Behaviour of drug solids Flashcards
Ion-Ion bonding Outline
Interactions between 2 charged atoms eg Na+ and Cl-
Ion-Dipole Bonding
2 Types of Reaction. Electron dense ( relative negative) areas bind to cation (positive). Electron deficient (relative positive) and anion. Eg Na+ and O in water
H bonding (Dipole-Dipole)
Interaction between H atom and F, O or N (highly electronegative). Eg in water delta positive H and delta negative O
Dipole - Dipole Outline
Unequal sharing of electrons in covalent bond resulting in areas of high electron density (delta negative) attracting areas of electron deficiency (delta positive)
Hydrophobic Interactions
Interaction between 2 hydrocarbon areas in a molecule. Eg folding of proteins with hydrophobic side chains
Solubility Def.
Max concentration of substance that dissolves given solvent (usually water) at given temp. Important bioavailability determinent
Dissolution Def.
Rate by which a compound goes from solid to solution in a solvent. High solubility = high dissolution rate. Reflects absorption characteristics
What molecule size dissolves Faster
Small particles = faster solution (lower limit. Small airy particles have slower ( more cohesive, air pockets)). Thus particle size manipulation gives more controlled release rate
Melting Point is Reflective of
The strength if intermolecular interactions for drug-drug
High Melting Point Indicates
High molecular cohesion = low solubility
High Boiling Point Indicates
High molecular cohesion = low miscibility of liquids
Sorption Def.
Water binding to substance interface or core. Unknown if it’s absorption or adsorption
Do crystal absorb much water
No as it has no water pockets. Molecules are bound too close together. Can’t penetrate
Does amorphus form absorb much water
Yes, has holes for water to penetrate and pockets for water. However due to thermodynamic instability it loses water time as it converts back to crystalline
Why codine has a lower boiling point then morphine
When forming coedine hydroxyl group is broken off morphine. This means it can’t form a dimer with H bonds. Producing a weaker molecules and higher solubility
Unit Cell Def.
Simplest repeat unit in a crystal
Crystal Lattice
Orderly 3D molecule arrangement of unit cells. Permits optimal attractive interactions between adjacent molecules
Crystal Habit Def
Shape of specific drug molecules. Difference observed by visual inspection
7 Unit Cell Types
Simple cubic outline, tetragonal, orthorhombic, rhombohedral, monoclinic, triclinic and hexagonal
Simple Cubic Outline
All sides same length. All angles are 90 degrees
Tetragonal
2 out 3 dimeson’s sides are same length. All angles are 90 degrees
Orthorhombic (1 of most common for drugs)
Dimension’s sides aren’t the same length. Angles are 90
Rhombohedral
All sides same length. Angles are the same size (not 90 degrees)
Monoclinic (1 of most common drug types)
Sides of 3 dimensions aren’t the same length. 2 angles 90 degrees 1 isn’t
Triclinic (1 of most common drug types)
No sides are of same length. No angles of same size
Hexagonal
2 out of 3 dimesions hav sides of same length. 2 angles are 90 degrees 1 angle 120 degrees
Hexagonal Unit Habits
Acicular (needle-like, doesn’t flow, damages cells), Prismatic, Tabular (plate-like, not arosynamic so shouldn’t be used as aeroslol, cause bridges in funnels). 1 unit makes can make different habits
Habit Type Considerations
Flow, Dispersibility, Aerodynamics, dissolution, solubility, bioavailability and compressibility
Habit Shapes
Tabular, Columnar, Equant, Plate, Blade and Acicular
Crystal Formation (/nucleation/ growth) Outline
Reverse of dissolution. Rate influences habit. Too fat = production of amorphous form (particles don’t have time to get in position). Done via; super saturation + cooling/evaporation/seed crystals/ precipitation (pH, water)
Polymorphism Def.
Phenomenon where molecules arrange more then 1 pattern in crystal. Tend to have different crystal habits. Different polymorphs of same drugs have different properties.
Most stable polymorphs have
Highest melting point
Anhydrous Def.
Substance in solid state dissolved by water
Solvates Def.
Solids with solvent in their crystal structure
Which is more soluble aqueous or non-aqueos
Non-aqueous as water is bound to water
Hydrates Def.
Water incorporated into crystal structure. Can lose water becoming sticky (efflorescent). 50% are monohydrate
Co-crystals Def.
Crystals composed of active drug’s species and another organic molecule H bonded to it (reducing melting point, increasing solubility). More stable then polymorphs
3 Outcomes Mixing Solids
2 phase coarse suspension(ad mixing), 2 phase eutectic (cooled molten mix, solvent evapouration), 1 phase solution (cooled molten, solvent evaporation)
are hydrates stable
Hydrates are more stable then anhydrous. Increased stability reduces solubility and reduces bioavailability
Lattice Type Differences
Energy, rigidity, hardness, shape, size, melting point, therapeutic application, dissolution and bioavailability
Lattice Shape Forming
Meta-stables are of higher solubility, not thermodynamically stable, interfacial tension
Glass Transition Temp (Tg) Def.
Temp below which material is in glassy state and is brittle. Above Tg molecules become more mobile and rubbery. Can be lowered by plasticers (making molecules more mobile)
Amorphus Characteristics
Melts over large temp range, glass transition temp, greater solubility then crystals, poor flowability, better compression properties then crystals, absorb water, destroyed crystals
Crystals Characteristic
Narrow melting range, melting point, defined geometry, polymorphism, 1 crystal stable at given temp/pressure, good flowability, poor compression
Particle size Outline
Crystalline/amorphus solids are called particles. Particle size reduction is done by milling, bashing, grinding and trituration (pestle and mortar)
Decreasing Particle Size Causes
Dissolution increase, increase solubility, pharmokinetics (slow/fast release), improves solid mixing, minimises size segregation (improving dose uniformity), increases degradation, decreases flowability (increased cohesion), increases pulmonary application (to lower limit), decreased wet ability
Particle size and drug action
Only molecular dispersions are absorbed acrosses epithelium. Choosing particle size increases control of release (release is more sustained, plasma toxicity is avoided)
Particle Size and Dissolution
Reduced particle size = decreased surface area = increased solvent contact = increased rate of solution
Particle Size Reduction and Solubility
Substances increased below threshold size. High interfacial tension with decreased particle size = increased solubility
Surface Free Energy Def.
Net inward force of attraction caused by chemical imbalance on surface. Shows as surface tension. Smaller particle = greater surface area = more energy in system = low flowability
Hygroscopicity Def.
Ability to take up water from atmosphere
Deliquescent
