Liquids and MR

Question 1

What are advantages of solutions

Answer 1

Homogenous system
* Drug uniformity is not necessary
Facilitate drug administration by oral and parenteral routes
Faster therapeutic responses
* Avoid first hepatic pass
Reduce potential for drug irritation in GIT
* With caps/tabs they can disperse on GI wall
Administrable by almost all routes of administration

Question 2

What are disadvantages of solutions

Answer 2

More difficult to store and transport
* May require refrigeration
* Cold chain = costly
More difficult to stabilise compared to solid product
More difficult to achieve accurate dosing for oral route
More difficult to mask unpalatable drug taste
More difficult to modify rate of drug release

Question 3

How can you enhance solubility of solutions

Answer 3

Co-solvency
pH adjustment and salt formation
Solubilisation
* Surfactant micelles
o Should not introduce foaming and toxicity
Complexation

Question 4

How can you enhance stability of solutions

Answer 4

Drug stability
* Use compatible excipients
* Reduce oxidation
o Antioxidants
o Chelating agents
o Control pH with buffering agents
o Sparging
* Formulate as powders for reconstitution
* Preservatives

Question 5

What are formulation requirements for solutions

Answer 5

Aqueous based
Neutral pH

Question 6

What are formulation requirements for topical

Answer 6

Aqueous or non-aqeuous vehicle
Formulated to evaporate to produce cooling effect

Question 7

What are formulation requirements for parenteral

Answer 7

Aqeuous or oil based
Comply wiht limits for pyrogens, endotoxins and visible particles
Neutral pH

Question 8

What are formulation requirements for nasal solution

Answer 8

Aqueous based with cosolvents
pH 5.5-6.5 preferred
Low buffering capacity

Question 9

What are formulation requirements for ocular

Answer 9

Aqueous based
Sterile with preservatives
Isotonic

Question 10

What are excipients required for solutions

Answer 10

Solvent
Solubilising agents
Stabilising agents
Preservatives
Viscosity modifiers
Tonicity adjusting agents
Taste modifiers
Colouring agents

Question 11

Examples of solvent

Answer 11

Water - purified, highly purified, water for injection and sterilised water for injection
Non aqueous solvents - alcohol, fixed oils
Esters
Dimethyl sulfoxide
Glycofurol

Question 12

Examples of pH modifying agents

Answer 12

Acidifying - HCl, Citric acid
Alkalising - NaCO3, NaOH
Buffering agents - Citric acid + sodium citrate, sodium acetate

Question 13

Examples of surfactants

Answer 13

Anionic - sodium stearate, sodium oleate
Cationic - cetrimide
Nonionic - Span, Tween, cetyl alcohol
Ampholytic - lecithin

Question 14

Examples of preservatives

Answer 14

Alcoholic and phenolic - ethanol, chlorbutol
Organic acids - benzoic acid, sorbic acids
Esters - methyl and propyl parahydroxybenzoic acid
Quaternary ammonium - cetrimide

Question 15

Examples of viscosity modifiers

Answer 15

Cellulose - methylcellulose, hydroylpropyl methylcellulose
Natural - xanthan gums, alginates
Vinyl - polyvinyl alcohol
Silicates - magnesium aluminium silicate
Polyacrylates - carbomers

Question 16

Examples of sweeteners

Answer 16

Nutritive - dextrose, fructose
Sugar alcohol - mannitol, sorbitol
High intensity - saccharin, aspartame

Question 17

Quality standards and compendial requirements for solutions

Answer 17

1. Uniformity of dosage units
2. Preservative and antioxidant concentration
3. Sterility, preservative efficacy and microbial tests
4. Physical attributes
5. Stability over proposed shelf life

Question 18

Differentiate the different drug release profiles

Answer 18

Question 19

When do you need to use MR formulations

Answer 19

Maintain drug therapeutic range over longer periods
Achieve chronotherapy
Improve therapeutic compliance
Achieve better health outcomes

Question 20

What are key features of MR formulations

Answer 20

Max dose for a unit peroral dosage form is 0.5 to 1g
Biological half life
Therapeutic index
Ideally BCS Class I

Question 21

Mechanisms required for MR

Answer 21

Drug dissolution - controlled
Diffusion of dissolved drug molecules
Swelling o carrier system
Erosion of carrier system
Stimuli responsive system

Question 22

Methods to achieve modified drug release

Answer 22

Polymer membrane system - diffusion through polymer membrane
Polymer matrix system - drug is distributed throughout polymer matrix
Polymer membrane-matrix system - drug diffusion through polymer membrane per polymer matrix
Inert bead system - drug coated on inert seed
Microporous membrane system - dissolves intestinal fluid
Repeat action delivery systems - multilayers of drug and coat \
Osmotically controlled systems

Question 23

Explain the components of osmotically controlled systems

Answer 23

Question 24

Patient counselling for MR

Answer 24

Dose and dosing frequency
Do not interchanged with conventional tablets dosage forms of the same drug
Do not interchange with another modified release system of the same drug
Do not crush or chew tablets
Ghost membranes may appear

Question 25

Quality standards and compendial requirements for MR

Answer 25

1. Physical characteristics
2. Uniformity of dosage units - content
3. Disintegration profile
4. Drug dissolution profile