Metformin or dimethylbiguanide is an orally-adminstered antihyperglycaemic drug used to treat patients with non-insulin dependent diabetes mellitus which acts by improving insulin sensitivity which in turn decreases insulin resistance (Bailey et al., 1996). The structure of metformin has nitrogen-containing functional groups, particularly amine and imine functional group and contains a guanidino group. Based on its structure, it can be deduced that the drug is prone to hydrolysis of the imine functional groups as well as oxidation and reduction of both amine and imine groups. Therefore, the possible degradation products that can be inferred from this are guanidine, amines and amides.
For a molecule such as metformin which would be susceptible to hydrolysis and redox, contact with moisture and air should be avoided by keeping the product in a dry place and ensuring that the containers are almost, if not, air tight and tightly closed.
Nateglinide Nateglinide is a novel D-phenylalanine derivative that stimulates the prandial release of insulin through the inhibition of the ATP-sensitive K channels in pancreatic -cells in the presence of glucose (Dunn and Faulds, 2000), which makes it chemically and pharmacologically unique among oral anti-diabetes drugs (Horton et al., 2000). The functional groups present in nateglinide, include amide, carboxyl and aromatic functional groups. All these groups can undergo hydrolysis as well as redox reactions leading to the production of D-phenylalanine, amides, amines, and possibly secondary alcohol (from the hydrolysis of the carboxyl group) as degradation products.
Given a molecule such as nateglinide, which would be very prone to hydrolysis, contact with moisture should be avoided by keeping it in a dry place andor putting a dessicant with it in the container. Keeping its container airtight would also be a helpful precaution which should be taken to avoid contact with air which also contains a significant amount of moisture depending on the relative humidity.
Pioglitazone
Pioglitazone belongs to a relatively new class of insulin-sensitizing agents known as thiazolidinediones used to treat type II diabetes mellitus non-alcoholic steatohepatatis or fatty liver (Miyazaki et al., 2002). It exists as a racemic mixture of enantiomers which may inter-convert in vivo but no differences in the pharmacologic activity was found between the two (Eckland and Danhof, 2000). The structure of this drug contains pyridine, ketone, ethoxy, sulfonyl and phenyl groups. The ketone, ethoxy and sulfoxide groups can undergo hydrolysis and redox reactions thereby leading to pyridine, phenyl, sulfoxide derivatives as possible major degradation products of the drug.
Similar to nateglinide, pioglitazones structure is also prone to hydrolysis, hence, contact with moisture should also be avoided as mentioned earlier.
Tolbutamide
Tolbutamide is a first generation potassium channel blocker, sulfonylurea oral hypoglycemic drug used in the management of type II diabetes if diet alone is not effective. However, it is not routinely used due to the higher incidence of adverse effects. Contrary to this, due to its short duration of action and rapid metabolism, the drug proves to be safe for use in elderly diabetics. The functional groups present in tolbutamides structure which are prone to hydrolysis and redox reactions are the phenyl, sulfonyl and amide groups. Possible degradation products of tolbutamide are p-toluenesulfonamide and butylisothiocyanate as well as phenyl, amide and sulfoxide derivatives.
olbutamide structure would be susceptible to hydrolysis and oxidation, therefore, keeping it in a dry place, placing a dessicant in its container and ensuring its container is airtight are precautions that should be employed to avoid its degradation while in storage.
Repaglinide
Repaglinide is an oral hypoglycemic agent, belonging to a new chemical class of insulin secretagogues (Moses et al., 1999). It possess all characteristics that are desired for treating type II diabetes patients such rapid absorption, short metabolic half-life (1 hour) (Wolffenbuttel et al., 1993), and novel insulin release profile (Graul and Castaer, 1996). The structure of repaglinide has carboxylic, ether, amide and phenyl functional groups. The hydrolysis and redox reactions that may occur in the carboxylic, ether and amide group may lead to aldehyde, alcohol, amine, phenyl derivatives as possible products of degradation.
Like nateglinide and pioglitazone, repaglinide would also be very prone to hydrolysis. To avoid its degradation, contact with moisture should be avoided by employing the measures discussed above.
It has been demonstrated the based on the structures of the following drugs, they are prone to degradation through hydrolysis and redox reactions. The degradation of pharmaceutical products has potential adverse effects which include loss of active ingredient, increase in the concentration of active, alteration in bioavailability, loss of content uniformity, decline in microbiological status, loss of pharmaceutical elegance and patient acceptability, formation of degradation products, loss of package integrity, reduction of label quality, and modification of any factor of functional relevance (Rhodes, 2000) therefore, measures should be considered in the manufacture, packaging and storage of these products. In the manufacture of drugs, oxidation can be prevented by filling out ampoules with oxidation-prone drugs under nitrogen (Rhodes, 2000). Moreover, the moisture content of the raw materials as well as the pharmaceutical products should be kept only at the required levels to prevent its hydrolysis. For packaging and storage, airtight bottles should always be ensured to prevent redox reactions to occur and dessicants should be placed with the products to prevent moisture and in turn, hydrolysis of the products.
The adverse effects that may be caused by the degradation of pharmaceuticals are not something which can be taken lightly. It can lead to serious repercussions that will affect both the manufacturers and most especially the consumerspatients which are the end users of the product. Thus, it is very important to study the structures of pharmaceuticals and correlate it with drug stability to be able to avoid its degradation, hence, such adverse effects.
For a molecule such as metformin which would be susceptible to hydrolysis and redox, contact with moisture and air should be avoided by keeping the product in a dry place and ensuring that the containers are almost, if not, air tight and tightly closed.
Nateglinide Nateglinide is a novel D-phenylalanine derivative that stimulates the prandial release of insulin through the inhibition of the ATP-sensitive K channels in pancreatic -cells in the presence of glucose (Dunn and Faulds, 2000), which makes it chemically and pharmacologically unique among oral anti-diabetes drugs (Horton et al., 2000). The functional groups present in nateglinide, include amide, carboxyl and aromatic functional groups. All these groups can undergo hydrolysis as well as redox reactions leading to the production of D-phenylalanine, amides, amines, and possibly secondary alcohol (from the hydrolysis of the carboxyl group) as degradation products.
Given a molecule such as nateglinide, which would be very prone to hydrolysis, contact with moisture should be avoided by keeping it in a dry place andor putting a dessicant with it in the container. Keeping its container airtight would also be a helpful precaution which should be taken to avoid contact with air which also contains a significant amount of moisture depending on the relative humidity.
Pioglitazone
Pioglitazone belongs to a relatively new class of insulin-sensitizing agents known as thiazolidinediones used to treat type II diabetes mellitus non-alcoholic steatohepatatis or fatty liver (Miyazaki et al., 2002). It exists as a racemic mixture of enantiomers which may inter-convert in vivo but no differences in the pharmacologic activity was found between the two (Eckland and Danhof, 2000). The structure of this drug contains pyridine, ketone, ethoxy, sulfonyl and phenyl groups. The ketone, ethoxy and sulfoxide groups can undergo hydrolysis and redox reactions thereby leading to pyridine, phenyl, sulfoxide derivatives as possible major degradation products of the drug.
Similar to nateglinide, pioglitazones structure is also prone to hydrolysis, hence, contact with moisture should also be avoided as mentioned earlier.
Tolbutamide
Tolbutamide is a first generation potassium channel blocker, sulfonylurea oral hypoglycemic drug used in the management of type II diabetes if diet alone is not effective. However, it is not routinely used due to the higher incidence of adverse effects. Contrary to this, due to its short duration of action and rapid metabolism, the drug proves to be safe for use in elderly diabetics. The functional groups present in tolbutamides structure which are prone to hydrolysis and redox reactions are the phenyl, sulfonyl and amide groups. Possible degradation products of tolbutamide are p-toluenesulfonamide and butylisothiocyanate as well as phenyl, amide and sulfoxide derivatives.
olbutamide structure would be susceptible to hydrolysis and oxidation, therefore, keeping it in a dry place, placing a dessicant in its container and ensuring its container is airtight are precautions that should be employed to avoid its degradation while in storage.
Repaglinide
Repaglinide is an oral hypoglycemic agent, belonging to a new chemical class of insulin secretagogues (Moses et al., 1999). It possess all characteristics that are desired for treating type II diabetes patients such rapid absorption, short metabolic half-life (1 hour) (Wolffenbuttel et al., 1993), and novel insulin release profile (Graul and Castaer, 1996). The structure of repaglinide has carboxylic, ether, amide and phenyl functional groups. The hydrolysis and redox reactions that may occur in the carboxylic, ether and amide group may lead to aldehyde, alcohol, amine, phenyl derivatives as possible products of degradation.
Like nateglinide and pioglitazone, repaglinide would also be very prone to hydrolysis. To avoid its degradation, contact with moisture should be avoided by employing the measures discussed above.
It has been demonstrated the based on the structures of the following drugs, they are prone to degradation through hydrolysis and redox reactions. The degradation of pharmaceutical products has potential adverse effects which include loss of active ingredient, increase in the concentration of active, alteration in bioavailability, loss of content uniformity, decline in microbiological status, loss of pharmaceutical elegance and patient acceptability, formation of degradation products, loss of package integrity, reduction of label quality, and modification of any factor of functional relevance (Rhodes, 2000) therefore, measures should be considered in the manufacture, packaging and storage of these products. In the manufacture of drugs, oxidation can be prevented by filling out ampoules with oxidation-prone drugs under nitrogen (Rhodes, 2000). Moreover, the moisture content of the raw materials as well as the pharmaceutical products should be kept only at the required levels to prevent its hydrolysis. For packaging and storage, airtight bottles should always be ensured to prevent redox reactions to occur and dessicants should be placed with the products to prevent moisture and in turn, hydrolysis of the products.
The adverse effects that may be caused by the degradation of pharmaceuticals are not something which can be taken lightly. It can lead to serious repercussions that will affect both the manufacturers and most especially the consumerspatients which are the end users of the product. Thus, it is very important to study the structures of pharmaceuticals and correlate it with drug stability to be able to avoid its degradation, hence, such adverse effects.
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