Pharmaceutical Technology I Lecture 1 Drying PDF

Pharmaceutical Technology I Lecture 1 Prof. Omaima Sammour Professor of Pharmaceutics & Industrial Pharmacy Prof. Omaima Sammour  Drying is an important operation involved  in primary stage of manufacturing (i.e. the synthesis of actives) and in the last stage of manufact...

Pharmaceutical Technology I Lecture 1 Prof. Omaima Sammour Professor of Pharmaceutics & Industrial Pharmacy Prof. Omaima Sammour  Drying is an important operation involved  in primary stage of manufacturing (i.e. the synthesis of actives) and in the last stage of manufacturing (before packaging)  The residual moisture content of a pharmaceutical product should be low enough to: a. Prevent product deterioration during storage b. Ensure free-flowing properties during use  Drying to the solid state may start with either a wet solid or a solution or a suspension of the material Prof. Omaima Sammour Prof. Omaima Sammour  Total moisture content of a wet solid: Is the total amount of liquid associated with a wet solid Not all of it can be easily removed by pharmaceutical driers The easily removable water is known as the “free moisture content” or “unbound water” The moisture which is more difficult to remove is the equilibrium moisture content because the solid equilibrates with the moisture present in the air Prof. Omaima Sammour  Equilibrium moisture content: Is the moisture content present in a solid under ambient conditions its value changes with: a. temperature b. humidity c. the nature of the solid It may be adsorbed on surfaces of the solid (to form a mono- or bi-layer on the solid surface) or impeded within its structure Prof. Omaima Sammour  Types of Drying Methods When considering how to dry a material, the following points should be considered: 1. Heat sensitivity of the material being dried 2. Physical characteristics of the material 3. Nature of the liquid to be removed 4. The scale of operation 5. Available sources of heat Prof. Omaima Sammour  General principles for efficient drying 1. Large surface area for heat transfer 2. Efficient heat transfer per unit area to apply sufficient latent heat of vaporization or heat of sublimation (in case of freeze drying) 3. Efficient mass transfer of evaporated water through any surrounding boundary layers 4. Sufficient turbulence to minimize boundary layer thickness 5. Efficient vapor removal i.e. low relative humidity of air at adequate velocity Prof. Omaima Sammour  It is convenient to categorize Pharmaceutical driers according to the heat transfer method they use Into: Convective Radiant Conductive Prof. Omaima Sammour  A) Convective Drying of Wet Solids 1) Fixed (static) bed convective driers e.g. Tray (or shelf) Drier (Batch Drier) Air flows in the direction of the arrows over each shelf in turn The wet material is spread on shallow trays resting on the shelves Electrical elements or steam-heated pipes are positioned as shown, so that the air is periodically reheated after it has cooled by passage over the wet material on one shelf before it passes over the material on the next Prof. Omaima Sammour Rate of drying in fixed beds: The rate at which drying occurs has been found to show certain phases, in which the change in moisture content is plotted against time Prof. Omaima Sammour 1- From A – B: the relationship is linear (constant-rate period) for given conditions of temp & humidity, most substances dry at a similar rate in the constant rate period The evaporation takes place from the wet surface of the solid & the surface remains wet in this period as a result of the liquid being replaced from below as fast as it is vaporized The end of the constant rate period B is referred to as “critical moisture content” Prof. Omaima Sammour 2- From B – C: The rate of loss of moisture decreases & is known as “the falling rate period” 1st falling rate period 2nd falling rate period Linear relationship there is a continuous i.e. the decrease in decrease in the drying drying rate is uniform rate until equilibrium moisture content is reached as the drying rate decreases, the heat input should be reduced Prof. Omaima Sammour  During the FFRP, the rate of drying falls steeply due to the drying of surface granules  The SFRP is influenced by the diffusion of moisture through the pores of the bed to the surface i.e, the plane of vaporization retreats from the surface into the body of the solid &  Applications of Tray drier: Useful for sticky or plastic substances, granular masses, pastes & precipitates Prof. Omaima Sammour  Advantages 1. Material loss is negligible since loading & unloading of trays can be handled carefully → hence, this dryer is very useful for valuable materials 2. It is a batch operation hence, useful when the material is available in small quantities 3. With the exception of dusty solids, materials of almost any physical form may be used Prof. Omaima Sammour  Disadvantages 1. Oxidisable & thermolabile materials can’t be dried 2. It takes a long time to dry, as the material is static 3. Labour requirements are high for loading & unloading operations 4. A long heating cycle is necessary for internal diffusion of heat or moisture Prof. Omaima Sammour 5. A large floor space is required for the oven & for tray loading facilities 6. Solvents are difficult to recover from the drying air 7. Moisture movement may cause the migration of soluble drugs or excipients  It is used in such cases where the quantity of material to be processed doesn’t justify investment in more expensive continuous equipment Prof. Omaima Sammour  2) Dynamic Convective Driers e.g. Fluidized – Bed Drier It is an excellent method of obtaining good contact between the warm drying air & wet particles Such units have replaced tray dryers in many processes Prof. Omaima Sammour  Sizes are available with capacities from 1kg in the laboratory to 500kg in production  These driers can be operated batch-wise (batch fluidized bed drier):  A charge of wet solids ( granular, non sticky, free flowing) in a perforated container attached to the bottom of the fluidizing chamber is fluidized by a stream of heated air (gas) until dry & then discharged (loading & unloading)  particles between 65mm - 10µm are the best for smooth fluidization (A mix of fine particles to coarse ones results in better fluidization) Prof. Omaima Sammour  Economic considerations make fluidized bed dryers attractive when large amounts of solids are to be handled i.e. in this case a “continuous dryer” is more suitable than a batch type  The fluidized bed dryer is also used as a classifier so that both drying & classification operations are accomplished simultaneously They can also be used for size enlargement & coating of materials Prof. Omaima Sammour  Advantages of fluidized-bed drying 1. Efficient heat & mass transfer gives high drying rates, so that drying times are shorter than with static-bed convection drier e.g. A batch of tablet granules can be dried in 20 – 30 min whereas a tray drier requires many hrs Apart from the economic advantage, the heat challenge to thermolabile materials is minimized Prof. Omaima Sammour 2. The fluidized state of the bed ensures that drying occurs from the surface of all individual particles & not just from the surface of the bed 3. The temperature of a fluidized bed is uniform & can be controlled precisely 4. The turbulence in a fluidized bed causes some attrition to the surface of the granule more spherical free-flowing product Prof. Omaima Sammour 5. The free movement of individual particles eliminates the risk of soluble materials’ intergranular migration 6. The containers can be mobile simple handling & movement around the production area 7. Short drying times high output Prof. Omaima Sammour  Disadvantages 1. The turbulence of the fluidized state excessive attrition of some materials damage to some granules production of too much dust 2. Fine particles may become entrained in the fluidizing air and must be collected by bag filters with care to avoid segregation & loss of fines 3. The vigorous movement of particles in hot dry air can lead to the generation of static electricity charges, so adequate electrical earthing may be essential Prof. Omaima Sammour  B) Conductive Drying of Wet Solids In this process, the wet solid is in thermal contact with a hot surface the bulk of heat transfer occurs by conduction Examples: 1. Vacuum oven 2. Vacuum tumbling drier Prof. Omaima Sammour 1- Vacuum Oven (Batch) Prof. Omaima Sammour  It consists of a jacketed vessel which can withstand vacuum within the oven & steam pressure in the jacket The supports for the shelves form part of the jacket, giving a larger area for conduction heat transfer Heat is supplied by passing steam or hot water through these hollow shelves, upon which the material may be placed in suitable trays Prof. Omaima Sammour  The steam or water heats the material → water evaporation under reduced pressure → water condensation in the condenser The oven can be closed by a door that can be locked to give an air tight seal Drying times are long (12 – 48 hrs) Rarely used nowadays for production, but are frequently used in development laboratories for drying small samples  Advantages: 1- Drying takes place at low temp → used for thermolabile substances 2- There is little air present → minimum risk of oxidation Prof. Omaima Sammour  2- Vacuum Tumbling Drier (Batch) It has found application in the pharmaceutical industry It resembles a large V/Y-cone mixer or double cone mixer → the vessel is steam jacketed & connected to a vacuum Is used for drying tablet granules, which tumble over the heated surface as the vessel slowly revolves Heat transfer rate > that attained in vacuum oven (where the material is static) Drying times: 2 – 3.5 hrs Prof. Omaima Sammour  C) Radiation Drying of Wet Solids) Heat transmission by radiation differs from heat transfer by conduction or convection, in that no transfer medium (solid, liquid or gas) needs to be present Heat energy in the form of radiation can travel through the atmosphere without loss If it falls on a body capable of absorbing it, it appears as heat although a proportion may be reflected or transmitted Prof. Omaima Sammour Use of infrared radiation: IR heating has been used in the past to dry wet granules, but it suffers from the disadvantage of being absorbed very quickly without penetrating far into the wet mass Therefore, it is now seldom used as a heat source in pharmaceutical manufacture Prof. Omaima Sammour  Use of microwave radiation: Microwave radiation (wavelength range 10mm – 1m) penetrates much better than IR radiation Microwaves are produced by an electronic device known as a Magnetron The penetration of microwaves into the wet product is so good that heat is generated uniformly within the solid → moisture evaporation It is used for drying granules Prof. Omaima Sammour  Advantages of microwave drying 1. Provides rapid drying at fairly low temp. 2. Most microwave energy is absorbed by the liquid in the wet material 3. The bed is stationary, avoiding the problems of dust & attrition 4. Solute migration is reduced as there is uniform heating of the wet mass 5. All the requirements of product & operator safety have been incorporated into machines without detracting from GMP considerations Prof. Omaima Sammour  Disadvantages of microwave drying 1. The batch size of commercial production microwave driers is smaller than those available for fluidized-bed driers 2. Care must be taken to shield operators from the microwave radiation, which can cause damage to organs such as the eyes & testes This is ensured by “fail safe” devices, which prevent the generation of microwaves until the drying chamber is sealed Prof. Omaima Sammour