Name

Beenish Zahra

Roll no:

RIPS_S09_41

Topic

Quality Control in Test 4 Purity

Subject

Inorganic Chemistry

Submitted to:

Madam Khadija

Date of Submission

24 may, 2010

Riphah Institute of Pharmaceutical Science

Inorganic Chemistry 1

Table of ContentsQuality Control & Test for Purity......................................................................3

Pharmaceuticals Testing..................................................................................3

Standards or specifications..............................................................................3

Physical specifications.....................................................................................3

Sources of Impurities in Medicines..................................................................3

Organic Impurities...........................................................................................4

Enantiomeric Impurities...................................................................................4

a) Method Related...........................................................................................4

b) Environmental Related................................................................................4

Exposures to adverse temperatures-...............................................................4

Light-especially UV light-.................................................................................4

Humidity-.........................................................................................................4

c) Dosage form Factors Related......................................................................4

a. Mutual interaction amongst ingredients......................................................4

b. Functional group-related typical degradation..............................................4

Ester hydrolysis- .............................................................................................4

Hydrolysis-.......................................................................................................4

Oxidative degradation-....................................................................................4

Photolytic cleavage-.........................................................................................4

Recommendations...........................................................................................4

During crystallization-......................................................................................4

Washing the wet cake-....................................................................................4

Drying-.............................................................................................................4

Importance of Pharmaceutical Quality Control................................................4

Reference:.......................................................................................................4

Quality Control & Test for Purity

Inorganic Chemistry 2

By dictionary definition “Quality Control” means checking and

directing the degree or grade of excellence of processes and products

Pharmaceutical industries have to adhere to a number of quality standards and practices for being able to sell medicines in the market. Quality systems like good laboratory practice (GLP), good manufacture practice (GMP) and good clinical practice (GCP) are specific to ph’l industry regulations. The principles of these systems primarily cover the procedure quality aspects on a formal basis and not much evaluation is done of the technical aspects.

Pharmaceuticals TestingTechniques used to determine that ph’ls conform to specified standards of identity, strength, quality, and purity. Conformance to these standards assures pharmaceuticals which are safe and efficacious, of uniform potency and purity, and of acceptable color, flavor, and physical appearance.

Standards or specifications and their attendant procedures are designed to provide desired characteristics and acceptable tolerances for all raw materials, intermediates, and finished products. Standards are established by the pharmaceutical manufacturer, official compendiums and regulations promulgated by the U.S. (FDA).

Physical specifications include such characteristics as bulk density, mesh size, color, odor, extraneous contamination such as fibers, and homogeneity. Chemical specifications usually include such characteristics as chemical or physiological potency, melting point, boiling range, optical rotation, moisture, heavy-metals content, chemical identity, solubility, and presence of chemical contaminants.

Sources of Impurities in MedicinesImpurities 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. The presence of these unwanted chemicals even in small amounts may influence the efficacy and safety of the pharmaceutical products.

There are 2 types of impurities in medicines:

Inorganic Chemistry 3

(1) Impurities associated in with active pharmaceutical ingredients

(2) Impurities that form are created during formulation and or with aging or that are related to the formulated forms.

According to ICH guidelines impurities associated with APIs are classified into the following categories:

Organic impurities (Process and Drug-related) Inorganic impurities Residual solvents

Organic ImpuritiesThese may arise during the manufacturing process or storage of the drug substance. They include the following:

Starting materials or intermediates- These are the most common impurities found in every API unless a proper care is taken in every step.

By-products- In the case of paracetamol bulk, diacetylated paracetamol may form as a by-product.

Degradation products- The degradation of penicillins and cephalosporins is a well-known example of degradation products. The presence of a ß-lactam ring as well as that of an a-amino group in the C6/C7 side chain plays a critical role in their degradation.

Reagents, ligands, and catalysts-

Enantiomeric Impurities

Inorganic impurities may also derive from the manufacturing processes used for bulk drugs. They are normally known and identified and include the following:

Reagents, ligands, and catalysts- Heavy metals- Other materials (eg, filter aids, charcoal)-

Apart from bulk drug-related impurities, the formulated form of API may contain impurities that form in various ways.

Inorganic Chemistry 4

a) Method Related

A known impurity, 1-(2,6-diclorophenyl)indolin-2-one is formed in the production of a parenteral dosage form of diclofenac sodium if it is terminally sterilized by autoclave.

b) Environmental Related

The primary environmental factors that can reduce stability include the following:

Exposures to adverse temperatures- Vitamins as drug substances are very heat-sensitive and degradation frequently leads to loss of potency in vitamin products, especially in liquid formulations.

Light-especially UV light- Several studies have reported that ergometrine as well as methyl ergometrine injection is unstable under tropical conditions such as light and heat.

Humidity- For hygroscopic products, humidity is considered detrimental to both bulk powder and formulated solid dosage forms. Aspirin and ranitidine are classical examples.

c) Dosage form Factors Related

Microbiological growth resulting from the growth of bacteria, fungi, and yeast in a humid and warm environment may result in oral liquid products that are unusable for human consumption.

a. Mutual interaction amongst ingredients

Most vitamins are very labile and on aging they pose a problem of instability in different dosage forms, especially in liquid dosage forms. Degradation of vitamins leads to drop in potency of active ingredients below pharmacopoeial specifications.

b. Functional group-related typical degradation

Ester hydrolysis- Examples included the following: Aspirin, benzocaine, cefotaxime, cocaine echothiophate, ethyl paraben, cefpodoxime proxetil.

Hydrolysis- Hydrolysis is a common phenomenon for the ester type of drugs, especially in liquid dosage forms. Examples include benzylpenicillin, barbitol, chloramphenicol, chlordiazepoxide, lincomycin, and oxazepam.

Inorganic Chemistry 5

Oxidative degradation- Hydrocortisone, methotrexate, adinazolam, hydroxyl group directly bonded to an aromatic ring, heterocyclic aromatic rings, nitroso and nitrite derivatives, and aldehydes are all susceptible to oxidative degradation.

Photolytic cleavage- Ergometrine, nNifedipine, nitroprusside, riboflavin, and phenothiazines are very labile to photo-oxidation. In susceptible compounds, photochemical energy creates free radical intermediates, which can perpetuate chain reactions.

Decarboxylation- p-amino salicylic acid AND rufloxacin., lose carbon dioxide from the carboxyl group.

RecommendationsDuring crystallization- The size of crystals sometimes determines the quality, especially the stability, of bulk drugs. Large-size crystals can entrap a minute amount of chemicals from the mother liquor, which ultimately causes the degradation of the drug

Washing the wet cake- Washing the wet cake or powder in the centrifuge should be thorough to remove unwanted chemicals including residual solvents.

Drying- Use of a vacuum dryer or a fluid-bed dryer is always preferable to a tray dryer in the pharmaceutical bulk drug industry. The high thermal efficiencies, reduction of drying time, and more uniform drying are helpful in drying sensitive drug substances.

Importance of Pharmaceutical Quality Control Shelf-life studies of drug substances in commercial dosage forms are an essential element of the QC process for manufactured pharmaceuticals. While there are well described test procedures available, getting a quick insight to possible shelf-life issues is valuable—and important. Rapid wet and dry or low and high temperature cycling provides a strong indication of potential issues.

Such test procedures can be carried out easily using an environmental scanning electron microscope (ESEM) in which temperature and humidity can be precisely controlled and dissolution processes are observable in real time, which provides an extraordinary level of insight into the process.

Inorganic Chemistry 6

Combining the ESEM with an Energy Dispersive Spectroscopy (EDS) detector also enables mapping the different elements in a formulated product to study the homogeneity of the product and the composition of all layers. The ion beam acts as a micro-scalpel, enabling investigation of a dosage form, such as a tablet, in all three dimensions. In this way the integrity of the tablet coating, for instance, can be investigated under the different environmental conditions required for shelf life testing.

FEI's Quanta 3D model provides great productivity for drug product characterization and pharmaceutical QC. The proprietary vacuum system of this microscope even allows high temperature experiments for phase transitions studies, as well as hydration and dehydration experiments to qualify the crystal behavior.

1. The art of preparing and dispensing drugs.2. A place where drugs are sold; a drugstore. Also called apothecary

Reference:

Inorganic Chemistry 7