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

Hydryllin syrup

Hydryllin syrup is used for cough. It is a product of Searle Pharmaceuticals.

Ingredients:
Its active ingredients are

1. Aminophylline (It is a bronchodilator i.e. eases breathing by opening the air passages to the lungs)
2. Ammonium chloride (It is an expectorant i.e. produces and getting rid of thick mucus in the respiratory passages)
3. Diphenhydramine (An antihistamine to treat allergies)
4. Menthol (Mint tasting compound obtained from peppermint oil)

Uses:
Cough Expectorant

Contraindications:
It is contra-indicated in patients of acute myocardial infarction or peptic ulcers.
It is also contra-indicated in patients who are hypersensitive to its components.

List of Cough Syrups from multi-national companies available in Pakistan:
1. Actifed DM Cough syrup (GSK)
2. Babynol Cough Syrup (Woodwards)
3. Benatuss Syrup (Johnson)
4. Benylin DM Syrup (Johnson)
5. Benylin E Syrup (Johnson)
6. Corex D Cough Syrup (Pfizer)
7. Cosome Cough Syrup (Merck)
8. Cosome E Cough Syrup (Merck)
9. Daycor Syrup (Abbott)
10. Nicor Syrup (Abbott)
11. Phensedyl-P syrup (Sanofi Aventis)
12. Rondec Cough Syrup (Abbott)
13. Rondec-C Cough Syrup (Abbott)
14. Sancos Syrup (Novartis)
15. Triaminic Cough Syrup (Novartis)
16. Tussivil Syrup (Pfizer)

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.