Definition of Impurity
Types of Impurities
Sources of Impurity
foreign unwanted matter present in a compound which are differ from the actual molecular formula.
According to ICH “An impurity in a drug of the new drug substance that is not the substance”.
Chemically a compound is impure if it contains undesirable foreign matter i.e. impurities. Thus chemical purity is freedom from foreign matter
Impurities can have unwanted pharmacological or toxicological effect that seriously impact product quality and patient safety.
The International Conference on Harmonization (ICH) has formulated a workable guideline regarding the control of impurities.
Impurities in pharmaceutical are the unwanted chemicals that remains with the active pharmaceutical ingredient (API’s), or develop during formulation or upon aging of both API and formulated API’s to medicine.
The presence of the unwanted chemicals, even in small amount , may influence the efficacy and safety of pharmaceutical product
Impurities in pharmaceuticals are the unwanted chemicals that remain with the active pharmaceutical ingredients (APIs), or develop during formulation, or upon aging of both API and formulated APIs to medicines.
Impurities in pharmaceuticals are the unwanted chemicals that remain with the active pharmaceutical ingredients (APIs), or develop during formulation, or upon aging of both API and formulated APIs to medicines.
Limit tests, Introduction, Definition,
Limit Test For Chlorides
Limit Test For Sulphates
Limit Test For Iron
Limit Test For Lead
Limit Test For Arsenic
This is chapter No 3 of Pharmaceutical Chemistry - I for Diploma in Pharmacy (D. Pharmacy) Details notes for Diploma in Pharmacy (D.Pharmacy) Students.
Impurities in pharmaceutical substancesShaliniBarad
Impurities definition
Sources of impurities
Effect/ type of impurities
Limit test definition
Limit test Importance,
Principle & procedure of Limit test for iron, chloride, sulphate, arsenic & heavy metals.
What is Pharmaceutical Chemistry
Introduction of Inorganic chemistry
What are Inorganic Compounds ??
Importance of Inorganic Pharmaceuticals Inorganic Chemistry ??
Difference between Organic Chemistry and Inorganic Chemistry
Definitions
Sources and Types of Impurities by Professor BeubenzProfessor Beubenz
Useful for B Pharmacy Students
Subscribe to the YouTube Channel #Professor_Beubenz
https://www.youtube.com/channel/UC84jGf2iRN5VjwnQqi6qmXg?view_as=subscriber
this presentation on limit test for sulphates is very helpful for the diploma and bachelor pharmacy students. this includes principle procedure reaction and observation of limit test.
Limit tests, Introduction, Definition,
Limit Test For Chlorides
Limit Test For Sulphates
Limit Test For Iron
Limit Test For Lead
Limit Test For Arsenic
This is chapter No 3 of Pharmaceutical Chemistry - I for Diploma in Pharmacy (D. Pharmacy) Details notes for Diploma in Pharmacy (D.Pharmacy) Students.
Impurities in pharmaceutical substancesShaliniBarad
Impurities definition
Sources of impurities
Effect/ type of impurities
Limit test definition
Limit test Importance,
Principle & procedure of Limit test for iron, chloride, sulphate, arsenic & heavy metals.
What is Pharmaceutical Chemistry
Introduction of Inorganic chemistry
What are Inorganic Compounds ??
Importance of Inorganic Pharmaceuticals Inorganic Chemistry ??
Difference between Organic Chemistry and Inorganic Chemistry
Definitions
Sources and Types of Impurities by Professor BeubenzProfessor Beubenz
Useful for B Pharmacy Students
Subscribe to the YouTube Channel #Professor_Beubenz
https://www.youtube.com/channel/UC84jGf2iRN5VjwnQqi6qmXg?view_as=subscriber
this presentation on limit test for sulphates is very helpful for the diploma and bachelor pharmacy students. this includes principle procedure reaction and observation of limit test.
Types and Sources of impurities.pptx Pharmaceutical Inorganic chemistry UNIT-...Ms. Pooja Bhandare
Types and Sources of impurities. Pharmaceutical Inorganic chemistry UNIT-I (Part-II) Impurities:
Impure Chemical Compound
Pure Chemical Compound.
Types of impurities: Organic Impurity, Inorganic impurity, Residual solvent, Sources of Impurities in Pharmaceuticals
The different sources of impurities in pharmaceuticals are listed below:
Raw material used in manufacture
Reagents used in manufacturing process
Method/ process used in manufacture or method of manufacturing
Chemical processes used in the manufacture
Atmospheric contamination during the manufacturing process
Intermediate products in the manufacturing process
Defects in the manufacturing process
Manufacturing hazards
Inadequate Storage conditions
Decomposition of the product during storage
Accidental substitution or deliberate adulteration with spurious or useless materials.
Test for purity: Pharmacopoeia prescribes the “Test for purity” for pharmaceutical substances to check their freedom from undesirable impurities.
Pharmacopoeia will decide and fix the limit of tolerance for these impurities.
For certain common impurities for which pharmacopoeia prescribes the test of purity are:
Colour, odour, taste
Physicochemical constants (Iodine value, saponification value, melting point, refractive index etc.)
Acidity, alkalinity, pH
Humidity (Estimation of moisture)
Cations and anions
Insoluble Constituent or Residue.
Ash, Water insoluble ash
Arsenic or lead
Loss on drying
Loss on ignition.
Effect of Impurities
Quality control drugs and pharmaceuticalsSHIVANEE VYAS
The term quality control is the most important in pharmaceutical industries. It is essential that a good quality product should be available to the doctors for treating patient or for the actual users. The term quality is applied to drugs and drug products which contributing directly or indirectly to the purity, safety & effectiveness of the products.
Define Impurities, 3 Types of Impurities, 13 Sources of Impurities - Raw martials, Reagents used, Methods used, Chemical process, Solvent, Atmospheric contamination, Intermediate process, Defect in manufacturing process, Manufacturing hazards, Impurities due to Storage condition, Impurities due to Crystal packing, Decomposition of product, Adulteration.
Sources of impurities, raw materials as a source of impurity, manufacturing methods as a source of impurity, reagents, solvents and reaction vessels as a source of impurity, manufacturing hazards as a source of impurity, physical and chemical stability of pharmaceuticals during storage, the reaction of pharmaceuticals with containers or storage vessels, thermal decomposition of pharmaceuticals, the use of water in the pharmaceutical industry, atmospheric contamination as a source of impurity, intermediate compounds as a source of impurity, cross-contamination of pharmaceutical powders, contamination of drugs by microbes, contamination of pharmaceuticals by particulate matter, errors in the manufacturing process as a source of impurity, storage of pharmaceuticals in amber-colored bottles, storage of drugs in a cool temperature, rubber closures as a source of impurity, natural sources of drugs, animal sources of drugs, plant sources of drugs, microorganism as a source of drugs, minerals as a source of drugs, effect of arsenic in human body, effect of excess of chlorine, iron and sulphate in human body, types of impurity.
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Acids and bases buffers ARRHENIUS CONCEPT
THE LEWIS CONCEPT-THE ELECTRON DONOR ACCEPTOR SYSTEM
BRONSTED-LOWRY CONCEPT (PROTON TRANSFER
THEORY
buffer action
ph scale
buffer capacity
acid base balance
isotonicity method
isotonic soltions
buffer solutions in pharmaceutical preparations
WHAT IS PHARMACOPOEIA?
TYPES OF PHARMACOPOEIA
HISTORY OF PHARMACOPOEIA
CONTENT OF PHARMACOPOEIA
WHAT IS MONOGRAPH?
PURPOSE OF MONOGRAPH
TYPES OF MONOGRAPH
IMPORTANCE OF CONTENT OF MONOGRAPH
MONOGRAPH DEVELOPMENT PROCESS
Recrystallization is the most convenient method for purifying organic compounds that are solids at room temperature.
Compounds obtained from natural sources, or from reaction mixtures, almost always contain impurities.
The impurities may include some combination of insoluble, soluble, and colored impurities. To obtain a pure compound these impurities must be removed.
Each type of impurity is removed in a separate step in the recrystallization procedure.
what is the best method to sell pi coins in 2024DOT TECH
The best way to sell your pi coins safely is trading with an exchange..but since pi is not launched in any exchange, and second option is through a VERIFIED pi merchant.
Who is a pi merchant?
A pi merchant is someone who buys pi coins from miners and pioneers and resell them to Investors looking forward to hold massive amounts before mainnet launch in 2026.
I will leave the telegram contact of my personal pi merchant to trade pi coins with.
@Pi_vendor_247
Currently pi network is not tradable on binance or any other exchange because we are still in the enclosed mainnet.
Right now the only way to sell pi coins is by trading with a verified merchant.
What is a pi merchant?
A pi merchant is someone verified by pi network team and allowed to barter pi coins for goods and services.
Since pi network is not doing any pre-sale The only way exchanges like binance/huobi or crypto whales can get pi is by buying from miners. And a merchant stands in between the exchanges and the miners.
I will leave the telegram contact of my personal pi merchant. I and my friends has traded more than 6000pi coins successfully
Tele-gram
@Pi_vendor_247
when will pi network coin be available on crypto exchange.DOT TECH
There is no set date for when Pi coins will enter the market.
However, the developers are working hard to get them released as soon as possible.
Once they are available, users will be able to exchange other cryptocurrencies for Pi coins on designated exchanges.
But for now the only way to sell your pi coins is through verified pi vendor.
Here is the telegram contact of my personal pi vendor
@Pi_vendor_247
Poonawalla Fincorp and IndusInd Bank Introduce New Co-Branded Credit Cardnickysharmasucks
The unveiling of the IndusInd Bank Poonawalla Fincorp eLITE RuPay Platinum Credit Card marks a notable milestone in the Indian financial landscape, showcasing a successful partnership between two leading institutions, Poonawalla Fincorp and IndusInd Bank. This co-branded credit card not only offers users a plethora of benefits but also reflects a commitment to innovation and adaptation. With a focus on providing value-driven and customer-centric solutions, this launch represents more than just a new product—it signifies a step towards redefining the banking experience for millions. Promising convenience, rewards, and a touch of luxury in everyday financial transactions, this collaboration aims to cater to the evolving needs of customers and set new standards in the industry.
The European Unemployment Puzzle: implications from population agingGRAPE
We study the link between the evolving age structure of the working population and unemployment. We build a large new Keynesian OLG model with a realistic age structure, labor market frictions, sticky prices, and aggregate shocks. Once calibrated to the European economy, we quantify the extent to which demographic changes over the last three decades have contributed to the decline of the unemployment rate. Our findings yield important implications for the future evolution of unemployment given the anticipated further aging of the working population in Europe. We also quantify the implications for optimal monetary policy: lowering inflation volatility becomes less costly in terms of GDP and unemployment volatility, which hints that optimal monetary policy may be more hawkish in an aging society. Finally, our results also propose a partial reversal of the European-US unemployment puzzle due to the fact that the share of young workers is expected to remain robust in the US.
how to sell pi coins at high rate quickly.DOT TECH
Where can I sell my pi coins at a high rate.
Pi is not launched yet on any exchange. But one can easily sell his or her pi coins to investors who want to hold pi till mainnet launch.
This means crypto whales want to hold pi. And you can get a good rate for selling pi to them. I will leave the telegram contact of my personal pi vendor below.
A vendor is someone who buys from a miner and resell it to a holder or crypto whale.
Here is the telegram contact of my vendor:
@Pi_vendor_247
If you are looking for a pi coin investor. Then look no further because I have the right one he is a pi vendor (he buy and resell to whales in China). I met him on a crypto conference and ever since I and my friends have sold more than 10k pi coins to him And he bought all and still want more. I will drop his telegram handle below just send him a message.
@Pi_vendor_247
Falcon stands out as a top-tier P2P Invoice Discounting platform in India, bridging esteemed blue-chip companies and eager investors. Our goal is to transform the investment landscape in India by establishing a comprehensive destination for borrowers and investors with diverse profiles and needs, all while minimizing risk. What sets Falcon apart is the elimination of intermediaries such as commercial banks and depository institutions, allowing investors to enjoy higher yields.
Exploring Abhay Bhutada’s Views After Poonawalla Fincorp’s Collaboration With...beulahfernandes8
The financial landscape in India has witnessed a significant development with the recent collaboration between Poonawalla Fincorp and IndusInd Bank.
The launch of the co-branded credit card, the IndusInd Bank Poonawalla Fincorp eLITE RuPay Platinum Credit Card, marks a major milestone for both entities.
This strategic move aims to redefine and elevate the banking experience for customers.
how to sell pi coins effectively (from 50 - 100k pi)DOT TECH
Anywhere in the world, including Africa, America, and Europe, you can sell Pi Network Coins online and receive cash through online payment options.
Pi has not yet been launched on any exchange because we are currently using the confined Mainnet. The planned launch date for Pi is June 28, 2026.
Reselling to investors who want to hold until the mainnet launch in 2026 is currently the sole way to sell.
Consequently, right now. All you need to do is select the right pi network provider.
Who is a pi merchant?
An individual who buys coins from miners on the pi network and resells them to investors hoping to hang onto them until the mainnet is launched is known as a pi merchant.
debuts.
I'll provide you the Telegram username
@Pi_vendor_247
BYD SWOT Analysis and In-Depth Insights 2024.pptxmikemetalprod
Indepth analysis of the BYD 2024
BYD (Build Your Dreams) is a Chinese automaker and battery manufacturer that has snowballed over the past two decades to become a significant player in electric vehicles and global clean energy technology.
This SWOT analysis examines BYD's strengths, weaknesses, opportunities, and threats as it competes in the fast-changing automotive and energy storage industries.
Founded in 1995 and headquartered in Shenzhen, BYD started as a battery company before expanding into automobiles in the early 2000s.
Initially manufacturing gasoline-powered vehicles, BYD focused on plug-in hybrid and fully electric vehicles, leveraging its expertise in battery technology.
Today, BYD is the world’s largest electric vehicle manufacturer, delivering over 1.2 million electric cars globally. The company also produces electric buses, trucks, forklifts, and rail transit.
On the energy side, BYD is a major supplier of rechargeable batteries for cell phones, laptops, electric vehicles, and energy storage systems.
what is the future of Pi Network currency.DOT TECH
The future of the Pi cryptocurrency is uncertain, and its success will depend on several factors. Pi is a relatively new cryptocurrency that aims to be user-friendly and accessible to a wide audience. Here are a few key considerations for its future:
Message: @Pi_vendor_247 on telegram if u want to sell PI COINS.
1. Mainnet Launch: As of my last knowledge update in January 2022, Pi was still in the testnet phase. Its success will depend on a successful transition to a mainnet, where actual transactions can take place.
2. User Adoption: Pi's success will be closely tied to user adoption. The more users who join the network and actively participate, the stronger the ecosystem can become.
3. Utility and Use Cases: For a cryptocurrency to thrive, it must offer utility and practical use cases. The Pi team has talked about various applications, including peer-to-peer transactions, smart contracts, and more. The development and implementation of these features will be essential.
4. Regulatory Environment: The regulatory environment for cryptocurrencies is evolving globally. How Pi navigates and complies with regulations in various jurisdictions will significantly impact its future.
5. Technology Development: The Pi network must continue to develop and improve its technology, security, and scalability to compete with established cryptocurrencies.
6. Community Engagement: The Pi community plays a critical role in its future. Engaged users can help build trust and grow the network.
7. Monetization and Sustainability: The Pi team's monetization strategy, such as fees, partnerships, or other revenue sources, will affect its long-term sustainability.
It's essential to approach Pi or any new cryptocurrency with caution and conduct due diligence. Cryptocurrency investments involve risks, and potential rewards can be uncertain. The success and future of Pi will depend on the collective efforts of its team, community, and the broader cryptocurrency market dynamics. It's advisable to stay updated on Pi's development and follow any updates from the official Pi Network website or announcements from the team.
What website can I sell pi coins securely.DOT TECH
Currently there are no website or exchange that allow buying or selling of pi coins..
But you can still easily sell pi coins, by reselling it to exchanges/crypto whales interested in holding thousands of pi coins before the mainnet launch.
Who is a pi merchant?
A pi merchant is someone who buys pi coins from miners and resell to these crypto whales and holders of pi..
This is because pi network is not doing any pre-sale. The only way exchanges can get pi is by buying from miners and pi merchants stands in between the miners and the exchanges.
How can I sell my pi coins?
Selling pi coins is really easy, but first you need to migrate to mainnet wallet before you can do that. I will leave the telegram contact of my personal pi merchant to trade with.
Tele-gram.
@Pi_vendor_247
Introduction to Indian Financial System ()Avanish Goel
The financial system of a country is an important tool for economic development of the country, as it helps in creation of wealth by linking savings with investments.
It facilitates the flow of funds form the households (savers) to business firms (investors) to aid in wealth creation and development of both the parties
3. A foreign unwanted matter present in a compound which are differ from the
actual molecular formula.
According to ICH “An impurity in a drug of the new drug substance that is not the
substance”.
Chemically a compound is impure if it contains undesirable foreign matter i.e.
impurities. Thus chemical purity is freedom from foreign matter
Definition of Impurity
4. What is Impurities..........?
Impurities can have unwanted pharmacological or toxicological effect that seriously
impact product quality and patient safety.
The International Conference on Harmonization (ICH) has formulated a workable
guideline regarding the control of impurities.
Impurities in pharmaceutical are the unwanted chemicals that remains with the active
pharmaceutical ingredient (API’s), or develop during formulation or upon aging of both
API and formulated API’s to medicine.
The presence of the unwanted chemicals, even in small amount , may influence the
efficacy and safety of pharmaceutical product
5. Impure Chemical Compound:
A compound is said to be impure if it is having foreign matter i.e Impurities.
Pure Chemical Compound:
A pure chemical compound refers to that compound which is having no foreign matter i.e. impurities.
Chemical purity means freedom from foreign matter.
Analytically 100 % pure substances are not available and traces of impurities must be
present.
Normally undesirable foreign materials are present in the pharmaceutical
substances.
6. Impuritiescommonlyfoundinmedicinalpreparations:
Impurities which have toxic effects on body and bring about unpleasant reactions when
present beyond certain limits. e.g. Lead and Arsenic salts.
The impurities which are able to make substance incompatible with other substances.
The impurities which if present beyond the limit, affect the storage property of the
pharmaceuticals.
The impurities which are harmless, but if present beyond the limit, it will lower the active
strength of the medicinal compound. E.g. Sodium salt in potassium salt.
The impurities which may bring about technical difficulties in the use of the substance.
Impurities such as taste, odour, color or appearance which can be easily detected by the senses
and make the substance unhygienic and unaesthetic. E.g. Sodium chloride becomes damp
because of the presence of traces of magnesium salts. Also phenolic impurities present in
sodium salicylate alters its odour.
7. Sources of Impurities:
Source of
Impurities
Raw
Materials Method of
Manufacturing
Reagents Used
Intermediate Products
Reagents used to
eliminate impurity
Solvents Used
Atmospheric
Contamination
Manufacturing Hazards
Contamination from
Matter
Cross Contamination
Contamination by
Microbes
Errors in Manufacturing
Errors in Storage &
Packaging
Instability of
Products
Chemical
Instabilities
Physical
Instabilities
Reaction with
Container
Temperature
8. Sources of Impurities in Pharmaceuticals
The type and amount of impurity present in the chemicals or pharmaceutical substances, depends
upon several factors like those listed below:
6) Intermediate products in the manufacturing
process
7) Defects in the manufacturing process
8) Manufacturing hazards
9) Inadequate Storage conditions
10) Decomposition of the product during storage
11) Accidental substitution or deliberate
adulteration with spurious or useless materials
1) Raw material used in manufacture
2) Reagents used in manufacturing process
3) Method/ process used in manufacture or
method of manufacturing
4) Chemical processes used in the manufacture
5) Atmospheric contamination during the
manufacturing process
9. Impurities known to be associated with these chemicals may be carried through the manufacturing
process and contaminate the final product.
Example
Rock salt--------à Calcium Sulphate (CaSO4) + Magnesium Chloride (MgCl2)= NaCl prepared
Rock salt contains small amounts of Calcium sulphate and Magnesium chloride.
Thus Sodium chloride prepared from this source will contain traces of Calcium and Magnesium
compounds.
Impurities such as Arsenic, Lead and Heavy metals are present in raw materials and hence are found
in substances. So, it is necessary to use pure chemicals and substances as raw materials for the
manufacturing process.
1. Rawmaterials employedin manufacture
10. Example:
Copper sulphate may be prepared by the action of sulphuric acid on copper
turnings:
Cu+ 2 H2SO4------------------------CuSO4 + 2 H2O + SO2
Copper turnings are known to have Iron and Arsenic as impurities.
If Large quantities of impurities are present in the raw material (e.g. Copper
turnings), they may enter the final product. (CuSO4.5H2O) Due to this I.P.
prescribes limit of tolerance for Arsenic as impurity to be not more than 8 parts per
million in copper sulphate. Similarly it prescribes a limit of Iron as impurity.
11. If reagents used in the manufacturing process are not completely removed by washing,
these may find entry into the final products.
Example:
Ammoniated mercury may be prepared by adding a solution of Mercuric chloride to dilute
ammonia solution.
HgCl2+ 2NH4OH-------------NH2HgCl + NH4Cl + 2 H2O
Soluble Soluble Ammoniated mercury (ppt) (soluble)
The precipitate of Ammoniated mercury (Final Product)contains ammonium hydroxide.
Thus, this precipitate is washed with cold water to remove ammonium hydroxide.
If it is not removed completely by washing with water, the final product may contain in it
Ammonium hydroxide as impurity.
2) Reagents used in the manufacturingprocess:
12. Many drugs and chemicals (usually organic) are manufactured from different raw
materials, by using different methods or processes.
Some impurities are incorporated into the materials during the manufacturing process.
The type and amount of impurity present in the drug/ chemical varies.
In certain drugs , a multiple-step-synthesis procedure is used , which produces
intermediate compounds.
The purification of intermediates is also important, otherwise the impurities present in the
intermediate will get incorporated in the final product.
Usually side reactions occur during the synthesis.
3) Method or the process usedin the manufacture:
13. Impurities of the product side reactions also occur in the substances. This may
introduce new impurities due to contamination by reagents and solvents at various
stages of the process as described below:
a) Reagents employed in the process
b) b) Reagents added to remove other impurities
c) Solvents
d) Action of solvents and reagents on reaction vessels
3) Method or the process usedin the manufacture:
14. a) Reagents employed in the manufacturing process:
Soluble alkali in Calcium carbonate arises from sodium carbonate used in the process.
Calcium carbonate is obtained by interaction of a soluble calcium salt and a soluble
carbonate and therefore the product will contain traces of soluble alkali, which the
washing process has failed to remove.
b) Reagents added to remove other impurities:
Potassium bromide contains traces of Barium, which is added in the manufacturing
process to remove excess of sulphate.
15. C) Solvents:
Water is the cheapest solvent available and has been used wherever possible.
Tap Water It has Ca+2, Mg+2, Na+, Cl-, SO4-2 and CO3-2 as impurities in
small amounts
Softened water It is obtained by allowing the tap water to pass through the
sodium form of Zeolite which removes divalent cations like Ca+2
and Mg+2 from tap water in exchange of sodium.
So, softened water contains Na+, Cl- ions as impurity.
De-mineralised
water
It is obtained by passing tap water through columns packed with
ion exchange resin. The water obtained from this process is free
from Ca+2, Mg+2, Na+, Cl-, SO4-2 and CO3-2 Thus the final
product is free from these impurities.
Distilled water It is considered the best but it is very costly.
16. During manufacturing process, some of the solvents and reagent may undergo reaction
with metals of reaction vessel and may dissolve these metals, which appear as
impurities in the final product.
Example:
Iron is known to contain Arsenic impurity.
The inorganic compounds manufactured in Iron vessel will contain Arsenic and Iron
as impurities.
Thus IP has prescribed limit test for Arsenic and Iron for most inorganic compounds.
d) Action of solvents and reagents on reaction vessels:
17. For the synthesis of drugs, many chemical reactions such as Nitration, Halogenation,
Oxidation, reduction, hydrolysis are involved.
In these chemical processes, different chemicals are used.
Tap water is generally used in the various processes and it is often having Cl-,Mg+2,
Ca+2 ions, which are generally found in the substance which is being manufactured.
4) Chemical process usedin the manufacture:
18. In the industrial areas, the atmosphere is contaminated with dust particles and
some gases like Hydrogen sulphide, Sulphur dioxide, and black smoke.
During the manufacture or purification of the pharmaceutical products, these impurities enter
the final products.
There are many pharmaceutical products which when manufactured are contaminated with
atmospheric CO2 and water vapour. E.g. NaOH absorbs atmospheric CO2.
2NaOH + CO2 --------------------------------Na2CO3 + H2O
Due to this reaction, NaOH should not be kept open for a longer time during its manufacture.
Therefore, IP has prescribed that Sodium hydroxide should not contain more than 3% of
sodium carbonate.
5) Atmospheric contamination duringthe manufacturingprocess
19. In many manufacturing processes, there are defects like imperfect mixing,
incompleteness, non-adherence to proper temperature, pressure, pH or reaction
conditions, which may give chemical compounds with impurities in them.
Example:
Zinc oxide may be prepared by heating metallic zinc to bright redness in a current of air.
The vapours of Zinc burn to form Zinc oxide which is collected as a fine white powder. But if
there is less heat or air or both, zinc metal is not completely converted to zinc oxide.
Thus the final product, Zinc oxide may still contain metallic zinc as impurity.
So, IP has prescribed a test for Zinc metal in zinc oxide.
6) Defectsin the manufacturing process:
20. There are some intermediates which are produced during the manufacturing process.
Sometimes these intermediates may be carried through to the final product as impurity.
Example:
Potassium iodide is prepared by reacting Iodine with Potassium hydroxide.
6KOH+ 3I2--------------------5KI + KIO3 + 3H2O
The resulting solution is first evaporated and then heated with charcoal.
KIO3 + 3C----------KI + 3CO
In this process if the intermediate product (KIO3) is not completely converted into KI, then
it may be carried through to the final product as an impurity.
7) Intermediateproducts in the manufacturingprocess:
21. a) Particulate contamination
b) Process errors
c) Cross contamination
d) Microbial contamination
e) Packing errors
8) Manufacturing hazards:
22. The presence of unwanted particulate matter can arise due to dirt, dust, glass,
porcelain or plastic fragments from sieves, granulating or tableting machines or
from product containers.
Ware and tare of equipment or improperly cleaned equipment may also cause
particulate contamination.
Clarity of solutions for injection is particularly important.
E.g. Metal particles which have been found in eye ointments packed in metal
tubes.
a) Particulate contamination:
23. Gross errors arising from incomplete solution of a solute in a liquid preparation must
be detected readily by the normal analytical control procedures.
Minor errors arise if the manufacturing tolerance for the quantity of active ingredient
in the product has been wide.
b) Process errors:
c) Cross contamination:
The handling of powders, granules, and tablets in large bulk creates air-borne dust,
which leads to cross contamination of the product.
So, face masks and special extraction equipment are used to protect operators from
harmful effects of drugs.
E.g. penicillin preparation requires special handling during its manufacture.
24. d)Microbial contamination:
Parenteral preparations and ophthalmic preparations require special care against
microbial contamination. Many liquid preparations and creams are liable to bacterial and fungal
contamination. So care should be taken.
E.g. Acacia, senna, tragacanth---à They should be controlled for Salmonellae.
e)Packing errors:
Products of similar appearance such as tablets of same size, shape, colour packed in similar
containers can constitute a potential source of danger. Improper labelling or destruction of
stock of unused labels also constitutes a major packaging hazard.
25. 9) Storage conditions:
The chemical substances when prepared have to be stored in different types of containers depending
upon:
Nature of the material
Batch size
Quantity
Many types of materials are used for storage purpose like plastic, polythene, iron vessels, stainless
steel and aluminum.Reaction of these substances
Leaching out effect: Alkalis stored in ordinary glass containers extract lead from it, which in found
as impurity in the final product.
Strong chemicals react with iron containers and extract Iron an impurity in final product.
Reaction of
these substances
With materials
of storage
vessels
The products
formed are found as
impurities in the
stored materials
26. Inadequate storage and their effects are as follows:
a) Filth: Stored products may become contaminated with dust, bodies of insects, animal and
insect excreta.
b) Chemical instability: decomposition because of light, traces of acid or alkali, air
oxidation, water vapour, CO2 and traces of metallic ions. e.g. light sensitive materials should be
stored in amber colored bottles.
c) Reactions with container materials: e.g. salicylic acid ointment must not be stored in
metal tubes.
d) Physical changes: The occurrence of changes in the physical form of drug like change in
crystal size can lead to change in efficiency of product.
e) Temperature effect: Chemical and physical changes occur if materials are not stored at
proper temperature.
27. Chemical decomposition, analysis or breakdown is the separation of a chemical
compound into elements or simpler compounds. It is sometimes defined as the exact opposite of a
chemical synthesis. Chemical decomposition is often an undesired chemical
reaction.
Some substances decompose on storing due to presence of air, light and oxygen. So, the
final product is contaminated.
Deliquescent substances, absorb water from the atmosphere and get liquefied.
Decomposition products appear as impurities in the substances.
10) Decomposition of the product during storage:
28. It is possible to avoid accidental substitution by storing the toxic substances
together separately or in a locked cupboard.
Many pharmaceutical chemicals are adulterated with cheaper substances.
E.g. The expensive potassium may be adulterated with sodium bromide.
11) Accidental substitutionor deliberateadulterationwithspuriousor useless materials:
29. The impurities present in the substances may give following effects:
Impurities having toxic effects may be injurious to health, if present above certain
limits.
Traces of impurities, may exert a cumulative toxic effect after a certain time.
Impurities may lower the active strength of the substance.
Impurity may decrease shelf life of substance.
Impurity may cause incompatibility with other substances.
Impurities may cause a physical or chemical change in the properties of the
substance, so making the substance medicinally useless.
May cause change in color, odour and taste.
Effect of Impurities:
30. Pharmacopoeia prescribes the “Test for purity” for pharmaceutical substances to
check their freedom from undesirable impurities.
Pharmacopoeia will decide and fix the limit of tolerance for these impurities.
For certain common impurities for which pharmacopoeia prescribes the test of
purity are:
Colour, odour, taste
Physicochemical constants (Iodine value, saponification value, melting point,
refractive index etc.)
Acidity, alkalinity, pH
Humidity (Estimation of moisture)
Cations and anions
Ash
Arsenic or lead
Loss on drying
Loss on ignition
Test for purity: