GlaxoSmithKline is a leading research-based pharmaceutical
company commit ted to excellence and i nnovation. We are
the second larges t life science company in the world a nd have
a leadership position in four major therapeutic areas – anti-
infectives, gastrointestinal/metabolic, respiratory and central
nervous system .
The source of our com petitive advant age is the energy and
commitment of our e mployees. Our missi on is to improve the
quality of human l ife to enable people to do mor e, feel better and
to live longer.
World-wide we empl oy over 110,000 people and have 80
manufacturin g sites in 37 countrie s. At our Cork Site in
Currabinny, which was e stablished in 1975, we man ufacture
the active ingredients of medical compounds. Our Currabinny
facility empl oys over 500 people, ma ny of whom are engaged
in development chemistry, analytical and quality chemistry and
chemical and process engineering.
The Cork facilit y is a strategic global new product i ntroduction
site within GSK’s ma nufacturing net work. We have a highly
automated manuf acturing facility, as well as an R& D Pilot Plant
with Pilot Plant Laboratories on site.
We are currently the p rimary product ion site for a number of
GSK’s top selling drug s which treat illnesse s such as depression,
Type 2 Diabetes, Conges tive Heart Failure, Ulcers, H IV, Ovarian
Cancer, Breast Cancer, Parkinson’s Disease and Arthritis.
GlaxoSmithKline also has a manufacturing and R&D facility in
Dungarvan, Co. Wate rford and sales and marketin g functions in
Dublin. GSK curren tly employs over 1,400 in Irelan d.
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Recrystallisation Benzoic Acid Determination Melting Point
of
and
of its
tapped sharply against the
desk causing the c rystals to
fall to the sealed en d. When
about 3 mm of crys tals are
in the base of the tube i t is
placed in the oil bat h. The
temperature at whi ch the
sample begins to mel t and
the temperature at w hich
it is completely me lted are
recorded.
To double check your
result, mix a samp le of
benzoic acid with s ome
pure benzoic acid. I f both
are pure benzoic aci d the
melting point wil l remain
the same but if the sa mple
is not pure benzoic ac id
then the melting po int will
be lowered.
How do I know I have a pure substance?
The melting point o f a substance is not the exac t point at which it melts
but rather the rang e of temperatur es from when th e samples sta rts to melt
until it has compl etely melted. The grea ter the range the more imp urities
present. A range of l ess than 1 °C indicates a pur e substance.
How is crystallisation used in industry?
The use of crystallisation in the pharmaceutical industry is an important
process for con trolling the physical propertie s, yield and purity of an
Active Pharmaceutical Ingredient (API). Many production processes
use c rystallisation in the fi nal stage of m anufacture to achie ve these
targets. Rece nt advances in crys tallisation proc ess monitoring allow f or
a better unders tanding of the process. Thes e advances allow crystals
with spec ifi c physical pro perties, for example par ticle size a nd shape,
to be created. It is pos sible to produce crys tals of varying par ticle size,
shape and form polymorphs of the same substance, bu t only one will be
suitable for drug d evelopment and manufac ture.
In industry, the way an API is fi ltered and dried can have a very signifi cant
impact on the physic al properties of the ma terial.
Calculating the percentage yield
After the cr ystallisation process the amo unt of sample will have been
reduced as impur ities have been remove d. To calculate how much of the
pure substance w as present in the initia l impure sample, the percentage
yield is calculated.
Mass of pure samp le (after recr ystallisation )
Mass of impure sa mple (before recr ystallisati on)
The percentage y ield is a good indica tor of the purity of th e initial
sample. A high perce ntage yield implie s a low concentrati on of
impurities, whe reas a low percentage yield indica tes a sample with a
lot of impurities .
Producing pure substanc es is a very importan t process,
especially in the pharmaceutical industry. Separating
insoluble solids from sol vents is easily achieved usi ng a
simple technique called fi ltration. Soluble solids again
are easily separated f rom solvents by evaporation, and
chromatography is used to separate a mixture of l iquids. But
what happens when we have two s oluble solids that we want
to separate? In this lesson we wi ll look at recrystallisation, a
commonly-used process in the pharmaceutical industr y.
What is recrystallisation?
Recrystall isation is a very im portant purifi cation technique, purifying
substances by re moving unwanted by-pr oducts. It is also u sed
to manufacture t he correct crys tal size and shape of a m aterial.
These factors can have a very signifi cant impact on how a
medicine acts w hen taken by a patient. T he same principles a nd
techniques of rec rystallisation c an be applied both on a labor atory and
industry scale.
What are the principles behind
recrystallisation?
The process depe nds on two principles; the f act that substances tend
to be more soluble in a hot so lvent than in cold solve nt, and that each
solute tends to behave as thou gh it were alone in the solvent .
How do I know what solvent to use?
Using the correc t solvent is a very important p art of the process. The
solute must be inso luble in the solvent at room te mperature, and as the
temperature of the s olvent increase s, the solubility o f the solute also
increases. It is a lso important that the im purities present are solub le in
the solvent at room temperature and insoluble at higher temperatures.
An excellent subs tance for showing t his process is benzoi c acid
(C6H5COOH). A molecul ar crystal rather than an ion ic crystal, shown
by its low melting po int of 122 °C, benzoic acid is u sed as an anti-
microbial agent and is found in tooth pastes, mouthwashes, cosme tics
and deodorants.
Impure benzoic aci d contains the impur ities phthalic ac id and
benzylbenzoa te. If the impure sampl e is dissolved in a mi nimal volume of
hot solvent – in this case boiling water – and fi ltered to remove insoluble
impurities, the re sulting solution will con tain dissolved benzoic ac id as
well as dissolved i mpurities.
Upon cooling, the be nzoic acid crys tals comes out of sol ution as its
solubiluty in th e solvent decreas es. The impuritie s will remain in solut ion
and can be fi ltered off.
It is very impor tant when carr ying out this experim ent that rubber glove s
are worn, because org anic substances can b e absorbed through t he
skin, and as well, gogg les should be worn to protec t your eyes from hot
liquids which may s pray out from the fl ask.
to be created. It is po ssible to produce crys tals of varying par ticle size,
polymorphs
suitable for drug d evelopment and manufac ture.
to be created. It is po ssible to produce crys tals of varying par ticle size,
shape and form
polymorphs
suitable for drug d evelopment and manufac ture.
targets. Rece nt advances in crys tallisation proc ess monitoring allow f or
a better unders tanding of the process. Thes e advances allow crystals
with spec ifi c physical prop erties, for example par ticle size a nd shape,
use c rystallisation in the fi nal stage of m anufacture to achie ve these
targets. Rece nt advances in crys tallisation proc ess monitoring allow f or
use c rystallisation in the fi nal stage of m anufacture to achie ve these
targets. Rece nt advances in crys tallisation proc ess monitoring allow f or
use c rystallisation in the fi nal stage of m anufacture to achie ve these
targets. Rece nt advances in crys tallisation proc ess monitoring allow f or
How can we check the purity of
our substance?
A pure s ubstance has a fi xed melting point while an impure substanc e
melts over a wide ran ge of temperatures an d at a lower temperature
than the pure subst ance. The melting points of almos t all substances
are available in tab les.
To check the melting poin t place a few cryst als of the sample on an
aluminium block which has a thermometer inserted. Use a hot plate
to heat the block slow ly. Watch the crystal s carefully and not e the
temperature at wh ich they begin to melt and the temper ature at which
they have all melted. C ompare this value wit h the value found on the
bottle of pure sub stance. Ano ther method of c hecking the me lting point of
crystals is to u se a narrow capillar y tube in an oil bath. The c apillary tube
has one end open and th e other end sealed. The open end is p ressed
into fi ne crys tals o f the substan ce and the turned upside down and
Beaker containing benzoic acid dissolved in
minimum amount of boiling water
Filter funnel with fluted filter paper to
speed up the filtrarion process. Insoluble
impurities left behind as residue
Conical flask with hot concentrated
benzoic acid solution which still contains
soluble impurities
Fig.1 Filtration to remove insoluble impurities
Pure benzoic acid cystals
Büchner funnel
Büchner flask
Water containing soluble impurities
Fig.2 After cooling, the remaining solution is fi ltered off
Thermometer
Benzoic acid crystals
Aluminium block
Bunsen burner
Fig.1 Finding the melting
point of benzoic acid
Percentage yield = x 100
You can fi nd out more about the work of
GlaxoSmithKline at www.gsk.com,
www.gsk.com/worldwide/ie.htm or at www.sta.ie
GlaxoSmithKline is a leading research-based pharmaceutical
company co mmitted to exc ellence an d innovation. We ar e
the second l argest lif e science co mpany in the worl d and have
a leadership position in four major therapeutic areas – anti-
infectives, gastrointestinal/metabolic, respiratory and central
nervous s ystem.
The source o f our competi tive advant age is the ene rgy and
commitme nt of our employe es. Our miss ion is to improve th e
quality o f human life to e nable people t o do more, feel be tter and
to live longer.
World-wid e we employ over 110,000 peop le and have 80
manufac turing sites i n 37 countrie s. At our Cork Si te in
Currabinny, whi ch was esta blished in 1975, we man ufacture
the active ingredients of medical compounds. Our Currabinny
facilit y employs over 5 00 people, ma ny of whom are en gaged
in development chemistry, analytical and quality chemistr y and
chemical and process engineering.
The Cork fac ility is a s trategic glo bal new produ ct introduc tion
site withi n GSK’s manufa cturing net work. We have a hig hly
automated m anufactu ring facili ty, as well as an R &D Pilot Plant
with Pilot Plant Laboratories on site.
We are current ly the primar y produc tion site for a nu mber of
GSK’s top selli ng drugs which treat illn esses such as depres sion,
Type 2 Diabetes, Co ngestive He art Failur e, Ulcers, HI V, Ovarian
Cancer, Breast Cancer, Parkinson’s Disease and Arthritis.
GlaxoSmithKline also has a manufacturing and R&D facili ty in
Dungarv an, Co. Waterf ord and sales a nd marketing f unctions i n
Dublin. GSK c urrently em ploys over 1,400 in Ir eland.
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Recrystallisation Benzoic Acid Determination Melting Point
of
and
of its
tapped sharply against the
desk causi ng the crystals to
fall to the sea led end. When
about 3 mm of cr ystals a re
in the base of t he tube it is
placed in th e oil bath. The
temperatu re at which the
sample beg ins to melt and
the tempera ture at which
it is comple tely melted a re
recorded.
To double check your
result, mi x a sample of
benzoic aci d with some
pure benzoic a cid. If both
are pure benzo ic acid the
melting poi nt will remai n
the same but i f the sample
is not pure ben zoic acid
then the mel ting point wil l
be lowered.
How do I know I have a pure substance?
The meltin g point of a subs tance is not t he exact poin t at which it me lts
but rather t he range of tempe ratures from w hen the sample s starts to m elt
until it has c ompletely melted. T he greater the range th e more impurities
present. A r ange of less th an 1 °C indica tes a pure subst ance.
How is crystallisation used in industry?
The use of crystallisation in the pharmaceutical industry is an important
process fo r controlli ng the physic al proper ties, yield a nd purity of a n
Active Pharmaceutical Ingredient (API). Many production processes
use crystallisa tion in the fi nal stage of manufacture to ac hieve these
targets. R ecent advances in c rystallisatio n process monitorin g allow for
a better un derstan ding of the proc ess. These a dvances all ow cryst als
with specifi c physic al prop erties, for example particle size and shape,
to be created. I t is possibl e to produce cr ystals of varying p articl e size,
shape and form polymorphs of the same substa nce, but only one will be
suitable f or drug develo pment and manu facture.
In industry, the way an API is fi ltered and dried can have a very signifi cant
impact on th e physical pro pertie s of the materia l.
Calculating the percentage yield
After th e crysta llisation p rocess the a mount of samp le will have bee n
reduced as i mpurities have been r emoved. To calculate how much o f the
pure subst ance was present in the i nitial impure sample, th e percentage
yield is calculate d.
Mass of pur e sample (after re crystallisa tion)
Mass of imp ure sample (before r ecrystallis ation)
The percen tage yield i s a good indica tor of the puri ty of the init ial
sample. A high p ercentag e yield implie s a low concen tration of
impuritie s, whereas a l ow percent age yield indi cates a sampl e with a
lot of impuri ties.
Producing pure substances is a ver y important process,
especially in the pharmaceutical industry. Separating
insoluble solids f rom solvents is easily achieved using a
simple technique called fi ltration. Soluble solids again
are easily separated from solvents by evaporation, and
chromatography is used to separate a mix ture of liquids. But
what happens when we have two soluble solids that we want
to separate? In this lesson we will look at recr ystallisation, a
commonly-used process in the pharmaceutical industry.
What is recrystallisation?
Recrys tallisat ion is a very im portan t purifi cation technique, purifying
substan ces by removin g unwanted by-p roducts. I t is also used
to manufac ture the corr ect crys tal size and s hape of a mater ial.
These factors can have a very signifi ca nt impact on how a
medicine ac ts when ta ken by a patient. T he same princ iples and
technique s of recrys tallisat ion can be app lied both on a la borator y and
industry scale.
What are the principles behind
recrystallisation?
The proces s depends on t wo princip les; the fac t that subst ances tend
to be more solub le in a hot solvent th an in cold solv ent, and that e ach
solute tends to behave a s though it wer e alone in the sol vent.
How do I know what solvent to use?
Using the cor rect solve nt is a very imp ortant p art of the pr ocess. The
solute must b e insoluble in the solvent a t room temper ature, and as th e
temperatu re of the solve nt increase s, the solubi lity of the so lute also
increase s. It is also imp ortant t hat the impuri ties prese nt are soluble i n
the solvent at room temperature and insoluble at higher temperatures.
An excellen t substanc e for showing t his proces s is benzoic acid
(C6H5COOH). A mo lecular cr ystal rat her than an io nic cryst al, shown
by its low melt ing point of 122 °C, be nzoic acid is u sed as an anti-
microbial agent and is found i n toothpas tes, mouthwa shes, cosme tics
and deodorants.
Impure benzo ic acid cont ains the impu rities pht halic acid and
benzylbe nzoate. If the impur e sample is dissol ved in a minimal volum e of
hot solvent – in this case boi ling water – and fi lte red to remove insoluble
impuritie s, the result ing solutio n will conta in dissolve d benzoic aci d as
well as diss olved impuri ties.
Upon cooli ng, the benzoic a cid crys tals comes o ut of soluti on as its
solubilut y in the solvent dec reases. The impur ities will remain in s olution
and can be fi ltered of f.
It is very im portant when ca rrying out this ex periment that rubbe r gloves
are worn, bec ause organic subst ances can b e absorbed t hrough the
skin, and as we ll, goggles sho uld be worn to protect your eye s from hot
liquids whi ch may spray ou t from the fl ask.
to be created. I t is possible to produce c rystal s of varyin g particl e size,
polymorphs
suitable f or drug develo pment and manu facture.
to be created. I t is possible to produce c rystal s of varyin g particl e size,
shape and form
polymorphs
suitable f or drug develo pment and manu facture.
targets. R ecent advances in c rystallisatio n process monitorin g allow for
a better un derstan ding of the proc ess. These a dvances all ow cryst als
with specifi c physica l prop erties, for example particle size and shape,
use crystallisa tion in the fi nal stage of manufact ure to achie ve these
targets. R ecent advances in c rystallisatio n process monitorin g allow for
use crystallisa tion in the fi nal stage of manufact ure to achie ve these
targets. R ecent advances in c rystallisatio n process monitorin g allow for
use crystallisa tion in the fi nal stage of manufact ure to achie ve these
targets. R ecent advances in c rystallisatio n process monitorin g allow for
How can we check the purity of
our substance?
A pure substance has a fi xed melting point while an i mpure subst ance
melts over a w ide range of tem peratures a nd at a lower tempe rature
than the pure s ubstance . The melting p oints of almo st all subst ances
are availabl e in tables.
To check the meltin g point place a f ew cryst als of the sam ple on an
aluminium block which has a thermometer inserted. Use a hot plate
to heat the blo ck slowly. Watch the c rystal s carefull y and note the
temperatu re at which the y begin to melt a nd the tempera ture at which
they have all mel ted. Compar e this value wi th the value fou nd on the
bottle of p ure substan ce. Another met hod of checki ng the melting po int of
cryst als is to use a narrow capi llary tube in an oil ba th. The capillary t ube
has one end op en and the othe r end sealed. T he open end is pre ssed
into fi ne crysta ls of the substance and the turned upside down and
Beaker containing benzoic acid dissolved in
minimum amount of boiling water
Filter funnel with fluted filter paper to
speed up the filtrarion process. Insoluble
impurities left behind as residue
Conical flask with hot concentrated
benzoic acid solution which still contains
soluble impurities
Fig.1 Filtration to remove insoluble impurities
Pure benzoic acid cystals
Büchner funnel
Büchner flask
Water containing soluble impurities
Fig.2 After cooling, the remaining solution is fi ltered off
Thermometer
Benzoic acid crystals
Aluminium block
Bunsen burner
Fig.1 Finding the melting
point of benzoic acid
Percentage yield = x 100
You can fi nd out more about the work of
GlaxoSmithKline at www.gsk.com,
www.gsk.com/worldwide/ie.htm or at ww w.sta.ie
