The standardization of ‘pharmaceutical chemicals’ and the dosage forms prepared therefrom plays a vital role so that the patient gets the ‘drug’ within the permissible limits of potency and tolerance.
The standards for pharmaceutical chemicals and their respective dosage forms, as laid down in, various
Official Compendia fulfil broadly the following three cardinal objectives, namely :
(a) Broad-based highest attainable standard,
(b) Biological response versus chemical purity, and
(c) Offical standards versus manufacturing standards.
Keeping in view the various methods of manufacture of a pharmaceutical substance vis-a-vis its standards of purity, types of impurity and changing pattern of stability, a broad-based highest attainable standard is always fixed. A few typical examples are stated below :
Though chemical purity is the topmost priority, yet the biological response of a pharmaceutical substance holds an equal importance. A wide variation of active ingredients ranging between 90% in one sample and 110% (± 10 per cent limit) in another sample could invariably be observed. Therefore, it has become absolutely essential to lay down definite standards so as to ensure that :
· Different laboratories may produce reasonably reproducible products.
· Difference in active ingredients in various lots may be minimised.
· Retention of acceptable level of potency.
· Freedom of toxicity during storage before use.
(i) Substances to be stored in well-closed, light-resistant containers e.g., isoniazid, nalidixic acid, nandrolone phenylpropionate, nitrofurazone.
(ii) Substances to be stored under nitrogen in tightly closed, light-resistant containers at a temperature between 2° and 10°C, e.g., nandrolone decanoate, nystatin, methylergometrine maleate, human normal immunoglobulin.
(iii) Substances to be stored in tightly-closed, light-resistant containers in a cool place, e.g., nitrofurantoin, pancreatin, oxyphenonium bromide.
(iv) Substances to be stored in tightly-closed, light-resistant containers in a cool place; for parenteral administration, the container should be sterile and sealed so as to exclude micro-organisms. e.g., kanamycin sulphate, novobiocin sodium, benzylpenicillin, lincomycin hydrochloride, chloramphenicol.
(v) Substances to be stored in well-closed containers, at a temperature not exceeding 30°C, e.g., procaine penicillin, pepsin, menthol, erythromycin.
The Offical Standards, as stipulated in the pharmacopoeias of various countries, e.g., IP BP, Eur. P., Int. P., USSRP, JP etc., of a pharmaceutical substance take cognizance of the purity, nature, methods and haz-ards of manufacture, precautions of storage and ultimately the conditions under which the product is to be used.
It is a well-known fact that a pharmaceutical substance can be prepared by adopting different routes of synthesis based upon the dynamic ongoing research in the field of organic-reaction-mechanisms. Relentless efforts are exerted vigorously by reputed research laboratories across the world to look for shorter routes of synthesis bearing in mind the cost-effectiveness of the final product. For instance : diclofenac sodium (an NSAID) can be manufactured by two methods, one using a bromo compound as a starting material while the other is based on a non-bromo compound. Nevertheless, the latter product is more in demand because it is completely devoid of bromine residues in the final product.
During the process of manufacture an unavoidable criterion is the loss of active ingredients. Therefore, all Official Standards for pharmaceutical chemicals and dosage forms should accomodate such losses caused due to loss in manufacture, unavoidable decomposition and storage under normal conditions for a stipulated period.
It has become an usual practice to include a ‘definite overage’ in certain dosage forms so as to compensate the noticeable losses caused either due to manufacturing or storage (anticipated decomposition), in order that the finished product may comply with the prescribed offcial standards after the stipulated duration of storage.
Official standards with regard to dosage form and packs, preservation and prevention from contamination in a variety of pharmaceutical products, such as eye-drops, multidose injections and antiseptic creams (external application) that may be prone to spoilage with prolonged repetitive usage should be well defined. The official standards, in general, legislate and control the presence of toxic impurities by prescribed ‘limit tests’ and also by more sophisticated analytical techniques using thin-layer chromatography (TLC), high performance thin-layer chromatography (HPTLC), gas-liquid chromatography (GLC) and high-performance liquid chromatography (HPLC).