Solution Microbiological Stability

Question 1

Non-sterile Solutions Examples

Answer 1

Solutions, Suspensions and Elixirs

Question 1

Sterile Solutions Examples

Answer 1

Eye drops, IV fluids, injections/vaccines and irrigations

Question 2

Non-sterile Solutions Advantageous Properties

Answer 2

Homogenous, fast therapeutically, easy swallow, better taste masking and reduced irritation

Question 3

Non-sterile Solutions Disadvantageous Properties

Answer 3

Less stable then sterile (accessible to microorganism growth, lower shelf life) and bulky transport

Question 4

Sterile solutions outline

Answer 4

Bacterial and pyrogen physical/chemical contamination free. Used mainly in parenteral dosage forms.

Question 5

Sources of Contamination Outline

Answer 5

Human Flora, water, dust/air/soil. In pharmacuetics: raw material contamination, manufacturing equipment contamination and manufacturer contamination (most common)

Question 6

Oral Solutions outline

Answer 6

Administered to GIT, Wide ranges of pH but average = 7. Excipients: buffers, preservatives, antioxidants, viscosity modifiers, solubility enhancers, flavours and colour aswell as active

Question 7

Oral Syrups Outline

Answer 7

Highly conc aqueous solutions containing sugar (or substitute with suitable chemical agent = diabetics). Excipients: water, sucrose (/substitute), preservatives, colours, flavours and active (soluble in syrup base)

Question 8

Oral Elixirs Outline

Answer 8

Clear hydroalcoholic solution. Excipients: purified water, alcohol, poly-alcohol cosolvents, sweetening agents, colour, preservatives (not needed if alcohol >12% w/v)

Question 9

European Pharmacopia Rules for Non-sterile Oral solutions

Answer 9

No Ecoli present, there must be less the 1000 aerobic bacteria and no more then 100 fungi per mg/ml.

Question 10

Considerations for multidose preparations

Answer 10

Requires certain preservatives

Question 11

Microbial Contamination Sources Outline

Answer 11

Facility (flow of personnel, waste and material), equipment, process, materials, utilities (institutes water/gas) and personnel

Question 12

Ubiquitous Bacteria

Answer 12

Bacteria that can adapt to survive in a variety of enviorments. Can cause contamination through multiple forms

Question 13

Non-sterile USP Microbiological Attributes Considerations

Answer 13

Product’s microbial stability be evaluated in terms of use, nature and potential hazard. Different categories have different frequency of testing. Tests include: total counts and microbial contaminants (with definitive limits)

Question 14

Why must parenteral dosage foerms be sterile

Answer 14

Most bypass immune defences (straight into circulation)

Question 15

Terminal Sterilisation Outline

Answer 15

Completed dosage form is placed in an autoclave (assuming it’s non-biodegradable and won’t evapourate). Put under 121 degrees C and 15lbs/inch^2 removing any contamination that exists intrinsically/ added during manufacturing

Question 16

Aseptic Technique Outline

Answer 16

Each component of dosage form has an individual sterilisation step and then combined together aseptically

Question 17

Antimicrobrial Agents Outline

Answer 17

Inhibit microorganism growth. Added to multidoses and single doses that can’t be terminally steralised. Tend not to use as can interfere with growth of human cells

Question 18

Sterile Solutions Regulations

Answer 18

EU GMP annex 1, European Pharmacopia, Pharmaceutical Inspection Convention and Pharmaceutical Convention Cooperation Scheme

Question 19

EU GMP Encompasses What

Answer 19

Clean room classification, monitoring, technologies, personnel, premises, equipment, sanitation, processing, sterilisation methods, aseptical filling and finishing

Question 20

How a drug molecule can be chemically destabilised

Answer 20

Hydrolysis, oxidation, photolysis and racemization

Question 21

How proteins can be chemically destabilised

Answer 21

Denaturation, aggregation, adsorption and fibrillation (sticking together due to opposite charges)

Question 22

Molecules most susceptible to hydrolysis

Answer 22

Carboxylic acid derivatives: esters, amides, acids and alkalis

Question 23

Hydrolysis Outline

Answer 23

Oxygen of water attacks carbonyl carbon (electron deficient C). Causing a donation of a substituent to the water. Eg an ester forms a carboxylic acid and an alcohol. Hydrolysis occurs in solutions, suspensions and emulsions

Question 24

Result of aspirin Hydrolysis

Answer 24

Aspirin donates a C2H2O group to water forming scalic acid and ethanoic acid

Question 25

Methods of Avoiding Hydrolysis

Answer 25

Avoid moisture contact during maufacture, packlage in blister packs in areas of controlled humidity and temp, drug should be kept at optimum pH (buffered), formulate as tablets/dry powders (not liquids)

Question 26

Oxidation Outline

Answer 26

Loss of electrons from a substance forming a free radical resulting in a chain reaction. Catalysed by enzymes. 3 steps: initiation, propagation and termination

Question 27

Oxidation Initiation Outline

Answer 27

Substance loses electrons becoming a free radical

Question 28

Oxidation Propagation Outline

Answer 28

Free radical takes electrons from another drug forming chain reactions

Question 29

Oxidation Termination Outline

Answer 29

2 free radicals pair together and propagation stops

Question 30

Oxidation Sensitivity Outline

Answer 30

Reflects stability of dosage form to high oxygen conc in air. Oxidation catalysed by oxygen, heavy metal ions and light, freee radicals.

Question 31

Substances sensitive to oxidation

Answer 31

Aldehydes, alcohols, phenols, alkaloids, unsaturated fats and oils

Question 32

Avoiding Oxidation Outline

Answer 32

Replace air in headspace with nitrogen, control pH, chelating agents, antioxidants and low temps

Question 33

Antioxidants Outline

Answer 33

Substances that are preferentially oxidised (instead of drug). Sodium metabisulfate, sodium bisulphate, ascorbic acid and tocopherols