow properties (injectability)

Question 13

Emulsions

Answer 13

Limitations:

• autoclaving –> heat stress?
• pyrogenicity
• risk of solubilising into container
• choice of surfactant affects particle size

Question 14

Powders for injection

Answer 14

Advantages:

• low temp little degradation
• light and porous
• no contact with air

Disadvantage:

• hygroscopic product
• slow
• expensive equipment