unit III

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GASTROINTESTINAL AGENTS:

GASTROINTESTINAL AGENTS

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Gastrointestinal tract Gastrointestinal tract (GIT) is a group of organs. It extends from the esophagus to the anus. The entrance to the system is the buccal cavity. The main portions of include: stomach, small intestine (duodenum, jejonum , and ileum), large intestine ( caecum , ascending, transverse and descending colons) and the rectum with the exit anus. Functions of stomach: D igestion of proteins in acidic medium takes place with pepsin enzyme acid ( HCl ). Functions of small intestine: Digestion of proteins, Digestion of carbohydrates and lipids and Absorption of digested foods, vitamins and minerals.

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ACIDIFYING REAGENTS OR ACIDIFIERS These are the drugs which are able to increase the acidity, in GIT. Types of acidifiers: Gastric acidifies: These are the drugs which are used to restore temporarily the acidity of the stomach in patients suffering from achlorhydria or hypochlorhydria . Urinary acidifiers: These are the drugs which are used to render acidic urine to enable treatment of some types of urinary tract disorders. Systemic acidifiers: These are the drugs which are able to neutralise the alkaline body fluids particularly blood, in patients who are suffering from systemic alkalosis. Acids: These are used as pharmaceutical aids in the preparation, laboratory quality control, etc.

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Ammonium chloride Molecular Formula: NH 4 Cl Molecular weight: 53.49 Synonym: Ammonium muriate It contains not less than 99.5% of ammonium chloride, calculated with reference to dried substance. Methods of Preparation: It is prepared by neutralizing hydrochloric acid with ammonia. The resulting solution of ammonium chloride is evaporated to dryness. NH 3 + HCl NH 4 Cl It is also prepared by treating ammonium sulpahte with sodium chloride. 2NaCl + (NH 4 ) 2 SO 4 2NH 3 + 2HCl + Na 2 SO 4 2NH 3 + 2HCl 2NH 4 Cl Physical Properties: It is a white, fine crystalline powder. It is odourless and has cooling saline taste. It is hygroscopic in nature. It is freely soluble in water but slightly soluble in alcohol. Its 0.8% w/v solution is isotonic with serum.

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Physical Properties: It is a white, fine crystalline powder. It is odourless and has cooling saline taste. It is hygroscopic in nature. It is freely soluble in water but slightly soluble in alcohol. Its 0.8% w/v solution is isotonic with serum. Chemical Properties: In its vapour form, it dissociates in ammonia and hydrochloric acid. NH 4 Cl NH 3 + HCI Assay: It is assayed by acid-base titrations. The neutral formaldehyde solution so that ammonium chloride will be converted to methanimine and hydrochloric acid. The liberated acid is titrated with 0.1 N NaOH using phenolphthalein as an indicator. Identification tests: It gives the reactions of ammonium salts and chlorides. A few mg of the substance is heated with sodium hydroxide solution, leading to the evolution of ammonia gas, which is recognizable by its odour and by its action on moist red litmus paper.

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Test for Purity: The sample is tested for the presence of following impurities like Arsenic, Sulphate, calcium, Iron and Heavy metals. Loss on drying should not be more than 1%. Uses: It is helpful in producing mild acidosis at a dose of 2 g orally. It gets rapidly absorbed and converted into urea in the liver, the decrease in pH of urine occurs due to liberation of its anion into the blood stream and extracellular fluids. It is also use as an ingredient in expectorant cough mixtures in doses of 300 mg to 1 g. It is given for its diuretic action especially to help the excreation of over dosage of basic drugs such as amphetamine and in the treatment of lead poisoning by increasing its extraction.

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Dilute hydrochloric acid Molecular Formula: HCl Molecular weight: 36.46 It contains 10% w/w of HCl (limit 9.5 to 10.5 %) Preparation: Hydrochloric acid (274 g) is added gradually to water (726 g) and mixed. Properties: It is colourless liquid. It is strongly acidic and has about 1.04 – 1.05 specific gravity. Identification: After neutralization, it gives reactions which are characteristics of chloride. When it is added to KMnO 4 soluiton , chlorine gas is liberated. Weight per ml a 25°C is 1.04 to 1.05 g. Test for purity: It has to be tested for As, heavy metals, bromide, iodide, sulphite and free chlorine.

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Bromide and Iodide: 5 ml of hydrochloric acid is diluted with 10 ml of water. To it 1 ml of chloroform and solution of chlorinated lime are added drop by drop with constant shaking. The chloroform layer should not become brown or violet. Sulphite : 1ml of hydrochloric acid is diluted with 10 ml of water. To it 5 drops of barium chloride solution and 0.5 ml of 0.001 N iodine are added. The colour of iodine should not get discharged. Free chlorine: 5 ml of hydrochloric acid is diluted with 10 ml of water. To it 1 ml of cadmium iodide solution and 1 ml of chloroform are added with shaking. The chloroform layer should not become violet within 1 min. Assay: an accurate amount, about 10 g of HCl is transferred to a stoppered flask which is having 40 ml of water. The solution is titrated with 1 N sodium hydroxide, using methyl orange as an indicator. NaOH + HCl NaCl + H 2 O Each ml of 1 N NaOH  0.03646 g of HCl

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Uses: It is use as an acidifier. Storage: It is store in well closed containers. Dose: 0.6 to 8 ml.

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ANTACIDS These are the drugs which are usually alkaline substances and used for neutralising excess acid in the stomach of patients suffering from hyper- chlorhydria (hyperacidity). These drugs give relief of pain due to hyper- chlorhydria . Antacids may be classified as: Systemic (absorbable) antacids: These are soluble, readily absorbable and capable of producing systemic electrolytic alterations and alkalosis e.g. sodium bicarbonate. Non-systemic (non-absorbable) antacids: These are not absorbed to a significant extent and thus do not exert an appreciable systemic effect. This group is further sub-divided as follows:

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Aluminium containing antacids: Examples are aluminium hydroxide, aluminium phosphate, dihydroxyaluminium aminoacetate, dihydroxyaluminium sodium carbonate, basic aluminium carbonate (gel). Calcium containing antacids: Examples are calcium carbonate, tribasic calciumphosphate. Magnesium containing antacids: Examples are magnesium carbonate, magnesium citrate, magnesium hydroxide, magnesium oxide, magnesium phophate, magnesium trisilicate. Combination antacid preparations: Examples are aluminium hydroxide gel and magnesium hydroxide, aluminium hydroxide gel and magnesium trisilicate, magaldrate (monoalium hydrate; hydrated magnesium aluminate), simethicone (defoaming agent) containing antacids, calcium carbonate containing antacid mixtures, alginic acid-sodium bicarbonate containing antacid mixtures

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The ideal requirements of an antacid : It should be insoluble in water and has fine particle form. It should not he absorbable or cause systemic alkalosis. It should be able to exert its effect gradually and over a long period of time. It should not be a laxative or cause constipation. It should not cause any side effects. It should be stable and readily available. The reaction between antacid and gastric hydrochloric acid should not produce large volume of gas. The antacid should buffer in the pH range 4 to 6. The antacid should probably inhibit pepsin, the proteolytic enzyme.

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ALUMINIUM COMPOUNDS AS ANTACIDS Aluminum hydroxide gel It is an aqueous white viscous suspension of hydrated aluminium oxide having varying amount, of basic aluminium carbonate. The preparation contains not less than 3.5 per cent and not more than 14 per cent w/w of aluminium oxide (A1 3 O 3 ). Preparation: It is prepared by adding a hot solution of potash alum slowly with constant stirring to sodium carbonate. After complete removal of carbon dioxide the precipitated aluminium hydroxide is filtered. It is washed thoroughly with hot water until it becomes free from sulphate ion and the precipitate is suspended in distilled water to the required strength. 3Na 2 CO 3 + 2KAl(SO 4 ) 2 + 3H 2 O 3Na 2 SO 4 + K 2 SO 4 + 2Al(OH) 3 + 3CO 2

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Properties: It is a white viscous suspension. A clear liquid gets separated when it is kept standing. Aluminium hydroxide gel gives astringent aluminium chloride hydrochloric acid. This results into nausea, vomiting and constipation. Al(OH) 3 + 3HCl AlCl 3 + 3H 2 O Identification: A solution in hydrochloric acid gives reactions which are characteristic of aluminium . When an equal volume of gel is diluted with distilled water, the pH of the solution should not be more than 7.5. Tests for purity: It has to be tested for alkalinity, ammonium salts, arsenic, chloride, sulphate and acid consuming capacity. Test for chloride: It is carried out by dissolving 0.5 g of gel in 5 ml of dilute HCl followed by boiling and cooling and diluting the solution to 100 ml with water and taking 25 ml of diluted solution after filtration for carrying out the limit test for chloride.

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Test for sulphate : It is carried out by dissolving 5 g of gel in 5 ml of dilute nitric acid, followed by heating. The solution is diluted after cooling with 200 ml of water. The solution is mixed well and filtered, if necessary. 10 ml of the filtrate is taken and after adding 2 ml of HCl the solution is used for carrying out limit test for sulphate and the test should comply. Acid-consuming capacity: An accurately weighed quantity of gel (1.5 ml) is taken in a flask. To it 50 ml of 0.1 N hydrochloric acid is added. The contents are shaken at 37°C for 1 hour. The solution is then titrated for excess of hydrochloric acid with 0.1 N sodium hydroxide using bromophenol blue as an indicator. 1 g of gel should consume not less than 12.5 ml and not more than 25 ml of 0.1 hydrochloric acid.

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Assay: Nearly 5 g of substance is accurately weighed and taken in a flask. To this 3 ml of hydrochloric acid is added. The solution is now warmed on a water bath. After cooling, this is transferred to a 100 ml volumetric flask and the volume is made up to 100 ml. Now 20 ml of the solution is taken from the volumetric flask into a conical flask and exactly 40 ml of 0.05 disodium edetate is added to it, followed by about 80 ml of water and a few drops of methyl red solution. To this 1N sodium hydroxide solution is added to neutralise this solution. This can be recognised by change of colour from red to yellow. Now the flask is warmed on a water bath for about 1/2 hour. To this 3 g of heaxmine is added. Also, the 0.5 ml of xylenol orange solution is added to it as an indicator. The mixture is now filtered with a standard 0.05 M lead nitrate solution until a violet colour appears at the end point due to the formation of lead xylenol orange complex. Factor: Each ml of 0.05 M disodium EDTA is equivalent to 0.002549 g of Al 2 O 3 .

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Storage: It is to be stored in well-closed containers and should not be allowed to freeze. For attractiveness it is usually dispensed in blue or amber coloured bottles. Uses: Aluminium hydroxide gel is a very effective slow-acting antacid. It does not get absorbed in alimentary canal and does not produce carbon dioxide. It is widely used in treatment of intestinal toxemia and hyperchlorhydria. It is able to neutralize gastric hydrochloric acid and causes absorption of toxins and gases. It does not cause system alkalosis. Dose: Its dose is 7.5 to 15 ml. It causes constipation and is therefore administered with magnesium salt which is a mild laxative.

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CALCIUM COMPOUNDS AS ANTACIDS Calcium carbonate Molecular Formula: CaCO 3 Molecular weight: 100.09 It is having not less than 98.0 % and not more than 100.5 % of CaCO 3. Preparation: on a commercial scale, calcium carbonate is obtained by mixing the boiling solution of calcium chloride and sodium carbonate and allowing the resulting precipitate to settle down. CaCl 2 + Na 2 CO 3 CaCO 3 + 2NaC1 The precipitate is collected on calico filter, and washed with boiling water, until it become free from chloride ions. Finally, the precipitate is dried.

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Properties: It occurs as fine, white, micro-crystalline powder. It is odourless and tasteless. It is almost insoluble in water and alcohol. The water solubility is increase by presence of CO 2 due to formation of soluble calcium bicarbonate and also by ammonium salts due to formation of free calcium ions. CaCO 3 + H 2 CO 3 Ca (HCO 3 ) 2 CaCO 2 + 2NH 4 + Ca 2 + + 2NH 3 + H 2 O + CO 2 Calcium carbonate neutralises acids with effervescence. CaCO 3 + 2HCl CaCl 2 + CO 2 + H 2 O Identification: It gives reactions which are characteristic of calcium and carbonates. Test for purity: It has to be tested for Al, Fe, phosphate and matter insoluble in HCl , As, heavy metals, chloride, sulphate , Ba , soluble alkali and loss on drying.

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Assay: Calcium carbonate may be assayed by the complexometric method. Direct titration is carried out in an alkaline medium. 1 g of an accurately weighed sample is moistened with sufficient quantity of water and HCl to get a clear solution. By adding more water, the volume is increased to 250 ml. To 50 ml of this solution 100 ml of water is added and its pH is adjusted to 12 with 15 ml of freshly prepared 1N NaOH solution. 40 mg of murexide and 3 ml solution of naphthol green are added and titrated with 0.05 M EDTA solution until a deep blue colour is obtained. Each ml of 0.05 M EDTA W 0.005005g of CaCO 3 .

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Uses: The precipitated chalk finds use externally as a dentifrice because it is having mild abrasive quality, It also finds use internally as an antacid. It is found that it can produce alkalosis in spite of its water insolubility. Its continued use as an antacid is not advisable. It is having a tendency to cause constipation and hence it is usually administered alternatively or along with magnesium salts. It is a rapidly acting non-systemic antacid. It neutralises gastric acid and forms calcium chloride. The latter is converted in intestine to an insoluble calcium salt which tends to be constipating. Hence calcium and magnesium antacids are usually given in combination. Dose: 1-4 g repeated according to need, usually six times a day.

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MAGNESIUM COMPOUNDS AS ANTACIDS Magnesium hydroxide Molecular Formula: Mg(OH) 2 Molecular weight: 58.32 . It is having not less than 95.0 per cent and not more than 100.5 per cent of Mg(OH) 2 . Preparation: The magnesium hydroxide obtained in the preparation of milk of magnesia is evaporated to dryness. It is also prepared by treating sea water or other natural brines with sufficient calcium hydroxide to precipitate magnesium as magnesium hydroxide, then washing and drying the precipitate. Properties: It is a white fine amorphous powder. It is almost insoluble in water yielding a solution which is slightly alkaline. It dissolves in dilute mineral acids. It slowly absorbs carbon dioxide from atmosphere, Magnesium hydroxide and its tablets have been official in N.F.

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Assay: An accurately weighed amount of sample is taken in a flask. To it 25 ml of 1N H 2 SO 4 is added. The excess of acid is back titrated with 1 N NaOH using methyl red as an indicator. Each ml of 1 N H 2 SO 4  0.02917 g of Mg (OH) 2 Uses: It is used as an antacid.

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SODIUM COMPOUNDS AS ANTACIDS Sodium bicarbonate Molecular Formula: NaHCO 3 Molecular weight: 84.01 Synonym: Baking soda It contains not less than 99 per cent and not more than the equivalent of 100.5 per cent of NaHCO 3 calculated with reference to the dried substance. Preparation: On a small scale, it is prepared by passing CO 2 gas through a solution of sodium hydroxide. The solution is concentrated to get the product. 2NaOH + CO 2 Na 2 CO 3 + H 2 O Na 2 CO 3 + H 2 O + CO 2 2NaHCO 3

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Assay: An accurately weighed amount of sample is taken in a flask. To it 25 ml of 1N H 2 SO 4 is added. The excess of acid is back titrated with 1 N NaOH using methyl red as an indicator. Each ml of 1 N H 2 SO 4  0.02917 g of Mg (OH) 2 Uses: It is used as an antacid.

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Properties: It occurs in white crystalline or amorphous powder having a saline taste. It is freely soluble in water but practically insoluble in alcohol. When heated to 100°C it gets converted into sesquicarbonate (Na 2 CO 3 , NaHCO 3 2H 2O ). It gives effervescence with acids. Its solution is alkaline in nature. Identification: It gives the reactions of sodium and carbonate. Its 1 per cent w/v solution has a pH not more than 8.6. Tests of purity: It is tested for alkalinity, Al, Ca, insoluble matter, As, Fe, heavy metals, chloride, sulphate and ammonium compounds. Clarity and colour of solution: Its 5.0 per cent w/v solution is clear and colourless.

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Loss on drying: It should not be more than 0.25 per cent. It is determined on 4.0 g by drying it over silica gel for four hours. Ammonium compounds: When 1 g is warmed with 10 ml of sodium hydroxide solution, no ammonia should be evolved. Assay: Its 1 g is weighed accurately. It is dissolved in 20 ml of water. Now it is titrated with 0.5 N sulphuric acid using methyl orange as an indicator. Each ml of 0.5 N H 2 SO 4  0.042 g of NaHCO 3 Uses: In medicine it is mainly used for its acid neutralizing properties. If finds use as an antacid and to combat with systemic acidosis. It is also used for preparing buffer solutions (NaHCO 3 + H 2 CO 3 ). Its aqueous solutions are used as local applicants for burns, insect bites etc. It is also a constituent of effervescent mixture. Dose: 300 mg to 2 g.

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COMBINATION OF ANTACIDS Many preparations which are having combination of antacids are being marketed. The idea behind such combination is to counteract the constipative action of calcium and aluminium, containing antacids with laxative effect of magnesium containing antacid. Sometimes the combination antacid preparation is having one with rapid onset of action with antacid with a longer duration of action. In another type, the antacids are combined with simethicon type of compounds which are having antiflatuluent action as they are antifoaming agents and cause dispersion of gases.

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Aluminium hydroxide magnesium carbonate co-driedgel: It is a co-precipitate of aluminium hydroxide and magnesium carbonate carefully dried to contain a critical proportion of water for antacid activity. It acts as an antacid that is given in doses of up to 1 g. Algicon tablets: The tablets are chewable, prepared by aluminium hydroxide-magnesium carbonate co-dried gel (360 mg), magnesium alginate (500 mg), magnesium carbonate (320 mg) and potassium bicarbonate (100 mg). Simeco tablets: It contain aluminium hydroxide-magnesium carbonate co-dried gel (282 mg), magnesium hydroxide (85 mg) and activated dimethicone (25 mg) Aluminium Hydroxie gel-Magnesium Trisilicate Combinations: This is one the more common combinations. It has laxative, constipative and protective effect.

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Magaldrate: It is a chemical combination of aluminum hydroxide and magnesium hydroxide. It contains the equivalent of 28 to 39% magnesium oxide and 17 to 25% of aluminium oxide. It occurs as a white, odourless, crystalline powder which is insoluble in water and alcohol, but soluble in dilute solution of mineral acids. Calcium carbonate containing antacid mixture: Calcium carbonate with aluminum hydroxide gel yields product which have a rapid onset with prolonged action. Three part combinations of calcium carbonate, aluminium hydroxide gel and magnesium containing antacid are also available.

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CATHARTICS Cathartics may be defined as those drugs which bring about defecation. They are beneficial in constipation and for expulsion of intestinal parasites. They are given for clearing bowels before surgery. Purgatives are also cathartics which act similarly but are mild in their action. Laxatives are the mild type of purgatives. Both these bring about the same effect but vary in and mechanism of action. Laxatives, cathartics and purgatives act by retaining fluid in the bowel, These may be administered by oral route or by rectal route.

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Mechanism of cathartics or purgative Stimulants: Ex: senna, rhubarb, cascara, podophyllum, castor oil, aloe etc. belongs to this class. Bulk purgatives: Examples: methylcellulose, sodium CMC, gum, ispagol etc. Lubricants: Substances such as liquid paraffin, glycerin, miner oils etc. act as lubricants and cause smooth clearance of the fecal material. Saline cathartics: These act by increasing the osmotic load of intestine by absorbing large quantity of water and thereby stimulate peristalsis. Poorly absorbable cations like calcium, magnesium and anions like phosphate, sulphate, tartrate are contributing to this effect.

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Mechanism of cathartics or purgative Stimulants: Ex: senna, rhubarb, cascara, podophyllum, castor oil, aloe etc. belongs to this class. Bulk purgatives: Examples: methylcellulose, sodium CMC, gum, ispagol etc. Lubricants: Substances such as liquid paraffin, glycerin, miner oils etc. act as lubricants and cause smooth clearance of the fecal material. Saline cathartics: These act by increasing the osmotic load of intestine by absorbing large quantity of water and thereby stimulate peristalsis. Poorly absorbable cations like calcium, magnesium and anions like phosphate, sulphate, tartrate are contributing to this effect.

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The saline cathartics are water soluble mainly inorganic chemicals and they are taken with plenty of water. This is helpful restricting excessive loss of body fluid and reduces nausea and vomiting. The saline laxatives are relatively free from side-effects when taken for brief periods. Patients on low sodium diet should not use the sodium containing saline laxatives. They may be administered by oral route (suspension or powder) or by rectal route (enema or suppository). Examples of saline laxative and cathartic agents are different magnesium salts such as magnesium hydroxide. magnesium sulphate , etc. and tartrate salts of sodium and potassium.

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Magnesium sulphate Molecular Formula: MgSO 4, 7H 2 O Molecular weight: 246.5 Synonym: Epsom salt It is having not less than 99.0 % and not more than 100 % of MgSO 4 calculated in reference to the ignited substance. Preparation: It is obtain by the action on magnesium carbonate or magnesium oxide or from native carbonate. MgCO 3 + H 2 SO 4 MgSO 4 + H 2 O + CO 2 The solution is filtered. The filtrate is evaporated to crystallization. It is manufactured by the action of sulphuric acid on the native carbonate or on previously calcined dolomite. When dolomite is used, magnesium sulphate passes into solution, and sparingly soluble calcium sulphate is deposited. MgCO 3 . CaCO 3 + 2H 2 SO 4 MgSO 4 + CaSO 4 + 2H 2 O + 2CO 2

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Properties: It occurs as colourless crystals having a cool, saline bitter taste. It effloresces in warm dry air. It is soluble in water and sparingly soluble in alcohol. When gently heated, it loses some of its water of hydration and gets converted into the monohydrate (white powder) which becomes anhydrous at 200°C. Identification: It gives reactions which are characteristic of magnesium and sulphate. Tests for purity: It has to be tested for As, Fe, Zn, heavy metals, and loss on drying. Loss on ignition: It is between 48.0 and 52.0 per cent and is determined on 1 g by drying in an oven at 105°C for two hours and igniting to constant weight at 400°C.

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Clarity and colour of solution: 5 g of magnesium sulphate is dissolved in sufficient water to produce 50 ml. It should give a clear and colourless solution. Acidity or alkalinity: 1 g of magnesium sulphate is dissolved in 10 ml of water. This solution is neutral to litmus solution. Assay: 0.3 g of the sample is weighed accurately. It is dissolved in 50 ml of water. To it 10 ml of strong ammonia-ammonium chloride solution is added. Now this solution is titrated with 0.05 M disodium ethylenediaminetetraacetate using 0.1 g of Mordant Black 11 mixture as indicator until the pink colour gets discharged from the blue. Each ml of 0.05 m disodium ethylenediaminetetraacetate  0.00602 g of MgSO 4 . Action and Uses: Magnesium sulphate is given orally in dilute solutions. About 5 g gives rise to laxative effect. Due to bitter and nauseating taste it is given in fruit juices. The mechanism of action is that magnesium sulphate does not get absorbed from intestinal tract and thus retains sufficient water within the lumen. The hydrostatic pressure is able to promote motor activity or peristalsis of bowel. Dose: 10-15 g. It is to be used with care in patients with impaired renal function.

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Sodium Orthophosphate Molecular Formula: NaHPO 4 .12H 2 O Molecular weight: 358.14 Synonym: Disodium hydrogen phosphate It contains not less than 98.5% and not more than 101% of Na 2 HPO 4 , which is calculated with reference to the substance dried at 130°C. Methods of Preparation: It is sodium salt of orthophosphoric acid or phosphoric acid. It is formed by the reaction of orthophosphoric acid with sodium hydroxide in calculated amount. H 3 PO 4 + 2NaOH Na 2 HPO 4 + 2H 2 O Industrially, it is prepared in a two-step process by treating calcium biphosphate (CaHPO 4 ) with sodium bisulphate (NaHSO 4 ) with precipitate calcium sulphate and monosodium phosphate (NaH 2 PO 4 ) remains in the solution form.

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CaHPO 4 + NaHS0 4 NaH 2 PO 4 + CaSO 4 In the second step, the resulting solution of monosodium phosphate is neutralized and finally results in the formation of sodium orthophosphate. NaH 2 PO 4 + NaOH Na 2 HPO 4 + H 2 O Physical Properties: It occurs as colourless , odourless , transparent crystals. Its anhydrous salt is hygroscopic in nature. It effervescence in air when warmed. It is insoluble in alcohol but soluble in water. Its aqueous solution has a pH between 8.0 - 11.0 i.e. moderately basic. Chemical Properties: On hydrolysis, it yields sodium hydroxide and phosphoric acid back from which it formed. Na 2 HPO 4 + 2H 2 O H 3 PO 4 + 2NaOH On heating, it gives pyrophosphate. 2Na 2 HPO 4 Na4P2O 7 + H 2 O On heating with ammonium chloride, table salt is formed. Na 2 HPO 4 + NH 4 Cl NaCl + Na.NH 4 HPO 4

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Assay: It is based on acid-base titration. 6 g of the salt is dissolved in 100 ml of water which is then titrated with 0.5 N H 2 SO 4 using bromocresol green as an indicator in at a pH of 4.5. Each 1 ml of 0.5 N H 2 SO 4  0.07098 g of Na 2 HPO 4 Identification Tests: To 5 ml neutral solution of sample, add 5 ml silver nitrate solution, a light yellow precipitates are formed, the colour retains even on boiling, which is readily soluble in 10 M ammonia solution and in dil. nitric acid. Test for purity: It is tested for alkalinity, arsenic, magnesium, heavy metals, sulphate and loss on drying. Uses: It is widely used as cathartics due to poor absorption of HPO 4 2- . In the form of oral solution, it is also used as anti-hypercalcemic. As a pharmaceutical aid, it is used as a buffering agent in various preparations. It is also used in conjunction with trisodium phosphate, in water softening treatment. Its presence prevents coagulation, in the preparation of condensed milk. In food industries, it is used to adjust pH. 7. It is used to treat constipation or to clean the bowel before a colonoscopy. It is used as an anti-caking additive in powdered products. Dose: 2-16 g in divided dose daily.

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Kaoline Molecular Formula: Al 2 O 3 .2SiO 2 .2H 2 O Molecular weight: 258 Synonym: china clay, hydrated aluminium silicate Preparation: It is a hydrated aluminium silicate, widely distributed in prepared when the rock is mined, executed, the impurities are washed with the flow of water and then powdered. Kaolin is found in two forms: Heavy Kaolin and Light Kaolin. Therefore the elutriated with water and large sized particles are separated. The turbid liquid is allowed to settle, heavy kaolin containing large particles and colloidal kaoline containing particles of small size are separated and dried. Physical Properties: Kaolin is slightly plastic like and is normally white in colour . It has an earthy or clay like taste. impurities. It is soapy to touch and its surface takes high polish on rubbing. Its fusion point range between 1700 - 1800°C. When moistened with water, it produces a darker colour and develops marked clay like odour .

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Chemical Properties: On heating, kaolin loses water molecules. It is decomposed by prolonged boiling or treatment with concentrated sulphuric acid. Test for Purity: Development of pink colour due to addition of phenolphthalein to an aqueous suspension indicates the presence of alkaline nature. Test for lead: For determining lead, the substance is digested with nitric acid. The reaction is centrifuged and in the supernatant liquid limit teat for lead is carried out. Test for Iron: Iron is detected by triturating kaolin with water, sodium salicylate is added, the mixture does not acquire more than a slight reddish tint. Uses: Kaolins are used as adsorbent, antidiarrhoeal and increase the bulk of faeces. It adsorbs toxins from alimentary tract and is thus beneficial in diarrhoea, Kaolin has also been used in the treatment of chronic ulcerative colitis.

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Bentonite Molecular Formula: Al 2 O 3 .4SiO 2 .H 2 O Molecular weight: 422.286 Synonym: Clay Bentonite is a name given to a particular clay that was originally found in Fort Benton, Eastern Wyoming. The name was given by W.C. Knight in 1898. Previously, it was called Taylorite , which was named after William Taylor, who first began to draw attention to the day deposits. In India, Bhavnagar and Kachchh districts of Gujarat and Barmer district of Rajasthan are major producers of bentonite . The sodium bentonite mined in Rajasthan tends to the be of lower quality and is used as foundry sand. Both activated and granular bentoniteare produced in the country.

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Physical Properties: It is a hydrated material having swelling and absorptive properties. Its powder mask has a binding property. It has excellent plasticity and lubricity. It has high shear and compressive strength. It has low permeability and low compressibility. It has good dry sealing properties. Bentonite clay has negatively charged molecules, which give adsorptive properties to it. Uses: It is use as cathartics due to absorption properties. It can remove toxic metals and chemicals following radiation treatment. It promotes healthy bacteria balance and detoxify the digestive system. It also support in detoxification. It is also use as an antidote in mercury poisoning. It is helpful in removing the internal parasites from digestive system. It is active against free radicals and can be used as antioxidant. It also helps in colon cleansing. It supports in boosting immune system.

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ANTIMICROBIAL AGENTS The agents which help in preventing or reducing infection due to microbes. Classification: Antiseptics Disinfectants Germicides Bacteriostatics Sanitizers

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Ideal properties of antimicrobial agent: It should possess antiseptic or germicide activity and not bacteriostatic activity. If the micro-organisms do not get killed, they may resume growth and bring about infections. It should have rapid onset and sustained activity. This will be able to reduce incidence of resistance. It must possess good therapeutic index indicating usefulness in the concentration employed. It should not cause local cellular damage or should not interfere with body defenses. It should show no systemic toxicity from topical applications. It should have in general broad spectrum of activity against bacteria, fungi, protozoa, virus etc. The topical antimicrobial agent should have favorable lipid-Water distribution coefficient so that its effectiveness has been best.

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Mechanism of action: The mechanism of action of antimicrobial agents may range from a mild astringent to powerful oxidative processes. Oxidation: Halogenation:

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Protein precipitation: Many metal ions exhibit protein binding or protein precipitation. The nature of interaction with protein takes place through polar group of protein which acts as ligands and this action in general is non-specific. Protein precipitants are not able to distinguish the protein of microbe and that of host. Germicidal action results when the concentration of ion becomes such that reaction get restricted largely to the parasite cell.

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Potassium permanganate Molecular Formula: KMnO 4 Molecular weight: 158.03 Synonym: Permanganic acid It contains not less than 99% and not more than 100.5`% of KMnO 4 . Preparation: Potassium permanganate is prepared by mixing a solution of potassium hydroxide with powdered manganese dioxide and potassium chlorate. The mixture is boiled, evaporated to yield the residue. 6KOH + 3MnO 2 + KClO 3 3K 2 MnO 4 + KCl + 3H 2 O By passing chlorine gas through potassium permanganate solution. 2K 2 MnO4 + 3Cl 2 6KMnO 4 + 6KCl

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Properties: It occurs in the form of dark purple prismatic crystal with metallic lustre . It is odourless but it tastes sweet and astringent. It decomposes at higher temperature. 2KMnO 4 K 2 MnO 4 + MnO 2 + O 2 It is a powerful oxidizing agent. 2KMnO 4 + H 2 O + KI 2MnO 2 + 2KOH + KIO 3 When hydrochloric acid is added to the solution of potassium permanganate, chlorine gas is liberated. 2KMnO 4 + 16HCl 12KCl + 2MnCl 2 + 8H 2 O + 5Cl 2 Assay: 3 gm of the substance is dissolved in 100 ml of water. Take 20 ml of this solution, add 1 gm of KI and 10 ml of 2 N HCl and titrate the liberated iodine with 0.1 M Na 2 S 2 O 3 using starch solution as an indicator. Each 1 ml of 0.1 M Na 2 S 2 O 3  0.003160 g of KMnO 4

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Identification Tests: It gets decomposed on heating, a black residue is obtained with evolution gas. The residue gives potassium hydroxide when water is added into it. The resulting solution gives characteristic test of K + ion. A solution of KMnO is acidified with sulphuric acid, and then heated to 70°C decolorized by the solution of hydrogen peroxide. Test for Purity: KMnO 4 is boiled with 95% aqueous alcohol to destroy the purple colour so that colour should not interfere with the limit test. The precipitated manganese dioxide is removed by filtration. 2KMnO 4 + 3CH 3 CH 2 OH 2KOH + 2MnO 2 + 3CH 3 CHO + 2H 2 O Take 20 ml of filtrate and perform the limit test for chloride and sulphate and the sample must comply the permissible limits.

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Storage: It should be stored in air tight containers, to avoid contact with organic matter. Caution: Great care should be taken in handling KMnO4 because dangerous explosion may occur if it is brought in contact with organic matter or any rapidly oxidisable substance. Uses: It is a topical anti-infective. Its solution is used as an antiseptic in mouth wash and for cleaning of ulcers. It is used in the treatment of urethritis. Because of its oxidizing property, it is used as an antidote in many venoms, barbiturates, alkaloids etc. Its solution is used in bath for eczema and acute dermatoses patients. It is commonly used as an antiseptic in veterinary practices.

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Hydrogen peroxide Molecular Formula: H 2 O 2 Molecular weight: 34.01 100 ml of hydrogen peroxide solution contains not less than 26%w/w and not more than 28% w/w of H 2 O 2 , corresponding to 100 times, its volume of available oxygen. It is an aqueous solution of hydrogen peroxide, it contains not Less than 6% w/w of hydrogen peroxide. Preparation: It is prepared by the action of sulphuric acid on barium peroxide. BaO 2 + H 2 SO 4 BaSO 4 + H 2 O 2 Hydrogen peroxide solution may be prepared by reaction of barium peroxide with phosphoric acid. Barium peroxide Barium phosphate is filtered. 2BaO 2 + 2H 3 PO 4 Ba 3 (PO 4 ) 2 + 3H 2 O 2 It can also be prepared by treating sodium peroxide with sulphuric acid. Na 2 O 2 + H 2 SO 4 Na 2 SO 4 + H 2 O 2

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Physical Properties: Hydrogen peroxide solution is colourless and odourless. Its taste is slightly acidic. It readily gets decomposed when come in contact with oxidisable organic metal. The decomposition of hydrogenperoxide is promoted by catalysts Cu, Fe and etc. while small quantity of sulphuric acid, phosphoric acid and alcohol retarded decomposition of hydrogen peroxide. It is a strong oxidizing agent and is miscible with water. Tests for identity: When made alkaline and heated, it gets decomposed with effervescence, evolving oxygen. To 1 drop, 20 ml of water, 1 drop of potassium chromate and 2 ml of solvent ether are added and shaken, Then, ether layer becomes blue.

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Tests for purity: It has to be tested for acidity, preservative, loss on evaporation, barium and stability. Acidity: 10 ml of hydrogen peroxide is first of all diluted with 20 ml of water. Then, it is titrated with 0.1 N sodium hydroxide, using methyl red as an indicator. Not less than 0.2 ml and not more than 1 ml of 0.1 N NaOH should not be required. Tests for barium: It is based upon treating, the H 2 O 2 with dilute H 2 SO 4 no turbidity should produce.

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Assay: Hydrogen peroxide and acidified potassium permanganate, both are oxidising agents. They two oxidising agents reduce one another with the evolution of gaseous oxygen. Hydrogen peroxide reduces KMnO 4 solution and causes its decolouration . At the end point, excess drops of KMnO 4 gives pink colour . Potassium permanganate itself acts as an indicator. The assay of hydrogen peroxide is carried out by the permanganate method. 10 ml of sample is diluted to 250 ml in a volumetric flask with purified water. to 25 ml of this solution, 10 ml of 5 N sulphuric acid added. Then the content are titrated with 0.1 N potassium permanganate solution, until a faint pink colour is obtained. Each ml of 0.1N KMnO 4  0.001701 g of H 2 O 2 Uses: Hydrogen peroxide is a strong oxidizing agent and yields nascent oxygen, and hence used for bleaching. It acts as an antiseptic and a germicide and hence is used for cleaning cut and wounds. It is effective antidote for phosphorus and cyanide poisoning. It is also use as a deodorant. The liberation of gaseous oxygen is able to exert an additional cleansing action on cuts and wounds. It is use for bleaching the hair.

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Chlorinated lime Molecular Formula: Ca( OCl )Cl,CaOCl 2 Molecular weight: 136.98 Synonym: Bleaching powder, chlorine of lime Chlorinated lime should contain not less than 30% w/w of available chlorine. Preparation: It is prepared by the action of chlorine on calcium hydroxide. Calcium hydroxide is spread on the shelves in a suitable container. The chlorine gas is introduced at the top of the chamber. Ca(OH) 2 + Cl 2 Ca( OCl ) Cl + H 2 O This process takes about 12-24 hrs.

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Properties: It is a dull white powder with characteristic odour . When exposed to air, it absorbs moisture and gradually decomposed. It is slightly acidic in water and alcohol. When bleaching powder is put in water, hypochlorite goes out in solution, because of this bleaching and oxidizing property. 2Ca( OCl ) Cl + CO 2 + H 2 O CaCO 3 + CaCl 2 Mode of Action: It works by chlorination of microorganism's protein, which ultimately leads to the destruction of protein and cell death. Identification Test: When the sample is treated with concentrated HCl , chlorine gas is evolved in large amount.

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Assay: Its assay is based on redox titration method. Chlorinated lime liberates the available chlorine as Cl 2 gas by the action of acid. Then, this free chlorine is allowed to react with potassium iodide to liberate iodine, the quantity of liberated iodine is then estimated by titration with 0.1 N Sodium thiosulphate . CaOC1 2 + 2CH 3 COOH Ca(CH 3 COO) 2 + H 2 O + CO 2 Procedure: Take 4 g of chlorinated lime with small quantity of water and transfer it make it to 1 L flask and make up the volume to the mark. Measure 100 ml of this suspension and transfer in another flask. Then it is titrated with 3 gm KI solution, acidified with 5 ml acetic acid, the liberated iodine is titrated against 0.1 N sodium thiosulphate using starch solution as an indicator. Each 1 ml of 0.1 N Na 2 S 2 O 3  0.003545g of available chlorine.

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Test for purity: It has been tested for its stability by heating it at 100°C for 2 hrs. It must not lose more than 3% w/w of available chlorine. Uses: Chlorinated lime has the bactericidal action. It is also used as disinfectant in wounds. It is used as a cleansing agent for water closets (toilets), drains and effluents. It is also used as an ingredient in the preparation of detergents. It is a powerful bleaching agent.

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Test for purity: It has been tested for its stability by heating it at 100°C for 2 hrs. It must not lose more than 3% w/w of available chlorine. Uses: Chlorinated lime has the bactericidal action. It is also used as disinfectant in wounds. It is used as a cleansing agent for water closets (toilets), drains and effluents. It is also used as an ingredient in the preparation of detergents. It is a powerful bleaching agent.

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