Lecture 3: Solid State Flashcards
solid state
-arranged in fixed geometric lattices/patterns
-crystalline or amorphous
crystalline solid
-highly ordered molecular packing
-long range 3D structure that generates diffraction of Xrays
-LOW mobility
Amorphous solid
-possess NO long-range order (lattice)
-does NOT give diffraction of X-rays
-HIGH mobility
-HIGH solubility
Crystalline solids vs amporphous
-more stable
-less hygroscopic
-relatively less water soluble
Polymorph
-chemically identical crystalline forms in different packing arrangements
-diamond vs graphite
-diff solubilities maybe?
-ritonavir
Ritonavir
-original soft gel was introduced with form I (form II was. unknown)
-2 years after introduction of norvir soft gel it started failing dissolution
-new crystal form had crystallized
-soft-gel withdrawn from market
-reformulated into tablets
-cost $9 mil
Solvate
substance that incorporates solvent molecules into crystal structure
Hydrate
-solvate that contains water in the molecule
-anhydrate (no water molecule)
-monodrate (one water molecule per drug molecule
Hydration affects:
-solubility
-dissolution
-bioavailability
X-ray diffraction (XRD) method
-determine crystalline forms
-amporphous material: lacks crystalline peaks
-diff crystalline forms have diff XRD patterns
condsiderations in dosage form in preformulation studies
-physical description
-microscopic examination
-vapor pressure
-melting point depression
Physical description
-solids, liquids, gasses
-ohysical properties: particle size, crystalline structure, melting point, solubility
Microscopic examination
-particle size
-size distribution
-shape
Vapor pressure
-indication of liquid’s evaporation rate
-relates to the rendency of particles to escape form the liquid
volatile
-substance with high vapor pressure at normal temps
-can migrate within solid dosage form
-safety concern: personnel exposure to volatile materials
