Quality control of pharmaceutical ingredients: developing a caking test for industry

Mark Leaper

Research output: Contribution to journalMeeting abstract

Abstract

Objectives - Powdered and granulated particulate materials make up most of the
ingredients of pharmaceuticals and are often at risk of undergoing unwanted
agglomeration, or caking, during transport or storage. This is particularly acute
when bulk powders are exposed to extreme swings in temperature and relative
humidity, which is now common as drugs are produced and administered in
increasingly hostile climates and are stored for longer periods of time prior to use. This study explores the possibility of using a uniaxial unconfined compression test to compare the strength of caked agglomerates exposed to different temperatures and relative humidities. This is part of a longer-term study to construct a protocol to predict the caking tendency of a new bulk material from individual particle properties. The main challenge is to develop techniques that provide repeatable results yet are presented simply enough to be useful to a wide range of industries.
Methods - Powdered sucrose, a major pharmaceutical ingredient, was poured
into a split die and exposed to high and low relative humidity cycles at room
temperature. The typical ranges were 20–30% for the lower value and 70–80% for
the higher value. The outer die casing was then removed and the resultant
agglomerate was subjected to an unconfined compression test using a plunger fitted to a Zwick compression tester. The force against displacement was logged so that the dynamics of failure as well as the failure load of the sample could be recorded. The experimental matrix included varying the number of cycles, the amount between the maximum and minimum relative humidity, the height and diameters of the samples, the number of cycles and the particle size.
Results - Trends showed that the tensile strength of the agglomerates increased
with the number of cycles and also with the more extreme swings in relative humidity. This agrees with previous work on alternative methods of measuring the tensile strength of sugar agglomerates formed from humidity cycling (Leaper et al 2003).
Conclusions - The results show that at the very least the uniaxial tester is a good
comparative tester to examine the caking tendency of powdered materials, with a
simple arrangement and operation that are compatible with the requirements of
industry. However, further work is required to continue to optimize the height/
diameter ratio during tests.
Original languageEnglish
Pages (from-to)A25
Number of pages1
JournalJournal of Pharmacy and Pharmacology
Volume60
Issue numberS1
DOIs
Publication statusPublished - Sep 2008
EventBritish Pharmaceutical Conference 2008 - Manchester , United Kingdom
Duration: 7 Sep 20089 Sep 2008

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Humidity
Quality Control
Industry
Pharmaceutical Preparations
Tensile Strength
Temperature
Climate
Particle Size
Powders
Sucrose

Cite this

@article{96771e2434694784b62b54baa32f9775,
title = "Quality control of pharmaceutical ingredients: developing a caking test for industry",
abstract = "Objectives - Powdered and granulated particulate materials make up most of theingredients of pharmaceuticals and are often at risk of undergoing unwantedagglomeration, or caking, during transport or storage. This is particularly acutewhen bulk powders are exposed to extreme swings in temperature and relativehumidity, which is now common as drugs are produced and administered inincreasingly hostile climates and are stored for longer periods of time prior to use. This study explores the possibility of using a uniaxial unconfined compression test to compare the strength of caked agglomerates exposed to different temperatures and relative humidities. This is part of a longer-term study to construct a protocol to predict the caking tendency of a new bulk material from individual particle properties. The main challenge is to develop techniques that provide repeatable results yet are presented simply enough to be useful to a wide range of industries.Methods - Powdered sucrose, a major pharmaceutical ingredient, was pouredinto a split die and exposed to high and low relative humidity cycles at roomtemperature. The typical ranges were 20–30{\%} for the lower value and 70–80{\%} forthe higher value. The outer die casing was then removed and the resultantagglomerate was subjected to an unconfined compression test using a plunger fitted to a Zwick compression tester. The force against displacement was logged so that the dynamics of failure as well as the failure load of the sample could be recorded. The experimental matrix included varying the number of cycles, the amount between the maximum and minimum relative humidity, the height and diameters of the samples, the number of cycles and the particle size.Results - Trends showed that the tensile strength of the agglomerates increasedwith the number of cycles and also with the more extreme swings in relative humidity. This agrees with previous work on alternative methods of measuring the tensile strength of sugar agglomerates formed from humidity cycling (Leaper et al 2003).Conclusions - The results show that at the very least the uniaxial tester is a goodcomparative tester to examine the caking tendency of powdered materials, with asimple arrangement and operation that are compatible with the requirements ofindustry. However, further work is required to continue to optimize the height/diameter ratio during tests.",
author = "Mark Leaper",
year = "2008",
month = "9",
doi = "10.1211/002235708785623471",
language = "English",
volume = "60",
pages = "A25",
journal = "Journal of Pharmacy and Pharmacology",
issn = "0022-3573",
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}

Quality control of pharmaceutical ingredients : developing a caking test for industry. / Leaper, Mark.

In: Journal of Pharmacy and Pharmacology, Vol. 60, No. S1, 09.2008, p. A25.

Research output: Contribution to journalMeeting abstract

TY - JOUR

T1 - Quality control of pharmaceutical ingredients

T2 - developing a caking test for industry

AU - Leaper, Mark

PY - 2008/9

Y1 - 2008/9

N2 - Objectives - Powdered and granulated particulate materials make up most of theingredients of pharmaceuticals and are often at risk of undergoing unwantedagglomeration, or caking, during transport or storage. This is particularly acutewhen bulk powders are exposed to extreme swings in temperature and relativehumidity, which is now common as drugs are produced and administered inincreasingly hostile climates and are stored for longer periods of time prior to use. This study explores the possibility of using a uniaxial unconfined compression test to compare the strength of caked agglomerates exposed to different temperatures and relative humidities. This is part of a longer-term study to construct a protocol to predict the caking tendency of a new bulk material from individual particle properties. The main challenge is to develop techniques that provide repeatable results yet are presented simply enough to be useful to a wide range of industries.Methods - Powdered sucrose, a major pharmaceutical ingredient, was pouredinto a split die and exposed to high and low relative humidity cycles at roomtemperature. The typical ranges were 20–30% for the lower value and 70–80% forthe higher value. The outer die casing was then removed and the resultantagglomerate was subjected to an unconfined compression test using a plunger fitted to a Zwick compression tester. The force against displacement was logged so that the dynamics of failure as well as the failure load of the sample could be recorded. The experimental matrix included varying the number of cycles, the amount between the maximum and minimum relative humidity, the height and diameters of the samples, the number of cycles and the particle size.Results - Trends showed that the tensile strength of the agglomerates increasedwith the number of cycles and also with the more extreme swings in relative humidity. This agrees with previous work on alternative methods of measuring the tensile strength of sugar agglomerates formed from humidity cycling (Leaper et al 2003).Conclusions - The results show that at the very least the uniaxial tester is a goodcomparative tester to examine the caking tendency of powdered materials, with asimple arrangement and operation that are compatible with the requirements ofindustry. However, further work is required to continue to optimize the height/diameter ratio during tests.

AB - Objectives - Powdered and granulated particulate materials make up most of theingredients of pharmaceuticals and are often at risk of undergoing unwantedagglomeration, or caking, during transport or storage. This is particularly acutewhen bulk powders are exposed to extreme swings in temperature and relativehumidity, which is now common as drugs are produced and administered inincreasingly hostile climates and are stored for longer periods of time prior to use. This study explores the possibility of using a uniaxial unconfined compression test to compare the strength of caked agglomerates exposed to different temperatures and relative humidities. This is part of a longer-term study to construct a protocol to predict the caking tendency of a new bulk material from individual particle properties. The main challenge is to develop techniques that provide repeatable results yet are presented simply enough to be useful to a wide range of industries.Methods - Powdered sucrose, a major pharmaceutical ingredient, was pouredinto a split die and exposed to high and low relative humidity cycles at roomtemperature. The typical ranges were 20–30% for the lower value and 70–80% forthe higher value. The outer die casing was then removed and the resultantagglomerate was subjected to an unconfined compression test using a plunger fitted to a Zwick compression tester. The force against displacement was logged so that the dynamics of failure as well as the failure load of the sample could be recorded. The experimental matrix included varying the number of cycles, the amount between the maximum and minimum relative humidity, the height and diameters of the samples, the number of cycles and the particle size.Results - Trends showed that the tensile strength of the agglomerates increasedwith the number of cycles and also with the more extreme swings in relative humidity. This agrees with previous work on alternative methods of measuring the tensile strength of sugar agglomerates formed from humidity cycling (Leaper et al 2003).Conclusions - The results show that at the very least the uniaxial tester is a goodcomparative tester to examine the caking tendency of powdered materials, with asimple arrangement and operation that are compatible with the requirements ofindustry. However, further work is required to continue to optimize the height/diameter ratio during tests.

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U2 - 10.1211/002235708785623471

DO - 10.1211/002235708785623471

M3 - Meeting abstract

VL - 60

SP - A25

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - S1

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