Pharmaceutical Inorganic Chemistry Notes PDF

# Pharmaceutical Inorganic Chemistry ## Complete Unit 1 Notes **Imperfect Pharmacy:** - **Instagram:** IMPERFECTPHARMACYOFFICIAL - **YouTube:** IMPERFECT PHARMACY - **Telegram:** IMPERFECT PHARMACY ## Pharmaceutical Chemistry - **Inorganic Chemistry:** - Study about inorganic compounds used i...

# Pharmaceutical Inorganic Chemistry ## Complete Unit 1 Notes **Imperfect Pharmacy:** - **Instagram:** IMPERFECTPHARMACYOFFICIAL - **YouTube:** IMPERFECT PHARMACY - **Telegram:** IMPERFECT PHARMACY ## Pharmaceutical Chemistry - **Inorganic Chemistry:** - Study about inorganic compounds used in pharmaceutical industry - **Organic Chemistry:** - Study about organic compounds used in pharmaceutical industry - **Medicinal Chemistry:** - Study about synthesis, identification, and development of drugs and medicines. ## Inorganic Compounds - Inorganic compounds will never contain carbon and hydrogen together. - Individual compounds, however, can contain any atom, for example: CO2, HCl, H2O ## Syllabus ### Unit I - Impurities in pharmaceutical substances - Limit Test ### Unit II - Acids, bases, and buffers - Major extra & intracellular electrolytes - Dental Products ### Unit III - Gastrointestinal Agents - Acidifiers - Antacids - Cathartics - Antimicrobials ### Unit IV - Miscellaneous Compounds - Expectorants - Emetics - Hematinics - Poisons & Antidote - Astringents ### Unit V - Radiopharmaceuticals ## Pharmacopoeia - Pharmacopoeia is derived from two Greek words: - Pharmakon: 'Drug' - Poeia: 'To make' - It is the legal and official book of standards of drugs issued by recognized authorities usually appointed by the government of each country. - Pharmacopoeia contains: - List of drugs and related substances - Sources - Prescription - Tests - Formulas - Uses - Doses - Storage Conditions ## Importance Of Pharmacopoeia - To maintain uniformity and control the standard of drugs available in the market. - To avoid adulterated drugs - Complete information of drugs and dosage forms - Reference for laboratory, industry, and academic institutions. ## Pharmacopoeia of Different Countries: - Indian Pharmacopoeia - British Pharmacopoeia - US Pharmacopoeia - European Pharmacoepeia - French Pharmacopoeia ## Indian Pharmacopoeia Commission - Indian Pharmacopoeia Commission is an autonomous institution of the Ministry of Health and Family Welfare which sets standards for all the drugs manufactured, sold, and consumed in India. ## Indian Pharmacopoeia - It is the official book of standards for drugs to define identity, purity, and strength for drugs imported, manufactured for sale, stocked, or distributed in India. - Indian Pharmacopoeia is published by IPC, the Indian Pharmacopoeia Commission - Its head office is in Ghaziabad, UP. - Indian pharmacopoeia is published by NISCAIR - NISCAIR stands for National Institute of Science Communication and Information Resources ## History of Indian Pharmacopoeia - In pre-independence days, the British Pharmacopoeia was used in India. - In 1946, the Government of India issued "The Indian Pharmacopoeial List" under the chairmanship of Sir R.N. Chopra, along with nine other members. - It was prepared by the Department of Health, Government of India, Delhi, in 1945. - In 1948, the Government of India appointed an Indian Pharmacopoeia Committee for preparing "Pharmacopoeia of India." - The Indian Pharmacopoeia Committee, under the chairmanship of Dr. B.N. Ghosh, published the first edition of IP in 1955. ## Father Of Indian Pharmacopoeia - Professor Mahadeva Lal Schroff ## List of Indian Pharmacopoeia: | Editions | Year | Addendum / Supplment | Number of Volumes | Monographs | | :------- | :---- | :-------------------- | :---------------- | :------------ | | 1st Edition | 1955 | Supplement 1960 | 2 | 986 | | 2nd Edition | 1966 | Supplement 1975 | 3 | 890 | | 3rd Edition | 1985 | Addendum 1989 | 2 | 261 | | | | Addendum 1991 | 1 | 261 | | | | Addendum 2000 | 1 | 1149 | | 4th Edition | 1996 | Addendum 2000 | 3 | 208 | | | | Addendum 2002 | 1 | 19 | | | | Addendum 2005 | 1 | 19 | | 5th Edition | 2007 | Addendum 2008 | 3 | 271 | | 6th Edition | 2010 | Addendum 2012 | 3 | 52 | | 7th Edition | 2014 | Addendum 2015 | 4 | 577 | | | | Addendum 2016 | 1 | 577 | | 8th Edition | 2018 | Addendum 2019 | 4 | 220 | ## Impurities - Impurity is any material that affects the purity of the material of interest. - The Presence of impurity may produce toxic effects. - It may lower the strength of the pharmaceutical substance. - Common impurities include lead, arsenic, iron, chloride, etc. ### Types of Impurities - *Organic Impurities*: - Arise during synthesis, purification, and storage of drug substances. - Can be identified or non-identified. - They may include starting materials, byproducts, synthesis intermediates, reagents, ligands, and catalysts. - *Inorganic Impurities*: - Often derive during the manufacturing process. - Generally identified - They basically include reagents, ligands, catalysts, heavy metals, and inorganic salts - *Residual Solvents*: - Arise during the manufacturing proces - Impurities that are present in the solvents used in pharmaceutical manufacturing ### Sources of Impurities - Raw Material - Reagent - Method - Solvents - Atmospheric Contamination - Reaction with Vessel - Packaging Error - Storage Conditions #### Raw Materials - Impurities from raw materials may be carried through the manufacturing process and contaminate the final product. - **Example:** Rock salt (CaSO4 + MgCl2) = NaCl Rock salt contains small amounts of calcium sulphate and magnesium chloride. 'NaCl' prepared from this source may contain calcium and magnesium traces. #### Reagent Used - If the reagent used in manufacturing is not completely removed by washing, then it may find its way into the final product. - **Example:** HgCl2 + 2NH4OH → NH2HgCl + NH4Cl In the above reaction, ammoniated chloride prepared contains ammonium hydroxide. If it is not removed by washing with water, then it may contaminate the final product. #### Method / Process - There are various methods and processes used in the manufacturing of pharmaceutical products. In certain drugs, a multiple step synthesis process is used, which produces intermediate compounds. - It is very important to purify these intermediate compounds; otherwise, they will contaminate the final product. #### Solvents - Most of the pharmaceutical products are manufactured using water as a solvent. - Generally, we use distilled or de-mineralized water, but sometimes, to reduce costs, we use softened waters that contain 'Na+' and 'Cl-' ions (as impurities) that can contaminate the final product. - *Tap Water* : Contains Ca2+, Mg2+, Na+ as an impurity - *Softened Water* : Contains Na+, Cl- as an impurity. - *De-mineralized water*: May contain organic impurities - *Distilled Water* : Best but costly #### Atmospheric Contamination - In industrial areas, the atmosphere is contaminated with dust particles and harmful gases. During manufacturing, products can react with these substances, become contaminated. - **Example:** NaOH reacts with atmospheric CO2 and gets contaminated. For this reason, NaOH should not be kept open for a long time. - That is why most of the industries build in outer areas, where pollution is very low. #### Reaction With Vessel - During manufacturing, some of the vessel solvents and reagents may undergo reaction with the vessel and contaminate the final product. - **Example:** Iron may contain arsenic as an impurity. Now, inorganic compounds that are manufactured in iron vessels may contain iron and arsenic as impurities. #### Packaging Errors - Products of similar appearance (such as tablets of the same shape, size, and color) are sometimes packed in similar containers, which can lead to potential sources of danger. - Improper labeling may also cause major packaging errors. #### Storage Conditions - After preparation, the final product should be stored in an appropriate container, depending upon the nature of the material, batch size, and quantity. - Generally, materials like plastic, iron, stainless steel, and aluminum are used for storage. Improper storage leads to reactions with these materials and contamination of the final product. ## Limit Test - Limit tests are quantitative or semi-quantitative tests designed to identify and control small quantities of impurity present in the substance. - **Limit** refers to the certain or fixed value. - **Test** Refers to examination or investigation. - Limit tests involve small comparisons of opalescence, turbidity, or color with fixed standards. -They are generally carried out in Nessler's cylinders. ### Limit Test In Our Syllabus: - Limit Test of Chloride - Limit Test of Sulphate - Limit Test of Iron - Limit Test of Arsenic - Limit Test of Lead - Limit Test of Heavy Metals ## Limit Test For Chloride: - **Principle:** The principle of the limit test of chloride is based on the reaction of soluble chlorides with silver nitrate in the presence of dilute nitric acid to form silver chloride, which appears as turbidity or opalescence. Cl- + AgNO3 dil-HNO3 AgCl + NO3- - **Why Nitric Acid?** - Nitric acid is added to the solution to make the solution acidic. - It dissolves other impurities. - It provides a common ion effect and helps silver chloride precipitate to make the solution turbid at the end of the process. - **Apparatus Required:** - Nessler's Cylinder - Glass Rod - Stand - **Chemicals Required:** - Dilute Nitric Acid (10%) ( [106 ml conc. HNO3 in 1000 ml Water] ) - Silver Nitrate (5%) ([5g AgNO3 in 100 ml water]) - Sodium Chloride ([0.05845g NaCl in 100 ml water]) - **Procedure:** | Test | Standard| | :---- | :-------- | |Specific amount of substance dissolved in a Nessler's cylinder as directed in the pharmacopoeia| Take 1 ml of 0.05845% w/v solution of NaCl in a Nessler's cylinder| | Add 10 ml dilute HNO3 | Add 10 ml dilute HNO3| | Dilute the solution to 50 ml with water.| Dilute the solution to 50 ml with water| | Add 1 ml silver Nitrate Solution| Add 1 ml silver Nitrate Solution| | Observe the opalescence/turbidity. | Observe the opalescence/turbidity| - **Observation:** - If the turbidity of the test solution is less than the turbidity of the standard solution, the sample will pass the limit test. - If the turbidity of the test solution is greater than the turbidity of the standard solution, the limit test fails. ## Limit Test for Sulphate: - **Principle:** The principle of the limit test of sulphate is based on the reaction of soluble sulphate with barium chloride to form barium sulphate in the presence of dilute hydrochloric acid, which appears as turbidity or opalescence. - **Apparatus Required:** - Nessler's Cylinder - Glass Rod - Stand - **Chemicals Required:** - Dilute Hydrochloric Acid - Standard Potassium Sulphate Solution - Barium Sulphate Reagent - **Preparation:** - Mix together: - 15 ml of 0.5M BaCl2 - 55 ml of H2O - 20 ml of alcohol - 5ml of 0.0181% w/v K2SO4 - Dilute the final mixture to 100 ml. - **Role of HCl:** - HCl provides an acidic medium. - It prevents precipitation of other radicals - **Chemical Reaction:** -2 SO4 + BaCl2 HCl BaSO4 + 2Cl- - **Procedure:** | Test | Standard | | :---- | :-------- | | Dissolve a specific amount of substance in a Nessler's cylinder as directed in the pharmacopoeia | 1 ml of 0.1089% w/v solution of K2SO4 in a Nessler's Cylinder | | Add 2 ml dilute HCl | Add 2 ml dilute HCl | | Dilute the solution to 45 ml with water | Dilute the solution to 45 ml with water | | Add 5 ml barium sulphate reagent | Add 5 ml barium sulphate reagent | | Observe the opalescence | Observe the opalescence | - **Observation:** - If the turbidity of the test solution is less than the turbidity of the standard solution, the sample will pass the limit test. - If the turbidity of the test solution is greater than the turbidity of the standard solution, the limit test fails. ## Limit Test for Iron: - **Principle:** The principle of the limit test of iron is based on the reaction between ferrous ions and thioglycolic acid in the presence of ammonia and citric acid to form ferrous thioglycolate complex which appears as a pale pink to deep reddish-purple color. Fe2+ + 2HSCH2COOH Citric acid → Fe (HSCH2COO)2 + 2H+ Fe2+ + 2 CH2SH CH2SH COO + 2H+ COO Fe CH2SH - **Apparatus Required:** - Nessler's Cylinder - Glass Rod - Stand - **Chemicals Required:** - Standard Iron Solution (Ferric ammonium sulphate) - Iron-free citric acid - Thioglycolic acid - Iron-free ammonia solution - **Role of Reagents:** - Thioglycolic acid: Converts ferric (Fe3+) ions into ferrous (Fe2+) ions. - Ammonia: Provides an alkaline medium - Citric acid: Prevents precipitation of iron with ammonia. - **Procedure:** | Test | Standard | | :---- | :-------- | | Dissolve the specific amount of sample in a Nessler's cylinder as directed in the pharmacopoeia, | Dissolve 2 ml of the standard iron solution in a Nessler's cylinder| | Dilute with 20 ml water | Dilute with 20 ml water | | Add 2 ml iron-free citric acid| Add 2 ml iron-free citric acid| | Add 0.1 ml thioglycolic acid | Add 0.1 ml thioglycolic acid | | Make the solution alkaline with ammonia | Make the solution alkaline with ammonia | | Dilute the solution with 50 ml water and observe.| Dilute the solution to 20 ml with water | - **Observation:** - If the intensity of the color of the test solution is less than the intensity of the color of the standard solution, the sample will pass the limit test. - If the intensity of the color of the test solution is greater than the intensity of the color of the standard solution, the sample fails the limit test. ## Limit Test for Arsenic: - **Principle:** The principle of the limit test for arsenic is based on the fact that arsenic in the arsenious state is easily reduced into Arsine gas, which on reaction with mercuric chloride, gives a yellow stain. 2 AsH3 + HgCl2 → Hg (AsH2)2 + 2HCl - **Apparatus Required:** - Gutzeit Apparatus - Glass Rod - Stand - **Chemicals Required:** - Standard Arsenic Solution - Potassium Iodide - Zinc - Stannous Chloride - Stannated HCl and Lead Acetate - **Role of Reagents:** - Zn / KI / SnCl2: Act as reducing agents - HCl: To make the solution acidic - Lead Acetate: To trap any hydrogen sulphide (if present) - **Procedure:** | Test | Standard | |:------| :--------| | Add a specific amount of test sample along with stannated HCI in a Gutzeit apparatus.| Dissolve the known quantity of standard arsenic solution with HCl in a Gutzeit apparatus.| |Add 1 gm of Potassium Iodide | Add 1 gm of Potassium Iodide | | To this add 5 ml SnCl2 | Add 5 ml stannous chloride| | Now add 10g granulated zinc | Add 10g granulated zinc | | Keep the solution aside for 40 minutes | Keep the solution aside for 40 minutes | - **Observation:** - If the stain produced by the test is less than the stain produced by the standard, the sample will pass the limit test. - If the stain produced by the test is greater than the stain produced by the standard, the sample fails the limit test.