Solution formulation and partitioning Flashcards
What are some of the typical ingredients in a solution formulation
API
Solvent
Excipients to help increase solubility
Excipients to control physical conditions
Excipients to maintain quality
What does choice of solvent depend on?
The use of the solution and nature and physiochemical properties of API
WATER
Water is the most widely used solvent :
Physiologically compatible and palatable
Lack of toxicity
Dissolves wide range of ionisable materials
Widely available
Types of water (1)
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.
Types of water (2)
Water for injections - prepared in a similar way to purified water but much more strict conditions
When are non aqueous solvents used ?
used if the substance is not properly soluble in water, not stable in water. Choosing a solvent depends on toxicity, sensitivity, stability, cost, flammability.
Non Aqueous solvents - fixed oils
Expressed from seeds, fruits or other plants
Non volatile
Used for intramuscular injection
Example - Almond Oil, Olive Oil, Soya oil etc.
Non-aqueous solvents - alcohols
Tend to be used as cosolvents
Osmotic Property Modifiers
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.
Viscosity enhancing agents
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
Antioxidants
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.
Preservatives (1)
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.
Problems with preservatives
Ad/absorption into packaging materials
Efficacy can be affected by pH of solution
Sweeteners (1)
Sucrose is a widely used sweetener . However, it can cause dental problems and is not suitable for diabetics.
What are some different types of sweeteners ?
Diabetic Preparations - Sorbitol, Mannitol, Xylitol and glycerol
Natural Sweeteners- Honey, liquorice
artificial sweeteners - aspartame, sucralose . Artificial sweeteners can give a bitter taste
Flavours
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
Colours (1)
Colours improve appearance of products.
Chose colours must have acceptable safety
Colours may need protection from UV light, oxidising or reducing agents, extreme pH.
Colours (2)
Natural colours usually more acceptable, but less bright and subject to variability
A particular colour can have many names
Partitioning Background
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.
Pharmaceutical applications
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.
What are preservatives used for ?
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.
What is sorption in infusion sets?
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.
How to determine logP
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.
