Lozenge

It is a type of candy or small pellet which is medicated or aromatic. It is intended for slow dissolution in the mouth and often a demulcent is used in lozenges i.e. a substance helpful in soothing the mucus membrane which is inflamed.

Transferosome

Transferosome is a proprietary drug delivery technology of the German company IDEA AG.

Transferosome means "Carrying body". It is a type of artifical vesicle and is considered to be suitable for carrying drug to required target.

Sublimation

Definition:
It is conversion of a substance in solid state to a gaseous state, which is not accompanied by the formation of liquid phase.

It is similar in some aspects to the distillation process.

Process of sublimation:
At normal pressures, most of the chemical substances either compounds or elements have three different states of matter at various temperatures. In these circumstances, change from solid state to gaseous state requires a median state that is liquid.

On the other hand, some of the chemical substances such as compounds and elements at certain pressures go directly from solid state to the gaseous state. This occurs when the atmospheric pressure applied on the material is very less to inhibit the molecules from going out of the solid state i.e. a substance go through the process of sublimation only if the vapor pressure is less than that of the triple point for that substance.

Triple point:
The triple point is the point possessing a fixed pressure and temperature at which the solid, liquid and gaseous phases of a material are able to co-exist independently.

If the vapor pressure over the solid substance is more than that of the triple point, the solid will convert to vapor after passage through the liquid phase. The following phase diagram will help to understand the triple point.

Line OA:
In this diagram, line OA shows the melting points of the solid substance at different pressures. In this line, left side shows the existence of solid form while the right side shows the existence of liquid form. This line shows the points of co-existence of the solid and the liquid.

Line OB:
The line OB shows the vapor-pressure curve of the liquid at different temperatures. Above this line liquid phase exists and below this line vapor phase of the substance exists. This line shows the points of co-existence of the liquid and the vapors.

Line OC:
The line OC shows the sublimation curve of the solid. This line shows the points of co-existence of the solid and the vapors at different states of temperatures and pressure.

Point O:
In this diagram, the point O represents the triple point.

Enthalpy:
Enthalpy of sublimation is equal to the sum of enthalpy of fusion and enthalpy of vaporization.

Sublimation process represents an endothermic phase transition as shown by the phase diagram.

Examples:
Nearly all of the solids have some tendency of conversion from solid to gaseous state at a particular temperature and pressure.

Elements:
Cadmium, Zinc, Arsenic, Carbon

Compounds:
CO2 (Dry ice), NH4Cl

Uses:
Its most important use is in freeze-drying.

Elutriation

The word “Elutriation” is derived from the Latin word “elutriare” meaning “to wash out”.

Definition:
It is the separation, purification or removal of something from a mixture by decanting, straining or washing.

Process of elutriation:
In the process of elutriation, the movement of the fluid, generally water or air, is in the opposite direction to that of the sedimentation process.

Types of elutriation:
According to direction:

Vertical elutriation:
In the gravitational process, the larger particles present in water (or any other liquid) will move vertically downwards with the affect of gravity while the small particles in the fluid travels straight up with the fluid. This is a type of vertical elutriation.

Horizontal elutriation:
If a water current of suspended particles is flowed through a settling chamber. The particles that move out of the water current are collected in the bottom of the chamber. This is a type of horizontal elutriation.

Centrifugal elutriation:
In this case the water current is caused to spin with some force resulting in the large centrifugal force on the suspended particles. The heavier particles will settle to the walls of the elutriator or to the bottom.

The DorrClone is an example of a centrifugal-type of classifier.

According to the type of fluid:

• Air elutriation

• Water elutriation

If the velocity of the fluid is smaller than the velocity of setting down of the particles then the particles will settle downwards. On the other hand, if the velocity of the fluid is larger than the velocity of setting down of the particles then the particles will be carried up along with the fluid.

Air elutriation will give precise separation of the particles and in less time than water elutriation.

Factors affecting elutriation:

Elutriation is affected by the

• velocity of the fluid

• the particle size : As the small sized particles will flow (upward) along the fluid while the large sized particles will move downwards (against the velocity of the fluid).

• position of the particle in the (tube containing) fluid

• density of the particle

In a tube, there exist different velocities i.e. the velocity is largest in the centre and is smallest along the walls of the tube. So the small sized particles move upward, when in the centre and in the meantime they are also pushed towards the wall of the tube. Where the velocity is smaller and here the small sized particles start to move downwards.

Process of removal of particles:

If the upward flow of the water (or any other liquid) is slightly increased, the small sized particles (which move down slowly) will move along the movement of the water (i.e. upward) and will be removed from the water. In this process, the medium sized particles will remain immobile and the heavier particles will continue to move downward.

The upward flow of water will then again be increased and the next smallest size particles will be removed. And in this way, particles of different sizes will be separated and obtained.

Centrifugation

It refers to the process of sedimentation by using centrifuge machine.

Basic idea behind centrifugation:
Centrifugation is based on the widely known idea of sedimentation by the use of centrifugal force, which represents a force that apparently moves a spinning or rotating object away from the axis of rotation in a curved path.

Centrifugal effect:
The processes using centrifugal force (F) can be described by the equations involving the gravitational constant (G). In this case, it is easy to determine the centrifugal force in the terms of the ratio of the centrifugal force to the gravitational force. In addition, this ratio represents the centrifugal effect (C).

Centrifugal effect (C) shows that how many times the centrifugal force is larger than gravitational force.

C = 2.013 dn^2

Where
d = diameter of rotation
n = speed of rotation

Here in this equation, “n” has the value in “s-1” and “d” has the value in “m”.


This equation shows that centrifugal effect is directly proportional to the diameter and to the square of the speed of the rotation i.e. greater will be the diameter of the tube or container more will be centrifugation and similarly for the speed of rotation.

Factors affecting centrifugation:

Centrifugation is basically affected by centrifugal effect. Moreover, nature of the liquid medium in which the particles are placed also affects the centrifugation.

Apparatus for centrifugation (Centrifuges):
Container is the most important part of centrifugation apparatus i.e. centrifuges. This container is used for the placement of a mixture or solution of solid and liquid or of a solution of two liquids.

This container is then rotated at greater speed resulting in the separation of the ingredients of the mixture takes place by the use of centrifugal force.

Mechanism for the separation in the apparatus of centrifugation:
A mixture of liquid or solid in a liquid of low density can be separated as the material of larger density is thrown in the outward direction to the bottom of the tube or container with a larger force. This results in the separation of pure, low-density liquid as a transparent or purified supernatant liquid which forms upper layer.

Types of centrifuges:

There are two basic types of centrifuges:

1. Sedimentation

2. Filtration

Sedimentation centrifuges:

The basic principle, in the sedimentation type of centrifuges, is difference in the densities of the ingredients of the mixture. In these types of centrifuges, the particles are settled to the wall by the action of the centrifugal force.

These types of centrifuges are used for the separation of ingredients of the mixture of solid in liquid as well as liquid in liquid.

Two types of centrifuges are based on the principle of sedimentation:

1. Bottle centrifuge

2. Disc type centrifuge

Bottle centrifuge:
It is mostly used centrifuge machine in the laboratories. It consists of a vertical rotating rod that causes the “bottle-type” containers or test tubes, which are fixed symmetrically, to be rotated in a horizontal plane resulting in the separation of the materials of varying densities. The vertical rod is rotated usually by means of electric motor. Sometimes, gas turbines can also be used for the rotation.

Disk type centrifuge:
It consists of vertical pile of thin conical disks, which are arranged in the manner of one on the top of another. The sedimentation of the particles takes place in the space between neighbouring cones. In this way, settling distance is greatly reduced, thereby increasing the rate at which the particles in the material are separated. The cones are adjusted in such a manner that heavier material moves down the surface easily upon reaching the inner surface of the cone.

Filtration centrifuges:

These types of centrifuges are used for the separation of the mixture of solid in liquid only performing the operation similar to the filtration process. These are also sometimes referred to as clarifiers.

It is same in the basic operation to the sedimentation types of centrifuges but instead of solid containers or tubes, it contains a porous wall or perforated containers or baskets, which causes the liquid phase to pass through it but keeps the solid phase on it.

Centrifuge based on the principle of filtration is “Basket centrifuge”.

Basket centrifuge:
Basket centrifuge consists of a porous wall and rotor which is cylindrical and tubular in structure. The porous wall is some times replaced by one or more of the fine mesh screens. The fluid go through the screen where as the particles larger in size are left on the screen.

Application of centrifugation:

Centrifugation is used for the separation of ingredients of a mixture of solid in liquid or liquid in liquid as the degree of separation achieved by centrifugation is of greater amplitude than the action due to gravity.

It is important specifically when the separation by normal filtration methods is difficult such as in the separation of fluids of highly viscous nature.

In the pharmaceutical research, it is considered as an important tool in determining the stability of emulsions.

Bottle centrifuge can be used for:

1. Finding the sediments present in crude vegetable and mineral oils
2. Determination of the butterfat content in the milk
3. Various clinical trials and tests

Disk type centrifuge can be used for refining of vegetable oils by removing soap stock

Basket centrifuge can be used for:

1. Drying and washing of several different kinds of crystals and fibrous materials
2. The preparation of cane sugar.

Bougies

Introduction:
Its name came from the town namely “bougie” in Algeria, which was famous for trading in wax. Its original meaning is “A candle made by wax”. These are the types of suppositories intended for insertion into the urethra, nostrils or ears.

It is also a medical instrument in the shape of cylinder, made up of a flexible tube.

Forms of bougie:
Bulbous bougie:
It is a form of bougie with a bulb shaped tip.

Eder-pustow bougie:
It is a form of metal bougie which resembles olive in shape. It may be used in esophageal stricture.

Elastic bougie:
A bougie made of rubber or latex.

Elbowed bougie:
A bougie with a bent near its tip.

Use:
It is used for opening of constricted areas in tubular organs such as urethra or esophagus and rectum, so, that medicines for local application or another instruments can easily be inserted in that part.

Types of properties of solutions

There are following three types of properties of solution:
1. Additive properties
2. Constitutive properties
3. Colligative properties

Additive properties:
These are the properties which are due to sum of corresponding properties of individual atoms or functional groups within the molecules e.g. molecular weight.

Constitutive property:
These are the properties which depend upon the structural arrangement of atoms within the molecules for example optical properties and surface and interfacial properties.

Colligative property:
These are the properties which depend upon the number of molecules present in solution.
Following are colligative properties of dilute solution:

1. Lowering of vapor pressure
2. Elevation of boiling point
3. Depression of freezing point
4. Osmotic pressure

Tincture

A tincture is an alcoholic extract (e.g. of leaves or other plant material) or solution of a non-volatile substance (e.g. of iodine, mercurochrome). To qualify as a tincture, the alcoholic extract is to have an ethanol percentage of at least 40-60% (80-120 proof) (sometimes a 90% (180 proof) pure liquid is even achieved). In herbal medicine, alcoholic tinctures are often made with various concentrations of ethanol, 25% being the most common. Other concentrations include 45% and 90%. Herbal tinctures do not always use ethanol as a solvent, though this is the most frequent. Other solvents include vinegar, glycerol, ether and propylene glycol, not all of which are used for internal consumption. However, where a raw solvent's pH factor is a sole consideration, the advantage of ethanol is that being close to neutral pH, it is a good compromise as a passive used solvent of both acidic and alkaline constituents where a tincturing methodology is concerned. Glycerine, when utilized in a tincture methodology's passive (i.e. 'non-critical') manner, is a poorer solvent generally, and vinegar, being acidic, is a better solvent of alkaloids but a poorer solvent of acids, which would result in the alkaloids being more present in the preparation than otherwise. However, for people who do not imbibe alcohol for medical, religious or moral reasons, non-alcoholic (glycerite) tinctures are an alternative.
Alcohol tinctures cannot be subjected to high temperatures and are thus considered a 'non-critical' passive methodology regarding this factor. This is one of the primary reasons why glycerol, due to early Eclectic medicine studies (now for the most part outdated concerning the subject), is typically seen as inferior to alcohol, when utilized in a non-critical tincture methodology fashion (which is how Eclectic medicine researchers utilized glycerol in their tincture making studies), since it does not exhibit the extractive potential of alcohol when used in a low temperature non-critical tincturing setting. Glycerol used in a non-critical tincturing methodology, as is typically done in the herbal products industry at large for instance, will result in a weak solution, whereas if glycerol is subjected to a contemporary innovative serialized methodology currently in the industry, the extractive potential of glycerol is quite astounding. Therefore, glycerite products made using such innovative serialized extraction technologies are showing great promise, even rivaling alcohol tinctures on numerous points.
Solutions of volatile substances were called spirits, although that name was also given to several other materials obtained by distillation, even when they did not include alcohol. In chemistry, a tincture is a solution that has alcohol as the solvent.

General Method of preparation:

A general method of preparation on how tinctures can be prepared is the following:

• Herbs are put in a jar and a spirit of 40% pure ethanol is added (80 proof Vodka, for example)
• The jar is left to stand for 2–3 weeks, shaken occasionally, in order to maximise the concentration of the solution.

To make a more precise tincture, more extensive measuring can be done by combining 1 part herbs with a water-ethanol mixture of 2-10 parts, depending on the herb itself. With most tinctures, however, 1 part water at 5 parts ethanol is used.

Advantages of Tincture:
Ethanol is able to dissolve substances which are less soluble in water, while at the same time the water content can dissolve the substances less soluble in ethanol. It is possible to vary the proportion of ethanol and water to produce tinctures with different qualities because of different substances. One example of this is tincture of Calendula officinalis, which is frequently used either at 25% ethanol or 90% ethanol. The solvent also acts as a preservative.

Disadvantages of tinctures

Chemically speaking, ethanol possesses a profound intrinsic denaturing and inert rendering quality. This quality accounts for a large part of ethanol's anti-microbial properties. This denaturing and inert rendering quality also has an undesired effect on many extracted botanical constituents. For instance, alcohol intrinsically fractures and denatures many highly complex aromatic compounds and denatures many extracted for polysaccharides. Other constituents are likewise subjected to denaturing and being rendered inert. The basic tenets of chemistry teach that anytime a biologically viable component is denatured or rendered inert, it will reduce or negate the prior biological viability. This factor needs to be seriously considered and weighed by the clinician or consumer when determining the hoped for biological viability of an ethanol-based botanical tincture both as to sought for efficacy and dosage considerations.
Ether and propylene glycol tinctures are not suitable for internal consumption and are instead used in such preparations as creams or ointments.

Examples of Tinctures:

Some examples that were formerly common in medicine include:

• Tincture of Cannabis sativa
• Tincture of Benzoin
• Tincture of cantharides
• Tincture of ferric citrochloride (a chelate of citric acid and Iron(III) chloride)
• Tincture of green soap (which also contains lavender)
• Tincture of guaiac
• Tincture of iodine
• Tincture of opium (laudanum)
• Camphorated opium tincture (paregoric)
• Tincture of Pennyroyal
• Warburg's Tincture (aka Tinctura Antiperiodica aka Antiperiodic Tincture), an antipyretic medicine of the 19th-century.

Examples of spirits include:

• Spirit of ammonia (also called spirit of hartshorn)
• Spirit of box, or ethanol, which was derived from the destructive distillation of boxwood
• Spirit of camphor
• Spirit of ether, a solution of diethyl ether in alcohol
• "Spirit of Mindererus", ammonium acetate in alcohol
• "Spirit of nitre" is not a spirit in this sense, but an old name for nitric acid (but "sweet spirit of nitre" was ethyl nitrite)
• Similarly "spirit(s) of salt" actually meant hydrochloric acid. The concentrated, fuming, 35% acid is still sold under this name in the UK, for use as a drain-cleaning fluid.
• "Spirit of vinegar" was glacial acetic acid and
• "Spirit of vitriol" was sulfuric acid
• "Spirit of wine" or "spirits of wine" is an old name for alcohol (especially food grade alcohol derived from the distillation of wine)
• "Spirit of wood" means methanol, often derived from the destructive distillation of wood

Elixir

An elixir is a clear, sweet-flavored liquid (usually containing alcohol) used in compounding medicines to be taken orally in order to mask an unpleasant taste and intended to cure one's ills.
When used as a pharmaceutical preparation, it contains at least one active ingredient dissolved in a solution that contains 15 to 50% by volume of ethyl alcohol and it is designed to be taken orally.

Types of Elixirs:

1. Non-medicated elixirs:
It is used as a solvent or vehicle for the preparation of medicated elixirs: aromatic elixirs (USP), isoalcholic elixirs (NF) or compound benaldehyde elixirs (NF).

2. Medicated elixirs

• Antihistaminic elixirs: used against allergy: chlorampheniramine maleate elixirs (USP), diphenhydramine HCl elixirs.
• Sedative and hypnotic elixirs: sedatives induce drowsiness and hypnotics induce sleep: pediatric chloral hydrate elixirs.
• Expectorant: used to facilitate productive cough (cough with sputum): terpin hydrate elixirs.
• Miscellaneous: acetaminophen (paracetamol) elixirs which are used as analgesic.

Composition:
An elixir is a hydro-alcoholic solution of at least one active ingredient. The alcohol is mainly used to:

• Solubilize the active ingredient(s) and some excipients
• Retard the crystallization of sugar
• Preserve the finished product
• Provide a certain sharpness to the taste
• Aid in masking the unpleasant taste of the active ingredient(s)
• Enhance the flavor.

The lowest alcoholic quantity that will dissolve completely the active ingredient(s) and give a clear solution is generally chosen. High concentrations of alcohol give burning taste to the final product.
An elixir may also contain the following excipients:

• Sugar and/or sugar substitutes like the sugar polyols glycerol and sorbitol.
• Preservatives like parabens and bezoates and antioxidants like butylated hydroxytoluene (BHT) and sodium metabisulfite.
• Buffering agents
• Chelating agents like sodium ethylenediaminetetraacetic acid (EDTA)
• Flavoring agents and flavor enhancers
• Coloring agents

Storage:
Elixirs should be stored in a tightly closed and light resistant container away from direct heat and sunlight.

Syrup

A syrup is a thick, viscous liquid consisting primarily of a solution of sugar in water, containing a large amount of dissolved sugars but showing little tendency to deposit crystals. The viscosity arises from the multiple hydrogen bonds between the dissolved sugar, which has many hydroxyl (OH) groups, and the water. Syrups can be made by dissolving sugar in water or by reducing naturally sweet juices such as cane juice, sorghum juice, or maple sap. Corn syrup is made from corn starch using an enzymatic process that converts it to sugars. Technically and scientifically, the term syrup is also employed to denote viscous, generally residual, liquids, containing substances other than sugars in solution.

Types of syrups:

1. Non-medicated syrup:
The syrup employed as a base for medicinal purposes consists of a concentrated or saturated solution of refined sugar in distilled water. The "simple syrup" of the British Pharmacopoeia is prepared by adding 1 kg of refined sugar to 500 mL of boiling distilled water, heating until it is dissolved and subsequently adding boiling distilled water until the weight of the whole is 1.5 kg. The specific gravity of the syrup should be 1.33. This is a 66° Brix solution.

2. Medicated syrup
 
Composition of medicated syrups
Medicated syrups are aqueous solutions containing sugar and at least one water soluble active ingredient.
The sugar is mainly used to:

• Preserve the finished product
• Aid in masking the unpleasant taste of the active ingredient(s)
• Enhance the flavour.

The concentration of sugar must approach but not quite reach the super-saturation point: the sugar concentration should be between 65 and 67% in weight. A lower percentage of sugar makes the syrup an excellent nutriment for yeast and other microorganisms. A sugar saturated syrup lead to crystallization of a part of the sugar under conditions of changing temperature.
Syrups may also contain the following excipients:

• Sugar polyols like glycerol, maltitol and sorbitol
• Preservatives like parabens and bezoates and antioxidants like butylated hydroxytoluene (BHT) and sodium metabisulfite.
• Acids like citric acid to prevent the recrystallisation of sugar
• Buffering agents
• Chelating agents like sodium ethylenediaminetetraacetic acid (EDTA)
• Flavouring agents and flavour enhancers
• Colouring agents
• Ethyl alcohol (3-4% in volume).

The syrup may also be sugar-free. The sugar is then replaced by sugar substitutes like the sugar polyols such as glycerol, isomaltol and sorbitol or artificial sweeteners like aspartame, neotame, sucralose and acesulfame potassium mixed to thickening agents like polyvinylpyrrolidone or polysaccharides like carrageenan, xanthan gum, and cellulose ethers. Sugar-free syrup will not contribute to dental caries.

Preparation of medicated syrups
Syrups are mainly prepared by the following method:

• Dissolve ingredients in purified water and because the sugar decreases the solubilizing properties of water, it is added generally at the end.
• Heat and/or agitate actively until the dissolution of all ingredients. If at least one of the ingredients is sensitive to temperature, mixing should take place without heating.
• Strain if needed
• Add sufficient purified water to make the right weight or volume.

Simple Syrup:

A basic sugar-and-water syrup used to make drinks at bars is referred to by several names, including liquid sugar simple syrup, sugar syrup, simple sugar syrup, gomme, and bar syrup. Simple syrup is made by stirring granulated sugar into hot water in a sauce pan until the sugar is dissolved and then cooling the solution. Generally, the ratio of sugar to water can range anywhere from 1:1 to 2:1.
Simple syrup can be used as a sweetener. However, since it gels readily when pectin is added, its primary culinary use is as a base for fruit sauces, toppings and preserves.

Soft gel

A softgel is an oral dosage form for medicine similar to capsules. They consist of a gelatin based shell surrounding a liquid fill. Softgel shells are a combination of gelatin, water, opacifier and a plasticiser such as glycerin and/or sorbitol(s).
Softgels are produced in a process known as encapsulation using the Rotary Die Encapsulation process invented by Robert Pauli Scherer. The encapsulation process has been described as a form/fill/seal process. Two flat ribbons of shell material are manufactured on the machine and brought together on a twin set of rotating dies. The dies contain recesses in the desired size and shape, which cut out the ribbons into a two dimensional shape, and form a seal around the outside. At the same time a pump delivers a precise dose of fill material through a nozzle incorporated into a filling wedge whose tip sits between the two ribbons in between two die pockets at the point of cut out. The wedge is heated to facilitate the sealing process. The wedge injection causes the two flat ribbons to expand into the die pockets, giving rise to the three dimensional finished product. After encapsulation, the softgels are dried for two days to two weeks depending on the product.
In recent years, manufacturers have been able to replace gelatin in the shell with other polymers based on, for example, starch and carrageenan.
Catalent Pharma Solutions is the current owner of the RPScherer technology .

Pills

A pill is a small, round, solid pharmacological oral dosage form that was in use before the advent of tablets and capsules. Pills were made by mixing the active ingredients with an excipient such as glucose syrup in a mortar and pestle to form a paste, then rolling the mass into a long cylindrical shape (called a "pipe"), and dividing it into equal portions, which were then rolled into balls, and often coated with sugar to make them more palatable.
In colloquial usage, tablets, capsules, and caplets are still often referred to as "pills" collectively.

Tablet

A tablet is a pharmaceutical dosage form.

It comprises a mixture of active substances and excipients, usually in powder form, pressed or compacted from a powder into a solid dose.

Excipients:
Excipients are the ingredients in dosage forms which are not medically active. The excipients can include diluents, binders or granulating agents, glidants (flow aids) and lubricants to ensure efficient tabletting; disintegrants to promote tablet break-up in the digestive tract; sweeteners or flavours to enhance taste; and pigments to make the tablets visually attractive.
A polymer coating is often applied to make the tablet smoother and easier to swallow, to control the release rate of the active ingredient, to make it more resistant to the environment (extending its shelf life), or to enhance the tablet's appearance.

Most popular form of tablet in use today:
The compressed tablet is the most popular dosage form in use today. About two-thirds of all prescriptions are dispensed as solid dosage forms, and half of these are compressed tablets. A tablet can be formulated to deliver an accurate dosage to a specific site; it is usually taken orally, but can be administered sublingually, buccally, rectally or intravaginally. The tablet is just one of the many forms that an oral drug can take such as syrups, elixirs, suspensions, and emulsions. Medicinal tablets were originally made in the shape of a disk of whatever color their components determined, but are now made in many shapes and colors to help distinguish different medicines. Tablets are often stamped with symbols, letters, and numbers, which enable them to be identified. Sizes of tablets to be swallowed range from a few millimeters to about a centimeter. Some tablets are in the shape of capsules, and are called "caplets". Medicinal tablets and capsules are often called pills. This is technically incorrect, since tablets are made by compression, whereas pills are ancient solid dose forms prepared by rolling a soft mass into a round shape. Other products are manufactured in the form of tablets which are designed to dissolve or disintegrate; e.g. cleaning and deodorizing products.

Tabletting formulations:
In the tablet-pressing process, it is important that all ingredients be fairly dry, powdered or granular, somewhat uniform in particle size, and freely flowing. Mixed particle sized powders can segregate during manufacturing operations due to different densities, which can result in tablets with poor drug or active pharmaceutical ingredient (API) content uniformity but granulation should prevent this. Content uniformity ensures that the same API dose is delivered with each tablet.
Some APIs may be tableted as pure substances, but this is rarely the case; most formulations include excipients. Normally, an pharmacologically inactive ingredient (excipient) termed a binder is added to help hold the tablet together and give it strength. A wide variety of binders may be used, some common ones including lactose, dibasic calcium phosphate, sucrose, corn (maize) starch, microcrystalline cellulose, povidone polyvinylpyrrolidone and modified cellulose (for example hydroxypropyl methylcellulose and hydroxyethylcellulose).
Often, an ingredient is also needed to act as a disintegrant to aid tablet dispersion once swallowed, releasing the API for absorption. Some binders, such as starch and cellulose, are also excellent disintegrants.
Small amounts of lubricants are usually added, as well. The most common of these is magnesium stearate and calcium stearate ; however, other commonly used tablet lubricants include stearic acid (stearin), hydrogenated oil, and sodium stearyl fumarate. These help the tablets, once pressed, to be more easily ejected from the die and for fine finishing of tablets.

Advantages and Disadvantages:
Tablets are simple and convenient to use. They provide an accurately measured dosage of the active ingredient in a convenient portable package, and can be designed to protect unstable medications or disguise unpalatable ingredients. Colored coatings, embossed markings and printing can be used to aid tablet recognition. Manufacturing processes and techniques can provide tablets special properties, for example, sustained release or fast dissolving formulations.
Some drugs may be unsuitable for administration by the oral route. For example, protein drugs such as insulin may be denatured by stomach acids. Such drugs cannot be made into tablets. Some drugs may be deactivated by the liver when they are carried there from the gastrointestinal tract by the hepatic portal vein (the "first pass effect"), making them unsuitable for oral use. Drugs which can be taken sublingually are absorbed through the oral mucosae, so that they bypass the liver and are less susceptible to the first pass effect. The oral bioavailability of some drugs may be low due to poor absorption from the gastrointestinal tract. Such drugs may need to be given in very high doses or by injection. For drugs that need to have rapid onset, or that have severe side effects, the oral route may not be suitable. For example salbutamol, used to treat problems in the pulmonary system, can have effects on the heart and circulation if taken orally; these effects are greatly reduced by inhaling smaller doses direct to the required site of action.

Tablet Properties:
Tablets can be made in virtually any shape, although requirements of patients and tableting machines mean that most are round, oval or capsule shaped. More unusual shapes have been manufactured but patients find these harder to swallow, and they are more vulnerable to chipping or manufacturing problems.
Tablet diameter and shape are determined by the machine tooling used to produce them - a die plus an upper and a lower punch are required. This is called a station of tooling. The thickness is determined by the amount of tablet material and the position of the punches in relation to each other during compression. Once this is done, we can measure the corresponding pressure applied during compression. The shorter the distance between the punches, thickness, the greater the pressure applied during compression, and sometimes the harder the tablet. Tablets need to be hard enough that they don't break up in the bottle, yet friable enough that they disintegrate in the gastric tract.
Tablets need to be strong enough to resist the stresses of packaging, shipping and handling by the pharmacist and patient. The mechanical strength of tablets is assessed using a combination of (i) simple failure and erosion tests, and (ii) more sophisticated engineering tests. The simpler tests are often used for quality control purposes, whereas the more complex tests are used during the design of the formulation and manufacturing process in the research and development phase. Standards for tablet properties are published in the various international pharmacopeias (USP/NF, EP, JP, etc.). The hardness of tablets is the principle measure of mechanical strength. Hardness is tested using a hardness tester. The units for hardness have evolved since the 1930s.
Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with low friction between the solid and die wall.
Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid are the most frequently used lubricants in tablets or hard gelatin capsules.


Manufacturing:
Manufacturing of the Tablet Blend:
In the tablet pressing process, the main guideline is to ensure that the appropriate amount of active ingredient is in each tablet. Hence, all the ingredients should be well-mixed. If a sufficiently homogenous mix of the components cannot be obtained with simple blending processes, the ingredients must be granulated prior to compression to assure an even distribution of the active compound in the final tablet. Two basic techniques are used to granulate powders for compression into a tablet: wet granulation and dry granulation. Powders that can be mixed well do not require granulation and can be compressed into tablets through direct compression.

Wet granulation:
Wet granulation is a process of using a liquid binder to lightly agglomerate the powder mixture. The amount of liquid has to be properly controlled, as over-wetting will cause the granules to be too hard and under-wetting will cause them to be too soft and friable. Aqueous solutions have the advantage of being safer to deal with than solvent-based systems but may not be suitable for drugs which are degraded by hydrolysis.

• Procedure
  • Step 1: The active ingredient and excipients are weighed and mixed.
  • Step 2: The wet granulate is prepared by adding the liquid binder–adhesive to the powder blend and mixing thoroughly. Examples of binders/adhesives include aqueous preparations of cornstarch, natural gums such as acacia, cellulose derivatives such as methyl cellulose, gelatin, and povidone.
  • Step 3: Screening the damp mass through a mesh to form pellets or granules.
  • Step 4: Drying the granulation. A conventional tray-dryer or fluid-bed dryer are most commonly used.
  • Step 5: After the granules are dried, they are passed through a screen of smaller size than the one used for the wet mass to create granules of uniform size.

Low shear wet granulation processes use very simple mixing equipment, and can take a considerable time to achieve a uniformly mixed state. High shear wet granulation processes use equipment that mixes the powder and liquid at a very fast rate, and thus speeds up the manufacturing process. Fluid bed granulation is a multiple-step wet granulation process performed in the same vessel to pre-heat, granulate, and dry the powders. It is used because it allows close control of the granulation process.


Dry granulation:
Dry granulation processes create granules by light compaction of the powder blend under low pressures. The compacts so-formed are broken up gently to produce granules (agglomerates). This process is often used when the product to be granulated is sensitive to moisture and heat. Dry granulation can be conducted on a tablet press using slugging tooling or on a roll press called a roller compactor. Dry granulation equipment offers a wide range of pressures to attain proper densification and granule formation. Dry granulation is simpler than wet granulation, therefore the cost is reduced. However, dry granulation often produces a higher percentage of fine granules, which can compromise the quality or create yield problems for the tablet. Dry granulation requires drugs or excipients with cohesive properties, and a 'dry binder' may need to be added to the formulation to facilitate the formation of granules.

Granule Lubrication:
After granulation, a final lubrication step is used to ensure that the tableting blend does not stick to the equipment during the tableting process. This usually involves low shear blending of the granules with a powdered lubricant, such as magnesium stearate or stearic acid.

Manufacture of the tablets 

Whatever process is used to make the tableting blend, the process of making a tablet by powder compaction is very similar. First, the powder is filled into the die from above. The mass of powder is determined by the position of the lower punch in the die, the cross-sectional area of the die, and the powder density. At this stage, adjustments to the tablet weight are normally made by repositioning the lower punch. After die filling, the upper punch is lowered into the die and the powder is uniaxially compressed to a porosity of between 5 and 20%. The compression can take place in one or two stages (main compression, and, sometimes, pre-compression or tamping) and for commercial production occurs very fast (500–50 msec per tablet). Finally, the upper punch is pulled up and out of the die (decompression), and the tablet is ejected from the die by lifting the lower punch until its upper surface is flush with the top face of the die. This process is simply repeated many times to manufacture multiple tablets.

Common problems encountered during tablet manufacturing operations include:

• poor (low) weight uniformity, usually caused by uneven powder flow into the die
• poor (low) content uniformity, caused by uneven distribution of the API in the tableting blend
• sticking of the powder blend to the tablet tooling, due to inadequate lubrication, worn or dirty tooling, and sub-optimal material properties
• capping, lamination or chipping. Such mechanical failure is due to improper formulation design or faulty equipment operation.

Tablet Compaction Simulator:
Tablet formulations are designed and tested using a laboratory machine called a Tablet Compaction Simulator or Powder Compaction Simulator. This is a computer controlled device that can measure the punch positions, punch pressures, friction forces, die wall pressures, and sometimes the tablet internal temperature during the compaction event. Numerous experiments with small quantities of different mixtures can be performed to optimise a formulation. Mathematically corrected punch motions can be programmed to simulate any type and model of production tablet press. Initial quantities of active pharmaceutical ingredients are very expensive to produce, and using a Compaction Simulator reduces the amount of powder required for product development.

Tablet Presses:
Tablet presses, also called tableting machines, range from small, inexpensive bench-top models that make one tablet at a time (single-station presses), with only around a half-ton pressure, to large, computerized, industrial models (multi-station rotary presses) that can make hundreds of thousands to millions of tablets an hour with much greater pressure. The tablet press is an essential piece of machinery for any pharmaceutical and nutraceutical manufacturer. Common manufacturers of tablet presses include Fette, Korsch, Kikusui, Manesty, IMA and Courtoy. Tablet presses must allow the operator to adjust the position of the lower and upper punches accurately, so that the tablet weight, thickness and density can each be controlled. This is achieved using a series of cams, rollers, and/or tracks that act on the tablet tooling (punches). Mechanical systems are also incorporated for die filling, and for ejecting and removing the tablets from the press after compression. Pharmaceutical tablet presses are required to be easy to clean and quick to reconfigure with different tooling, because they are usually used to manufacture many different products.

Tablet Coating:
Many tablets today are coated after being pressed. Although sugar-coating was popular in the past, the process has many drawbacks. Modern tablet coatings are polymer and polysaccharide based, with plasticizers and pigments included. Tablet coatings must be stable and strong enough to survive the handling of the tablet, must not make tablets stick together during the coating process, and must follow the fine contours of embossed characters or logos on tablets. Coatings are necessary for tablets that have an unpleasant taste, and a smoother finish makes large tablets easier to swallow. Tablet coatings are also useful to extend the shelf-life of components that are sensitive to moisture or oxidation. Opaque materials like titanium dioxide can protect light-sensitive actives from photodegradation. Special coatings (for example with pearlescent effects) can enhance brand recognition.
If the active ingredient of a tablet is sensitive to acid, or is irritant to the stomach lining, an enteric coating can be used, which is resistant to stomach acid, and dissolves in the less acidic area of the intestines. Enteric coatings are also used for medicines that can be negatively affected by taking a long time to reach the small intestine, where they are absorbed. Coatings are often chosen to control the rate of dissolution of the drug in the gastrointestinal tract. Some drugs will be absorbed better at different points in the digestive system. If the highest percentage of absorption of a drug takes place in the stomach, a coating that dissolves quickly and easily in acid will be selected. If the rate of absorption is best in the large intestine or colon, then a coating that is acid resistant and dissolves slowly would be used to ensure it reached that point before dispersing. The area of the gastrointestinal tract with the best absorption for any particular drug is usually determined by clinical trials.

Pill Splitters:
It is sometimes necessary to split tablets into halves or quarters. Tablets are easier to break accurately if scored, but there are devices called pill-splitters which cut unscored and scored tablets. Tablets with special coatings (for example enteric coatings or controlled-release coatings) should not be broken before use, as this will expose the tablet core to the digestive juices, short-circuiting the intended delayed-release effect.

The Simplex Method

It is a mathematical optimization method, which is used in many operations including pharmaceutical operations and processes.Simplex algorithm is adopted for simplex method.

Simplex method was developed by George Dantzig in 1947. He was an American mathematician.
The name of the algorithm is derived from the concept of a simplex. "Simplex" represents a geometric figure. Simplex is represented by the minimum number of dimensions of the space such as a line is represented by the two dimensional space and triangle is represented  by the two dimensional space (i.e. corners - 1 = dimensions). From these illustrations it can be clear that for two independent variables or factors the shape of the simplex will be triangle. Simplices are not actually used in the method, but one interpretation of it is that it operates on simplicial cones and these become simplices with an additional constraint.

Simplex method works on linear programs in standard form.

Effectiveness:
Simplex is one of the most effective methods of optimization.

Evolutionary operations in Optimization

Evolutionary operations is also referred to "EVOP" and is well suited for the production side of the industry.

In this prcoess, constant repetition and careful planning of the production process such as formulation is used to move towards better processes.

Pharmaceutical Incompatibility

Introduction:
Incompatibility refers to the inability of something or some process to co-exist with another process or thing.
So, Pharmaceutical incompatibility refers to the inability of a pharmaceutical substance to exist in combination with another pharmaceutical entity.

Types of Incompatibility:

There are three types of incompatibility:

1. Therapeutical incompatibility

2. Chemical incompatibility

3. Pharmaceutical or physical incompability

1. Therapeutical incompatibility:

This incompabitlity is resulted due to the combination of drugs having antagonistic or opposing properties.

2. Chemical incompatibility:
This type of incompatibility is resulted due to the formation of undesirable new product when two or more drugs are combined.

Examples of Chemical incompatibility:
1. Precipitation
2. Colour change
3. Effervescences
4. Decomposition

Types of Chemical Incompatibility:
Chemical incompatibility can be intentional i.e. a prescriber knowingly gives incompatible drugs, or unintentional i.e. prescriber does not know that the drugs are incompatible.

There are two types of chemical incompatibility:

1. Tolerated
In this type of incompatibility, chemical reaction can be reduced by mixing the solution in dilute forms or by changing the order of mixing.

2. Adjusted
In this type of incompatibility, change in the formulation is needed with a compound of equal therapeutic value e.g. in the mixture of caffeine citrate and sodium salicylate, caffeine citrate is replaced with caffeine.

3. Pharmaceutical or physical Incompatibility:
This type of incompatibility results by the slow or immediate formation of decomposed solutions or precipitates, when the drugs are combined in a pharmacy setup or laboratoy.

Examples of Pharmaceutical or physical incompatibility:
1. Insolubility
2. Liquefaction
When the substances with low melting points such as camphor, menthol and thymol  are mixed together, a liquid mixture i.e. eutectic mixture is formed and this process is known as liquefaction.

3. Precipitation
Precipitation can result when the solvent in which the solute is insoluble is added to the solution. Resins are normally not soluble in water. So, the tinctures of resins may form precipitate on addition to water.

4. Immiscibility

Correction of pharmaceutical or physical incompatibiliy:

This can be corrected by using one or more of the following methods:

1. Addition of suspending agents or thickening agents:
In the following prescription tragacanth (mucilage or compound powder) is used as a suspending agent.

Phenacetin 3g
Caffeine 1g
Orange Syrup 12ml
Water upto 90ml

As Phenacetin is an indiffusible substance.

On the other hand, tinctures of resins are made soluble in water by the addition of some thickening agents or with vigorous stirring and shaking.

2. Emulsification:
Water and oil are immiscible in each other and they can be made miscible by the addition of Emulsions. This is known as Emulsification.

3. Changing the mixing or order of prescription

4. Changing the form of ingredients i.e. from liquid to solid form or from hydrous form to anhydrous form:
This is often helpful in increasing the solubility of a substance e.g.a solution of ephedrine sulfate, an alkaloidal salt, and liquid paraffin is not possible as alkaloidal salt of ephedrine sulfate is not soluble in liquid paraffin but anhydrous form of ephedrine is soluble in it. So we use anhydrous form.

Examples of Incompatibility:
1. Acids are incompatible with alkaline salts, carbonates and oxides. They causes the precipitation of albumin. So, acids are prescribed alone.

2. Bases and alkaline carbonates must not be prescribed alongwith other drugs in solution. They may precipitate metallic and alkaloidal salts.

Bibliography:
A text-book of materia medica and pharmacy for medical students

**REPRINT** Introduction to materia medica and pharmacology, including the elements of medical pharmacy, prescription writing, medical Latin, toxicology, and methods of local treatment


Survey of active pharmaceutical ingredients-excipient incompatibility: Nature and mechanism

Incompatibilities in prescriptions: For students in pharmacy and medicine and practicing pharmacists and physicians

Prescription writing: Including weights and measures, preparation of solutions, doses, administration and incompatibilities

Davis's Drug Guide for Nurses

Paste, Poultice, Plaster and Suppository

Q: What do you mean by paste?
Ans: These are preparations having finely dispersed solids in the preparation.

Q: What do you mean by poultice?
Ans: These are slightly wet substances for application on the injury. These are composed of hydrophilic substances or basis having the ability of retention of heat containing solid or liquid active substances.

Q: What do you mean by medicated plaster?
Ans: These are preparations having one or more active substances. These are made in such a way that they remain in close contact with the skin at body temperature, so that the active substances can be absorbed slowly and easily through the skin or protect the skin from external environment.

Q: What do you mean by suppository?
Ans: It represents the small solid which is dissolvable at body temperature. It is usually in the form of cone or cylinder. It is usually inserted into the rectum, vagina (suppositories for vaginal insertion are called as pessaries) or urethra, nostrils or ears (Suppositories for insertion into urethra, ears or nostrils are called as bougies).
------------------------
Books reading:
The Immortal Life of Henrietta Lacks

New Atkins for a New You: The Ultimate Diet for Shedding Weight and Feeling Great.

The Other Brain: From Dementia to Schizophrenia, How New Discoveries about the Brain Are Revolutionizing Medicine and Science

Brain Rules: 12 Principles for Surviving and Thriving at Work, Home, and School

Galenical Preparation and Concoctions

Q: What do you mean by Galenical preparation?
Ans: A medicinal preparation containing one or several active plant ingredients and produce so that inert constituents and other undesirable content of the plant remain undissolved.
 
Q: How the galenical preparations are characterized?
Ans: The galenical preparations are characterized by an improved and enhanced release of the active principle and a higher efficiency.
 
Q: What galenical preparation contains?
Ans: The galenical preparation contain various herbal and chemical concoctions with varying degree of dosing strength and dosage form.
 
Q: What galenical preparation comprise for oral application?
Ans: The preparation for oral application comprise a coating resistant to gastric juice and a core comprise of an ergot alkaloid and of a sterile ester.
 
Q: What is the composition of galenical preparation?
Ans: The galenical preparation composed mainly of herbal or vegetable matter.
 
Q: What do you mean by concoctions?
Ans: It means to make something by combining or mixing different ingredients in a new way.

-------------------------
Further Reading:
The Immortal Life of Henrietta Lacks

The Other Brain: From Dementia to Schizophrenia, How New Discoveries about the Brain Are Revolutionizing Medicine and Science

A Short History of Nearly Everything

Extraction and maceration

Extraction:
Extraction is the process of separation of medicinally active substances of plant or animal from a mixture by a mechanical or chemical action such as by distillation or pressure.
This separation is done with the help of dissolving one or more of the substances in a solvent in which it is easily soluble and are separated on the basis of their physical or chemical properties.

Forms of Extraction:

Liquid-liquid Extraction:
It is also referred to as Solvent extraction or Partitionaing. Often the solute is miscible in one solvent and immiscible in the other solvent and this thing is used in the process of Solvent extraction.
If the solute is present in an aquous solvent than it can be separated by pouring another solvent in this solution which is immiscible with the previous solvent. The solute will also be dissolved in the other solvent and in this way the solute will be easily separated by separating one of the solvents.

In solvent extraction, two immiscible liquids are shaken together. The more polar solutes dissolve preferentially in the more polar solvent, and the less polar solutes in the less polar solvent based on the famous statement "like dissolves like".
With the help of liquid-liquid extraction, the standard of a chemical is improved after a chemical reaction.

Instrument used:
Separating funnel is used in laboratories.

Uses of Solvent Extraction:
Solvent extraction is used in
1. Ore processing,
2. Nuclear reprocessing, 
3. The processing of perfumes,
4. The production of fine organic compounds,
5. The production of vegetable oils and biodiesel, and other industries.

Measures of effectiveness

Distribution ratio (D):
Distribution ratio is also referred to as partition co-efficient. This ratio gives indication of the quality of extraction. Distribution ratio is the ratio of concentration of a solute in organic phase and the concentration of the same solute in aquous phase.

D = Conc. of solute in organic phase / conc. of solute in aquous phase

Distribution ratio is dependent on the temperature, concentration of the chemical entities in the system and some other parameters in and around the system.

Separation Factor:
The ratio of two distribution ratios is the separation factor.

Separation factor = Distribution ratio for one solute / Distribution ratio for the other solute

With the help of this ratio, it is easy to assess the ability of the system to separate two solutes.

Decontamination factor:
This factor is used to represent the ability of a process to remove an impurity or contaminant from a product.
Techniques

Batchwise single stage extractions

This is commonly used on the small scale in chemical labs. It is normal to use a separating funnel. For instance, if a chemist were to extract anisole from a mixture of water and 5% acetic acid using ether, then the anisole will enter the organic phase. The two phases would then be separated.
The acetic acid can then be scrubbed (removed) from the organic phase by shaking the organic extract with sodium bicarbonate. The acetic acid reacts with the sodium bicarbonate to form sodium acetate, carbon dioxide, and water.

Multistage countercurrent continuous processes

These are commonly used in industry for the processing of metals such as the lanthanides; because the separation factors between the lanthanides are so small many extraction stages are needed. In the multistage processes, the aqueous raffinate from one extraction unit is fed to the next unit as the aqueous feed, while the organic phase is moved in the opposite direction. Hence, in this way, even if the separation between two metals in each stage is small, the overall system can have a higher decontamination factor.
Multistage countercurrent arrays have been used for the separation of lanthanides. For the design of a good process, the distribution ratio should be not too high (>100) or too low (<0.1) in the extraction portion of the process. It is often the case that the process will have a section for scrubbing unwanted metals from the organic phase, and finally a stripping section to obtain the metal back from the organic phase.
Multistage Podbielniak contactor centrifuges produce three to five stages of theoretical extraction in a single countercurrent pass, and are used in fermentation-based pharmaceutical and food additive production facilities.

Extraction without chemical change

Some solutes such as noble gases can be extracted from one phase to another without the need for a chemical reaction. This is the simplest type of solvent extraction. When a solvent is extracted, two immiscible liquids are shaken together. The more polar solutes dissolve preferentially in the more polar solvent, and the less polar solutes in the less polar solvent. Some solutes that do not at first sight appear to undergo a reaction during the extraction process do not have distribution ratio that is independent of concentration. A classic example is the extraction of carboxylic acids (HA) into nonpolar media such as benzene. Here, it is often the case that the carboxylic acid will form a dimer in the organic layer so the distribution ratio will change as a function of the acid concentration (measured in either phase).
For this case, the extraction constant k is described by k = [[HA_organic]]²/[[HA_aqueous]]

Solvation mechanism

Using solvent extraction it is possible to extract uranium, plutornium, or thorium from acid solutions. One solvent used for this purpose is the organophosphate tri-n-butyl phosphate. The PUREX process that is commonly used in nuclear reprocessing uses a mixture of tri-n-butyl phosphate and an inert hydrocarbon (kerosene), the uranium(VI) are extracted from strong nitric acid and are back-extracted (stripped) using weak nitric acid. An organic soluble uranium complex [UO₂(TBP)₂(NO₃)₂] is formed, then the organic layer bearing the uranium is brought into contact with a dilute nitric acid solution; the equilibrium is shifted away from the organic soluble uranium complex and towards the free TBP and uranyl nitrate in dilute nitric acid. The plutonium(IV) forms a similar complex to the uranium(VI), but it is possible to strip the plutonium in more than one way; a reducing agent that converts the plutonium to the trivalent oxidation state can be added. This oxidation state does not form a stable complex with TBP and nitrate unless the nitrate concentration is very high (circa 10 mol/L nitrate is required in the aqueous phase). Another method is to simply use dilute nitric acid as a stripping agent for the plutonium. This PUREX chemistry is a classic example of a solvation extraction.
Here in this case D_U = k TBP²[[NO₃]]²

Ion exchange mechanism

Another extraction mechanism is known as the ion exchange mechanism. Here, when an ion is transferred from the aqueous phase to the organic phase, another ion is transferred in the other direction to maintain the charge balance. This additional ion is often a hydrogen ion; for ion exchange mechanisms, the distribution ratio is often a function of pH. An example of an ion exchange extraction would be the extraction of americium by a combination of terpyridine and a carboxylic acid in tert-butyl benzene. In this case
D_Am = k terpyridine¹carboxylic acid³H+⁻³
Another example is the extraction of zinc, cadmium, or lead by a dialkyl phosphinic acid (R₂PO₂H) into a nonpolar diluent such as an alkane. A non-polar diluent favours the formation of uncharged non-polar metal complexes.
Some extraction systems are able to extract metals by both the solvation and ion exchange mechanisms; an example of such a system is the americium (and lanthanide) extraction from nitric acid by a combination of 6,6'-bis-(5,6-dipentyl-1,2,4-triazin-3-yl)-2,2'-bipyridine and 2-bromohexanoic acid in tert-butyl benzene. At both high- and low-nitric acid concentrations, the metal distribution ratio is higher than it is for an intermidate nitric acid concentration.

Ion pair extraction

It is possible by careful choice of counterion to extract a metal. For instance, if the nitrate concentration is high, it is possible to extract americium as an anionic nitrate complex if the mixture contains a lipophilic quaternary ammonium salt.
An example that is more likely to be encountered by the 'average' chemist is the use of a phase transfer catalyst. This is a charged species that transfers another ion to the organic phase. The ion reacts and then forms another ion, which is then transferred back to the aqueous phase.
For instance, the 31.1 kJ mol⁻¹ is required to transfer an acetate anion into nitrobenzene, while the energy required to transfer a chloride anion from an aqueous phase to nitrobenzene is 43.8 kJ mol⁻¹. Hence, if the aqueous phase in a reaction is a solution of sodium acetate while the organic phase is a nitrobenzene solution of benzyl chloride, then, when a phase transfer catalyst, the acetate anions can be transferred from the aqueous layer where they react with the benzyl chloride to form benzyl acetate and a chloride anion. The chloride anion is then transferred to the aqueous phase. The transfer energies of the anions contribute to that given out by the reaction.
A 43.8 to 31.1 kJ mol⁻¹ = 12.7 kJ mol⁻¹ of additional energy is given out by the reaction when compared with energy if the reaction had been done in nitrobenzene using one equivalent weight of a tetraalkylammonium acetate.

Kinetics of extraction

It is important to investigate the rate at which the solute is transferred between the two phases, in some cases by an alteration of the contact time it is possible to alter the selectivity of the extraction. For instance, the extraction of palladium or nickel can be very slow because the rate of ligand exchange at these metal centers is much lower than the rates for iron or silver complexes.

Aqueous complexing agents

If a complexing agent is present in the aqueous phase then it can lower the distribution ratio. For instance, in the case of iodine being distributed between water and an inert organic solvent such as carbon tetrachloride then the presence of iodide in the aqueous phase can alter the extraction chemistry.
Instead of being a constant it becomes = k[[I₂._Organic]]/[I₂._Aqueous] [[I^-._Aqueous]]
This is because the iodine reacts with the iodide to form I₃^-. The I₃^- anion is an example of a polyhalide anion that is quite common.

Industrial process design

In a typical scenario, an industrial process will use an extraction step in which solutes are transferred from the aqueous phase to the organic phase; this is often followed by a scrubbing stage in which unwanted solutes are removed from the organic phase, then a stripping stage in which the wanted solutes are removed from the organic phase. The organic phase may then be treated to make it ready for use again.
After use, the organic phase may be subjected to a cleaning step to remove any degradation products; for instance, in PUREX plants, the used organic phase is washed with sodium carbonate solution to remove any dibutyl hydrogen phosphate or butyl dihydrogen phosphate that might be present.

Equipment

Two layers separating during a liquid-liquid extraction.  An organic MTBE solution is extracted with aqueous sodium bicarbonate solution. This base removes benzoic acid as benzoate but leaves non-acidic benzil

(yellow) behind in the upper organic phase.

While solvent extraction is often done on a small scale by synthetic lab chemists using a separatory funnel or Craig apparatus, it is normally done on the industrial scale using machines that bring the two liquid phases into contact with each other. Such machines include centrifugal contactors, thin layer extractors, spray columns, pulsed columns, and mixer-settlers.

Solid-Phase Extraction:
It is one of the most important form of extraction for the purification and separation of a large number of chemicals on small scale like in laboratory.
In this process, the substance is dissolved in a solvent and is passed throught a bed or layer of adsorbent having uniform particle sizes. The substance is separated either by adsorption of the solvent or the substance itself into the adsorbent.

Types of Extraction techniques:
1. Continuous Extractions
2. Batch Extractions
3. Extractions involving partition between two immiscible liquids

Questions and Answers:

Q: What is extraction?

Ans: Extraction is withdrawal of dissolved constituents from crude drugs through the use of selective solvent in which the desired constituents are soluble.

Q: What are the processes of extraction?
Ans: The principle methods of drug extractions are,

• Maceration

• Percolation

Frequently a combination of percolation and maceration is used in extraction.

Q: What is maceration?
Ans: The word maceration comes from a latin word “macerare” meaning “to soak”.

Q: What is the principle of maceration?
Ans: It is a process in which the properly comminuted drug is permitted to soak in menstruum until the cellular structure is softened and penetrated by the menstruum and the soluble constituents are dissolved.

Q: How soluble contents are settled down in Maceration?
Ans: As the soluble constituents dissolved in the menstrum, they tend to settle to the bottom as a result of an increase in the specific gravity of the liquid due to its added weights.

Q: In which type of drugs Maceration is used?
Ans: For drugs containing little or no cellular material such as benzoin, aloe, and tolu, which dissolve almost completely in the menstruum, maceration is the most efficient method of extraction

Q: On which temperature Maceration is performed?
Ans: Maceration is usually conducted at a temperature of 15-20 C for 3-5 days or until the soluble matter is dissolved.

Q: Why dipping is essential in Maceration?
Ans: Occasional dipping of the drug bag may facilitate the speed of extraction.

Q: What do you mean by menstruum?
Ans: Menstruum refers to the solvent, which is used to extract ingredients from plant or animal origin.

Further Reading:
Remington: The Science and Practice of Pharmacy (Remington the Science and Practice of Pharmacy)

British Pharmacopoeia 2010

Textbook of Pharmaceutics

Percolation

Q: What is percolation?

Ans: Percolation is the package of the raw material into a column and the solvent is allowed to percolate through it.

Although some materials may be packed into a percolator in the dry state e.g. Ginger, most drugs require preliminary moistening.

Q: What is the principle of percolation?
Ans: It is a process in which a comminuted drug is extracted of its soluble constituents by the slow passage of the suitable solvents through the column of a drug.

Q: What do you know about percolator and percolate?
Ans: The drug is packed in a special extraction apparatus termed as percolator with the collective extractive called the percolate.

Q: What is preliminary moistening?
Ans: The solid material is mixed with sufficient amount of solvent and the moist mass is allowed to stand for 4 hours in a well-closed vessel. This is preliminary moistening.

Q: Why preliminary moistening important?
Ans: This preliminary moistening is important because the dried tissues may swell on contact with the solvent and if packed in the dry condition subsequent swelling might decrease the porosity of the material and choke the column.

Preliminary moistening also makes the fine particles less liable to be washed out of the column during percolation.

Q: Defined the methods of percolation?
Ans: There are two methods of percolation which are given below:

• Commercial scale

• Small scale

Q: What is the commercial method for the percolation?
Ans: The drug is supported on a preforated metal plate covered with sacking or straw. The top of the apparatus is removable and provided with portholes for inspection and running in of solvent. At the base the outlet is fitted with a tap and a pipe leads the top of a second percolator in order to use the solvent more efficiently.

Q: What is the small scale method for percolation?
Ans: On small scale glass percolators can be used and the raw material is supported in a loose plug of tow or other suitable substance which has been previously moistened with solvent.
Q: What is reserved percolation?
Ans: Liquid extracts are more concentrated preparations than tinctures and percolation to exhaustion will produce a preparation that is much diluted. It is therefore necessary to decrease the volume of the percolate by evaporation.

In certain instances such as in Liquorice Liquid Extract, the whole of the percolate may be concentrated by evaporation.

Q: How Ipecac syrup is prepared?
Ans: Ipecac syrup is prepared by percolation. It is prepared by adding glycerin and syrup to an extractive of powdered ipecac obtained by percolation.

The drug ipecac which consists of the dried rhizome and roots of Cephaelis ipecacuanha containing emetine, cephaeline and psychotrine. These ingredients are extractive from the powdered ipecac by percolation with the hydro-alcoholic solvent.

Further Reading:
Remington: The Science and Practice of Pharmacy (Remington the Science and Practice of Pharmacy)

British Pharmacopoeia 2010

Textbook of Pharmaceutics