Solution Excipients Flashcards
Excipient Outline
Everything in dosage form except the intentionally therapeutically active substance
Excipient Specification Outline
Regulatory documents outlining the chemical nature and degradation potential of an excipient. Done by regulatory bodies and pharmacopeia labs
Ideal Excipient Outline
Chemically and Physically stable, low microbial content, compatible with drug + other excipients, packaging compatibility, non-toxic, inexpensive, palatable and easy to process
Excipient Sources Outline
Natural, semi-synthetic and synthetic
Excipient Natural Sources
Mineral oil (petroleum distillation and paraffin wax), water and surfactants (lecithin-egg yellows-emulsifiers
Excipient Semi-synthetic Sources
cellulose derivatives (gelling agents) and pegylated coconut oil (emulsifiers)
Common Solution Excipients
Solvents, solubility/permeability enhancers, antimicrobrial stabilisers, chemical stabilisers, physical stabilisers, palatability enhancers and processing enhancers
Solvent Outline
A substance that dissolves another to produce a solution. Water is most common (non-toxic even in high conc and absorbs a lot of ions).
Grades of Water Outline
Purified, Highly Purified, Water for injection and sterilised water for injection
Cosolvents Outline
Water miscible liquid, increases solvents lipophilicity
Cosolvent Considerations
Toxicity, irritancy, sensitising potential (tissue damage over time), flammability, cost, stability, compatibility and route of admin (eg external = greater irritancy tolerance)
Ethanol as a Cosolvent
Route: oral, topical and paraenteral. Cools during evapouration. Only used in adults (children don’t have alcohol dehydrogenase), drowsy effects
Propylene Glycol Outline
Polyhydric (2 OH groups) alcohol. Oral, topical, parenteral and octic routes
Glycerol Outline
3 hydroxyl groups per alcohol molecule. Route: oral, rectal and parenteral
Why might you use an oil cosolvent instead of an alcohol
Available for pediatric use, doesn’t evapourate as easily. NB be careful of people’s allergies
Fixed oil
Non-volatile plant-based oil. Commonly triglycerides of fatty acids from seeds.
Acidifiers Def
Substances that donate H+ ions to increase acidity (decrease pH) of solution. Alters solubility and permeability of substance. Eg citric acid and HCl
Alkalizers Def
Substances that donate an OH-, increasing alkaline of solution (increases pH). Alters solubility and permeability. Eg potassium hydroxide and sodium bicarbonate
Solubilisers Def
Increase apparent solubility of derug. Substance with hydrophilic outer region and drugs dissolves in internal lipophilic regions. Eg cyclodextrin and polysorbates
Manufacturing and Processing Excipients
Wetting agent, levigating agent, clarifiers, humectants and bulking agents
Wetting agent Outline
Hydrophobic powder displaces air and allows it to be wetted by water. Water covers particle and increases contact with air (liquid has to be energetically favourable)
Levigating Agents Outline
Liquid/ semi-solids used to reduce particle size. Grinding on an ointment slab
Clarifiers Outline
Filter aids adsorb any undissolved solid particles, subsequently removed by filtration. Leaves a clear solution. Eg crospividone
Humectants Outline
Lower vapour pressure and just reducing chance of evapouration eg glycol
Bulking Agents Outline
H bonds with protein instaed of water. Prevents the denaturation of proteins. Ensure stability of dosage forms. Eg trhalose
Preservatives Outline
Substance that extend the shelf life of medicines. Preventing oxidation and bacterial growth (bactericidal and bacteriostatic)
Preservative Selection Criteria
No toxicity/irritation/sensitivity, inhibit bacterial growth, broad spectrum, soluble and must be active over wide pH (doesn’t need to meet all criteria)
Where do you get info on excipients
Inactive Ingredients Database
Quaternary Ammonium Compounds Outline
Very effective perservative. Positively charged N bound to 4 other elements. Positively charged over all pHs (non proton sensitive). Not for internal use (irritant).
Parabens Def
Structurally similar akyl, esters of p-hydroxybenzoic acids. Greater activity (more permeable) as C chain increases but less soluble. Chelating agents increase activity
Preservatives in sterile dosage forms
Need to autoclave
Methyl Paraben Outline
Active at pH 4-9 (decreasing activity at high pHs), autoclaved in aqueous solutions, may sorb to certain plastics
What is a beneficial property of antimicrobial
Having both antibiotic and antifungal. Minimise amount of excipient required eg Benzoic acid, sorbic acid
Benzoic acid Outline
Only active (absorbed) at low pH (<4), only sparingly soluble in water. Works by intracellular acidification and protein binding making cell membranes leaky
Sorbic acid outline
Optimal between pH 4.5 and 6. Weaker acidifer then benzoic acid. Acts as surfactant due to carboxylic tail. Can be oxidised into toxix biproduct (uncommon).
Preservative Efficacy Testing outline
Challenge complete product (full dosage form) to up to a million bacterial cells. Use log fold reduction to measure efficacy. Shows how well product responds overtime to bacteria (in the 1000s). Test organism example: pseudomonas aeruginosa
Why aren’t there preservatives to prevent hydrolysis
Due to water usually existing in excess no substance will ever really be preferentially hydrolysed
Oxidation Outline
Adding O or removing H from compound. Changing drug structure, reducing shelf life. 3 steps: initiation, propogation (chain reaction) and termination
Antioxidant Outline
Reducing agents that are themselves preferentially oxidised in the presence of the drug (preventing drug from being oxidised). They stop process at initiation step of reaction
True Antioxidants Outline
React with free radicals stopping process at propagation eg
Reducing antioxidants Outline
Reducing agents that are preferentially oxidised stopping process at initiation eg sorbic acid
Synergists Outline
Enhance antioxidants eg EDTA
Palatability enhancers
Optimising taste, smell, texture, sight and sound.
Children preferences
Sweet with no undertones (bitter, sour, ect). Have stronger taste receptors
Sour chemical property
acidic
Salty chemical property
cations and anions
Bitter chemical property
High Mw
Sweet chemical properties
polyhydroxyl compounds
Sharp chemical properties
Unsaturation
How to mask tate
Flavour blending (eg acid and lemon), Flavour overshadowing, suspension/emulsion formation, viscosity enhancers (eg carbomer, adsorption/complexation of drug, cooling/heating sensation (tounge irritation) and sialagogue (increased salivation = less time in mouth eg citric acid)
