PAPQC Lab Schedule 2013-Final

7/27/2019 PAPQC Lab Schedule 2013-Final

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UNIVERSITY OF HERTFORDSHIRE

SCHOOL OF PHARMACY

M.PHARM., LEVEL 3:

PHARMACEUTICAL ANALYSIS, PRODUCTION & QUALITY CONTROL

Semester B, 2013

PHARMACEUTICS LABORATORIES:

SOLID DOSAGE FORM MANUFACTURE AND EVALUATION
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University of Hertfordshire School of Pharmacy

Pharmaceutical Analysis, Production & Quality Control

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This booklet contains information regarding the practicals in Pharmaceutical Analysis, Production and Quality

Control. It outlines the methods that you will use in the practical sessions this year. In doing so, it contains a

detailed description of the manufacturing process, and an outline of the evaluation laboratory session. Further

details on the latter can be found in lecture notes on the PAPQC website on StudyNet and the British

Pharmacopeia.

Please ensure that you are familiar with the School of Pharmacy policies for working in laboratories. If you

require clarification on our policies for working in a laboratory then please ask the module lead.

Lecture Notes

The lecture course in this module significantly supports the practical sessions. Please ensure that you bring them

with you to the laboratory session, as they will help you plan and organise your work.

Batch Record Sheets and Log Books

These will be available via the PAPQC site on StudyNet. Please PRINT BRS and bring them with you to the

laboratory session. You are also required to keep a laboratory book during these lab sessions, which can be

inspected by staff during practicals. You will need to submit the BRS and test results from the evaluation lab at

the end of the lab sessions and these will provide a valuable aid when writing up your report.


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COLLUSION AND PLAGIARISM

Plagiarism is a serious breach of academic conduct and will be dealt with according to the university

regulations. Coursework should always be your OWN work.. All work done by other people should be

acknowledged and you should ensure that you use the faculty referencing guidelines on how to reference other

peoples work in your written essays and reports. You must be aware that the University takes collusion,plagiarism and cheating very seriously and you will be severely penalised for any of these offences. Brief

descriptions of collusion and plagiarism, and advice on how to avoid committing such a breach of theregulations are given below. However, full details may be found in via your Student Handbook.

Collusion

Collusion is working together to produce assessed work in circumstances where this is forbidden. The

University Regulations define collusion as the representation by an individual of work which he or she hasundertaken jointly with another person as having been undertaken independently of that person. You will

always be encouraged to discuss the results you have generated in practicals with the people you worked with

but you should always write up your reports and laboratory logbook on your own using your own graphs and

tables.

Plagiarism

Plagiarism is a form of academic dishonesty. The University regulations define plagiarism as the

representation by an individual, whether intentionally or otherwise, of another persons work as their own or

use of another persons work without acknowledgement. If you follow the guidelines given in Appendix 9 you

will avoid plagiarism. There are severe penalties for plagiarism. Key aspects are summarised below:

All the work in your report must be carried out by you and all the results given in your report must havebeen obtained by youexcept where you give due acknowledgement to others;

All the written work (prose or text) must be written by you in your own words, except where you give dueacknowledgement to others and use quotation marks, and except also for occasional brief phrases of no

special significance which may be taken from other peoples work without such acknowledgement and use

of quotation marks; If when you acknowledge the source of a piece of information, you must always rewrite the information in

your own words which conveys your understanding of the information;

All the figures and diagrams in your report must be devised and produced by you, except where you givedue acknowledgement to others.

In scientific writing any reader should be able to follow an audit trail to the source of the information. The

reader needs to be able to verify the truth of what is being stated.

Plagiarism is academic misconduct. Students should note that it is a requirement of all Schools of

Pharmacy to report all cases of academic misconduct to the Royal Pharmaceutical Society of Great

Britain.


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LABORATORY RULES FOR PHARMACEUTICAL ANALYSIS, PRODUCTION &

QUALITY CONTROL

The Health and Safety of students and staff is of paramount importance in all laboratories. The rules listed

below must be adhered to at all times in laboratories, and any breach of these rules, particularly where this maycause harm to yourself or to others, will be treated as a serious disciplinary matter.

GENERAL LABORATORY RULES

Laboratory classes begin punctually as specified in your timetables. It is your responsibility to attend these

classes on time. Latecomers will not be admitted and alternative classes will not be provided for latecomers,

unless a satisfactory explanation of lateness is provided. This is particularly important in this module, as all the

laboratory practicals are group exercises.

As a minimum requirement, clean white laboratory coats must be worn at all times. Failure to do so is a breach

of Health and Safety regulations, and will mean that you are excluded from the laboratory. In addition, you may

be required to wear additional specific clothing depending upon the nature of the work being carried out.

No smoking, eating, drinking or chewing gum is permitted in the laboratories.

Mobile telephones must be switched off in laboratories. Please ensure that your mobile telephone is switched off

(not on silent) during laboratory classes. You will be excluded from laboratories and awarded a mark of zero forthat particular practical if you fail to adhere to this rule.

Safety spectacles and masks mustbe worn at all times when dangerous chemicals or reagents are employed.

You will be notified of such requirements as appropriate at the start of laboratory classes. Failure to comply with

repeated instructions to wear safety masks will result in exclusion from the laboratory. Again, you may be

required to wear additional laboratory clothing depending on the nature of specific practicals.

Accidents or breakages should be reported to a member of staff immediately.

Instrument failure should be reported to a member of staff immediately.

All equipment to be used by others must be cleaned immediately after use. Experiments are not considered to

be completed until you have cleaned us all the equipment and reagents you have used during the course of the

laboratory. Please note that marking schemes will reflect this.

Please ensure that you work in a clean and safe manner at all times. Please note that practical schedules may

include aspects of clean and safe working in the marking schemes.

Laboratory books, such as Martindale, the Pharmaceutical Codex and British Pharmacopoeia, should not be

used in the "working" area, i.e., at your bench. They should only be used away from areas where chemicals are

being used.

Please return all chemicals used in the laboratory to where you found them. If you persistently fail to adhere tothis rule you will be excluded from the laboratory.

Coats, bags and clothing may be stored in the area(s) provided and are not to be otherwise located in the

laboratory.

Students who put themselves or others at risk of injury by neglecting these rules will be immediately excluded

from the laboratory and may face further disciplinary measures.


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LABORATORY RULES FOR THE SOLID DOSAGE FORM MANUFACTURING

SUITE

Please note that these rules are in addition to, and not in place of, the general rules for laboratory safety, listed

elsewhere in this document.

Due to the use of speciali st pharmaceuti cal manufacturi ng equipment, you will not be able

to enter the manufactur ing sui te once a practical has started. You wil l not be able to attend

an al ternative session (unless you have good reason for being l ate) and you may lose

marks.

Please note that specific regulations will be used for each manufacturing session. You will be fully briefed of

these at the start of the class, and the Health & Safety documents will be available to view during, and between,

laboratory sessions. If you miss the start of a laboratory session without good reason you will not be omitted.

Please note that, as you are involved in group work, such unprofessional behaviour may be potentially

detrimental to your colleagues.


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Part One. Tablet Manufacture

Aims and objectives

The aims of these practical sessions are to illustrate the process involved in the production of conventionalimmediate release tablets formed by compression following a wet granulation process. It will also highlight

your abilities to work in a group, and to fairly and maturely discuss working practices in this group, and to

organise workloads fairly and equitably.

At the end of this practical, you will be able to describe the formation of granules for tablet compression,

describe the compression process of granules to form tablets, discuss the suitability of a pharmaceutical

manufacturing facility, to calculate the amounts of drugs and excipients required for yours tablets, to discuss

and contextualise the clinical relevance of the manufacture and evaluation processes, and to demonstrate

effective and professional group-working.

Experimental

Part One

Tabletting Processing

The drug you will use is sodium saccharide. It is a white odourless powder that is soluble in 1.5 parts water,

and has a pKa of 1.6. There are no known incompatibilities with this drug and any of the excipients.

The aim of this practical is to produce a batch of tablets (weighing approximately 500 mg) each containing 33%

w/w of the drug substance. The formula to be used is:

Drug 33% w/w

Lactose q.s.

Methycellulose (to be used as a 8% w/w

solution)

8% w/w

Magnesium stearate 1% w/w

Disintegrant ? % w/w

TOTAL to 500 mg

Notes:

1. You will need to choose the disintegrant for your formulation from either a conventional disintegrant, such

as maize starch, or a superdisintegrant, examples are Ac-di-sol (Cross-linked sodium carboxymethylcellulose),

EXPLOTAB (Sodium Starch Glycolate /cross-linked sodium carboxymethyl starch) and Kollidon CL

(Crospovidone/Cross-linked polyvinyl pyrrolidone). We will discuss with you at the start of the practical and

one disintegrant will be provided to each group. You will also need to decide the concentration of the

disintegrant depending on the type you use, based on the knowledge from lectures and textbooks.

2. The disintegrant is often added in two stages. Half is added before granulation, and the remaining half is

added after granulation and before compression; this is to ensure complete disintegration of both the tablet

and the compressed granules contained therein.

3. The lubricant is added to the dry granules prior to compression and the weight of lubricant to be added in is

based on the weight of the dry granules obtained after sieving.

Each laboratory group will be given a different formulation, varying in the concentration and type of

disintegrant used. This variation may have a significant, and specific, effect on the results of your evaluation

tests. You will need to discuss this effect in your lab report.


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Summary of the manufacturing process

The process that you will carry out is a generalised wet granulation process, with the following steps:

Check that the drying oven has been switched on and is at a suitable temperature. Please ask a member oftechnical staff if you have any issues.

Weigh out the drug and excipients make sure you get the right amount of each formulation ingredient,and that you weigh out enough materials in total so that you can carry out all your evaluation tests next

week. You should take into account that you may lose a significant amount of your formulation as you

progress through this experiment (ideally aim for 700 - 800 tablets).

Note: the binder methycellulose is to be used as an 8% w/w solution. The percentage of the binder in the

formulation (6% w/w) is based on this solution.

Mix this initial mixture in the v-shaped blender, add the binding solution, and mix for at least 5 10minutes, checking after 5 minutes if possible.

Transfer this mixture to the granulator make sure the mesh is fitted, and that you have something inwhich you can collect your granules.

Dry your granules using the oven and the moisture balance Re-granulate, if required make sure the screen has been cleaned and is dry before being used again Sieve, using a suitable size of sieve Weigh out the remaining excipients (calculate the amount of lubricant to be used based on the dry

granules obtained), add them to your granules, and mix in the cube mixer for five minutes.

Make your tablets!


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Part Two. Tablet Evaluation

Please check StudyNet regularly to see which session you have been allocated.

Aims and objectives

The aim of this session is for your group to assess the quality of a batch of tablets (not necessarily the tablets

that you made yourselves) by completing a series of BP tests.

The Tests

You are required to carry out six tests:

Dissolution Uniformity of drug content Disintegration Friability Hardness Uniformity of tablet mass

As part of your work, you should organise among yourselves how this work will be divided across your group.

This will be discussed at the start of the laboratory class. Please be aware that you may be working with other

groups of students, and that you may have to tailor your work plan accordingly. Please make full use of

available resources, include any suitable Pharmacopoeia.

Experimental

Methods for disintegration, friability, hardness and uniformity of tablet mass are given in the lecture notes, to

be found on the PAPQC StudyNet site. It is also advised that you check British Pharmacopeia for full details of

the tests. Staff will assist you in the technical use of equipment in laboratories, but will not design or develop

your protocols for you. Please refer to these notes before the practical, and bring them with you to the

laboratory if you feel that you need them. Other methods are listed below.

Measurement of the uniformity of drug content.

This section outlines a method you can use in order to determine the uniformity of drug content in the tablets

you are testing. You may still have to refer to the lecture notes to discuss the limits of the test, and whether or

not the samples you are analysing pass or fail the test. The key steps you need to carry out are:

Develop a method to extract the drug effectively from the tablets. Determine the concentration of the drug in the extraction solution.

Using a mortar and pestle, crush an appropriate number of tablets (one tablet in each mortar). Add

approximately 5 mLper tabletof a 50:50 distilled water and methanol mixture to the crushed tablet and wash

through a fan-folded filter paper into a 100 mL volumetric flask. Rinse the pestle and mortar several times with

the 50:50 distilled water and methanol mixture and pass through the filter paper. Make the solution up to

volume. (The crucial point is you dissolve the drug completely and transfer it into the flask completely)

Examine this solution by UV spectroscopy. You may have to dilute your sample in order to fit in the

concentration range of your calibration curve. If you have to dilute your sample please do so in a systematic

manner, i.e., a 1-in-10 dilution, for example.


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Dissolution Testing

Use the dissolution apparatus as instructed by staff. Remember that you will have to analyse the contents of

the dissolution sample at regular intervals by UV analysis, so please make sure that you, as a group, co-

ordinate this experiment with the uniformity of drug content experiment, so that you can share the same

analytical method.

Take three tablets and place each of them into a metal dissolution baskets this will be demonstrated by a

member of staff. Perform the BP Dissolution Test for 45 minutes see lecture notes for details. As part of this

test please remember to, at the end of the experiment, inspect the contents of the metal basket and report

your findings. Make sure you operate the experiment of the correct temperature and replace the sample you

withdraw from the vessel with fresh medium.

Determine the amount of drug in the sample using UV spectroscopy. Remember to filter your sample before

you conduct the UV measurement.

Development of the UV assay method

You need to develop an UV assay method for both the uniformity of drug content and dissolution tests. Below

are the key steps:

1). Determination of the drugs wavelength of maximum absorbance, max.

Determine the max and record this value in your laboratory notebook. Use only this value for all

subsequent UV analysis.

2). Production and validation of a calibration graph, or equivalent method, to allow a quantitative

determination of drug concentration in your samples.

The crucial part is to determine the concentration range of your calibration curve. Since this calibration

curve will be used for both the uniformity of content and dissolution tests, the ideal is that this range willcover all the sample concentrations of both tests. If this cannot be achieved, you may need to choose the

concentration range based on one test and dilute the samples of another test to fit into the range (choose

wisely which test samples you want to dilute, so that you can minimize the number of dilutions you have to

make). Now think about the sample concentrations of these two tests:

Uniformity of content: based on the drug content in each tablet and the volume you dissolve theminto, the theoretical concentration should be calculated.

Dissolution test: you are taking samples regularly from the start to the complete dissolution, so yoursample concentration range could be within 5% to 100% drug dissolved. Based on the drug content in

each tablet and the volume of the dissolution medium, you should be able to calculate this range.

Once you decided the concentration range, you can make a stock solution and dilute it into the requiredconcentrations within the range. Below are some guidelines:

Stock solution: Dissolve 100 mg of the drug standard in a volume of 100 mL. Dilute this stock solution into the required concentrations within the concentration range you have

chosen. Again, use a meaningful dilution technique in a systematic manner. Check what pipettes and

volumetric flasks are available in the lab (if what you need is not available and they are reasonable,

ask a member of technical staff for assistance).

This is an outline method only. Given your previous experience in the Analytical Science module, we have

provided a brief outline method for you to consider. You are expected to research fullyand justifyyour

chosen method, and to have this ready for your Evaluation laboratory. You need to discuss your method with

academic staff at the beginning of the lab before you start the experiments.

Documents

PAPQC Lab Schedule 2013-Final