L31 Solutbility TJ and GT Flashcards
A solution is defined as:
a mixture of two or more components to form a homogenous molecular dispersion.
A solution can be a…
solid dissolved in another solid, a liquid or a gas
solubility depends on the
solvation energy of the solute in the solvent overcoming both the crystal lattice energy of the solid + the energy to create space for the solute in the solvent.
–> Other factors intrinsic to the drug molecule include lipophilicity, ionisation potential and size
What is dissolution rate affected by and what is solubility affected by
Dissolution is affected by particle size, distribution, and the dissolution media, degree of agitation of the solid. Basically the Noyes Whitney parameters, so don’t forget viscosity/ surface area for diffusion
solubility is affected by Temperature and pH, hydrophobicity, hydrophilicity, the solvent and surface area of drug.
What are the consequences of poor dissolution in drug development?
Poor dissolution will influence the ability to achieve efficacious and toxicology relevant exposure in animals
It will also affect the bioavailability of the drug.
The process by which a tablet or capsule -> granules is known as
disintegration
The process by which a granule-> fine particles is known as
disaggregation
Sometimes, solubility in some compounds can be poor. what causes this?
- High crysallinity or a high melting point
- Zwitter Ions
- Salts may be insoluble
- Drug must have a high log P value
- Molecular weight can be too high
- Lacking an ionisable group
What methods can we employ to improve stability?
solid state modification (particle size/polymorph/new salt)
- Liquid systems (co-solvents, lipid based system, solutions, emulsions)
- Additives/ complexes (surfactants, cyclodextrins, polymers)
- Carrier mediated systems (liposomes/nanoparticles/ solid dispersions)
How can solid state modification improve drugs stability?
solid-state modification improve drug solubility by the addition of polar groups, such as carboxylic acid, ketones, amines which can increase hydrogen bonding between the drug and the water molecules, thus resulting in an increase in solubility.
Can polymorphs influence solubility? why?
Yes because different polymorphs have different crystal lattice energies
what co solvents are used to improve stability
propylene glycol and ethanol, although ethanol is not always used in arab countries because haram
how do surfactants improve solubility?
They are amphipathic with both hydrophilic and hydrophobic properties. When placed in water, the surfactants will form micelles
What is complexation
Complexation is a method used to increase solubility. It relies on weak forces such as:
- London forces
- Hydrogen bonding
- Hydrophobic interactions
As complexation agent increases, solubility also increases, up to a certain point. This can be enhanced by the addition of polar groups
there are three main types of surfactants:
Cationic: Cetyl Trimethyl ammonium bromide
Anionic: SLS
Non ionic: Tween 80
