Essentials of Pharmaceutical Engineering: (Unit Operations)

By Deeliprao Derle and Mrudula Bele

This book mainly aims in guiding the teachers and students, the fundamental principles of Pharmaceutical Engineering. This book helps the students in overcoming the obstacles faced by them in understanding the aspects of Pharmaceutical Engineering. Topics, which usually confuse the students, are explained along with applications to broaden their mental horizon regarding the subject. This book is meant to serve as an introductory text for undergraduate students doing Bachelor of Pharmaceutical Sciences (B. Pharm). It will also prove useful to people working in pharmaceutical and allied industries. In keeping with its initiatory approach to pharmaceutical engineering, only the important aspects of the subject have been discussed in a simple and easily comprehensible manner.
Contents
1. Stoichiometry 2. Flow of Fluids 3. Material Handling Systems 4. Filtration and Centrifugation 5. Crystallization 6. Dehumidification and Humidity Control 7. Materials of Construction 8. Corrosion 9. Industrial Hazards and Safety Precautions 10. Heat Transfer 11. Evaporation 12. Distillation 13. Drying 14. Size Reduction 15. Mixing 16. Automated Process Control Systems 17. Extraction
About the Author
Deeliprao Derle has obtained his B. Pharm. and M. Pharm. (Pharmaceutics) and Ph. D. (Pharmaceutics) degrees from University of Pune, Pune. He is working in NDMVP's, College of Pharmacy, Nasik. His academic career spans over twenty years. He has guided many M. Pharm. and Ph. D. research students and has more than 80 papers, presentations and publications. He has authored many pharmacy books. He has presented many research papers in international conferences held at Bangkok, Thailand, Singapore, and Tokyo, Japan. His current area of research includes formulation development, complexations, microencapsulations and controlled drug delivery dosage forms, etc. He is Academic Council Member of University of Pune, Pune and Faculty Member of Pharmaceutical Sciences, University of Pune, Pune. Mrudula Bele has obtained B. Pharm and M. Pharm (Pharmaceutics) degrees from University of Pune, Pune. She is lecturer in Pharmaceutics in NDMVP's, College of Pharmacy, Nasik. She has a teaching experience of about eight years. Her current areas of research include pharmaceutical excipients and their compatibility studies and controlled drug delivery.

• Language: English
• Publisher: BSP BOOKS
• Release date: Oct 22, 2019
• ISBN: 9789386717450

Book preview

Bibliography

CHAPTER 1

Stoichiometry

1.1 Introduction

Pharmaceutical engineering deals with those industrial processes in which raw materials are converted to useful products. The useful product may be a bulk drug, a drug formulation or an excipient. The bulk drugs may be of plant, animal, synthetic or microbiological origin. The synthetic drugs may need a series of chemical reactions to be carried out followed by a number of purification and separation steps. The drugs of plant or animal origin may require some physical isolation steps. e.g., salicylic acid is acetylated to form aspirin followed by its crystallization and filtration.

Manufacturing of antibiotics invoves use of precursors and microorganisms by fermentation technology.

Manufacturing of a dosage form involves conversion of a drug (chemicals) into medicines like tablets, capsules or liquid orals.

In all above mentioned processes, many common steps may be involved. Many of the processes involve transfer of heat between hot and cold fluids. Or in many processes, the end product requires filtration followed by drying e.g., a drug being synthesized requires filtration and drying. And granules during manufacturing of tablets also require drying. Thus, any pharmaceutical or chemical industry would need series of unit processes that involve chemical reactions and unit operations that involve physical processes.

1.2 Unit Operations

Each chemical process frequently consists of a fewer number of distinctive individual steps. Each step is called a unit operation. e.g., Drying, evaporation.

1.3 Unit Processes

Unit process is the one that combines several unit operations in a series to achieve a complete physical or chemical process.

Consider an example of a physical process of separation of a salt from its solution. The unit operations involved are:

Consider a process of manufacturing from benzene.

The unit processes involved in the above operation are nitration, reduction and acetylation. Each unit process consists of several operations. e.g., Nitration of benzene to nitro benzene involves following unit operations:

1.4 Scientific Principles of Unit Processes

Knowledge of many elementary physical and chemical laws is essential to understand unit processes.

The two basic laws that govern unit operations are law of conservation of matter and law of conservation of energy. The law of conservation of matter is the material balance i.e., input = output. The material balance is often estimated by moral concentration or mole fractions.

The law of conservation of energy states that for any form of energy, energy input = energy output. Different forms of energies that are considered are heat, mechanical, electrical, chemical and radiation energy.

1.4.1 Material Balance

The law of conservation of matter states that matter cannot be created or destroyed. It can only be changed from one form to another. Thus the material entering the process can either accumulate or leave the process. The principle of material balance can be applied to an equipment or to the entire process.

Estimation of Material Balance

In a chemical reaction, material balance can be accounted by measuring the amount of all the components. The amount is expressed in concentration units like % w/w, or % w/v. However, it is more convenient to express the amounts in molal units.

Mole: A mole of any pure substance is defined as a quantity of that substance whose mass is equal to its molecular weight.

In a chemical reaction, the molecular unit is gram mole or pound mole.

These values are useful while selecting the amount of each ingredient to be added to the reaction mixture.

Molality: Molality is expressed as:

The unit is mole/kg. Molality is often used in theoretical studies

Mole fraction: For an individual component, mole fraction is expressed as:

1.4.2 Energy Balance

The law of conservation of energy states that energy input and output of the process are always same. But the energy balance equation must include all types of energies involved in the process viz heat, mechanical, chemical, electrical.

1.4.3 Gas Laws

The ideal gas law is expressed as :

PV = nRT

Where P = pressure, V = volume, T = absolute temperature, n = no. of moles of gas.

This law is applicable only to ideal gas and no actual gas obeys this law. However, for majority of gases it is sufficiently accurate. The law indicates that the volume of gas is directly proportional to number of moles, absolute temperature and inversely proportional to pressure.

The equation shows that under definite conditions of temperature and pressure, a gas always occupies a definite volume. This is called mole volume.

1 gm mole of ideal gas occupies 22.41 lit at 0 oC and 760 mm pressure.

Dalton’s law of partial pressures states that the total pressure exerted by mixture of gases is equal to the sum of pressures that would be exerted by each of the gases if it alone occupied the total volume.

Amagat’s law of partial volumes states that in a mixture of ideal gases, each gas occupies the fraction of the total volume equal to its own mole fraction and to be at the total volume of the mixture.

1.4.4 Primary and Secondary Quantities

The units in which physical quantities are measured are divided into two groups. Some are chosen as primary or fundamental units and the remaining ones are expressed in terms of the primary ones. The later ones are called secondary units. Length, mass, time, heat and temperature are the primary units. Some of the secondary units are force, mass, acceleration etc.

The two important unit systems are centimetre-gram-second or cgs system and foot-pound-second or fps system.

1.4.5 Equilibrium Relationships

Some systems spontaneously undergo a change in a definite direction. In doing so, they ultimately reach a state where no further action takes place. Such state is called an equilibrium state. e.g., when a hot body comes in contact with a cold body, they exchange temperatures till their temperatures become equal. The process of heat exchange apparently stops at this point. This is called an equilibrium state and it represents the end point of naturally occurring processes.

Rate of a Process

The rate of a process/reaction may be studied by studying the changes in the concentration. The rate may be expressed mathematically as:

In a process of heat transfer, driving force is the difference in temperature, AT.

Steady State and Unsteady State

If the operating conditions in a system are varying with time, the system is said to be in unsteady or in transient state.

e.g., A heating coil is immersed in cold water. The temperature difference between the coil and water does not remain constant but changes with time. Thus the heat transfer process is in unsteady state till it reaches equilibrium.

If the conditions do not vary with time, the system is said to be in steady state.

1.5 Dimensions and Units

Any physical quantity has to be measured in units. Variety of units are often employed which makes the system very complicated. Moreover, the systems of the units may also vary e.g., metric system or English system. The quantity measured in one unit can always be converted to other unit by multiplying by a fixed factor.

1.5.1 Dimensional Formulae

When the measured quantity is expressed in secondary units, its dimensional formula expresses the way in which the secondary unit is related to the fundamental units for the quantity in question.

E,g,: Accleration = velocity/time

and velocity = distance / time

When the acceleration symbol ‘a’ is written in square brackets [a], it means - the dimensional formula of the quantity is. Each dimensional formula has the form M" Lp Θγwhere M, L and Θ represent dimensions of mass, length and time respectively.

1.5.2 Dimensionless Equations

If all the terms in an equation have the same units, it is said to be ‘dimensionally homogenous’

A dimensionally homogenous equation may be used without regard to conversion factors for any set of primary units.

e.g.: The vertical distance (z) travelled by a freely falling body in time Θ, if the initial velocity is u0 is given as:

If we write the dimensional formula for each term in the equation :

So, dimension of each term is length. If we divide each term by z, dimensions of all terms cancel out

Thus, each term on the right side of the equation is dimensionless. They are called dimensionless groups.

1.5.3 Dimensional Equations

Relationships derived by experimentation, are usually not dimensionally homogenous. These equations are called dimensional equations.

e.g: The rate of sedimentation of particle by stoke’s law is given as :

The dimensions of h/t are not those of the right hand side. Hence this is a dimensional equation.

1.5.4 Dimensional Analysis

Theoretical or mathematical methods sometimes fail to solve some physical problems in chemical engineering. Such problems, for which no theoretical equation is written are sometimes solved by experimentation.

Dimensional analysis is an important tool to convert emperical relationships into theoretical principles. Dimensional analysis assumes that there must exist a relationship among all the factors affecting a process. It is based on the fact that, if a theoretical equation exists among the variables affecting a physical process empirical that equation must be dimensionally homogenous. The factors affecting the process may be grouped into a smaller number of dimensionless groups and these groups enter the final equation. However, dimensional analysis does not yield a numerical equation and an experiment is required to complete the solution to the problem.

CHAPTER 2

Flow of Fluids

2.1 Introduction

Fluids are the materials that deform continuously or flow as long as the shear stress is applied, but are unable to achieve an equilibrium under applied shear stress.

Many materials in the manufacture of bulk drugs and pharmaceuticals are in the form of fluids. Similarly, there is increasing tendency to handle powdered or granular material in the form in which they behave as solids i.e., fluidization. Thus concept of fluids covers liquids, gases and fluidized solids. If stress is applied uniformly over all boundaries and the fluid decreases in volume showing proportionate increase in density, it is considered compressible. Liquids for general purpose are considered non-compressible and gases as compressible. The study of fluids is divided into:

(i) Study of fluids at rest i.e., fluid statics.

(ii) Study of fluids in motion i.e., fluid dynamics.

2.2 Fluid Statics

Pressure: It is defined as force exerted per unit area, and the force is product of mass and gravitational acceleration, F = mg but for a substance p = V

where p is density and v is volume and .•. m = p.V F = p.V.g But P = F/A i.e., F = P.A

The pressure of fluid varies with depth. If we consider fluid at depth z below the surface and A is the surface area, the volume will be z.A.

Therefore the force exerted will be F = p.z.A.g.

But the total force is the sum of force exerted on the surface of liquid and force of liquid

Fig. 2.1

Consider a stationary column of fluid as shown in the Fig.2.2. The pressure Ps is acting on the surface of the fluid. The stationary column is maintained at constant pressure by applying pressure P at point A. Let the cross-section area of the fluid be S and is constant throughout. The force acting on the liquid at different levels of the liquid column can be determined. The forces acting on each side of point 1 are mutually nullified. The forces in newtons acting below and above point 1 are evaluated.

Fig. 2.2 Hydrostatic Pressure.

Force acting on the liquid at point1 = force on the surface + force exerted by the liquid column above at point 1.

But Force = Pressure × area of cross section

Pressure on point 1 × surface area = (pressure on the surface × Surface area) + (mass × acceleration)

Λ Pj = Ps + hi pg

Similarly for point 2,

P2 = Ps + h2 pg

2.3 Pressure Measurement

Pressure of a fluid may be measured by using manometers. Manometers are the pressure measuring devices which measure pressure by measuring height differential.

2.3.1 Simple Manometer

A simple manometer consists of a U tube. The shaded portion of the U-tube is filled with a liquid A having density pA pounds/ft³ (Fig. 2.3). The arms of the tube above liquid A are filled with a fluid B of density pB pounds/ft³. A pressure of P1 pounds/ft² is exerted on one arm of the tube and pressure P2 pounds/ft² is exerted on the second arm. As a result of difference in pressure P1 - P2, the meniscus in the one arm of the tube is pushed upwards compared to the other arm. The purpose of the manometer is to measure pressure differential P - P2 by means of the reading R.

Lets consider five different points 1, 2, 3, 4, 5 in the U tube as shown in Fig. 2.3.

Fig. 2.3 Simple Manometer.

But point 2 and 3 are in the same horizontal plane

^ P2 = P3

equating eq. 2 and 3,

2.3.2 Inclined Manometer

For measuring small difference in pressure, the simple manometer is modified as shown in Fig.3.4. In this one arm of the U-tube is made inclined instead of keeping both the arms vertical. The arm is inclined in such a manner that for a small value of R, the meniscus must move considerable distance R1, a is the angle of inclination for the inclined arm.

Fig. 2.4 Inclined Manometer.

Now

Λ R = R1 sin a

2.3.3 Differential Manometer

For the measurement of small pressure differentials this instrument is used (Fig. 2.5). The two arms are filled with two immiscible liquids A and C whose densities are almost nearly equal. Enlarged chambers are provided in both the arms, so that the position of the meniscus at points 2 and 6 does not change appreciably with changes in reading R. The distance between points 1 and 2 can be considered equal to points 7 and 6. In order to find out the pressures at point 1 to 7, The two arms is used.

Fig. 2.5 Differential Manometer.

1P1

2P1 + apBg

3P 1 + apBg + bpAg

4P 2 + a pBg + dpAg + R pcg

5P2 + a pBg + dpAg

6P2 + apBg

But pressure at points 3 and 4 are equal

2.3.4 Bourdon Tube Pressure Gauge

Fig. 2.6 Bourdon Tube Pressure Gauge.

It is a mechanical pressure measuring device (Fig. 2.6). Such mechanical elements are designed to operate under a pressure change by bending, deforming, or deflecting depending on the pressure variation. Such elements are termed as transducers because they can take one form of energy from the measuring source and supply energy of a different kind to an indicating, recording or controlling system. A pressure gauge may take energy from the air compressed in the cylinder and supply enough mechanical power to move a pointer across a scale to indicate or record the pressure in the cylinder.

Scientist Eugene Bourdon invented a pressure gauge which was then named after him. He stated that a round tubing which has flattened and bent in a circular arc will tend to return to its original shape when pressure is applied in it. A simple form of Bourdon gauge consists of a length of thin walled metal tubing which has been flattened to approximately an elliptical cross section and then rolled into C shape. The tube has a pressure inlet at one end and the other free end i.e., tip is sealed. Tube is made up of bronze, Stainless steel, Nickel alloys etc.

Under pressure, the elliptical section tends to change its shape to circular form. The deflection of tube is measured. Apart from C-shaped Bourdon tube, spiral and helical gauges are also available.

2.3.5 Electrical Methods of Pressure Measurement

Strain gauges: When a wire or other electrical conductor is stretched elastically its length is increased and diameter is decreased. Both these changes result in increase in electrical resistance of the conductor. Devices that measure change in resistance of an electric conductor due to application of pressure are called as strain gauges.

Bonded gauges: They are bonded directly to the surface of the electrical elements whose strain is to be measured.

Unbonded gauges: They consist of a fixed frame and an arm which moves w.r.t frame in response to measured pressure.

Peizo resistive Transducers: It is a modification of conventional strain gauge. It uses a single crystal semiconductor wafer, usually Si, whose resistance varies with distortion.

Peizo electric transducers: Certain crystals produce a potential difference between their surfaces when stressed in appropriate direction. Peizo electric pressure transducers generate a potential difference proportional to a pressure generated stress.

2.4 Fluid Dynamics

2.4.1 Mechanism of Fluid Flow

Osborne Reynolds performed experiments to study flow of fluids. A glass tube was connected to a reservoir of water in such a way that the velocity of water flowing through the tube could be varied at will. In the inlet end of the tube a nozzle was inserted through which a fine stream of coloured water could be introduced. Reynolds found that:

(i) When the velocity of water was low the dye formed a smooth, thin straight streak down the pipe and there was no mixing perpendicular to tube axis of pipe. This type of flow where all the motion is in the axial direction is called as laminar flow or viscous flow.

(ii) As the velocity of water was increased, the dye was mixed throughout the pipe. The rapid, haphazard motion in all directions along which the axial motion caused rapid mixing of the dye. This type of flow is called as turbulent flow. The velocity of water at which the laminar flow changes to turbulent flow is called as critical velocity.

(iii) Reynolds observed a region of unreproducible results between the laminar and turbulent flow region. This region is called as transition region. In this region, flow is either laminar or turbulent. The laminar flow switches to turbulent flow in this region due to effect of outside disturbances like roughness of wall, vibration of equipment etc.

Fig. 2.7

2.4.2 The Reynold’s Number

Reynolds observed that critical velocity depends on diameter of the tube, the velocity of the fluid, its density and its viscosity. Further Reynolds showed that the four factors must be combined in one way only, namely

where

DuP is known as the Reynolds number

2.4.3 η Bernoulli’s Theorem

When the principles of conservation of energy is applied to flow of fluids, the resulting equation is called Bernoulli’s theorem. Bernoulli’s theorem is only a special case of law of conservation of energy.

Fig. 2.8 Development of Bernoullis theorem.

Consider a system represented in Fig. 2.8. It represents a pipe transferring a liquid from point A to point B. The pump supplies the energy to cause the flow. Consider that 1 lb liquid enters at point A. Let the pressure at point A be PA lb force/sq. ft. Let the average velocity of the liquid be PA fps and let the specific volume of liquid be VA Cu ft/lb. Line MN represents the horizontal datum plain. Point A and B are at the height X Aand XB respectively from the datum plain.

The potential energy of a pound of liquid at A has a potential energy equal to XA ft -

U²

lb. The velocity of liquid is XA ft-lb. The kinetic energy of liquid = A ft lb.

2gc

A pound of liquid enters the pipe against a pressure PA lb force/sq ft. Therefore work done on a pound of liquid equal to PA VA ft lb is added to the energy.

The total energy of the system is the sum of all the three energies.

Total energy = Potential energy + Kinetic energy + Pressure energy

U²

Total energy of 1 lb of liquid at A = XA + A + PA VA

2gc

After steady state when one pound of liquid enters at point A another pound is displaced at B, according to principle of conservation of mass. It will have energy

where UB, PB and VB are velocity pressure and specific volume respectively at point B.

If there are no addition or losses the energy content of one pound of liquid entering at A is exactly equal to its energy at B, according