physical properties of matter Flashcards
what are aerosols
pharmaceutical aerosols are pressurised packages that contain the therapeutically active ingredient: dissolved, suspended or emulsified
in a propellant which id capable of expelling the product through N opened valve
OR
dispersion of a solid or liquid as very fine particles in a gas
types of aerosols
metered dose inhalers MDI, nebulisers or DPI dry powder inhaler
MDI
metered dose inhaler, most common, aerosol created when valve is opened, drug usually created in small particles suspended in liquid propellant or can be dissolved in the propellant, propellant evaporates rapidly as leaves device leaving drug to be inhaled
nebulisers
oldest form, produce mist of a drug containing water droplets for inhalation, jet nebulisers use source of pressurised air to blast a steam of air through drug containing water reservoir producing droplets
electronic nebulisers use mechanical vibration of a plate or mesh to produce droplegs
DPI
dty powder inhaler, aerosol is a powder until inhaled, often add large particles of lactose monohydrate to help entertainment of drug particles and make filling easier
upon inhalation, powder is broken ip into constituents by turbulence or mechanical device releasing drug to be inhaled in the lungs
sugar particles intended to be left in the device or in the mouth/throat
liquified gas aerosol
canister contains propellant vapour and liquefied propellant
here, an equilibrium is established between the liquified propellant and its vapour, when valve is opened, the pressure forces some of the liquid up the dip tube and out into the atmosphere, the aerosol propellant vaporises and so disperses the active ingredients
although some if the liquid has now been used, equilibrium conditions are rapidly established by the vaporisation of more propellant and the original pressure is restored. the vapour pressure will therefore remain constant
nature of extrusion depends on both pressure and actuator
propellants
used to be chlorofluorocarbons CFCs(propellant gas) but they destroy ozone layer
so now replaced by hydrofluoroalkanes HFAs
most common HFA 134a and HFA 227
compressed gas aerosol
canister contains compressed gas and solvent
here an inert gas under pressure is used ticexpel the liquid. the pressure in the canister falls during usage
vapour pressure
id increase temperature then increase motion of the liquid leads to greater tendency fir escape into vapour phase.
variation of vapour pressure with temperature may be expressed in terms of molar enthalpy of vaporisation of the liquid
boiling points of liquids
the temp at which the vapour pressure of the liquid equals the prevailing atmosphere pressure, alters depending on pressure of enviroment
molar enthalpy vapoeisation
the heat absorbed (constant pressure) when 1 mole of liquid vaporises at the normal b.p.
clausius clapeyron equation
variation of vapour pressure with temp js described as clausius clapeyron equation
(graph of Log P against 1/T
amorphous material
broad mpt range, globular in shape, isotropic, no diffraction, yield&flow
crystalline material
narrow mpt range, regular faces and edges, anisotropic, diffract light, fracture/cleave under pressure
3 steps to crystallisation
supersaturation, formation of nuclei, crystal growth
diffraction and crystals
crystals diffract X-rays because the molecules are arranged in an ordered fashion. when an x ray beam strikes a crystal surface at some angle, part of the beam is scattered by the layer of atoms at the surface. the unscattered part of the beam penetrates to the second layer of atoms where again a fraction is scattered and so on.
the cumulative effect of this scattering from the regularly spaced centres of the crystals is diffraction of the beam in the same way as visible light is diffracted by a reflection grating
may be viewed as reflections from crystal planes. the distance between bonded atoms are comparable to the wavelength of the x ray beam
why do x rays scatter
it is the electron clouds of the atoms in the crystal that scatter the x rays. the amount of scatter depends on the atomic number Z. a crystal has atoms/ions/molecules in identical positions and so the x rays are scattered in an identical way
this leads to a diffraction pattern which is seen as a series of spots on an imaging plate. the electron density indicated by the pattern can be reconstructed using a computer allowing bond lengths and angles to be determined
what is braggs law
for constructive interference 2dsin theta =n lambda
diffraction observed if x rays scattering from a plane add in phase
path difference =2d sin theta = difference between 2 layers. d is the spacing between planes and theta is angle of incidence. scatted in phase if path difference is n lambda
n is integer and lambda in x ray wavelength
what are crystal lattices
regular 3D arrangements of equivalent lattice points in space
lattice points define unit cells -smallest repeating internal unit that has the symmetry characteristic of the solid - an atom, ion or molecule
cubic unit cells
all sides equal length, all angles 90 degrees
can get: primitive cubic(PC 1 atom), body centred cubic (BCC 2 atoms), face centred cubic (FCC4 atoms)
simple cubic unit cell- each atom is a corner of a unit cell and is shared among 8 unit cells. each edge is shared with 4 cells, each face is part of two cells
diffraction from a single crystal
a rays striking a single crystal will produce diffraction spots in a sphere around the crystal. each diffraction spot corresponds to a single point in the lattice. the distribution of diffraction spots is dependent on the crystal structure and the orientation of the crystal in the diffractometer
crystal habits
compounds crystallise into different habits (morphologies)
they usually have the same internal structure and the same x ray patterns
what is polymorphism
polymorphism occurs when the molecules are arranged in two or more different ways
e,g, carbon (graphite, diamond, buckminsterfullerene)
they are packed differently in the crystal lattice, differences in the orientation or conformation of the molecules, this causes differences in the x-ray diffraction pattern
other differences include m.p., solubility, different habits
solid state properties
the unit cell of polymorphic crystals have different dimensions
the preparation of different polymorphs involves manipulating the conditions of crystallisation
polymorphic changes may occur during processing:
density, m.p., hygroscopicity, electrical and optical properties, physical and chemical stability, dissolution velocity and apparent solubility
drug produce stability, dissolution and bioavailability, quality, safety and efficacy of drug product
bioavailibility
rate and extent to which a substance is absorbed and circulated around the body
due to different solubilities and dissolution fates for some polymorphs, marked differences in bioavailability can occur
characterisation of polymorphs
methods used to characterise polymorphs;
demonstration of an inequivalent substance by single crystal x ray diffraction is currently regarded as the definitive evidence of polymorphism
x ray powder diffraction cam also be used to provide unequivocal proof or polymorphism
other methods include microscopy, thermal analysis and spectroscopy
DSC
differential scanning calorimetry (DSC) can detect different melting points if they exist, also ant solid-solid transitions caused by one form changing into another can be detected as an endothermic peak
TGA
thermal gravimetric analysis
constant hearing rate
initial and final temp, heating rate
data - weight v tune and weight v temp
hot stage microscopy
can detect different m.p. and see transitions
can detect the loss of solvent by covering in solicone oil, indicated by the formation of bubbles at appropriate temp. this enables us to distinguish between solvates and polymorphs
the fourth state of matter
liquid crystal
liquid- flows, isotropic properties, optically transparent, 1 refractive index
crystal- doesn’t floe, anisotropic properties, direction dependant, 3 refractive indices
LC s ads orientationally ordered fluids
they are mesogens
liquid crystal phase
esophase
clearing temperature
the LC temp higher than isotropic phase transition temp
thermotropic definition
behaviour as a function of temp
organic
elongated, flat, rigid along axes, contain dipoles and easily polarisable groups
may be orientated by electric or magnetic fields
lyotropic
solutions of compound exhibit LC behaviour
birefringence
ability to rotate plate of plane polarised light with more than or 2 refractive indicies
types of LC
thermotropic (temp dependant)
- nematic (thread like)-orientational ordering
- smectic (soap like)reaches at lower temp than nematic- more order-layer ordering
- cholesteric(similar to nematic only in helices)
lyotropic (formed in solutions)
thermotropic LC phases and ordering
crystalline solid, long range ordering
smectic, layer ordering
isotropic liquid, random ordering
nematic, orientational ordering
liquid crystal display devices
LCD, weak electrical signal>optical response.
don’t emit light- modify by scattering;change in optical density or colour
low operating voltages compatibles with LCs
low power consumption, less heat produced
good contrast in strong light
chirality and LCs
reinitiser- interaction between asymmetric molecules
cholesteric phase- chiral nematic
molecules want to be parallel but due to chiral interaction there is a slight angle between them
cholesteric LCs reflect light with a wavelength equal to the pitch, the pitch depends on temp so colour reflected also depends on temp, pitch also depends on pressure, electric and magnetic fields
lyotropic LCs
solvent induced aggregation of molecules
solution exhibit liquid crystallinity
essential structural features; amphiphillic, 2 distinct regions within molecule (polar and non polar)
micelle formation
very low surface concentration, monomeric solution
CMC- hydrophobic effects, monomers>spherical aggregates
micellar solution increase surface conc
