Leon lachman industrial pharmacy ebook

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Theory and Practice of Industrial Pharmacy by Lachman 4th edition pdf. For Download click here. Download. Posted by khuram sajjad at The Theory and Practice of Industrial Pharmacy. Front Cover. Leon Lachman, Herbert A. Lieberman, Joseph L. Kanig. Lea & Febiger, - Medical - The Theory and Practice of Industrial Pharmacy Leon Lachman,Herbert A. Lieberman,Joseph L. Kanig Snippet view -

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Leon Lachman Industrial Pharmacy Ebook

[Leon Lachman] the Theory and Practice of Industrial Pharmacy - Ebook download as PDF File .pdf) or read book online. Theory and Practice. 78 MB Download✌ If Any Download Issue Please Comment Below. The theory and practice of industrial pharmacy [Leon Lachman] on presemorboecuad.cf *FREE* shipping on qualifying offers. From the preface - This book will be.

Figure 14 Ordered mixing by adhesion. Page 18 Figure 15 Segregation by pouring. Page 19 the mix. However, if no particulate adhesion is present, segregation of the mix easily takes place on further handling. Adhesional forces of particles may create ordered units of near identical composition depending on the process. Partial solubilization or the use of a binding agent during wet granulating approximates the same effect as shown in Fig. Figure 14b shows that particles in an assemblage may also be coated with other ingredients to give an ordered mix either as individual or coated particle agglomerates. The major difference between the mechanical and the adhesional and coated ordered mixing is the degree of force holding the ingredients in each type of the ordered units together. Ordered mixing is not only beneficial in approaching a perfect mixture, but it minimizes the possibility of segregation of a mixture by holding the ingredient ratio constant via the intact ordered units. Segregation occurs primarily as a result of wide differences in particle size in a dry mixture. Segregation may be produced by pouring a powder from one container to the next as is done by emptying the contents of a blender into another hopper or into drums. This is illustrated in Figure 15a.


A portion of the book deals with sliding or rolling contact and collision. Bharadwaj, Woodhead Publishing, This book focuses on modeling and simulation tools pertinent to drug product manufacturing, especially those that can result in significant process improvements and cost savings. The author includes case studies, modeling principles, the role of modeling in manufacturing quality risk management, and modeling applications for continuous manufacturing and biologics.

Pharmaceutical Process Engineering, Anthony J. It covers basic principles so scientists can easily convert bulk products into patient-ready dosage forms.

Pharmaceutical Process Scale-Up, Michael Levin, Marcel Dekker, This book details theory and practice of transferring pharmaceutical processes from laboratory-scale to pilot-plant and production-scale, reflecting rapid changes in the field.

Drawing on the experience of contributing researchers, the book employs dimensional analysis as a unified scientific approach to quantify similar processes on different scales.

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Topics include tableting scale-up and compaction, regulatory appendices, risk evaluation, and validation. Mechanics of Inhaled Pharmaceutical Aerosols, W.

Finlay, Academic Press, This book provides in-depth information on common aerosol-drug delivery devices, including nebulizers, dry powder inhalers and propellant metered-dose inhalers. The author details aerosol behavior in the respiratory tract including evaporating and condensing droplets as well as lung geometry, inhalation patterns and fluid mechanics.

Paul, Victor A. Kresta, Wiley-Interscience, The authors detail the trade-offs among various mixers pertinent to their specific applications: gear, top-entry, side-entry, bottom-entry, on-line and submerged mixers. The book contains a CD that shows mixers in action along with a usage overview. Principles of Powder Technology, M. Rhodes, Wiley, This reference presents the fundamental engineering properties of materials that are essential to design and operation of industrial equipment and processes.

As industry calls for greater expertise in this field, expert contributors offer data about problems involved in handling massive solids, gases and liquids.

New editions have kept pace with the changes in pharmacy curricula, particularly industrial pharmacy. By presenting the topics in layers from basics to in-depth discussions, the text enables easy conception of a-to-z of product development. The author includes information on solid-surface physical properties, friction theory, techniques for measuring particle adhesion, and fracture mechanical properties of powders.

While the book focuses more on models than on the physics of granular material, the authors present many applications to real systems. Its content on powder technologies in gas and liquid phases extends from particles and powders to powder beds and from basic problems to actual applications. Recent editions incorporate significant field advances.

The reference presents state-of the-art contributions from leading finite element method specialists. Advanced Pharmaceutical Solids, Jens T. Note the differences in assays of each table. Note that the random mixed sample shows some variation as it should when compared to the perfect mixture which will show no spread in the assay if samples in the same manner.

Statistically, one may sample using one or two approaches: a by not returning the sample to the mixture after evaluating it, or b by returning the sample to the mixture after its evaluation.

Lackman pharmacy book

Destructive testing Page 28 Page 29 Page 30 such as putting the sample into solution for assay will not permit the latter sampling approach b. Therefore, it is necessary to use destructive sampling when checking for distribution of ingredients in a mixed formula.

On the other hand, when working in production quantities hundreds of kg , the unit dose sampling of samples is infinitely small when compared to the entire population and may be tested as in b above returning the samples to the mix before the next sampling.

There are two golden rules of sampling [30]: 1. This is usually not the choice of the experimenter, but rather limitations of the system.

For example: a number of ingredients are placed in a blender for mixing. The mixer is activated for various lengths of mixing time. After each time interval, a number of samples are removed to determine homogeneity of the mixture.

The object: to determine the optimum blending time. How is each sample removed from a mixer to follow the golden rule of sampling? The powder mixture usually cannot be sampled from a moving stream because of a the configuration of the mixer i. Therefore, one is left with several less than desirable options including: 1.

Scoop sampling has two basic drawbacks: 1. Scooping from the top of a container of powder may produce a sample which has segregated on standing, i. Scooping cannot remove a sample from the middle or bottom of a blender or container without considerable disturbance of the mixture. The thief probe also has several drawbacks: 1. As the thief is inserted into the powder bed, some compaction takes place around the thief and flow into the thief opening may be poor.

Page 31 Figure 20 Unit dose thief samplers. Courtesy Sampco, Salem, South Carolina. As the thief is inserted in the powder bed it may carry material from the surface of the mixture down into the mixture depending on the diameter of the thief. This may place a portion of top sample down at the lower portion of the thief, and if a compartmentalized thief is used, the lower samples are biased or contaminated with top sample. However, from a practical point of view, the thief probe sample is preferred over the scoop because samples can be taken from deep within the powder bed, and a reasonable degree of random sampling is achieved.

To further minimize the drawbacks using a thief probe, a small diameter thief probe is available see Fig. The sample sizes that are removed approximate a tablet unit dose. This allows assay of the entire sample after it has been removed, which eliminates inadvertent excessive handling of a large sample in the lab to obtain a small enough sample to assay.

This eliminates possible segregation before the sample has been assayed. Excessively handled, large samples usually do not represent the population removed from the sampled enclosure, or the Page 32 population being samples in the enclosure drum, mixer, storage hopper, etc. Probably the most significant measure of quality of a mixture is how the blend actually performs, and the uniformity of the final product.

Material Properties: Basic Concepts of Dry BlendingThe Unit Particle Since mixing plays such an important role in tableting, an understanding of the characteristics of the materials being mixed is paramount. Many of the studies presented in the literature, and used previously in examples, deal with binary mixtures of physically and chemically similar materials which can easily be differentiated for the study by color, size, or assay.

However, pharmaceutical, binary, particulate systems in tableting are the exception, and results dealing with binary systems have limited applicability in industrial practice. Each component in a mixture has distinct physical characteristics which contribute to, or detract from, the completeness uniformity of a mixture. Therefore, it is important to define and characterize the unit particles that make up the mixture, whether it is a premix of a wet granulation, a direct compression formula, or the addition of lubricants, etc.

Figure 21 is an illustration of several different types of particles handled in tablet granulation mixing. The unit particles in a system may range from the less-than-1 mm-size pure substance raw material particle to the 8 to 12 mesh multicomponent granule held together by a binder.

Since dry mixing is a dynamic state of an assemblage of particles, the properties of the unit particle must be discussed in terms affecting these dynamics.


There are three properties intrinsic to each component in the mixture: composition physicochemical structure , size and size distribution , and shape [31].

Composition of each particle is its qualitative and quantitative makeup [32]. Each unit of pure substance has its own molecular composition and arrangement that distinguishes it from all other materials, and dictates its behavior in part as a powder per se, or in combination with other tablet mixture ingredients.

Chemical composition is important, because chemical reactivity limits a material's use with other tableting components, e. The same applies to components that may affect the stability of a mixture such as the potential Schiff Base reaction between certain sugars and amines when in contact even in the dry state.

Physically, the molecular makeup determines crystallinity manifested as color, hardness, tackiness, general appearance, etc. Particle size and size distribution of the unit particles have considerable impact on the flow properties of powders and therefore, the dynamics of mixing.

Table 5 shows, in general, the effect of particle size on the flow properties of powders. Table 6 is a list of some common substances used in the pharmaceutical industry, and their flow characteristics. A very complete and detailed list of materials and their characteristics Page 33 Figure 21 Several different types of particles encountered in tablet granulation dry blending.

Smaller particles Page 34 Table 5 Effect of Particle Size on Powder Flow Particle Type of flowa Reason size Flow is usually good if Mass of individual particles is shape is not interfering relatively large mm b mesh Flow properties may be a Mass of individual particles is small problem with many pure and increased surface area amplifies mm substances and mixtures effects of surface forces 60 mesh mm Figure 22 Effect of electrical forces on fine particles.

Page 35 the agglomerated particles behave as a single large mass particle Fig. Flow may be better in this case, but the dynamics of distributing these small particles during mixing is very poor.

Fine powder particles also create potential dust conditions which may require operators to wear respirators for safe handling, and may also create potentially dangerous dust explosion hazards. Particle size distribution of unit particles as suggested in the above discussion may also have an effect on the flow of a powder, i. Although it has been stated that cohesive forces are strong in powders composed of particles 10 mm or less in size, each powder has a critical size where cohesive forces begin to affect the powder flow properties.

An example of this is shown in Table 7. The angle of repose a or the angle of slip is a relative measure of the friction between powder particles but also is a measure, for the most part, of the cohesiveness of fine particles.

The angle of repose may be measured in several ways as shown in Figure Methods 1 and 2 are both dynamic angle of repose measurements: the powder in Method 1 flows from a filled powder funnel onto a smooth surface where the angle is measured as illustrated, and in Method 2 the powder is moving in a rotating drum while the angle is measured as shown. Method 3 gives the static angle of repose, because the powder container is removed and the powder does not, or is not flowing before the measurement.

Since many factors enter into the angle of repose such as particle size, shape, moisture content, etc. However, certain generalizations can be made regarding the angle of repose: 1. Material is hygroscopic which decreases flowability Very dusty.

Material is hygroscopic which decreases flowability Fluid powder The two density powders are slippery and very dusty. Material Fluid cohesive powder is hygroscopic which decreases flowability Cohesive powder Flow becomes extremely poor if packed 0. Flow becomes poor when packed. Some 0. Flow becomes poorer when packed Source: Carr, R.

Page 38 Figure 23 Angle of repose. Page 39 Table 7 Critical Particle Size of Raw Materials Raw material Critical particlea Wheat starch mm Boric acid mm aCohesive forces diminish at this particle size range and have little affect on raw material flow properties as the particle size increases above this range.

Size distribution of a powder also has an effect on the packing characteristics, and therefore the bulk density of the powder. This is illustrated in Figure 24, which shows how the smaller particles of a size distribution occupies interstices between the larger particles creating a more densely packed powder. Densely packed powders usually have flow difficulties.

Particle shape affects powder inter-particle friction, and consequently the flow properties of the powder.

Figure 25 shows general particle shapes and their effects on powder flow. Materials composed of particles with rounded edges such as a and b in Figure 25, will flow more readily than those with sharper edges c , or two dimensional flat, flake-like particles e.

Poor flow is usually encountered with particles having Figure 24 Effects of particle size distribution on the bulk density of a powder. Page 40 Figure 25 General particle shapes and their effect on power flow. Bridging refers to the stoppage of powder flow as a result of particles which have formed a semirigid or rigid structure within the powder bulk. It is apparent that particle shape affects the angle of repose of a powder, particularly powders with low magnitude surface forces as found with particles greater than mm, and some low free-surface energy-fine powders such as talc hydrous magnesium silicate and cornstarch [34].

It must be remembered that all of the properties discussed above are intimately interrelated, and, although each one must be considered individually, they must also be considered as an entire group of variables when evaluating powder flow properties.

Mixing Equipment A general classification of mixers is shown in Table 8. Types of mixers can be divided first into two broad categories: a batch type, and b continuous. By far and large, the most prevalent type used in the pharmaceutical industry today is the batch type that mixes a sublot or total lot of a formula at one time, i.

The continuous mixer, on the other hand, is usually dedicated to a single high-volume product. Ingredients are continuously proportioned into the mixer and collected from the continuous discharge. The lot size is usually determined by a specified length of mixing time which may range from 8 to 24 hr, depending on the process.

Batch-Type Mixers.

The first general class of mixers are those that create particle movement by rotation of the entire mixer shell or body.

A schematic of four types listed in Table 8 is seen in Figure 26, while a slant, double-cone mixer a modification of the double cone is shown in Figure Batch Type 1.

Rotation of the entire mixer shell or body with no agitator or mixing blade a. Barrel b. Cube c. V-shaped d. Double cone e. Slant double cone 2. Rotation of the entire mixer shell or body with a rotating highshear agitator blade a. V-shaped processor b. Double cone formulator c. Slant double cone formulator 3.

Stationary shell or body with a rotating mixing blade a. Ribbon b. Sigma blade c. Planetary d. Conical screw 4. High-speed granulations stationary shell or body with a rotating mixing blade and high-speed agitator blade a. Bowl 5. Air mixerstationary shell or body using moving air as agitator a. Fluid bed granulator b. Fluid bed drier B. Page 43 Figure 27 The twin shell V-blender.

However, the V-shaped blender Fig. The term blending is used in relation to these pieces of equipment because they mix the dry powders with a minimum of energy imparted to the powder bed as a result of tumbling the powders. The rotating shell blenders with no high speed agitator bar are used only for dry mixes and have no packing glands seals around shafts entering the chamber to cause potential problems.

Modifications, such as the addition of baffles, to increase mixing shear have been made to these types of blenders. The slant, double cone design is unique in that it eliminates the dead spot that may occur in the double cone mixer Fig. The advantage of using the V-shaped, doublecone, and slant double-cone blenders include: Page 44 Figure 28 Double-cone blender.

Minimal attrition when blending fragile granules 2. Large capacity equipment available 3. Easy to load and unload 4. Easy to clean 5. Minimal maintenance The primary disadvantages are: 1.

High head space needed for installation particularly with V-shaped mixers 2. Segregation problems with mixtures having wide particle size distribution and large differences in particle densities 3. Tumbling-type blenders not suitable for fine particulate systems because there may not be enough shear to reduce particle agglomeration 4.

Serial dilution required for the addition of low dose active ingredients if powders are free flowing Page 45 Figure 29 Slant double-cone mixer.

Courtesy Gemco, Middlesex, New Jersey. Blending efficiency is affected by the load volume factor as shown in Table 9. Blender speed may also be a key to mixing efficiency in that the slower the blender, the lower the shear forces. Although higher blending speeds provide more shear, more dusting may be prevalent causing segregation of fines, i. There is also a critical speed which, if approached, will diminish blending efficiency of the mixer considerably. As the revolutions per minute rpm increase, the centifugal forces at the extreme points of the mixing chamber will exceed the gravitation forces required for blending, and the powder will gravitate to the outer walls of the blender shell.

It should be noted that bench scale blenders turn at much higher rpm than the large blenders, usually in proportion to the peripheral velocity of blender extremes.

Page 46 Table 9 Effect of Powder Fill on Blending Time of Double-Cone Blendersa Volume percent of blender Approximate blend time minutes filled with powder charge in production-size blenders 50 10 65 14 70 18 75 24 80b 40b aBlending done in double-cone blenders and times measured to obtain comparable blends bUniform blend not attainable with this fill level Source: Sweitzer, G. The double-cone blender is usually charged and discharged through the same port, whereas the V-shaped blender may be loaded through either of the shell hatches or the apex port.

Emptying the V-shaped blender is normally done through the apex port. The second general class of mixers is a modification of the tumbling blenders shown schematically in Figure 30 with the addition of a high-speed rpm agitator mixing blade.

This agitator blade is situated as shown in Figure 31, and gives added versatility to the tumbling blenders by virtue of the high shear attainable.

The advantages with the addition of the agitator bar to the tumbling blender include: 1. Good versatility in that both wet and dry mixing can be accomplished in the blender. Figure 31 V-shaped blender with agitator mixing assembly. Courtesy of Gemco, Middlesex, New Jersey. Page 48 2. A wide range of shearing force may be obtained with the agitator bar design permitting the intimate mixing of very fine as well as coarse powder compositions. Serial dilution more than likely may not be needed when incorporating low dose active ingredients into the mixture.

The disadvantages include: 1. Possible attrition of large more friable particles or granules in a mixture as a result of the high-speed agitator mixer. Scale-up can prove to be a problem in that direct scale-up based on geometry, size, and peripheral velocity in many cases does not work. Experimental work is advised on the size mixer planned for the process if possible.

Cleaning may be a problem depending on design, since the agitator assembly must be removed and packings changed for a product changeover. Potential packing seal problems packings are used to prevent leakage through the shaft entrance into the mixing chamber and to prevent the blender contents from contaminating the bearings. The mixers with agitator bars, in most cases, are also available with a separate liquid dispensing system Fig.

These units, known as processors or formulators may also have a steam jacket around the shell of the blender for heating the wet powder or granulation, and a vacuum system to remove the granulating liquid vapors during drying. In essence, the entire granulating and drying step may be accomplished in one piece of equipment. A schematic of this operation is shown in Figure A typical sequence of operating steps for the processor or formulator would read as follows: 1.

Prepare granulating solution and adjust feed rate through pump. Charge the blender with ingredients to be granulated.

Turn on vacuum to 15 in. Premix the dry solids at normal processor shell rpm and run agitator mixer during blending. Pump granulating solution into processor or formulator with agitator bar running and turn on full vacuum in. Mix until granulation is properly wet up stop processor or formulator, relieve vacuum, and open to examine granulation.

Shut off agitator mixer and reduce the blender shell speed to minimum rpm for drying. Dry until solvent collector contains the specified quantity of solvent to be removed from the granulation do a material balance of solvent in and solvent out. The difference equals solvent remaining in chamber.

Check the loss of drying LOD after drying is completed. Empty granulation into a hopper or drums for further processing. Page 49 Figure 32 Separate liquid dispensing system. Page 50 Figure 33 Schematic of V-shaped blender, processor. The problems encountered with the operation include packing gland seal leakage under vacuum, and the granulation sticking to the sides of the blender shell. These problems can be often overcome by careful packing of the agitator mixer packing gland s , optimizing the shell temperature and granulation composition and optimizing the granulating solution addition rate, and developing the proper sequence of steps during granulating.

The processors and formulators are loaded and unloaded the same way as the V-shaped and double-cone blenders. The third category of mixers is mechanically different from the tumbling shell-type blenders, i. The blades naturally have different configurations for each of the specific designs, and move the solid-solid or liquid-solid mixtures by the force exerted through a motor driven drive shaft.

Schematics of the more commonly used designs are seen in Figure The ribbon mixer derives its name from the ribbon shaped blades which transverse the entire length of the U-trough and are attached to the drive shaft by struts not shown in the side view of the Figure 34a schematic. The ribbon mixer Fig.