This section deals with some of the methods and procedures commonly employed in a pharmaceutical laboratory.
* Sifting / Sieving
A SOLUTION is a chemically and physically homogenous mixture of two or more substances.
The term solution generally denotes a homogenous mixture that is liquid, even though it is possible to have homogenous mixtures that are solid or gaseous.
Thus, it is possible to have solutions of solids in liquids, liquids in liquids, gases in liquids, gases in gases and solids in solids.
Characteristics of a true solution -
(i) Are not distinguishable by their surfaces of separation.
(ii) Are not separable by filtration or such forces as gravity.
(iii) Can be obtained back in pure form by such methods as crystallization and evaporation.
(iv) Retain their characteristic properties within the mixture to reveal their existence, although they may not be exactly identical with the properties when they exist separately.
Solute and Solvent
Any solution consists of two components, viz. the dissolved substances called the solute and the medium in which the solutes are uniformly dispersed, known as solvent.
Saturated, Unsaturated and Supersaturated solution The concentration of a solution is the quantity of the solute contained in a definite weight or in a definite volume of the solution. Solutions with high solute contents are called concentrated solutions and those with low solute contents are called dilute solutions.
Concentration of a solution may be varied from a very low to a sufficiently high value by dissolving more and more quantities of the solute in a given quantity of the solvent. But during this act of dissolving, it is found that, at a given temperature, as the amount of solute is increased, the rate of dissolution decreases and more vigorous stirring for a longer time is required for the dissolution. After that, a state is reached when the medium refuses to dissolve any further quantity of the solute. This is known as saturation and such a solution is called a saturated solution.
If a solution contains less amount of the solute than what is necessary for preparing its saturated solution in the given volume of the solvent and at the given temperature, then such a solution is called an unsaturated solution.
Under certain conditions, it is possible to prepare a solution that contains more amount of the solute in a given volume of the solvent than is necessary to make a saturated solution at a given temperature. Such a solution is called a supersaturated solution.
By this term is meant how much of a substance dissolves in a given solvent. When stating the solubilities of chemical substances, the term 'soluble' is sometimes used in a general sense irrespective of concomitant chemical change. Statements of approximate solubilities, for which no figures are given, are intended to apply at ordinary room temperature.
When the exact solubility of a pharmacopoeial substance is not known the descriptive term is used to indicate its solubility.
DESCRIPTIVE TERMS RELATIVE QUANTITIES OF SOLVENT FOR 1 PART OF SOLUTE
Very soluble Less than 1 part
Freely soluble From 1 to 10 parts
Soluble From 10 to 30 parts
Sparingly soluble From 30 to 100 parts
Slightly soluble From 100 to 1000 parts
Very slightly soluble From 1000 to 10000 parts
Practically insoluble More than 10000 parts
METHOD OF SOLUTION
In order to facilitate solution, it is advisable to pulverize the substance that is to be dissolved. This is explained by the increase in the surface of the solute exposed to the solvent when reduced to a fine powder. After powdering the substance and mixing it with the solvent, agitating the mixture of the substance and the solvent can facilitate solution. The ordinary method of dissolving a substance is by reducing the substance to a comparatively fine powder in a mortar, then adding the solvent and agitating until solution is accomplished.
Trituration, in homoeopathy is carried out for those drug substances that are insoluble in liquid vehicles like alcohol and water. This is done, on a definite scale, with the aid of sugar of milk till the potency of 6X is reached on the decimal scale or 3C on the centesimal scale. The potentized drug substance, at this stage consists of triturated sugar of milk, soluble in water and trace of the drug substance in strength of 1/1000000. One part of this is taken and fifty parts of water are added to it. This singular part of the potentized mixture now seems to be soluble in water due to the solvent properties of sugar of milk, alongwith the trace of the drug substance, which is insoluble in the crude state.
DECANTATION is a process of slowly and carefully pouring out liquids from one vessel to another without disturbing the sediments that have been accumulated at the bottom of the liquid.
It is rather a crude method of separating a liquid from its insoluble heavy solid contents that settle down at the bottom. Apparatus for decantation is a flask or beaker, provided with a lip.
The liquid, with the solid, insoluble impurities that are heavy, is allowed to stand for a while. This allows the sediments to settle down. Sedimentation is the simplest method of separating an insoluble solid from a liquid. When an insoluble solid remains suspended in a liquid (e.g. suspension of clay in water), the solid particles tend to settle down at the bottom of the vessel, if such a mixture is allowed to stand undisturbed for sometime. This process of settling down is known as sedimentation and the solid that settles at the bottom of the vessel is called sediment. To facilitate the removal of the decanted liquid, a glass rod is used.
It is manifestly impossible by this means to thoroughly remove all the liquid, as no matter how carefully decantation is continued, certain portions of the sediment will get disturbed and flow out with the decanted liquid. Allowing the decanted fluid to pass through a filter to collect the escaping sediment prevents this. This process is unsuitable for solid insoluble impurities that are light and hence floating in the liquid, for which filtration becomes essential.
This method is applied in cases of mother tincture or solutions or other liquid preparations.
FILTRATION is an efficient physical process of separation of a liquid from substance(s) insoluble in that liquid with the help of a filtering medium through which only the liquid (filtrate) can pass but not the other substances (residue) insoluble in that liquid.
Filtration involves the separation of a liquid, through a filtering medium, from the insoluble solid impurities present in that liquid. The insoluble substance retained by the filtering medium is called 'residue' and the liquid passing through the filtering medium is called the 'filtrate'.
The filtering medium may consist of a filter paper (Whatman series), cotton, cellulose pulp, felt, asbestos, woven metal, sand, earth, coke, sawdust, cork, carbon, silica, porcelain or porous stone or sintered glass. Usually, in laboratory procedures, a filter paper is used.
The rate of filtration can be increased by - 1. Increasing the pressure difference across the filter.
2. Reducing the viscosity of the liquid.
3. Increasing the surface area of the filter.
4. Using a filter medium of high porosity.
Hot filtration Some liquids can be filtered only when quite hot, and with certain easily fusible solids, the best method of purification is by filtering them in the molten state, as in the case with wax. In all such cases, the funnel must be kept warm, and for such purposes, various forms of hot filtration devices have been devised.
In ordinary processes of filtration, the liquid filters through very slowly and some means of increasing the flow becomes necessary. This is accomplished by fitting the receiving bottle with a two-holed rubber stopper. Through one perforation, the neck of the funnel passes, while the other is fitted with a bent glass tube connected with a pump, that rarefies the air within the receiving bottle. In such cases, the pressure of the atmosphere acting on the surface of the liquid in the filter is greater than the pressure within the receiving bottle. The filtering medium is fortified to the sides of the funnel to prevent its rupture. This increases the rate of filtration.
Straining (Coarse Filtration)
This is used to remove large foreign particles from viscous preparations and heterogeneous systems like suspensions. The material commonly used for this purpose is well-rinsed absorbent cotton wool or cotton gauze, a small plug of which is placed in a conical funnel. Also, well-rinsed muslin may be used, held in a special strainer to keep it taut.
In the preface to the fifth volume of ' The Chronic diseases ', Hahnemann comments -
Dilutions exist almost solely in objects of taste and colour. A solution of salty and bitter substances becomes continually more deprived of its taste the more water is added, and eventually it has hardly any taste, no matter how much it may be shaken. So, also, a solution of colouring matter, by the admixture of more and more water, becomes at last almost colourless, and any amount of shaking will not increase its colour.
APPLICATIONS OF HEAT
EVAPORATION is the simple process of removing a liquid slowly from a solution.
Conditions affecting evaporation
1. The amount of heat - The greater the source of heat, the more rapid is the evaporation.
2. The amount of atmospheric pressure - Lesser the atmospheric pressure, lower the temperature necessary to bring the liquid to a state of ebullition. This is done in vacuum pans.
3. The amount of humidity in air - Liquids evaporate more rapidly in dry air than in humid air.
4. The character of solvent - A thin mobile liquid evaporates more readily than a dense, viscid liquid.
Evaporation by boiling
Here, heat is necessary to facilitate evaporation by boiling. The main factor is the extent of surface exposed to the source of heat and hence, the character and material of the vessel.
Evaporation below the boiling point
The main factor is the extent of surface exposed to air. The pharmaceutic application of evaporation below the boiling point is generally limited to the desiccation of substances and the evaporation of liquids that are apt to be decomposed when heated on wire gauze and hence heated on a water bath. Constant stirring facilitates the process of evaporation.
In some cases, liquids are evaporated without recourse to any external heat, that is at ordinary temperature and this is called as spontaneous evaporation.
DISTILLATION is a process of converting a liquid into a gas and condensing the gas back into a liquid.
This is a good process of purifying volatile substances. Distillation method is employed for the purification of water and alcohol. If such a liquid contains impurities less volatile than itself, the impure product is placed in a still and heated, whereupon the substance desired will distill leaving the less volatile substance behind. The liquid thus purified is called a 'distillate'. In other words, distillation is evaporation of a liquid and subsequent condensation of its vapor.
To convert a liquid into a vapor involves the utilization of heat energy. To condense a vapor back to liquid form, chilling of vapor is necessary.
The apparatus required for distillation consists primarily of a boiler, in which the liquid is vaporized and the condenser, in which the vapors are chilled until they are condensed to the liquid form. This combination of boiler and condenser is commonly called the 'still'.
Bumping This phenomenon is a disagreeable accompaniment of many cases of distillation occurring in a flask. In some cases the liquid does not boil steadily under application of heat, but at times the ebullition ceases for a few moments, then suddenly resumes, with a force sufficiently explosive to cause a spattering of the liquid, if not a fracture of the flask. This is eliminated by insertion of pieces of pumice stone or glass.
The substance to be distilled is taken in the round-bottomed distilling flask having a side tube at the top. This side tube is connected by means of a cork to one end to one end of the Liebig condenser, the other end being inserted into the receiving flask to receive the distillate. The mouth of the distilling flask is closed with a rubber cork and a thermometer is inserted into the cork for noting the temperature of the vapour. The distilling flask is placed on the tripod stand with wire gauze. A few pieces of pumice stone or glass are added to avoid bumping. The liquid in the distilling flask is heated. When the boiling point of the particular liquid is reached, the vapors produced travel through the condenser, cool down, condense into liquid, and collect in the receiver.
MODIFICATIONS OF DISTILLATION FRACTIONAL DISTILLATION
Fractional distillation is the method used for separating a mixture of several liquids of different boiling points, as in the case of organic liquids. To achieve such separations, a condenser alongwith a fractioning column is used instead of a single straight condenser. The fractionating columns are so designed that the vapours of the higher boiling liquid (less volatile) are preferentially condensed and return to the distilling flask, where the vapors of the low boiling liquid (more volatile) are allowed to pass on and condense to liquid in the condenser, thus facilitating the separation of liquids. In order to carry out the distillation thoroughly, the distillates need to be redistilled and this yields the distillates in a much more pure form.
Liquids that are susceptible to decomposition at their normal boiling points are distilled at reduced pressures, when they boil at lower temperatures.
This is effected by connecting the distilling flask, through the condenser and the receiver to a suction pump.
SUBLIMATION is the process of distilling a solid; of converting the solid into a vapor and condensing the vapor back to a solid.
The object of sublimation, like distillation is to obtain a volatile drug in a purer form. Sublimation is also one method of obtaining crystals.
If the vapors are condensed directly over the vaporizing substance, if the condenser is but little cooler than the temperature of vaporization, the sublimate will form in a solid mass - a cake sublimate. If, on the other hand, the condensing space is on one side, hence considerably cooler than the vessel in which the substance is vaporized, we get a fine powder - a powdered sublimate.
No artificial means of refrigeration are needed in sublimation, the air being sufficiently cool to condense the vapor into a solid form.
This is noticed in substances like camphor, iodine, benzoic acid, naphthalene and ammonium chloride and is hence used for the purification of the same.
A given mixture, say of sand and iodine is taken in a mortar and thoroughly mixed with the pestle. The mixture is then transferred to the evaporating dish, placed on a sand bath over the tripod stand. A funnel, placed inverted, the outer surfaces of which are wrapped with filter paper soaked in water, covers the mixture in the dish. The dish, with the mixture is warmed slowly by heating the sand bath with a Bunsen burner. Iodine will sublime and collect on the cooled inner surface of the funnel in the form of small violet crystals. Scrapping the inner surface of the funnel collects iodine.
DESICCATION is a process of removing water from a substance at moderate temperature, differing from exsiccation, which means removing the water from a substance at high temperatures.
Desiccation is employed to aid in the preservation of the drug; to reduce the bulk of same; and to facilitate comminution. This is employed in the process of estimating the moisture content of a drug. Desiccation helps in preservation by preventing the formation of mold. It is an established fact that when many organic substances are allowed to remain in a permanently moist condition, moldiness and ultimate decomposition result.
Desiccation is not only the drying, but means the removal of moisture from any drug. Hence, it reduces the bulk of a substance. The presence of moisture in a fresh drug renders it impossible to reduce the same to a powder, and if attempted by pounding the drug in a mortar, a pulp results. Hence the process of desiccation facilitates comminution.
PRECIPITATION PRECIPITATION is the process of separating a solid from its solution by the aid of physical or chemical action.
The substance so separated is called 'precipitate' and the liquid remaining above the precipitated substance is termed the 'supernatant liquid'.
A precipitate differs from sediment in that a precipitate is separated out from its former state of solution, while sediment has never been dissolved. Precipitation may be due to chemical or physical causes. The most important phase of precipitation is that involving chemical action, wherein the two reacting substances are dissolved in separate portions of water, and on mixing these solutions, an insoluble body is formed and precipitated.
Precipitation due to pure physical causes can be from a hot supersaturated solution on cooling that gives the precipitate of the excess of dissolved substances. Likewise, solution of such substances that are more soluble in cold water than in hot water will be precipitated when heated, through change in temperature.
Substances are precipitated chiefly to purify the same. Another object of precipitation is to obtain the substance in fine powder, the insoluble matter usually separating out in an extremely fine state of subdivision. The third object of precipitation is for its value in chemical testing.
CRYSTALLIZATION is the process of separating substances in forms possessing definite geometric shapes.
When the solution of a solid substance in a liquid, saturated at a higher temperature is allowed to cool down, it is usually found that a quantity of the solid held in solution is deposited at the bottom spontaneously in the form of particles with regular geometric shapes. These particles are called crystals and the process of formation of crystals is known as crystallization.
Crystals are homogenous solids with definite geometric shapes and bounded by definite number of plane faces meeting in sharp edges. For example, crystal of sodium chloride is cubic and that of alum is double pyramid. If a perfect crystal is broken, then it breaks in smaller crystals and all of which are similar as the bigger mother crystal. Solids that have no crystalline shape are known as amorphous.
Principle of Crystallization
It is done by cooling saturated solution of solid in a liquid when crystals with definite geometric shape come out gradually from the solution and collect at the bottom.
Different methods of Crystallization
* By cooling a hot saturated solution
* By the gradual evaporation of a solution
* By fusion and partial cooling
* By effecting change in the character of the solvent
The crystallization method is applicable especially in the purification of sugar of milk in Stapf's process.
Water of Crystallization
When crystallized out from saturated solutions, many compounds separate in combination with one or more molecules of water. These water molecules are called water of crystallization. The number of molecules of water, thus associated with a compound, depends upon the temperature at which crystallization takes place and the same compound may form more than one hydrate.
SIFTING / SIEVING
SIFTING is a process of separating finer portions of comminuted drugs from the coarser particles by the use of a sieve. This is determining particle size.
In using a sieve, the ground drug is taken therein and the particles permitted to fall through the meshes by gently tapping the sieve with a spatula handle or the knuckle. It is imperative that all portions of the same drug should be reduced to a uniform powder.
In this technique, particles of a powdered mass are placed on a screen made up of uniform apertures.
By the application of some type of motion to the screen, particles smaller than the aperture are made to pass through. The sieve motion generally is either
(i) Horizontal, which tends to loosen the packing of the particles in contact with the screen surface, permitting the entrapped sub-sieve particles to pass through;
(ii) Vertical, which serves to agitate and mix the particles as well as to bring more of the sub-sieve particles to the screen surface;
(iii) Oscillation, the sieve is mounted in a frame that oscillates back and forth;
In the sieving process, the powder is passed over a perforated screen, so that particles sufficiently small will pass through, while those that are oversize will be retained on the sieve.
To obtain a distribution of particle size it is necessary to carry out a series of tests with sieves of different sizes.
Discuss in brief
* Sifting / Sieving
1. Which one of the following substance has the property of sublimation
(b) Argentum nitricum
(d) Ferrum metallicum
2. Which one of the following method is used during the process of preparation of sacchrum lactis
3. The process of separation of two or more miscible liquids having different boiling points by application of heat and later condensing the vapors is known as
4. The process of separating out the tincture with force from solid drug material is termed as
5. Fractional distillation is very useful in the purification of
(a) Organic liquids
(b) Inorganic liquids
ANSWERS: 1 (c); 2 (b); 3 (a); 4 (d); 5 (a).