What properties to liquid crystals have?
Flow properties similar to liquid
Optical properties similar to solid
What are liquid crystals?
An intermediate state of matter with an ordered arrangement of atoms or molecules
How are liquid crystals described?
With having birefringence
What is birefrengence?
The ability to split light into 2 rays travelling at different speeds, directions and refractive indexes
What are three different structures and arrangements of crystals?
Lyotropic LC: long ranged orientational order achieved by the additions of a solvent
Thermotropic LC: occur within a certain temperature range
Metallotropic LC: contains metals
What is polarised light?
Light that travels in one single direction
What are the two filtering units of the polarised light microscope?
Polariser which is added to the optical pathway beneath the specimen. This filters the light
Analyser which is placed over the front of the lens objective in the body of the microscope
What happens to the polarised light if the sample displays biefrengence?
Some of the light will go through the molecule, one of the rays will be blocked by the analyser
What substance are isotropic?
Substances which do not display birefrengence e.g. Water, amorphous solid
What substances are anisotropic?
Substances which do display birefrengence e.g. Liquid crystals, crystalline solid
What is seen in an isotropic sample under a polarised microscope?
Light goes through sample without a change in direction will be blocked by the analyser, so you see a black background
What is seen in an anisotropic sample under a polarised microscope?
You see shininess with a dark background.
Dark background is due to the light being blocked by the analyser
The shininess is due to some light being able to pass through due to the sample displaying birefrengence
Why would some systems retain their optical properties when mixed with other components while other systems dont?
If the system is dissolved in the other component the optical properties will be lost as the system will no longer be liquid crystalline, however if a system is not dissolved and is suspended in the other component, its optical properties will be retained as it has not lost its crystalline structure
What are the benefits and disadvantages of choosing a crystalline solid as a dosage form for a drug?
+ drug is very stable
+ there is a sharp melting point
- harder to dissolve
- so harder to absorb
- cknsequently, lower bioavailability
What are the advantages and disadvantages of using an amorphous solid as a drug formulation?
+ easier to dissolve
+ easily absorbed
+ higher bioavailability
- less stable, has a variable melting point
What are the four different types of solid forms?
Polymorphs, amorphous, solvate, salt
What are the different kinds of particles that can constitute the different solid forms?
Active molecule Solvent molecule Acid Deprotonated molecule Protonated active molecule
What is crystalline arrangement?
Ordered arrangement of atoms or molecules
Often organised in Long range order and symmetrical
The compounds can have more than one crystalline arrangement, such compounds are called polymorphs
What is amorphous structure?
Structure of solids which have a random arrangement of atoms or molecules
This lacks long range order characteristic of crystals
What is the difference between liquids and liquid crystals?
Liquids have a random arrangement of atoms or molecules
Liquid crystals are an intermediate state of matter and have an ordered arrangement of atoms or molecules
They display flow properties similar to liquids
What is anisotropic property?
Where a substance displays differences in the optical properties of a material when measured along different axes
The substance has optical properties that vary with the orientation of incident light
They affect light differently in different directions
What are isotropic properties?
Where molecules of a substance are in random motion and orientation
The optical properties of the material is identical in all directions so no birefrengence is observed
What are some examples of anisotropic materials?
What are examples of isotropic substances?
Liquid paraffin in oil ohase
Water in aqueous phase,
Cod liver oil in oil phase
What must be considered when developing a formulation?
When drug substance is first produced it has to be certain that the desired solid form is obtained in a consistent, pure and reproducible manner
During formulation, must ensure that no undesireable transformation takes place
Solvents that generate solvates should be avoided
(If solvate is generated and then desolvated during the final formulation step then the final polymorph could differ from the original one)
The solid form should not be transformed during storage
Changes in the solubility after taking the drug may make the drug ineffective or toxic
In the choice of a crystalline or amorphous formulation for a drug which one is better?
Crystalline because it is the most thermodynamically stable polymorph.
Although it has low solubility and bioavailablility, this is a small price to pay for the large advantage of chemical stability
Solubility can be improved using techniques like cosolvent addition, complexation, salt forms, etc.
What are some examples of polymorphic drugs?
What are the differences between different forms of ranitidine-HCl?
The drug is an H2 receptor atagonist
FormI MP: 134-140°C
FormII MP: 140-144°C
In environments of high humidity there is a preferential lose of form II so form I more stable in high humdity
What are the differences between polymorphs of aspirin?
Form II reverts back to form I at ambient temperatures
This indicates that I is more stable than II
What are the differences in polymorphs of paracetemol?
Form I has a MP of 169°C
Form II has a MP of 157°C
Form III is highly unstable
It also has poor compression properties
What are the differences between the polymorphs of carbamazepine?
Beta polymorph was developed from solvent of high dielectric constant (i.e. High polarity)
Alpha polymorph was developed from a solvent of low dielectric constant
In the gibbs triangle, where do we find 100% of a substance?
At the tip/edge
What are the ideal properties of a cosolvent?
It increases the solubility of the solute in the solvent
It increases the miscibility of the other two components
It must be miscible in both components
What happens when the cosolvent is soluble in both liquids?
The mutual solubility of the liquid pair is increased