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).
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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.

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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

Extracts

Q: Define Extract?

Ans: Extracts are defined as concentrated preparation of vegetable or animal drugs obtained by removal of active constituents of the respective drug with menstruum, evaporation of all or nearly all of solvent, and adjustment of the residual masses or powders to the prescribed Standards.

Q: How many types of extracts are there?
Ans: There are three types of extracts:

• Semi liquid

• Solid extracts (Plastic masses)

• Powdered extracts (Dry powder)

Q: How the extracts are mostly prepared?
Ans: Mostly, extracts are prepared by extracting the drug by percolation.

Q: Why extracts are to be protected from heat?
Ans: The use of heat is avoided where possible because of potential injurious of active constituents

Q: Give some examples of extracts.
Ans: The examples of extracts are

• Extracts of Pure glycyrrhiza

• Extracts of Belladonna

Q: Define Fluid Extract?
Ans: USP define Fluid extract as being preparation of vegetable drugs containing alcohol as solvent or as a preservative or both, so that unless otherwise specified in an individual monograph, each milliliter contains the therapeutic constituents of 1g of the standard drug it represents.

Q: How unwanted colloidal material is separated and removed from fluid extract?
Ans: The fluid extract can be separated from the oil, concentrated by evaporation and re-extracted with strong alcohol to removed unwanted colloidal material.

Q: How degradation of fluid extract can occur?
Ans: Fluid extracts are subject to degradation by enzyme action.

Q: How degradation by enzyme is inhibited?
Ans: This can be inhibited by including alcohol to give a concentration of 25% or more but enzyme is not destroyed and concentration must be taken to avoid subsequent condition in which the enzyme activity can be restored.

Q: What are the Solvents and their advantages used in fluid extract?
Ans: Solvents used in fluid extract are

• Alcohol

• Water

• Solvent ether

• Acetic acid

Advantages of water and/or alcohol:

• It is cheap.

• It is non toxic.

• It can dissolve wide range of chemical substances.

• It flame and non-flamable.

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

British Pharmacopoeia 2010

Infusion, Decoction and Tisane

Q: What is infusion? And also write some examples.

Ans: Infusions are liquid preparations, which are either prepared by infusion process or by diluting 1 part of concentrated infusion with 9 parts of water OR An infusion is the outcome of steeping plants with a desired flavor in water or oil.

Examples:

• Concentrated compound gention infusion.

• Concentrated senega infusion.

Q: What type of appratus is used in the preparation of infusion?
Ans: The simplest form of apparatus consists of BEAKER or a TEAPOT but special pots known as INFUSION POTS can also be used.

Q: How infusion is extracted?
Ans: The drug to be extracted is placed at the bottom of the pot, water is added and the content stirred occasionally or the drug may be enclosed in a piece of MUSLIN and suspended just below the level of the water.

The drug is allowed to remain in contact with water for the required time, which is usually 15 minutes. After the specified time, the liquid is strained and dispensed.

The marc is not pressed to avoid expression of colloidal cells into the final. Volume of the preparation is not adjusted by adding more of the vehicle otherwise dilution of active constituent will take place.

Q: How many types of infusion are used?
Ans: There are two types of infusion

• Freshly prepared infusion

• Concentrated infusion

Q: What do you know about the two types of infusions? And also give their examples.
Ans: 1. Freshly prepared infusion:

These must be used within 24 hours of its preparation.

Examples:

• Infusion of Senna.

• Infusion of quassia.

2. Concentrated infusion:

This infusion must be prepared by maceration or percolation process and alcohol is also used as a menstruum or a preservative.

Example:

• Concentrated infusion of Chirata.

• Concentrated infusion of gentian.

Q: What do you mean by decoction?
Ans: It is a method of extraction by boiling of dissolved chemicals, or plant material, which may include stems, roots, bark and rhizomes.

Decoctions differ from most teas, infusions, or tisanes in that they are usually boiled. The term is used colloquially in South India to refer to black coffee prepared by the traditional method.

Q: What is the etymology of decoction?
Ans: The term dates back to 1398, from present participle stem of Latin decoquere, (meaning to boil down), from de- + coquere "to cook".

Q: Write about process of decoction.
Ans: Decoction involves:

• First mashing and

• Then boiling in water to extract oils , volatile organic compounds and other chemical substances.

Q: How decoction is done in herbalism?
Ans: In herbalism, decoctions are usually made to extract fluids from hard plant materials such as roots and bark. To achieve this, the plant material is usually boiled for 8–10 minutes in water. It is then strained.

Q: What do you mean by tisane?
Ans: It is a type of infusion of flowers and leaves used in the form of herbal beverages such as herbal tea.

(This blog will help you in the preparation of Pharmacy Exams)

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Interesting books on Ancient medicines:

Aromatic Waters

Q: What are aromatic waters?

Ans: Aromatic waters are saturated solutions (unless otherwise specified) of volatile oils or other aromatic or volatile substances in distilled water. They are usually employed for flavoring. They are clear and free from solid impurities.

Q: Classify aromatic waters?

Ans:

• Simple aromatic waters

• Concentrated aromatic waters

Q: What do you know about concentrated aromatic waters?

Ans: These products are alcoholic, non-aqueous preparations containing 2% of volatile oils. They are forty times stronger than the ordinary aromatic waters. Many volatile oils contain aromatic part and non-aromatic part. The aromatic portion is much more soluble in a weak alcohol than the non-aromatic portion.

Q: What do you know about camphor water?

Ans: They are made by mixing racemic camphor with ethanol and by adding sufficient amount of water.

Q: What are the uses of camphor water?

Ans: Camphor water has been used as the vehicle in ophthalmic solutions owning to its ability to contribute refreshing, stimulating effect to the preparation.

Q: How aromatic waters smell?

Ans: They possess an odor similar to the plant or volatile substance from which they are made. They are free from foreign odor.

Q: How aromatic waters should be stored?

Ans: Aromatic water deteriorates with time and it should be made in small quantities and protected.

(These Viva Type Questions will help you to prepare for Pharmacy Exams)

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Interesting books:

Tinctures

Q: What are tinctures?

Ans: These are alcoholic or hydroalcoholic solutions made from materials of plant origin or from chemical substances. Most of the tinctures are prepared by percolation or by maceration.

Q: What is the method generally used for the preparation of tinctures?
Ans: Herbs are placed in a container and a spirit containing 40% pure ethanol is added. The jar is placed for 2-3 weeks and shaken occasionally so that the concentration can be increased of the solution.

Q: What are the examples of tincture?
Ans: Iodine tincture, alcoholic tincture, digitalis tincture, belladonna tincture

Q: What do you know about iodine tincture?
Ans: It is a hydroalcoholic solution having

• Elemental iodine i.e. 2%,

• Potassium iodide i.e. 2.4%, so that the dissolution is facilitated and

• Alcohol i.e. 47%.

Q: What is the use of iodine tincture?
Ans: It is used as an antiseptic/germicide for scratches and cuts on the surface of the skin. It has been used as a skin disinfectant before surgery but is now largely replaced by organic forms of iodine.

Q: What do you know about belladonna tincture?
Ans: It is a green hydroalcoholic liquid having the alkaloids scopolamine and atropine and other substances that are extracted from the leaves of Atropa belladonna.

Q: What is the use of belladonna tincture?
Ans: Earlier it was widely used in treatment of ulcer or the palliative treatment of diarrhea, either alone or in combination with antacids and insoluble clays.

Q: What do you mean by palliative treatment?
Ans: It means the relief of mental and physical pain or symptoms without actually treating the causes, especially in patients suffering from a fatal (dying) illness.

(These Viva type Questions can help you in the preparation of pharmacy exams)
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Further Reading:

Surface tension

Q: What do you mean by surface tension?

Ans: It represents the intermolecular attraction due to cohesive quality at the surface of the liquid, in contact with another fluid or solid, which tends to move the molecules of the liquid inside from the surface.
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Further Reading: