EXAM 3 L3 Flashcards
Three physical states of matter for dosage forms
Solid State
Liquid State
Gas state
Crystalline Solid def.
Solid form displaying highly ordered molecular packing. The long range 3D ordered structure will generate diffraction of X rays (LOW MOBILITY)
Amorphous Solid Def.
A non-crystalline solid that possesses NO long-range order and DOES NOT give diffraction of x-rays (HIGH MOBILITY, HIGH SOLUBILITY)
Crystal solid properties
Physically more stable
Less hygroscopic
Relatively less water soluble
Amorphous solid properties
Physically less stable (tend to transform to stable crystalline form)
More hygroscopic
Relatively more water soluble
Polymorph def.
Chemically identical crystalline forms in which the constituent molecules adopt different packing arrangements (crystalline forms)
Ritonavir story
Soft gel - form I
Two yrs after, it started failing dissolution
Analysis = crystal form crystallized
Solvate def.
A substance that incorporates solvent molecules into crystal structure
Hydrate def.
A hydrate is a solvate that contains water in the molecule
Anhydrate means no water molecule
(Monodrate = one water molecule per drug molecule)
Hydration affects…
Solubility, dissolution, and bioavailability
What is X-ray diffraction (XRD) method used for?
To determine crystalline forms
Diff. in XRD peaks for amorphous vs. crystalline forms
Amorphous - lacks crystalline peaks (relatively flat)
Crystalline - have different XRD patterns (Spiked)
General considerations in dosage form design:
Preformulation studies
Physical Descriptions
Microscopic Examination
Vapor Pressure
Melting Point
Preformulation studies:
Physical description
Microscopic examination
Vapor pressure
Melting point depression
Physical description/properties:
Solids, Liquids, Gases
Properties: Particle size, crystalline structure, melting point, solubility
Microscopic examination
Particle size
Particle size distribution
Particle shape
Vapor Pressure
Vapor pressure is an indication of a liquid’s evaporation rate. It relates to the tendency of particles to escape from the liquid (or a solid). A substance with a high vapor pressure at normal temps. is often referred to as volatile
Volatile drugs
Can migrate within a solid dosage form
Safety concern: Personnel exposure to volatile materials
Melting point
The melting point, of a pure crystalline solid is defined as the temperature at which the pure liquid and solid exist in equilibrium
Identity
Purity determination
General Considerations in dosage form cont.
Preformulation studies (cont)
Solubility
Solubility and pH
Dissolution
Membrane permeability
Partition coefficient
pKa/dissociation constants
