6. Drying

riruwebi's version from 2016-05-21 15:03

Section 1

Question Answer
powder/tablet needs low/no moisture- water could cause:hydrolysis of active, microbial growth, influence powder flow and compactability
what is drying?removal of all or most liquid by supplying latent heat- gives thermal vaporisation
what ways can heat be supplied?convective (flow of hot air), conductive (hot surface), radiation (IR/ microwave)
what challenges does the removal of granulating fluid present?difficult to remove all, can cause drug break down, drug excipients have diff affinities for water
to understand drying requirements we need to discuss...moisture content of wet solids, total/equilibrium moisture content, relative humidity
unbound water is easily lost until EMC is reached, what needs to be done to lose water past that?reduce moisture content of air, this can be done by a desiccator (small scale) or air conditioning (large scale)
what are the stages of water loss?water lost by evaporation, EMC reached, then silica gel reduces RH of air by 5-10%, phosphorous pentoxide then reduces RH to 0-2%
if lower content is needed what is necessary in terms of packaging?product must be sealed
what must be considered in selection of drying methodsensitivity of material to heat, physical characteristics of material, type of liquid to be removed, need for asepsis, scale of process, available heat sources
principles for effective drying?large SA, efficient heat transfer, effect mass transfer (turbulent flow) efficient vapour removal (low RH air at suitable velocity)

Section 2

Question Answer
what are fixed/static bed convective driers?wet material on shallow trays & placed in oven through which heated air flows (heat is from electrical elements or steam-heated pipes) as air is moving, heat energy is transferred by convection currents
what are the drawbacks of fixed bed convective driers?heat transfer is relatively poor so drying is slow, drying time often overnight or even 24 hours, uneven drying, also solute migration
how can fixed be convective driers be speeded up?ensuring a brisk flow of turbulent air, by keeping the air %RH low by periodic heating to maintain air temp (e.g. directed-circulation air drier
what are dynamic convective driers? (e.g. fluidised bed)heated filtered air blown or drawn through a powder bed. this needs to be at a sufficient volume flow rate (VFR) to fluidise product. if too high powder becomes entrained on filter
how are fluidised bed driers designed?bowl shaped & passage of air designed so powder particles are blown up in the centre of the bowl and suspended individually in turbulent air stream. particles fall back towards the sides moves to the bottom, then blown up again so material circulates evenly.
why do fluidised bed driers maintain a large contact area between air and powder?keep boundary layers thin, increases heat and mass transfer
advantages of fluid bed over tray drying?very efficient, short drying time (minimised thermal damage) even drying, uniform bed temp, turbulance of bed causes attrition making smoother more spherical particles and more free flowing material, reduces solute migration risk, product container easily moved.
disadvantages of FBDturbulence may cause excessive attrition (dust), fines may collect on filter (care needed to avoid loss/segregation) hot dry air, fine dust, static generate explosion risk
what are conductive driers?wet solid in contact with hot surface. can e used in conjunction with low pressure (e.g. vacuum oven) though mainly for small development samples. wet solid placed on trays then pressure reduced to 0.05 bar, at which point water boils at 30oC
what are the advantages and disadvantages of vacuum ovens?advantages: drying at low temp, reduced oxidation (low air) disadvantages: size of oven, material may aggregate, drying fairly slowly, solute migration can occur

Section 3

Question Answer
what is radiation drying?IR and microwave radiation will provide heat but IR doesn't penetrate well. microwaves much better penetration, works by causing resonance in water molecules results in heat
advantages and disadvantages of radiation drying?advantages: rapid and low temp, efficient Disadvantage: batch size small
what is solute migration?during drying solvent moves to granule surface, if excipients/drugs soluble in solvent they also travel to surface. this leads to local variability in conc of excipients/drug
what is inter-granular migrationliquid moves from granule to granule e.g. static bed, can cause uneven dis. of active so product fails content uniformity test
what is intra-granular migration?can occur during fluid bed, solutes accumulates at surface of granule, then may be removed due to abrasion/friction, drug accumulates in dust, so total conc may be out of spec
other effects of solute migration?mottling of tablets (colour migrates to surface, granules fracture), migration of soluble binder (can be bebeficial in it accumulates at surface makes them harder and more resistant to abrasion, more effective binding)
ways to minimise solute migration?use less granulative fluid (modern high shear mixer-granulators need less) prepare smallest granules that will flow (mottling less noticeable), avoid tray drying, if intragranular migration is problem consider microwave/vacuum
what forms of drying are there for solutions?to dry solutions there is spray drying and freeze drying
what is spray drying?idea is to spread liquid to large SA, solution/suspension atomised into small droplets, then sprayed into hot moving air
spray dried products are recognisable because?uniform in appearance, hollow spheres with small hole
the shape of spray dried products arises from the drying process, how is this?droplet enters air stream, outside dries to form crust, liquid in centre vapourises forming hole. particle size is controlled by droplet size
advantages of spray drying?efficient (droplets dry quickly, particles only in drier for few secs so dont reach high temp, particle size controllable) flows well, compacts easily, rapid dissolution possible
disadvantages of spray drying?equipment large, expensive, overall thermal efficiency low as large volumes of air pass through chamber without contacting particles and leaves fairly hot
uses of spray drying?thermolabile products, lactose for use in tablet and capsule manufacture, powdered antibiotics for reconstitution into syrups, small spherical particles for lung delivery, can be used for aseptics

Section 4

Question Answer
what is freeze drying?used for very heat sensitive materials, involves forming a solution or suspension, freezing it at low temp (e.g. -20oC) reducing pressure above material, removing water by sublimation
practical aspects of freeze drying?dissolved materials reduce freezing point so tempurature must be reduced to between -10 and -30. Also sublimation is from the surface so is v slow so need to increase SA and reduce water thickness, large vol of vapou produced at low pressure so must be removed quickly to prevent pressure rising and liquid forming
stages in freeze drying?1. freeze liquid, reduce pressure with vacuum pump, 2. apply heat just sufficient to cause sublimation but not enought to raise material temp (primary drying), 3. material after primary drying is v. porous with approx 0.5% moisture, 4. can heat up to approx 50oC to remove this moisture (secondary drying), 5. sealed under vacuum or in controlled atmosphere
advantages of freeze drying?minimal loss of enzyme activity or chemical decomposition, enhanced rate of dissolution (high SA because porous) no concentration of sol during drying (high salt denatures proteins)
disadvantages of freeze drying?product v hygroscopic (needs careful packaging and drying generally done in final container) slow and expensive.