Pharmaceutical Analysis The term pharmaceutical analysis has two parts: i. Pharmaceutical: In pharmacy whatever we do is basically related to drugs.

We deal with different types of drugs, their formulation, mechanism and so on. So anything related to drug is called pharmaceutical. Analysis: Analysis is the process which is used to analyse the manufactured products. It is an important ob in any industry. !efore analysing anything we have to set some features. This is called specification.

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So, "Pharmaceutical Analysis is the process whereby we ensure the #uality of pharmaceutical products which are manufactured in pharmaceutical industry.$ The Art & Science of Pharmaceutical Analysis If we want to be a good pharmaceutical analyst we have to %now the science and art of pharmaceutical analysis. The analysis of drug is based on sound scientific principles. &or a good analyst the %nowledge of chemistry and mathematics are compulsory. 'hemistry and mathematics are both important in different methods and techni#ues li%e titrimetry and gravimetry and in the more modern approaches to precise measurement, as e(emplified by absorptiometry and radioactimetry. This is the scientific part of the pharmaceutical analysis. )n the other hand, a good analyst must have the practical e(perience also. As he has to wor% in a laboratory he hast to %now the tools and techni#ues of his profession, is able to e(ercise udgment of mind into action in the laboratory. &or e(ample while doing different analytic procedure we have to use different tools. So we have to %now how to handle them. !oo%s don*t teach us how to use or operate them. We can only learn those when we wor% in a laboratory In pharmaceutical analysis these two things is very much important. In some cases many highly trained scientists have little mastery over the most fundamental laboratory procedures. The art of pharmaceutical analysis is mastered in the laboratory and, in this respect, e(perience is the best teacher. What is level of purity? +very drug what we use has a specific label claim. &or e(ample the label of paracetamol claims that it has ,-- mg of active constituent. !ut in practical life it is not #uite possible to maintain the label claim. There is always slight deviation from the original label claim for different reasons. So, pharmacopoeias and other drug.

control legislation permit a manufacturer to mar%et a product that contains slightly less or slightly more than that claimed on the label. &or e(ample, for big doses of drugs li%e ,-- mg paracetamol pharmacopoeias allows /0-1 deviation. )n the other hand for low doses drugs this deviation rate is much lower. &or these types of drugs the allowed deviation rate is /,1. This is %nown as level of purity. In addition, every pure drug or chemical has certain amount of impurities and it is #uite impossible to remove all the impurities from them. So in the time of analysis pharmacopoeias provide the analyst with monographs that deal with pure drugs or chemicals, and these may allow for no more than 0 to 0.,1 impurity. Why Certain Deviation from Label Claim Is Permitted? It is not possible to ensure the label claim, that*s why deviation is allowed. With respect to the dosage form, these deviations are permitted for three reasons. &irst, compounding error is the most common reason of deviation. In the time of production compounding error can happen. The loss of compound due to dusting, removing from the pac%et or anything else can cause compounding error. So it is understood that no drug can be put into dosage form without some compounding error. Second, some drugs deteriorate. It is inherent property of those drugs. These types of drugs are unstable and gradually deteriorate on standing. The pharmacopoeias recogni2e this and sum the effect into the total allowable deviation from the label claim. Third, 3o method of analysis is so precise that it provides the analyst with recovery values free of error. This is %nown as analytical error. In pharmaceutical analysis different methods are used. Sensitive methods can detect minor error. 4!ut if the concentration of drug at the site of action under minimum therapeutic effect that is called sub therapeutic concentration. In sub therapeutic concentration the drug doesn*t show its effect. +very drug has a specific therapeutic window. After minimum effective concentration the drug starts its effect and after ma( effective concentration it causes to(icity. 5igh doses of drugs have large therapeutic window and small doses of drug has small therapeutic window.6 What Can an Analyst Do to minimi e the Deviation? !r" Analyst !nly #nsures the $uality%#&plain Analyst*s duty is to minimi2e the deviations. !ut the analyst has no control over compounding error and the deterioration of the drugs. 5e can only ensure the analytical error is as small as by possible by

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Performing all operations carefully and #uantitatively. Insisting on a ma(imum of cleanliness in the laboratory. Paying particular attention to the theoretical implications of each step in the analytical procedure.

Analysts are only chec% post. They only chec% the #uality. They can*t do anything in production. &or ensuring best #uality they can chec% the #uality of the raw materials before buying as #uality starts from the buying the raw materials and chec% the final products before they are sent to the mar%et. Choosin' the Correct Tools In pharmaceutical analysis we have to use different types to tools for different methods. So we should have a clear concept about the tools and their uses. A method of analysis rarely specifies the type of container, flas%, separatory funnel or other apparatus that is to be used in a particular operation. So the analyst should use common sense and choose the right tools for the operation. &or e(ample, a 0-ml graduated cylinder would not be used to measure 0- ml of the solution. It is obviously wrong to use a 7,- ml +rlenmeyer flas% if the total volume does not e(ceed ,- ml. In such titrations a 07, ml +rlenmeyer flas% is the container of choice. The analyst must study the method and on the basis of e(perience and8or common sense, choose the tools that provide a ma(imum of efficiency and a minimum of error. Identification of Container While wor%ing in the lab we have to tag the apparatus which we used or going to use. Tagging apparatus is very important. !ecause. . It can cause health ha ard. As we deal with different types of chemicals, among them some would be highly to(ic and in urious to health. &or e(ample we use different types of concentrated acids for different purpose. If we don*t tag the apparatus which we used to carry this to(ic elements other people can use it. It will then cause serious ha2ardous situation. So for avoiding this ha2ardous and accidental situation we must identify the containers. It can create o(ner)s confusion. If one uses a certain container and if he doesn*t tag his name then another person may thing that container doesn*t belong to anybody and he may start using that container. This can ruin one e(periment. It can also cause se*uential confusion. A method of analysis is not complete unless it has been carried out at least two, and preferably three times. It is very important to mar% carefully each container that is used in completing the operation. If one doesn*t identify the container he will surely

forget which sample is in which bea%er. !y neglecting the seemingly insignificant operation, one can loose the whole wor%. +iltration &iltration process is carried out by passing the li#uid through a filter to remove the solids. It is mainly done to remove the unwanted e(cipients. &or dissolution filtration is necessary in analysis because other ingredients affect the analysis result. &or this reason the suspended solid is removed and discarded before the analysis is continued. In some cases, solids suspended in li#uids are often encountered during the analysis of the pharmaceuticals. In certain instances, the solids must be #uantitatively recovered for further processing. 4Suspensions can*t be filtered because the solid which is the drug is suspended in the li#uid. So if we filter suspension then the solid phase is removed.6 Dryin' the Sample There are two types of moistures. They are. i. 9nbound :oisture: :ost solids tend to absorb moisture when e(posed to the atmosphere. This is called unbound moisture. This moisture must be removed before the sample is weighed or treated in some other manner. It is necessary to consider the natural state of the substance being analysed. &or e(ample, ephedrine may contain as much as ;1 water and is analysed without being sub ected to drying process. !ound :oisture: Some drugs may contain water of crystalli2ation this is called bound moisture. Since this forms part of the molecule, the analysis is carried out with this in mind.

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If the moisture is adsorbed at some stage in the analytical process, it must be removed. If it is present before the analysis begins, the analyst must e(ercise common sense and decide if it should be removed. If moisture is natural contaminant, the drug should be analysed without prior treatment. 5owever, if the drug is being used as a primary standard in some analytical process, the moisture must be removed before the substance is weighed. ,ecordin' the ,esultIn pharmaceutical analysis, results of different procedures should be recorded. !ecause it is the analyst who gives his stamp of approval to a particular pharmaceutical and if circumstances so warrant, he must be able to recall all data pertinent to that product. Individuals differ in their ability to remember facts and

figures, but no analyst is e(cused from the tas% of %eeping a neat and detailed laboratory record boo%. Ag good record boo% lends itself to the easy chec%ing of calculations and measures. So if any problem occurs the analyst can go through the record boo% and finds out the mista%es. In this way record boo%s stop from reporting foolish results. &eatures of a <ood =ecord !oo%: i. ii. iii. iv. Purity"The #uality or condition of being pure.$ "A #uantitative assessment of homogeneity or uniformity.$ Importance: As the drugs are ta%en by patients, purity is an important factor. If the drug has too much impurity then the drug will either give sub.therapeutic effect or it will cause to(icity. &or e(ample, If the I> drugs have contamination has contamination it will cause ha2ardous situation in patient body. So, the standardi2ation of pharmaceutical chemicals ?and the dosage forms prepared therefore plays a vital role so that the patient gets the drug within the permissible limits of potency and tolerance. ContaminationAs we all %now contamination in drugs can cause serious health problems. !ut ma(imum contamination is accidental contamination. In some cases contamination caused by e(cipients does not create that much ha2ard rather than active ingredient. So medicines should be chec%ed before they are sent to mar%et. &or e(ample, In ectable medicines should be filtered and clarified. They are three types of contamination. i. Particulate 'ontamination: Include accidental inclusion of atmospheric pollutants, e.g. silica, Aluminium o(ide, sulphur or glass, porcelain, metallic or plastic fragments from sieves etc. It happens mainly in the The laboratory record boo% should be bound and all the result must be recoded in in% as they are accumulated. The pages should be numbered +ach page, as it is used, is dated and signed by the analyst =esults and procedural details should be entered in the boo% so that a second analyst can easily repeat the wor% and chec% all calculations.

time of production. So the measurement of clarity of solution for in ection is important. ii. 3on.particulate 'ontamination: It is mainly caused by atmosphere which is contaminated S)7, 5S, ')7, water vapor and many more. It can constitute a ha2ard to product manufactured or stored under less than ideal condition. 'ross contamination: Accidently mi(ing of two different drugs is %nown as cross contamination. It is caused by. a. The handling of powders granules and tablets in large bul% fre#uently creates a considerable amount of air.borne dust. If it is not controlled then it can cause cross contamination of products. b. If the instruments are not cleaned properly. c. If one product is replaced with other. In some cases cross contamination can cause serious problems in our body. Suppose in one company paracetamol and an antibiotic is produced in the same machine. 3ow if paracetamol is produced before the antibiotic there will be some paracetamol dust in the air or in the machine. So when we produce antibiotic in the same machine the paracetamol dust will mi( with the antibiotic and it will cross contaminate the antibiotic. !ut as the amount of paracetamol is very low it won*t give any therapeutic effect. )n the other hand if the antibiotic is prepared first and the antibiotic dust cross contaminate the paracetamol then it will cause serious problem. !ecause the amount antibiotic present in the paracetamol is very low it may not give any therapeutic effect. !ut our body become resistant on that antibiotic. And in future when we ta%e that antibiotic that will not give any %ind of therapeutic effect. Purity StandardsThe standardi2ation of ?pharmaceutical chemicals* and the dosage forms prepared therefrom play 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 )fficial 'ompendia fulfil broadly the following three cardinal ob ectives, namely: @aA !road.based highest attainable standard, @bA !iological response versus chemical purity, and @cA )fficial standards versus manufacturing standards. @aA !road.based highest attainable standard:

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Beeping 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 fi(ed. &or e(ample, Pharmacopoeia has given a standard of purity for Aspirin and that is CC., . 0--.,1. If we can attain the standard then the standard of the product will be high. @bA !iological response versus chemical purity In D' chemically purity is very important. !ut it is not the only important thing. As drugs are used by humans, we should also give importance to biological response. If any compound is 0--1 pure before production, the end product of that compound may not be 0--1 pure. A wide variation of active ingredients ranging between C-1 in one sample and 00-1 @/ 0- per cent limitA in another sample could invariably be observed. Therefore, it has become absolutely essential to lay down definite standards so as to ensure that: E Fifferent laboratories may produce reasonably reproducible products. E Fifference in active ingredients in various lots may be minimised. E =etention of acceptable level of potency. E &reedom of to(icity during storage before use. &or e(ample, @iA Substances to be stored in well.closed, light.resistant containers e.g., isonia2id, nalidi(ic acid, nandrolone phenylpropionate, nitrofura2one. @iiA Substances to be stored under nitrogen in tightly closed, light. resistant containers at a temperature between 7G and 0-G', e.g., nandrolone decanoate, nystatin, methylergometrine maleate, human normal immunoglobulin. @cA )fficial standards versus manufacturing standards: Pharmacopoeia gives us a range, not a specific amount. &or e(ample, if pharmacopoeia says that a drug can deviate /0-1 then it will be its official standard. !ut if the formulator decided to give /,1 deviation then it will be manufacturing standard. :anufacturing standards are laid down by licensing authorities on the basis of information supplied by the manufacturer on #uality trial and typical manufacturing test batches of the material. In contrast the )fficial Standards, as described in the different pharmacopoeias e.g. 9SP, !P, IP etc are available to all users of the materials. They are designed to set permissive limits tolerance for the accompanied product at the time it reaches the patient.

It is a well.%nown fact that a pharmaceutical substance can be prepared by adopting different routes of synthesis based upon the dynamic on.going research in the field of organic.reaction.mechanisms. =elentless efforts are e(erted vigorously by reputed research laboratories across the world to loo% for shorter routes of synthesis bearing in mind the cost.effectiveness of the final product. Definite !vera'eSome compounds deteriorate easily. It is their inherent property. After PF if we do D' it will give perfect result. !ut after certain time it starts to deteriorate and we can*t get the perfect therapeutic effect from that drug. &or e(ample, antibiotics are very prone to deteriorate. So if we start a seven day course of an antibiotic we may get the right amount of therapeutic effect on the first day. !ut as the drug deteriorates day by day we can*t get the same therapeutic effect on the seventh day. So some e(tra amount of active ingredients is added with the label claim. This e(tra amount is called overage. This is done to deteriorate prone medicines so that medicines give therapeutic effect even the last date of shelf life. Pharmacopoeia gives us a range for overage. !ut it is the decision of manufacturer that how much overage he wants to use. The specific amount of overage that a manufacturer wants to use is called definite overage.