The impurities in drug products can be attributed not only to the drug substance or inert ingredients used for formulating a drug product; but they can also be brought into the drug product through the formulation process or by contact with packaging of the various impurities that can be found in drug products.

1. The impurities in drug products can be attributed not only to the drug substance or inert ingredients used for formulating a drug product; but they can also be brought into th
“Any component of the drug product that is not the chemical entity defined as the drug substance or an excipient in the drug product.” (ICH Q6A: Specifications). It is impo
Different Types of Impurities in Pharmaceuticals
Organic Impurities
Organic impurities are often process-related or drug-related pharmaceutical impurities. These types of contaminants are most likely to arise during the synthesis, purification, and storage of the drug substance. O
Inorganic Impurities
Inorganic impurities often derive from the manufacturing process. These impurities are often reagents, ligands, catalysts, heavy or residual metals, inorganic salts, filter aids, or charcoals. Inorganic contaminants
Residual Solvents
The third type of impurity in pharmaceuticals is residual solvents. These impurities are residuals of solvents present in the manufacturing process. Solvents used in pharmaceutical manufacturing are defined by t
The three different types of impurities in pharmaceuticals include organic, inorganic, and residual solvents. Most of these impurities occur due to manufacturing processes, degradation, storage conditions, excipie
Abstract
Various regulatory authorities such as the International Conference on Harmonization (ICH), the United States Food and Drug administration (FDA), an
DEFINITION OF IMPURITIES IN PHARMACEUTICALS
An impurity is considered as any inorganic or organic material or residual solvents other than the drug substance or ingredients that arise out of synthesis or unwanted chem
Impurities that are genotoxic at trace levels are also of great concern due to human carcinogen and their detection at trace levels are of increasing concern in pharmaceutica
Health risks in pharmaceutical products
The effect of elemental impurities in drug substances and drug products may arise from several different sources like residual catalysts that were added intentionally in synt
Summarizing the effects of impurities
We know that to get almost pure substances is very difficult and some traces of impurities are always present. So the impurities present in the substances may have the follo
•Impurities may bring about incompatibility with other substances.
•Impurities may lower the shelf life of the substances.
•Impurities may cause difficulties during formulation and the use of the substances.
•Sometimes impurities change the physical and chemical properties of the substances.
•The therapeutic effect can be decreased.
•Shows the toxic effect after a certain period.
•Injurious when present above certain limits.
•It may change the odor, color, the taste of the substance.
•It may affect its potency if the compounds have foreign matter or impurities.
Effects of Impurities in Pharmaceuticals
Sources of Impuries in Pharmaceucal
The root of impuries in drugs is from various sources and phases of the synthec process and development of pharmaceucal dosage forms. Bulk of the impuries are character
According to the ICH impuries are labeled as organic impuries, inorganic impuries and residual solvents
SOURCES OF IMPURITY IN MEDICINES
According to the International Conference on Harmonization (ICH) guidelines, impurities associated with APIs are classified in different ways.
Organic Impurities
Organic impurities are the most common impurities found in every API unless proper care is taken in every step involved, throughout the multi-step sy
Figure 2
Production of paracetamol from intermediate, p-Amin-ophenol
Oxidative degradation
Hydrocortisone, methotrexate, adinazolam, hydroxyl group directly bonded to an aromatic ring (e.g., phenol derivatives such as catecholamines and mo
Decarboxylation
Some dissolved carboxylic acids, such as p-aminosalicylic acid, lose carbon dioxide from the carboxyl group when heated, in the case of photoreaction o
Hydrolysis
Hydrolysis is a common phenomenon for the ester type of drugs, especially in liquid dosage forms. Examples include benzyl penicillin, barbitol, chloram
Figure 3
Ester hydrolysis of benzocaine
pharmaceutical drug candidates. Part 1. Amer.
Pharm. Review. 2001; 4(1): 70-78
REFERENCES
1. Ah uja Satin de r. Im purit ies Ev aluat io n of
Pharmaceuticals. New York: Marcel Dekker; 1998.
2. a) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Substances. Q3A®. Federal Register. 2000; 65(140):
45085-45090.
b) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Products. Q3B®. Federal Register. 2000; 65(139):
44791-44797.
c) International Conferences on Harmonization,
Impurities—Guidelines for residual solvents. Q3C.

2. The impurities in drug products can be attributed not only to the drug substance or inert ingredients used for formulating a drug product; but they can also be brought into th
“Any component of the drug product that is not the chemical entity defined as the drug substance or an excipient in the drug product.” (ICH Q6A: Specifications). It is impo
Different Types of Impurities in Pharmaceuticals
Organic Impurities
Organic impurities are often process-related or drug-related pharmaceutical impurities. These types of contaminants are most likely to arise during the synthesis, purification, and storage of the drug substance. O
Inorganic Impurities
Inorganic impurities often derive from the manufacturing process. These impurities are often reagents, ligands, catalysts, heavy or residual metals, inorganic salts, filter aids, or charcoals. Inorganic contaminants
Residual Solvents
The third type of impurity in pharmaceuticals is residual solvents. These impurities are residuals of solvents present in the manufacturing process. Solvents used in pharmaceutical manufacturing are defined by t
The three different types of impurities in pharmaceuticals include organic, inorganic, and residual solvents. Most of these impurities occur due to manufacturing processes, degradation, storage conditions, excipie
Abstract
Various regulatory authorities such as the International Conference on Harmonization (ICH), the United States Food and Drug administration (FDA), an
DEFINITION OF IMPURITIES IN PHARMACEUTICALS
An impurity is considered as any inorganic or organic material or residual solvents other than the drug substance or ingredients that arise out of synthesis or unwanted chem
Impurities that are genotoxic at trace levels are also of great concern due to human carcinogen and their detection at trace levels are of increasing concern in pharmaceutica
Health risks in pharmaceutical products
The effect of elemental impurities in drug substances and drug products may arise from several different sources like residual catalysts that were added intentionally in synt
Summarizing the effects of impurities
We know that to get almost pure substances is very difficult and some traces of impurities are always present. So the impurities present in the substances may have the follo
•Impurities may bring about incompatibility with other substances.
•Impurities may lower the shelf life of the substances.
•Impurities may cause difficulties during formulation and the use of the substances.
•Sometimes impurities change the physical and chemical properties of the substances.
•The therapeutic effect can be decreased.
•Shows the toxic effect after a certain period.
•Injurious when present above certain limits.
•It may change the odor, color, the taste of the substance.
•It may affect its potency if the compounds have foreign matter or impurities.
Effects of Impurities in Pharmaceuticals
Sources of Impuries in Pharmaceucal
The root of impuries in drugs is from various sources and phases of the synthec process and development of pharmaceucal dosage forms. Bulk of the impuries are character
According to the ICH impuries are labeled as organic impuries, inorganic impuries and residual solvents
SOURCES OF IMPURITY IN MEDICINES
According to the International Conference on Harmonization (ICH) guidelines, impurities associated with APIs are classified in different ways.
Organic Impurities
Organic impurities are the most common impurities found in every API unless proper care is taken in every step involved, throughout the multi-step sy
Figure 2
Production of paracetamol from intermediate, p-Amin-ophenol
Oxidative degradation
Hydrocortisone, methotrexate, adinazolam, hydroxyl group directly bonded to an aromatic ring (e.g., phenol derivatives such as catecholamines and mo
Decarboxylation
Some dissolved carboxylic acids, such as p-aminosalicylic acid, lose carbon dioxide from the carboxyl group when heated, in the case of photoreaction o
Hydrolysis
Hydrolysis is a common phenomenon for the ester type of drugs, especially in liquid dosage forms. Examples include benzyl penicillin, barbitol, chloram
Figure 3
Ester hydrolysis of benzocaine
pharmaceutical drug candidates. Part 1. Amer.
Pharm. Review. 2001; 4(1): 70-78
REFERENCES
1. Ah uja Satin de r. Im purit ies Ev aluat io n of
Pharmaceuticals. New York: Marcel Dekker; 1998.
2. a) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Substances. Q3A®. Federal Register. 2000; 65(140):
45085-45090.
b) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Products. Q3B®. Federal Register. 2000; 65(139):
44791-44797.
c) International Conferences on Harmonization,
Impurities—Guidelines for residual solvents. Q3C.

4. The impurities in drug products can be attributed not only to the drug substance or inert ingredients used for formulating a drug product; but they can also be brought into th
“Any component of the drug product that is not the chemical entity defined as the drug substance or an excipient in the drug product.” (ICH Q6A: Specifications). It is impo
Different Types of Impurities in Pharmaceuticals
Organic Impurities
Organic impurities are often process-related or drug-related pharmaceutical impurities. These types of contaminants are most likely to arise during the synthesis, purification, and storage of the drug substance. O
Inorganic Impurities
Inorganic impurities often derive from the manufacturing process. These impurities are often reagents, ligands, catalysts, heavy or residual metals, inorganic salts, filter aids, or charcoals. Inorganic contaminants
Residual Solvents
The third type of impurity in pharmaceuticals is residual solvents. These impurities are residuals of solvents present in the manufacturing process. Solvents used in pharmaceutical manufacturing are defined by t
The three different types of impurities in pharmaceuticals include organic, inorganic, and residual solvents. Most of these impurities occur due to manufacturing processes, degradation, storage conditions, excipie
Abstract
Various regulatory authorities such as the International Conference on Harmonization (ICH), the United States Food and Drug administration (FDA), an
DEFINITION OF IMPURITIES IN PHARMACEUTICALS
An impurity is considered as any inorganic or organic material or residual solvents other than the drug substance or ingredients that arise out of synthesis or unwanted chem
Impurities that are genotoxic at trace levels are also of great concern due to human carcinogen and their detection at trace levels are of increasing concern in pharmaceutica
Health risks in pharmaceutical products
The effect of elemental impurities in drug substances and drug products may arise from several different sources like residual catalysts that were added intentionally in synt
Summarizing the effects of impurities
We know that to get almost pure substances is very difficult and some traces of impurities are always present. So the impurities present in the substances may have the follo
•Impurities may bring about incompatibility with other substances.
•Impurities may lower the shelf life of the substances.
•Impurities may cause difficulties during formulation and the use of the substances.
•Sometimes impurities change the physical and chemical properties of the substances.
•The therapeutic effect can be decreased.
•Shows the toxic effect after a certain period.
•Injurious when present above certain limits.
•It may change the odor, color, the taste of the substance.
•It may affect its potency if the compounds have foreign matter or impurities.
Effects of Impurities in Pharmaceuticals
Sources of Impuries in Pharmaceucal
The root of impuries in drugs is from various sources and phases of the synthec process and development of pharmaceucal dosage forms. Bulk of the impuries are character
According to the ICH impuries are labeled as organic impuries, inorganic impuries and residual solvents
SOURCES OF IMPURITY IN MEDICINES
According to the International Conference on Harmonization (ICH) guidelines, impurities associated with APIs are classified in different ways.
Organic Impurities
Organic impurities are the most common impurities found in every API unless proper care is taken in every step involved, throughout the multi-step sy
Figure 2
Production of paracetamol from intermediate, p-Amin-ophenol
Oxidative degradation
Hydrocortisone, methotrexate, adinazolam, hydroxyl group directly bonded to an aromatic ring (e.g., phenol derivatives such as catecholamines and mo
Decarboxylation
Some dissolved carboxylic acids, such as p-aminosalicylic acid, lose carbon dioxide from the carboxyl group when heated, in the case of photoreaction o
Hydrolysis
Hydrolysis is a common phenomenon for the ester type of drugs, especially in liquid dosage forms. Examples include benzyl penicillin, barbitol, chloram
Figure 3
Ester hydrolysis of benzocaine
pharmaceutical drug candidates. Part 1. Amer.
Pharm. Review. 2001; 4(1): 70-78
REFERENCES
1. Ah uja Satin de r. Im purit ies Ev aluat io n of
Pharmaceuticals. New York: Marcel Dekker; 1998.
2. a) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Substances. Q3A®. Federal Register. 2000; 65(140):
45085-45090.
b) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Products. Q3B®. Federal Register. 2000; 65(139):
44791-44797.
c) International Conferences on Harmonization,
Impurities—Guidelines for residual solvents. Q3C.

25. The impurities in drug products can be attributed not only to the drug substance or inert ingredients used for formulating a drug product; but they can also be brought into th
“Any component of the drug product that is not the chemical entity defined as the drug substance or an excipient in the drug product.” (ICH Q6A: Specifications). It is impo
Different Types of Impurities in Pharmaceuticals
Organic Impurities
Organic impurities are often process-related or drug-related pharmaceutical impurities. These types of contaminants are most likely to arise during the synthesis, purification, and storage of the drug substance. O
Inorganic Impurities
Inorganic impurities often derive from the manufacturing process. These impurities are often reagents, ligands, catalysts, heavy or residual metals, inorganic salts, filter aids, or charcoals. Inorganic contaminants
Residual Solvents
The third type of impurity in pharmaceuticals is residual solvents. These impurities are residuals of solvents present in the manufacturing process. Solvents used in pharmaceutical manufacturing are defined by t
The three different types of impurities in pharmaceuticals include organic, inorganic, and residual solvents. Most of these impurities occur due to manufacturing processes, degradation, storage conditions, excipie
Abstract
Various regulatory authorities such as the International Conference on Harmonization (ICH), the United States Food and Drug administration (FDA), an
DEFINITION OF IMPURITIES IN PHARMACEUTICALS
An impurity is considered as any inorganic or organic material or residual solvents other than the drug substance or ingredients that arise out of synthesis or unwanted chem
Impurities that are genotoxic at trace levels are also of great concern due to human carcinogen and their detection at trace levels are of increasing concern in pharmaceutica
Health risks in pharmaceutical products
The effect of elemental impurities in drug substances and drug products may arise from several different sources like residual catalysts that were added intentionally in synt
Summarizing the effects of impurities
We know that to get almost pure substances is very difficult and some traces of impurities are always present. So the impurities present in the substances may have the follo
•Impurities may bring about incompatibility with other substances.
•Impurities may lower the shelf life of the substances.
•Impurities may cause difficulties during formulation and the use of the substances.
•Sometimes impurities change the physical and chemical properties of the substances.
•The therapeutic effect can be decreased.
•Shows the toxic effect after a certain period.
•Injurious when present above certain limits.
•It may change the odor, color, the taste of the substance.
•It may affect its potency if the compounds have foreign matter or impurities.
Effects of Impurities in Pharmaceuticals
Sources of Impuries in Pharmaceucal
The root of impuries in drugs is from various sources and phases of the synthec process and development of pharmaceucal dosage forms. Bulk of the impuries are character
According to the ICH impuries are labeled as organic impuries, inorganic impuries and residual solvents
SOURCES OF IMPURITY IN MEDICINES
According to the International Conference on Harmonization (ICH) guidelines, impurities associated with APIs are classified in different ways.
Organic Impurities
Organic impurities are the most common impurities found in every API unless proper care is taken in every step involved, throughout the multi-step sy
Figure 2
Production of paracetamol from intermediate, p-Amin-ophenol
Oxidative degradation
Hydrocortisone, methotrexate, adinazolam, hydroxyl group directly bonded to an aromatic ring (e.g., phenol derivatives such as catecholamines and mo
Decarboxylation
Some dissolved carboxylic acids, such as p-aminosalicylic acid, lose carbon dioxide from the carboxyl group when heated, in the case of photoreaction o
Hydrolysis
Hydrolysis is a common phenomenon for the ester type of drugs, especially in liquid dosage forms. Examples include benzyl penicillin, barbitol, chloram
Figure 3
Ester hydrolysis of benzocaine
pharmaceutical drug candidates. Part 1. Amer.
Pharm. Review. 2001; 4(1): 70-78
REFERENCES
1. Ah uja Satin de r. Im purit ies Ev aluat io n of
Pharmaceuticals. New York: Marcel Dekker; 1998.
2. a) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Substances. Q3A®. Federal Register. 2000; 65(140):
45085-45090.
b) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Products. Q3B®. Federal Register. 2000; 65(139):
44791-44797.
c) International Conferences on Harmonization,
Impurities—Guidelines for residual solvents. Q3C.

32. The impurities in drug products can be attributed not only to the drug substance or inert ingredients used for formulating a drug product; but they can also be brought into th
“Any component of the drug product that is not the chemical entity defined as the drug substance or an excipient in the drug product.” (ICH Q6A: Specifications). It is impo
Different Types of Impurities in Pharmaceuticals
Organic Impurities
Organic impurities are often process-related or drug-related pharmaceutical impurities. These types of contaminants are most likely to arise during the synthesis, purification, and storage of the drug substance. O
Inorganic Impurities
Inorganic impurities often derive from the manufacturing process. These impurities are often reagents, ligands, catalysts, heavy or residual metals, inorganic salts, filter aids, or charcoals. Inorganic contaminants
Residual Solvents
The third type of impurity in pharmaceuticals is residual solvents. These impurities are residuals of solvents present in the manufacturing process. Solvents used in pharmaceutical manufacturing are defined by t
The three different types of impurities in pharmaceuticals include organic, inorganic, and residual solvents. Most of these impurities occur due to manufacturing processes, degradation, storage conditions, excipie
Abstract
Various regulatory authorities such as the International Conference on Harmonization (ICH), the United States Food and Drug administration (FDA), an
DEFINITION OF IMPURITIES IN PHARMACEUTICALS
An impurity is considered as any inorganic or organic material or residual solvents other than the drug substance or ingredients that arise out of synthesis or unwanted chem
Impurities that are genotoxic at trace levels are also of great concern due to human carcinogen and their detection at trace levels are of increasing concern in pharmaceutica
Health risks in pharmaceutical products
The effect of elemental impurities in drug substances and drug products may arise from several different sources like residual catalysts that were added intentionally in synt
Summarizing the effects of impurities
We know that to get almost pure substances is very difficult and some traces of impurities are always present. So the impurities present in the substances may have the follo
•Impurities may bring about incompatibility with other substances.
•Impurities may lower the shelf life of the substances.
•Impurities may cause difficulties during formulation and the use of the substances.
•Sometimes impurities change the physical and chemical properties of the substances.
•The therapeutic effect can be decreased.
•Shows the toxic effect after a certain period.
•Injurious when present above certain limits.
•It may change the odor, color, the taste of the substance.
•It may affect its potency if the compounds have foreign matter or impurities.
Effects of Impurities in Pharmaceuticals
Sources of Impuries in Pharmaceucal
The root of impuries in drugs is from various sources and phases of the synthec process and development of pharmaceucal dosage forms. Bulk of the impuries are character
According to the ICH impuries are labeled as organic impuries, inorganic impuries and residual solvents
SOURCES OF IMPURITY IN MEDICINES
According to the International Conference on Harmonization (ICH) guidelines, impurities associated with APIs are classified in different ways.
Organic Impurities
Organic impurities are the most common impurities found in every API unless proper care is taken in every step involved, throughout the multi-step sy
Figure 2
Production of paracetamol from intermediate, p-Amin-ophenol
Oxidative degradation
Hydrocortisone, methotrexate, adinazolam, hydroxyl group directly bonded to an aromatic ring (e.g., phenol derivatives such as catecholamines and mo
Decarboxylation
Some dissolved carboxylic acids, such as p-aminosalicylic acid, lose carbon dioxide from the carboxyl group when heated, in the case of photoreaction o
Hydrolysis
Hydrolysis is a common phenomenon for the ester type of drugs, especially in liquid dosage forms. Examples include benzyl penicillin, barbitol, chloram
Figure 3
Ester hydrolysis of benzocaine
pharmaceutical drug candidates. Part 1. Amer.
Pharm. Review. 2001; 4(1): 70-78
REFERENCES
1. Ah uja Satin de r. Im purit ies Ev aluat io n of
Pharmaceuticals. New York: Marcel Dekker; 1998.
2. a) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Substances. Q3A®. Federal Register. 2000; 65(140):
45085-45090.
b) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Products. Q3B®. Federal Register. 2000; 65(139):
44791-44797.
c) International Conferences on Harmonization,
Impurities—Guidelines for residual solvents. Q3C.

36. The impurities in drug products can be attributed not only to the drug substance or inert ingredients used for formulating a drug product; but they can also be brought into th
“Any component of the drug product that is not the chemical entity defined as the drug substance or an excipient in the drug product.” (ICH Q6A: Specifications). It is impo
Different Types of Impurities in Pharmaceuticals
Organic Impurities
Organic impurities are often process-related or drug-related pharmaceutical impurities. These types of contaminants are most likely to arise during the synthesis, purification, and storage of the drug substance. O
Inorganic Impurities
Inorganic impurities often derive from the manufacturing process. These impurities are often reagents, ligands, catalysts, heavy or residual metals, inorganic salts, filter aids, or charcoals. Inorganic contaminants
Residual Solvents
The third type of impurity in pharmaceuticals is residual solvents. These impurities are residuals of solvents present in the manufacturing process. Solvents used in pharmaceutical manufacturing are defined by t
The three different types of impurities in pharmaceuticals include organic, inorganic, and residual solvents. Most of these impurities occur due to manufacturing processes, degradation, storage conditions, excipie
Abstract
Various regulatory authorities such as the International Conference on Harmonization (ICH), the United States Food and Drug administration (FDA), an
DEFINITION OF IMPURITIES IN PHARMACEUTICALS
An impurity is considered as any inorganic or organic material or residual solvents other than the drug substance or ingredients that arise out of synthesis or unwanted chem
Impurities that are genotoxic at trace levels are also of great concern due to human carcinogen and their detection at trace levels are of increasing concern in pharmaceutica
Health risks in pharmaceutical products
The effect of elemental impurities in drug substances and drug products may arise from several different sources like residual catalysts that were added intentionally in synt
Summarizing the effects of impurities
We know that to get almost pure substances is very difficult and some traces of impurities are always present. So the impurities present in the substances may have the follo
•Impurities may bring about incompatibility with other substances.
•Impurities may lower the shelf life of the substances.
•Impurities may cause difficulties during formulation and the use of the substances.
•Sometimes impurities change the physical and chemical properties of the substances.
•The therapeutic effect can be decreased.
•Shows the toxic effect after a certain period.
•Injurious when present above certain limits.
•It may change the odor, color, the taste of the substance.
•It may affect its potency if the compounds have foreign matter or impurities.
Effects of Impurities in Pharmaceuticals
Sources of Impuries in Pharmaceucal
The root of impuries in drugs is from various sources and phases of the synthec process and development of pharmaceucal dosage forms. Bulk of the impuries are character
According to the ICH impuries are labeled as organic impuries, inorganic impuries and residual solvents
SOURCES OF IMPURITY IN MEDICINES
According to the International Conference on Harmonization (ICH) guidelines, impurities associated with APIs are classified in different ways.
Organic Impurities
Organic impurities are the most common impurities found in every API unless proper care is taken in every step involved, throughout the multi-step sy
Figure 2
Production of paracetamol from intermediate, p-Amin-ophenol
Oxidative degradation
Hydrocortisone, methotrexate, adinazolam, hydroxyl group directly bonded to an aromatic ring (e.g., phenol derivatives such as catecholamines and mo
Decarboxylation
Some dissolved carboxylic acids, such as p-aminosalicylic acid, lose carbon dioxide from the carboxyl group when heated, in the case of photoreaction o
Hydrolysis
Hydrolysis is a common phenomenon for the ester type of drugs, especially in liquid dosage forms. Examples include benzyl penicillin, barbitol, chloram
Figure 3
Ester hydrolysis of benzocaine
pharmaceutical drug candidates. Part 1. Amer.
Pharm. Review. 2001; 4(1): 70-78
REFERENCES
1. Ah uja Satin de r. Im purit ies Ev aluat io n of
Pharmaceuticals. New York: Marcel Dekker; 1998.
2. a) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Substances. Q3A®. Federal Register. 2000; 65(140):
45085-45090.
b) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Products. Q3B®. Federal Register. 2000; 65(139):
44791-44797.
c) International Conferences on Harmonization,
Impurities—Guidelines for residual solvents. Q3C.

38. The impurities in drug products can be attributed not only to the drug substance or inert ingredients used for formulating a drug product; but they can also be brought into th
“Any component of the drug product that is not the chemical entity defined as the drug substance or an excipient in the drug product.” (ICH Q6A: Specifications). It is impo
Different Types of Impurities in Pharmaceuticals
Organic Impurities
Organic impurities are often process-related or drug-related pharmaceutical impurities. These types of contaminants are most likely to arise during the synthesis, purification, and storage of the drug substance. O
Inorganic Impurities
Inorganic impurities often derive from the manufacturing process. These impurities are often reagents, ligands, catalysts, heavy or residual metals, inorganic salts, filter aids, or charcoals. Inorganic contaminants
Residual Solvents
The third type of impurity in pharmaceuticals is residual solvents. These impurities are residuals of solvents present in the manufacturing process. Solvents used in pharmaceutical manufacturing are defined by t
The three different types of impurities in pharmaceuticals include organic, inorganic, and residual solvents. Most of these impurities occur due to manufacturing processes, degradation, storage conditions, excipie
Abstract
Various regulatory authorities such as the International Conference on Harmonization (ICH), the United States Food and Drug administration (FDA), an
DEFINITION OF IMPURITIES IN PHARMACEUTICALS
An impurity is considered as any inorganic or organic material or residual solvents other than the drug substance or ingredients that arise out of synthesis or unwanted chem
Impurities that are genotoxic at trace levels are also of great concern due to human carcinogen and their detection at trace levels are of increasing concern in pharmaceutica
Health risks in pharmaceutical products
The effect of elemental impurities in drug substances and drug products may arise from several different sources like residual catalysts that were added intentionally in synt
Summarizing the effects of impurities
We know that to get almost pure substances is very difficult and some traces of impurities are always present. So the impurities present in the substances may have the follo
•Impurities may bring about incompatibility with other substances.
•Impurities may lower the shelf life of the substances.
•Impurities may cause difficulties during formulation and the use of the substances.
•Sometimes impurities change the physical and chemical properties of the substances.
•The therapeutic effect can be decreased.
•Shows the toxic effect after a certain period.
•Injurious when present above certain limits.
•It may change the odor, color, the taste of the substance.
•It may affect its potency if the compounds have foreign matter or impurities.
Effects of Impurities in Pharmaceuticals
Sources of Impuries in Pharmaceucal
The root of impuries in drugs is from various sources and phases of the synthec process and development of pharmaceucal dosage forms. Bulk of the impuries are character
According to the ICH impuries are labeled as organic impuries, inorganic impuries and residual solvents
SOURCES OF IMPURITY IN MEDICINES
According to the International Conference on Harmonization (ICH) guidelines, impurities associated with APIs are classified in different ways.
Organic Impurities
Organic impurities are the most common impurities found in every API unless proper care is taken in every step involved, throughout the multi-step sy
Figure 2
Production of paracetamol from intermediate, p-Amin-ophenol
Oxidative degradation
Hydrocortisone, methotrexate, adinazolam, hydroxyl group directly bonded to an aromatic ring (e.g., phenol derivatives such as catecholamines and mo
Decarboxylation
Some dissolved carboxylic acids, such as p-aminosalicylic acid, lose carbon dioxide from the carboxyl group when heated, in the case of photoreaction o
Hydrolysis
Hydrolysis is a common phenomenon for the ester type of drugs, especially in liquid dosage forms. Examples include benzyl penicillin, barbitol, chloram
Figure 3
Ester hydrolysis of benzocaine
pharmaceutical drug candidates. Part 1. Amer.
Pharm. Review. 2001; 4(1): 70-78
REFERENCES
1. Ah uja Satin de r. Im purit ies Ev aluat io n of
Pharmaceuticals. New York: Marcel Dekker; 1998.
2. a) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Substances. Q3A®. Federal Register. 2000; 65(140):
45085-45090.
b) International Conferences on Harmonization,
Draft revised Guidance on Impurities in new drug
Products. Q3B®. Federal Register. 2000; 65(139):
44791-44797.
c) International Conferences on Harmonization,
Impurities—Guidelines for residual solvents. Q3C.