Pharmaceutical Materials Flashcards
Parts of a drug
Active ingredient and excipients
Properties of a solid dosage formulation depend on …..
Chemical composition and solid structure of both drugs and excipients
What does using a different solid form of the same drug do
Alters the bioavaliability of the drug
Alters the stability of dosage forms
Influence the way in which the dosage forms can be processed and manufactured
Important for the regulatory control of drugs and dosage forms
Bioavailability defition
% of dosage that enters the systemic circulation
A drug must be in .. before it can cross the GIT wall
Solution
Different physical forms may have different:
Stabilities, chemical reactivities, flow, compression and water sorption properties
Molecule?
Entity containing a number of atoms held by covalent bonds
Particle?
Microscopic structure containing millions of molecules held by non-covalent bonds
Powder?
Visible mass of particles
Crystalline materials
Ordered, periodic arrangement.
Unit cell repeated in 3D’s
Have a melting point
Amorphous materials
No long range order
Non-random local structure
Have a glass transition temperature
What do crystal systems do
Reflect symmetry of arrangement of mols in the crystal
Used to identify solid forms of rugs
Most drugs are triclinic, monoclinic or orthorhombic
Polymorphism
Different crystal structures of the same compound
Diffent MP and solubility’s but the same solution/melt
Polymorph stability
At a given T and P only one form can be stable - the one with the lowest free energy (G)
Monotropic relationship
The same form is stable irrespective of temperature
Enantiotropic relationship
Either of the 2 forms may be stable depending on the temperature
Caffine polymorphisms forms
Form II changes to form I at 140dgrees
Form I then melts at 238degrees
Polymorph stability
Difficult to tell wether you have a stable form or not because the metastable form may take a very long time to transform to the stable form
Product shelf life`
2-3 years
Drug must remain stable over this period
How many Polymorph does a drug have
Depends on how hard you look
Apsirin has 2 and paracetamol has 3 that we know of
Crystal formation occurs in consecutive steps:
Supersaturation of solution -> nucleation
Crystal growth
Molecules diffuse to crystal surface and attatch to the growin crystal
Crystal habit types
The external shape of the crystal
Tabular
Platy
Prismatic
Acicular
Changes in crystal habit
Changes in crystal growth conditions can change the habit
Increase in the degree of supersaturation tends to yeild longer needles and thinner plates
Polymorph
Internal arrangement of the molecules in the crystal
Appearance of crystals with different habits often indicates…..
The presence of Polymorphs but habit and polymorphism are different and may change independently
Amorphous solid
Lacks long range order that is characteristic of a crystal.
Internal structure of interconnected blocks.
Synthesis of amorphous materials
Rapid cooling
Fast precipitation
High energy milling
Freeze drying
Glass transition of amorphous solid
At the glass transition temperature, the amorphous regions experience transition from rigid state to more flexible state making the temperature at the border of the solid state to rubbery state.
Amorphous dissolution
Less stable than crystaine so easer to dissolve
Resulting solution is supersaturated
Practical implications of amorphous
All amorphous systems will; recrystallise eventually
Solvent
the liquid in which the material is dissolved
Solvate
crystalline material that contains one or more molecule(s) of the solvent as part of the unit cell structure
Hydrate
a solvate where the solvent molecule is water, i.e., water of crystallisation
Anhydrous
no water of crystallisation is present
Pseudopolymorph
an alternative (bad) term for solvate
Solvate formation
Prepared by crystallisation from the solvent in question
Can form unexpectedly when the drug is in contact with a liquid
Hydrate Stoichiometry
• Usually highly specific ratios of water to drug, which leads to monohydrate, dihydrate, trihydrate
• A particular drug can have more than one hydrate form
• Channel hydrates tend to be unstable
Hydrate properties
Different MP, solubility’s and dissolution rates compared to anhydrous form
Hydrate dissolution
Anhydrous = breaking up solid into molecules (endo) and interaction with solvent (exo)
Hydrate = interaction with water already taken place
Multi component solid forms
Contain the drug and another molecule or ion
Salt
Solvate
Co-crystals
