Solution formulation and partitioning

Question 1

What are some of the typical ingredients in a solution formulation

Answer 1

API
Solvent
Excipients to help increase solubility
Excipients to control physical conditions
Excipients to maintain quality

Question 2

What does choice of solvent depend on?

Answer 2

The use of the solution and nature and physiochemical properties of API

Question 3

WATER

Answer 3

Water is the most widely used solvent :

Physiologically compatible and palatable

Lack of toxicity

Dissolves wide range of ionisable materials

Widely available

Question 4

Types of water (1)

Answer 4

Potable water ( drinking water)

Water for preparation ( purified water) freshly boiled and cooled

Purified Water - water purified by distillation, ion exchange or reverse osmosis. Water is stored in a way which prevents growth of bacteria.

Question 5

Types of water (2)

Answer 5

Water for injections - prepared in a similar way to purified water but much more strict conditions

Question 6

When are non aqueous solvents used ?

Answer 6

used if the substance is not properly soluble in water, not stable in water. Choosing a solvent depends on toxicity, sensitivity, stability, cost, flammability.

Question 7

Non Aqueous solvents - fixed oils

Answer 7

Expressed from seeds, fruits or other plants

Non volatile

Used for intramuscular injection

Example - Almond Oil, Olive Oil, Soya oil etc.

Question 8

Non-aqueous solvents - alcohols

Answer 8

Tend to be used as cosolvents

Question 9

Osmotic Property Modifiers

Answer 9

Make solution isotonic with tissue fluid to avoid pain and irritation

Necessary for Injections

Sodium chloride, potassium chloride, mannitol and dextrose are usually used

Added after all other ingredients.

Question 10

Viscosity enhancing agents

Answer 10

Viscosity must allow solution dose to be measured accurately

Viscosity increased to enable aqueous based topical solutions to remain in place for longer time

Some solutions have increased viscosity without need for additives

Question 11

Antioxidants

Answer 11

Used to enhance stability of therapeutic agents that are susceptible to oxidation.

Antioxidants exhibit higher oxidative potential that the drug

Both water-soluble and water-insoluble antioxidants are available.

Question 12

Preservatives (1)

Answer 12

Most water containing pharmaceutical solutions will support microbial growth. Contamination comes from raw materials or introduced during manufacture.

Preservatives should be chemically stable over the shelf life of the product.

Have low toxicity, odourless and stable.

Question 13

Problems with preservatives

Answer 13

Ad/absorption into packaging materials

Efficacy can be affected by pH of solution

Question 14

Sweeteners (1)

Answer 14

Sucrose is a widely used sweetener . However, it can cause dental problems and is not suitable for diabetics.

Question 15

What are some different types of sweeteners ?

Answer 15

Diabetic Preparations - Sorbitol, Mannitol, Xylitol and glycerol

Natural Sweeteners- Honey, liquorice

artificial sweeteners - aspartame, sucralose . Artificial sweeteners can give a bitter taste

Question 16

Flavours

Answer 16

Flavours to mask a salty taste - Butterscotch, apricot, peach and vanilla etc.

Flavours to mask a bitter taste - Cherry, Mint etc

Flavours to mask a sweet taste - Vanilla, fruit and berry

Flavours to mask a sour taste - Citrus and raspberry

Question 17

Colours (1)

Answer 17

Colours improve appearance of products.

Chose colours must have acceptable safety

Colours may need protection from UV light, oxidising or reducing agents, extreme pH.

Question 18

Colours (2)

Answer 18

Natural colours usually more acceptable, but less bright and subject to variability

A particular colour can have many names

Question 19

Partitioning Background

Answer 19

Drugs and excipients often encounter two immiscible phases usually one aqueous and one liquid phase. Chemicals added to one phase will partition into the other depending on the relative affinities.

Question 19

Pharmaceutical applications

Answer 19

Drugs need to cross cell membranes in order to act. Cell membranes are lipids so drugs must have a reasonable logP for good absorption to take place. (Partition coefficient). Drugs with high logP tend to be absorbed relatively quickly because of a relatively high liquid solubility.

Drugs with low logP tend to have good aqueous solubility but might not be absorbed as well. There may be other way for drugs to cross cell membranes such as active transport mechanisms.

Drugs with high logP may have a long half life in the body because they partition into body fat.

Question 20

What are preservatives used for ?

Answer 20

Use in emulsions

Antimicrobial preservatives added to creams and other emulsions to prevent spoilage.

Usually need to add two or more preservatives with different logPs so one is partitioned into the oil phase and the other in the aqueous phase.

Question 21

What is sorption in infusion sets?

Answer 21

Drugs sometimes given to hospital pt via infusion which requires the use of a plastic bag to hold the drug in. Drugs can adsorb of absorb into plastic, lowering available drug concentration.

Question 22

How to determine logP

Answer 22

Take known quantities of an aqueous solvent and an oily organic solvent.

Add a known amount of drug and mix at constant temp for suitable time

Allow two liquid phases to separate, then determine drug concentration in one or both phases.