Tablet Testing Handbook PDF

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Lab handout booklet for semester 1 MDU lab....

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School of Pharmacy Faculty of Science and Engineering

5PY022: Medicines in Development and Use Practical Book 1: TABLET TESTING

The Experiments:    

Friability Hardness Disintegration Dissolution

Name Student Number

5PY022: Medicines in Development and Use - 1 of 41 ©WLL

& ZE 2020 – 2021

Instructions Due to the COVID-19 pandemic, you will be provided with the information as part of this booklet to take you through some experiments, which will be carried out by a member of a pharmaceutical formulation development team to test a batch of tablets for use in human patients. All the relevant information on how the tablet testing protocols should be carried out will be explained with additional supplementary video links to aid your understanding. You are also strongly advised to refer to additional reference resources (e.g. British Pharmacopoeia (BP) monograph) to further aid with your understanding. You will be provided with some sample data to write up your practical report. You will be expected to engage with the literature via portals such as ScienceDirect (www.sciencedirect.com), and include appropriate references to journal articles (including e- and online journals), text books, reputable websites (e.g. BP, MHRA, medicines.org), etc. as and when required throughout the article. Please refer to the details on CANVAS for information on the deadline for submission of the short communication article. All reports should be submitted as a Microsoft WORD document (“.doc”, “.docx” file). Your work will be subjected to Turnitin, hence please ensure that you are familiar with the regulations and guidelines relating to academic misconduct. For full details, please refer to the university’s “ Academic misconduct” website.

Background Reading for Tablets and Tabletting: • • • •

Aulton, M.E. (2006). Pharmaceutics: The Science of Dosage Form Design (third edition). Churchill Livingston. Florence, A. and Attwood, D. (2006). Physiochemical Principles of Pharmacy (fourth edition). Pharmaceutical Press. Sinko, P. J. (2005). Martin’s Physical Pharmacy (fifth edition). Lippincott, Williams and Wilkins. Watson, D. G. (2005). Pharmaceutical Analysis (second edition). Elsevier.

REMEMBER: Your School of Pharmacy staff are here to help you, but not to do the work for you. Please make an appointment via SAMS to talk to us if you have any issues. If you don’t inform us of problems or seek our guidance, we cannot help you .

5PY022: Medicines in Development and Use - 2 of 41 ©WLL

& ZE 2020 – 2021

The following information will provide you with some guidance on what to include in your report: Introduction EACH BULLET POINT SHOULD BE 1 – 4 SENTENCES ONLY. See International Journal of Pharmaceutics (2014), 476: 223-231. P1: Prescribing and uses of Aspirin • • •

Uses / what is it prescribed for? Disease(s) overview, including symptoms and pathophysiology (Treatment – unless covered in the paragraph below)

P2: API (Aspirin – acetyl salicylic acid) • • • • •

•

Chemistry Mechanism of action Dosing / regimen (BNF – British National Formulary) Side effects Current formulations (tablets, liquids – refer to BNF) Need for new formulation?

P3: Chosen formulations •

• •

How are they formulated IN GENERAL TERMS (e.g. types of tablets (oral, disintegration….), method of production (direct compression….), etc.) and how does this affect their performance during preparation, packaging, storage, as well as in vitro and in vivo behaviour? Why are they good / cheap? Why are they prescribed for the conditions mentioned in P1

P4: The tablet formulations • •

Functional group (e.g. disintegrant): What is the mechanism of action and what does it give the formulation Why and how do the two formulations help with delivery of Aspirin

P5: Concluding paragraph of intro. (2 – 3 sentences) “Therefore, the aim of this investigation was to investigate two solid dosage formulations of ……..”

Materials and Methods * For this practical, you can say: Refer to methods in the practical booklet.

Results and Discussion Conclusions Acknowledgements (This section is optional)

References (this section should be presented using the appropriate Harvard reference formatting – more information is available via https://www.wlv.ac.uk/lib/skills-for-learning/referencing/)

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Marking Scheme for the tablets report:

Introduction

Results and discussion

Conclusions

Data Analysis

References

EXCELLENT Introduction provides an in-depth lead in to the report. Includes details for prescribing and uses of aspirin, a detailed overview of API, overview of the preparation of tablets (different tablet types, function of excipients) and the pharmaceutical rationale for the formulations. Results and discussion provide in-depth, commentary on the data. Includes experimental details (where relevant), an overview of the underlying physicochemical properties of the tablet formulation and/or the constituent excipients.

GOOD Introduction provided a good/adequate lead into the report. Includes some details for prescribing and uses of aspirin, a brief back API, overview of the preparation of tablets (different tablet types, function of excipients) and/or the pharmaceutical rationale for the formulations. Results and discussion provide a commentary on the data. Includes some consideration of experimental details (where relevant), makes reference to the underlying physicochemical properties of the tablet formulation and/or the constituent excipients.

The conclusion provides a thorough summary with appropriately referenced pharmaceutical rationale. Insightful proposals for further experiments / formulation improvements are also included. A range of data analysis techniques are evident including appropriate presentation of data in graphical form and statistical analysis, in addition to justification for the treatment of data. All references are correctly cited using the Harvard reference citation formatting both in the references list and in the text. A good range of sources are included, such as journal articles, books, web articles (e.g. guidance from the regulator, MHRA), etc.

The conclusion provides a good summary with appropriately referenced pharmaceutical rationale. Some suggestions for further experiments / formulation improvements should also be included. A range of data analysis techniques are evident including appropriate presentation of data in graphical form and statistical analysis. > 80 % of the references are correctly cited using the Harvard reference citation formatting both in the references list and in the text. A range of sources are included, such as journal articles, books, web articles (e.g. guidance from the regulator, MHRA), etc.

ACCEPTABLE Introduction includes some mention of the details for prescribing and uses of aspirin, a brief back API, overview of the preparation of tablets (different tablet types, function of excipients) and/or the pharmaceutical rationale for the formulations. Some points may not be included. Results and discussion give limited analysis and discussion of the data. May include some experimental details (where relevant), give limited consideration of the underlying physicochemical properties of the tablet formulation and/or constituent excipients. The conclusion provides an adequate summary for the report but not all relevant material is included. The material should be appropriately referenced. Some consideration of pharmaceutical rationale is included. Appropriate presentation of data in graphical form and evidence of some statistical analysis is presented.

POOR Introduction briefly covers the relevant points which lead into the report. The provided information showed limited understanding to the topic and contains a lot of missing information.

> 60 % of the references are correctly cited using the Harvard reference citation formatting both in the references list and in the text. At least two types of sources are included, such as journal articles and books.

< 40 % of the references are correctly cited using the Harvard reference citation formatting both in the references list and in the text. Only one type of source is included, such as journal articles or books.

Results and discussion consist of descriptive narrative of the data presented with no consideration of the underlying physicochemical properties of the tablet formulation and/or the constituent excipients.

The salient points of the report are not considered in the conclusion and material is not appropriately referenced. Consideration of pharmaceutical rationale is absent. Some data is presented graphically, although this may not be in an appropriate format.

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Additional background information about the tablets formulations which will be used for this activity Both manufacturers were tasked to produce standard uncoated oral 300 mg aspirin tablets. The excipients incorporated in the tablet formulations are summarised in the table below: Manufacturer X: 300 mg uncoated aspirin tablet Aspirin Potato starch Lactose Talc

Manufacturer Y: 300 mg uncoated aspirin tablet Aspirin Quinine sulphate Microcrystalline cellulose (E460) Maize starch Calcium stearate Hydroxypropyl methylcellulose (E464) Polyethylene glycol

British Pharmacopoeia Monographs In the following sections you will find BP specifications for the se tests:

•

Friability and hardness

•

Disintegration

•

Dissolution

For each set of tests, you will need to read through the guidelines dictated by the BP and familiarise yourself with both the experimental and data analysis requirements. There are tables included in this guide with some data for you to write up your experimental report. If you have any queries about the equipment or experimental parameter s for a given test, please get in touch with a member of the practical or strand team.

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NOTE: The following information has been extracted directly from the British Pharmacopoeia (BP) website.

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TABLETS (Ph Eur monograph 0478) Tablets comply with the requirements of the European Pharmacopoeia. These requirements are reproduced below. Ph Eur The requirements of this monograph do not necessarily apply to preparations that are presented as tablets intended for use other than by oral administration. Requirements for such preparations may be found, where appropriate, in other general monographs; for example Rectal preparations (1145), Vaginal preparations (1164) and Oromucosal preparations (1807). This monograph does not apply to lozenges, oral pastes and oral gums. Where justified and authorised, the requirements of this monograph do not apply to tablets for veterinary use. DEFINITION Tablets are solid preparations each containing a single dose of one or more active substances. They are obtained by compressing uniform volumes of particles or by another suitable manufacturing technique, such as extrusion, moulding or freeze-drying (lyophilisation). Tablets are intended for oral administration. Some are swallowed whole, some after being chewed, some are dissolved or dispersed in water before being administered and some are retained in the mouth where the active substance is liberated. The particles consist of one or more active substances with or without excipients such as diluents, binders, disintegrating agents, glidants, lubricants, substances capable of modifying the behaviour of the preparation in the digestive tract, colouring matter authorised by the competent authority and flavouring substances. Tablets are usually straight, circular solid cylinders, the end surfaces of which are flat or convex and the edges of which may be bevelled. They may have break-marks and may bear a symbol or other markings. Tablets may be coated. Where applicable, containers for tablets comply with the requirements for materials used for the manufacture of containers (3.1 and subsections) and containers (3.6 and subsections). Several categories of tablets for oral use may be distinguished: — uncoated tablets — coated tablets — effervescent tablets — soluble tablets — dispersible tablets — orodispersible tablets — gastro-resistant tablets — modified-release tablets — tablets for use in the mouth

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— oral lyophilisates PRODUCTION Tablets are usually prepared by compressing uniform volumes of particles or particle aggregates produced by granulation methods. In the manufacture of tablets, means are taken to ensure that they possess a suitable mechanical strength to avoid crumbling or breaking on handling or subsequent processing. This may be demonstrated using the tests described in chapters 2.9.7. Friability of uncoated tablets and 2.9.8. Resistance to crushing of tablets. Chewable tablets are prepared to ensure that they are easily crushed by chewing. Subdivision of tablets: Tablets may bear a break-mark or break-marks and may be subdivided in parts, either to ease the intake of the medicinal product or to comply with the posology. In the latter case, subdivision must be assessed and authorised by the competent authority. In order to ensure that the patient will receive the intended dose, the efficacy of the breakmark(s) must be assessed during the development of the product, in respect of uniformity of mass of the subdivided parts. Each authorised dose must be tested using the following test. Take 30 tablets at random, break them by hand and, from all the parts obtained from 1 tablet, take 1 part for the test and reject the other part(s). Weigh each of the 30 parts individually and calculate the average mass. The tablets comply with the test if not more than 1 individual mass is outside the limits of 85 per cent to 115 per cent of the average mass. The tablets fail to comply with the test if more than 1 individual mass is outside these limits, or if 1 individual mass is outside the limits of 75 per cent to 125 per cent of the average mass. In the manufacture, packaging, storage and distribution of tablets, suitable means are taken to ensure their microbiological quality; recommendations on this aspect are provided in chapter 5.1.4. Microbiological quality of non-sterile pharmaceutical preparations and substances for pharmaceutical use. TESTS Uniformity of dosage units (2.9.40) Tablets comply with the test or, where justified and authorised, with the tests for uniformity of content and/or uniformity of mass shown below. Herbal drugs and herbal drug preparations present in the dosage form are not subject to the provisions of this paragraph. Uniformity of content (2.9.6) Unless otherwise prescribed or justified and authorised, tablets with a content of active substance less than 2 mg or less than 2 per cent of the total mass comply with test A. If the preparation has more than 1 active substance, the requirement applies only to those substances that correspond to the above conditions. Unless otherwise justified and authorised, coated tablets other than film-coated tablets comply with test A irrespective of their content of active substance(s). Uniformity of mass (2.9.5) Uncoated tablets and, unless otherwise justified and authorised, film-coated tablets comply with the test. If the test for uniformity of content is prescribed or justified and authorised for all the active substances, the test for uniformity of mass is not required.

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Dissolution A suitable test may be carried out to demonstrate the appropriate release of the active substance(s), for example one of the tests described in chapter 2.9.3. Dissolution test for solid dosage forms. Where a dissolution test is prescribed, a disintegration test may not be required. Uncoated tablets DEFINITION Uncoated tablets include single-layer tablets resulting from a single compression of particles and multi-layer tablets consisting of concentric or parallel layers obtained by successive compression of particles of different composition. The excipients used are not specifically intended to modify the release of the active substance in the digestive fluids. Uncoated tablets conform to the general definition of tablets. A broken section, when examined under a lens, shows either a relatively uniform texture (single-layer tablets) or a stratified texture (multi-layer tablets) but no signs of coating. TESTS Disintegration (2.9.1) Uncoated tablets comply with the test. Use water R as the liquid. Add a disc to each tube. Operate the apparatus for 15 min, unless otherwise justified and authorised, and examine the state of the tablets. If the tablets fail to comply because of adherence to the discs, the results are invalid. Repeat the test on a further 6 tablets omitting the discs. Chewable tablets are not required to comply with the test. Coated tablets DEFINITION Coated tablets are tablets covered with one or more layers of mixtures of various substances such as natural or synthetic resins, gums, gelatin, inactive and insoluble fillers, sugars, plasticisers, polyols, waxes, colouring matter authorised by the competent authority and sometimes flavouring substances and active substances. The substances used as coatings are usually applied as a solution or suspension in conditions in which evaporation of the vehicle occurs. When the coating is a very thin polymeric coating, the tablets are known as film-coated tablets. Coated tablets have a smooth surface, which is often coloured and may be polished; a broken section, when examined under a lens, shows a core surrounded by one or more continuous layers with a different texture. PRODUCTION Where justified, uniformity of mass or uniformity of content of coated tablets other than filmcoated tablets may be ensured by control of the cores.

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TESTS Disintegration (2.9.1) Coated tablets other than film-coated tablets comply with the test. Use water R as the liquid. Add a disc to each tube. Operate the apparatus for 60 min, unless otherwise justified and authorised, and examine the state of the tablets. If any of the tablets has not disintegrated, repeat the test on a further 6 tablets, replacing water R with 0.1 M hydrochloric acid. Filmcoated tablets comply with the disintegration test prescribed above except that the apparatus is operated for 30 min, unless otherwise justified and authorised. If coated tablets or film-coated tablets fail to comply because of adherence to the discs, the results are invalid. Repeat the test on a further 6 tablets omitting the discs. Chewable coated tablets are not required to comply with the test. Effervescent tablets DEFINITION Effervescent tablets are uncoated tablets generally containing acid substances and carbonates or hydrogen carbonates, which react rapidly in the presence of water to release carbon dioxide. They are intended to be dissolved or dispersed in water before administration. TESTS Disintegration Place 1 tablet in a beaker containing 200 ml of water R at 15-65 °C; numerous bubbles of gas are evolved. When the evolution of gas around the tablet or its fragments ceases the tablet has disintegrated, being either dissolved or dispersed in the water so that no agglomerates of particles remain. Repeat the operation on 5 other tablets. The tablets comply with the test if each of the 6 tablets used disintegrates in the manner prescribed within 5 min, unless otherwise justified and authorised. Soluble tablets DEFINITION Soluble tablets are uncoated or film-coated tablets. They are intended to be dissolved in water before administration. The solution produced may be slightly opalescent due to the added excipients used in the manufacture of the tablets. TESTS Disintegration (2.9.1) Soluble tablets disintegrate within 3 min, using water R at 15-25 °C. Dispersible tablets DEFINITION Dispersib...