Preparation of Purified Water Distillation Stills in various capacity first portion of distillate (10% of total volume) is discarded since

e many foreign volatile substances are usually found in urban drinking water. Also, the last portion of water (10% of original volume of water) is discarded and not subjected to further distillation because it might contaminate the previously collected portion of distillate. Ion- exchange More advantages than distillation because there is no requirement of heat and complex distillation apparatus is expensive. Ion- exchange

This method permits ease of operation, minimal maintenance, and a more mobile facility. Water is passed through a column of cation and anion exchangers consisting of water- insoluble synthetic polymerized phenolic, carboxylic, amino, or sulfonated resins of high molecular weight. 2 Types of Resins 1. Cation or acid exchangers which permits the exchange of cations in solution (tap water) with hydrogen ion from the resin 2. Anion or base exchange resins which permit the removal of anions. The 2 processes are successively or simultaneously employed to remove both cations and anions from water. Cation Exchange: H-resin + M + X- + H20 M-resin + H + H20 (Pure) LEGEND: M means metal or cation X means anion Anion Exchange Resin-NH2 + H + X + H2O

Resin-NH2 HX + H20 (Pure) Water that is purified by this manner is referred to as deionized or demineralized water. Reverse osmosis Cross flow or tangential membrane filtration A pressurized stream of water is passed parallel to the inner side of filter membrane core. A portion of the feed water, or influent, permeates the membrane as filtrate, while the balance of the water sweeps tangentially along the membrane to exit the system without being filtered. The filtered portion is called permeate. The water that has passed through the system is called concentrate containing the contaminants rejected by the membrane. Equipped with membrane filters Microfiltration (0.1 -2 ug) like bacteria Ultrafitration (0.01 0.1 ug) like virus Nanofiltration (0.001 0.01 ug) like organic compounds with MW range of 300-1,000 Reversed osmosis- (<0.001 ug) including viruses, bacteria, pyrogens, and organic molecules and 90 to 99% of ions. 2. Alcohol Next to water but considered the primary solvent for many organic compounds 94.9 96% ethanol by volume 99.5% is dehydrated alcohol Miscible with water, preserving action Alcohol content limits: Under 6 y/o 0.5% 6 to 12 y/o 5% Over 12 and adults 10% 3. Diluted alcohol Mixture of equal volumes alcohol and water

Final volume of the mixture is not the sum of the individual volumes of the 2 components because liquids contract upon mixing and the final volume is generally about 3% less than what would otherwise be expected. Frequently, combination of ethanol and water (Hydroalcoholic mixture) allows easier dissolution of both lipophilic and hydrophilic molecules. Depending on the proportion used, ethanol may impart antimicrobial and preservative effects. 4. Rubbing alcohol 70% of ethanol, additives Nlt 355 mg per 100 ml content of sucrose octa-acetate or 1.4 mg of denatonium benzoate Formula 23-H acetone, methyl isobutyl ketone volatile, flammable Rubefacient, germicide, antiseptic, vehicle for topical preparation 5. Isopropyl rubbing alcohol 70% isopropyl External application as rubefacient and soothing rub and as a vehicle for topical products 91% is for diabetic patients in preparing needles and syringes for hypodermic injections of insulin and for disinfecting the skin. 6. Glycerin Clear, syrupy liquid, sweet taste Miscible with water and alcohol Viscous, preservative action 7. Propylene glycol Viscous liquid, miscible with water and alcohol Hydrocarbons or glyceryl esters. Peanut, sesame, corn, cottonseed, and mineral oil are most frequently chosen as solvents or vehicles. Methods of Preparation Simple solutions

done by dissolving the solute in a suitable solvent, which may contain other ingredients, which stabilize the active ingredients.

Solution by chemical reaction is prepared by reacting two or more solutes with each other in a suitable solvent. Example: Aluminum Subacetate Topical Solution.

Solution by distillation consists of distilling the volatile principles from a drug inside a copper wire cage, which allows the free passage of vapors and boiling water

Solution by extraction Drugs or pharmaceutical necessities vegetable or animal origin are often extracted with water or with water containing other substances. Methods: Maceration, percolation, digestion, decoction, infusion Maceration is the process in which the solid ingredients are placed in a stoppered container with the whole of the solvent and allowed to stand for a period of at least three days, with frequent agitation. The mixture is strained and the marc pressed, and the combined liquids are clarified by filtration or by decantation after standing. Percolation is where the active ingredients are extracted from a macerated drug mass in a narrow coneshaped vessel open at both ends (percolator) through the passage of an extracting liquid called menstruum.

Digestion This is a form of maceration in which gentle heat is used during the process of extraction.

Infusion is a dilute solution of the readily soluble constituents of crude drugs for a short period of time which either cold or boiling water is added.

Decoction extracts water-soluble and heat stable constituents from crude drugs by boiling in water for 15 minutes, cooling, straining and passing sufficient cold water through the drug to produce the required volume.

Complex Solution this is a combination of at least two of the above procedures with or without controlled application of heat. Dosage forms categorized as Solutions are classified according to route of administrations such as: Oral Solutions Oral Solutions are liquid preparations, intended for oral administration, that contain one or more substances with or without flavoring, sweetening, or coloring agents dissolved in water or cosolvent-water mixtures. Oral solutions may be formulated for direct oral administration to the patient or they may be dispersed in a more concentrated form that must be diluted prior to administration. Topical Solutions Topical Solutions are solutions, usually aqueous but often containing other solvents such as alcohol and polyols, intended for topical application to the skin, or as in the case of Lidocaine Oral Topical Solution, to the oral mucosal surface. The term lotion is applied to solutions or suspensions applied topically. Otic Solutions Otic Solutions, intended for instillation in the outer ear, are aqueous, or they are solutions prepared with glycerin or other solvents and dispersing agents (e.g. Antipyrine and Benzocaine Otic Solution and Noemycin and Polymyxin B Sulfates and Hydrocortisone Otic Solutions). SYRUPS concentrated aqueous preparations of sugar-substitute with or without added flavoring agents and medicinal substances. Syrups containing flavoring agents but not medicinal substances are called non-medicated or flavored vehicles. When purified water alone is used in making the solution of sucrose, the preparation is known as syrup or simple syrup. In addition to sucrose certain other polyols such as glycerin or sorbitol may be added to retard crystallization of sucrose or to increase the solubility of the added ingredients. a concentrated or nearly saturated solution of sucrose in water. A simple syrup contains only sucrose and purified water (e.g. Syrup USP).

Syrups containing pleasantly flavored substances are known as flavoring syrups (e.g. Cherry Syrup, Acacia Syrup, etc.). Medicinal syrups are those to which therapeutic compounds have been added (e.g. Guaifenesin Syrup) Advantages

Provides a pleasant means of administering a liquid form of disagreeable tasting drug. They may particularly effective in the administration of drugs to youngster, since their pleasant taste usually dissipates any reluctance on the part of the child to take the medicine. The fact that syrups contain little or no alcohol adds to their favor among parents. (1) the sugar, usually sucrose, or sugar-substitutes used to provide sweetness and viscosity (2) anti-microbial preservatives, Benzoic acid (0.1 0.2%) Sodium benzoate (0.1 0.2%) Methylparabens, propyl- and butylparabens (0.1%) Alcohol (15% - 20%) (3) flavorants (4) colorants. Others: contain special solvents, solubilizing agents, thickeners, or stabilizers.

Non-sucrose Syrups glucose, fructose non-sugar polyols (sorbitol, glycerin, propylene glycol, mannitol), polyols, though less sweet than sucrose, have the advantage of providing favorable viscosity, reducing cap-locking (which occurs when sucrose crystallizes) In some cases acting as cosolvents and preservatives. A 70% sorbitol solution is commercially available for use as a vehicle. non-nutritive artificial sweeteners (aspartame, saccharin) when a reduction in calories or glucogenic properties is desired, as with the diabetic patient.

non-nutritive sweeteners do not impart the characteristic viscosity of syrups and require the addition of viscosity adjusters, such as methylcellulose. Methods of Preparation Solution with heat Agitation without heat Addition of sucrose to a prepared medicated liquid or a flavored liquid Percolation

Non-aqueous solutions are those solutions which contain solvents other than water, either alone or in addition to water. Alcohol or a binary mixture containing alcohol is the most commonly used nonaqueous solvent. For many of the official syrup theirs no officially designated method of preparation. This is due to the fact that most official syrup is available on a commercial basis and is not prepared extemporaneously by the pharmacist. For many of the official syrup theirs no officially designated method of preparation. This is due to the fact that most official syrup is available on a commercial basis and is not prepared extemporaneously by the pharmacist.

ELIXIRS defined by the USP as "clear, sweetened, hydroalcoholic liquids intended for oral use. alcohol content ranges from 5-40% (10-80 proof), The addition of aqueous solutions to elixirs may cause turbidity or separation by lessening the alcohol concentration. By simple solution with agitation Medicated or non medicated Commonly used elixirs: Aromatic elixir Compound Benzaldehyde elixir Iso-alcoholic elixir

Advantages

Compared to syrups, elixirs are usually less sweet and less viscous because they contain a lower proportion of sugar.

The hydroalcoholic character elixirs are better able than aqueous syrup to maintain both water soluble and alcohol soluble components in the solution. Also because of their stable characteristic and the ease of which they are prepared (by simple solution), from a manufacturing stand point, elixirs are preferred over syrups. Medicated elixirs are formulated such that a patient receives the usual adult dose of the drug in convenient measure. For most elixir, one or two teaspoonfuls ( 5 or 10ml) provide the usual adult dose of the drug.

Components of Elixirs The proportion of alcohol present in elixirs varies widely since the individual components of the elixirs have different water and alcohol solubility characteristic. Each elixir requires specific blend of alcohol and water to maintain all of the components in solution. Such that -- Naturally, for those elixirs containing agents which have poor water solubility the proportion of the alcohol required is greater than for elixirs prepared from components having good water solubility. In addition to alcohol and water, other solvents, as glycerin and propylene glycol, are frequently employed in elixirs as adjunct solvents. Elixirs having a high alcoholic content usually utilized an artificial sweetener as saccharin, which is required only in small amounts, rather than sucrose, which is only slightly soluble in alcohol and requires greater quantities for equivalent sweetness. All Elixirs contain flavoring material to increase their palatability and most elixirs have coloring agents to enhance their appearance. Elixirs containing over ten to twelve percent of alcohol are usually self-preserving and do not required the addition of an anti-microbial agent for their preservative. Methods of Preparation Simple Solution With Agitation - and / or by the admixture of two or more liquid ingredients. Alcohol soluble and water soluble components are generally dissolved separately in alcohol and in purified water, respectively. Then the aqueous solution is added to the alcoholic solution, rather than the reverse, in order to maintain the highest possible alcoholic strength at all times so that minimal separations of the alcohol soluble components occur. When the two solutions are completely mixed the mixture is made to volume with the specified solvents or vehicle.

Frequently the final mixture will not be clear, but cloudy, due principally to the separation of some flavoring oils by the reduced alcoholic concentration. If this occurs, the elixirs is usually permitted to stand for a prescribed number of hours, to ensure the saturation of the hydroalcoholic solvents and to permit the oil globules to coalesce so that they maybe more easily remove by filtration. Talc, a frequent filter aid in the preparation of elixirs, has the ability to absorbs the excessive amounts of oils and there for assist in their removal from the solution. The presence of Glycerin, syrup, sorbitol, and propylene glycol in elixirs generally contributes to the solvent effect of the hydroalcoholic vehicle, assist in the dissolution of the solute, and enhances the stability of the preparation. However the presence of these materials adds to the viscosity of the elixirs and shows the rate of their filtration. TINCTURES

are alcoholic or hydroalcoholic solutions prepared from vegetable or chemical substances. The concentration of solute varies up to 50% Tinctures are alcoholic solutions of nonvolatile substances which are generally extracted by maceration or percolation. Tinctures are prepared chiefly by percolation and maceration. Percolation is the procedure of choice when the crude drugs are cellular in structure; plant exudates tend to become impacted in the percolator and stop the flow so that maceration is preferred in such preparations. Moderately coarse powders are preferred, because coarse powders are slowly penetrated by the menstruum and fine powders tend to clog the percolator. Aromatic Waters Diluted Acids Spirits WATERS

AROMATIC

These are clear, aqueous solutions saturated with volatile oils or other aromatic or volatile substances like orange flower oil, peppermint oil, rose oil, anise oil, etc. No longer widely used Aromatic substances are low in water solubility Used in perfuming and flavoring

Diluted

Acids

Are aqueous solutions prepared by diluting the corresponding concentrated acids with purified water Expressed in % w/v while strength of concentrated acid is in % w/w

Preparation of Diluted Acids Absolute HCl, a concentrated acid, contains NLT 35 g and NMT 38 g of solute per 100 g of acid and has an average of 36.5% w/w in strength. To prepare 100mL of dil. HCl from the conc. HCl, one would require 10g of solute. By dimensional analysis, one would get a 27.39 g of conc. HCl to supply 10 g of solute for preparing 100 mL of the needed dil. acid.

SPIRITS Also known as essences are alcoholic or hydroalcoholic solutions of volatile substances (usually volatile oils) with alcohol contents ranging from 62-85% (124-170 proof). They are most frequently used as flavoring agents. used for their medicinal effect Most spirits are a convenient means of obtaining a proper amount of a flavoring oil. All essences have a high alcohol content, and the addition of water invariably causes turbidity and separation. Whisky and Brandy are prepared by distillation. Compound Orange Spirit, Camphor Spirit, and Compound Cardamon Spirit are prepared by simple solution. Peppermint Spirit, USP is prepared by solution with maceration Advantages Spirits can contain a greater concentration of alcohol than the corresponding aromatic waters. Methods of Preparation

Depending upon the materials utilized, spirits maybe prepared by simple solution, solution by maceration, or distillation. The spirits most recently official in the USP/NF were aromatic ammonia spirit, camphor spirit, compound orange spirit, and peppermint spirit.

Non-Aqueous Solutions Liniments Collodions Are alcoholic or oleaginous solutions or emulsions of various medicinal substances intended to rubbed on the skin Liniments containing alcoholic or hydroalcoholic vehicles are used as rubefacient, counterirritant, and for penetrating the skin Oleaginous liniments are for massage purposes and less irritating. Volatile oils are not applied to broken or bruised skin areas Solvents for oleaginous substances are almond oil, arachis oil, sesame oil, cottonseed oil, or volatile substances like wintergreen oil or turpentine. Combination of fixed oils and volatile oils may be done. Are never taken internally Emulsion liniments or insoluble-containing liniments must have a Shake well. label. Are prepared in the same manner as solutions, emulsions, or suspensions.

COLLODIONS are liquid preparations containing nitrocellulose pyroxylin (soluble gun cotton or collodion cotton) in a mixture of ethanol and ethyl ether. Pyroxylin is obtained by the action of Nitric and Sulfuruc acids. used as topical protectives or as a topical drug vehicle. made "flexible" by the addition of castor oil Are flammable and stored in well-closed containers and protected from light Are externally used Must be applied on the skin with a fine camel s hair brush or glass applicator. After the application, filmy residue of pyroxylin is left providing an occlusive protective coating to the skin. Must have a label of For external use only Collodions Collodions are clear or slightly opalescent viscous liquid.

Are prepared by dissolving 4% w/v pyroxylin in 3:1 mixture of ether and alcohol. Flexible Collodions

Prepared by adding 2% camphor and 3% castor oil to collodion. Castor oils makes the product flexible for ease in skin areas that are normally moved. The camphor gives a water-proof effect. alicylic Acid Collodions 10% solution of salicylic acid in flexible collodion. It is used as keratolytic. Since SA is irritating, white petroleum is applied to the healthy skin prior to application.

GLYCERINS Also known as Glycerites are solutions in composed of no less than 50% glycerin by weight. They are extremely viscous and are rarely used in practice and are generally limited to use in topical products

Liquid Preparations Prepared by Extraction Processes Fluidextracts Are liquid preparations of vegetable drugs by percolation Alcohols are used as solvents, preservative or both. Because concentrated, they are too potent and bitter. This made them modified by the addition of flavorants or sweetening agents before use or used as drug source of other liquid dosage forms like syrups. Are concentrated preparations of vegetable or animal drugs obtained by removal of the active constituents by the menstruum Are potent and usually between 2 and 6 times as potent as the crude drug Percolation is the method used followed by distillation for reduction of volume. Extracts are in 3 forms

a. Semiliquid extracts or those with syrupy consistency prepared without the intent of removing all or even most of the menstruum b. Pilular or solid extracts of a plastic consistency prepared with nearly all of the menstruum removed c. Powdered extracts prepared to be dry by the removal of all of the menstruum

Pilular and powdered extract differ in the amount of remaining solvent in the former preparation. Pilular extract is used in plastic dosage forms like ointments and pastes. Powdered extracts are used as powders, capsules, and tablets.

Disperse System Consists of dispersed phase and dispersion medium Particles of dispersed phase vary in size SUSPENSIONS 0.1nm - 0.5um colloidal dispersion 10 50 um coarse dispersion 0.5 10 um fine dispersion