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PHARMACEUTICALS

JACQUES MICHAUD
Cerestar
Application Centre Pharma & Chemical
Vilvoorde, Belgium

Pharmaceutical
confectionery

ard boiled candies,


lozenges, hard or soft
gums, tablets, chewing
gums, all these sweets
are usually more related to the food
industry than to the pharmaceutical
area. Although, medicated
confectionery is widely used in the
formulation of drugs for many
indications such as minor throat
irritations, coughs, colds, respiratory
tract congestion and allergies. Other
medicines containing active
ingredients such as antacids,
vitamins, herbal extracts can also be
formulated as confectionery
products. Various carbohydrates can
be used in the preparation of these
confectionery products (Table I) and
besides the classical sugar or
glucose based recipes, a complete
range of polyols now allows the
formulation of sugar-free products
avoiding the risk of tooth decay
especially when drugs have to be
delivered to children.
The most common formulations of
medicated confectionery products are
manufactured in the form of high
boiled candies utilising plastic moulding
or depositing methods. Table II gives a

non extensive list of active substances


formulated in this format. The
manufacturing methods are very similar
to the classical boiling techniques. A
cooked sugar base, sucrose and
glucose syrup are blended in the
proportion of 50% to 60% sucrose
with 40% to 50% glucose syrup. The
ratio is variable and depends upon the
type of equipment and the recipe, the
most important parameter to be taken
into account is the prevention of sugar
crystallisation. The glucose syrups used
are mostly 40 DE (dextrose equivalent)
syrups which can show a full variety of
carbohydrate profiles. Special high
maltose syrups allow to decrease the
proportion of sugar down to 20%. It
has a positive influence on the
transparency of the hard boiled candy
by limiting the risk of graining linked to
sucrose re-crystallisation during storage.
The discoloration is also improved
thanks to a lower cooking temperature
of the candy mass Actives and flavours
can be incorporated in batch proportion
by sprinkling over the surface of the
gradually spreading batch on the slab.
As the risk for dental caries is
more recognised by the public, sugar
free formulations of hard boiled

Table I - Typical confectionery applications

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PHARMACEUTICALS

candies are more and more applied.


sweetener is not
Table II - Typical applications of hard boiling candies
Due to the fact that they cannot be
necessary. The syrup
Indication
Active ingredient
metabolised by the mouth
compositions enables
Streptococci, polyols are not
the gelatine to
Throat infections
Amylmetacresol
contributing to the lowering of the
achieve its full gelling
Mouth and throat infections
Benzocaine
oral pH, therefore they are ideal
power. By varying
Bronchial
catarrh
and
cough
relief
Benzoin
tincture
substitutes to sugar and glucose
gelatine level and
Sore
throat
relief
Camphor
syrup in confectionery products.
type, maltitol syrup
Pharyngitis
Cetyl pyridinium chloride
Figure 1 shows the relative
level and cooking
Mouth and throat infections
Chlohexidine
sweetness of classical polyols in
temperature, any
hydrochloride
comparison to that of sucrose.
traditional texture
Cough
suppressant
Diphenhydramine
Maltitol syrup is currently the most
profile from very soft
hydrochloride
used polyol for the manufacture of
to hard pastille type
Cough relief and decongestant
Eucalyptus oil
sugar-free medicated hard candy. Its
gums can be
Sore throat relief
Hexylresorcinol
main advantages in comparison with
obtained. Due to the
alternative bulk sweeteners being high
low viscosity of
Cough relief and nasal decongestion
Liquid tolu
sweetness (between 80% and 90%
maltitol syrup, the
Cough and sore throat relief,
Menthol
compared to sucrose and good
mass is easy to
decongestant
masking properties of the possible
handle and moulding
Cough relief and nasal decongestant
Pine oil
bitterness of the active ingredients.
at high dry substance
Cough and sore throat relief,
Thymol
Maltitol gives transparent candies with a
is possible.
decongestant
smooth glossy surface and a pleasant
Maltitol is also a
Throat infection
Phenol
sweetness. Due to its excellent heat
very good sweetener
stability, there is no colour development
in combination with
during boiling. Candies containing
gum arabic for the
granulated using a wet binder, then
maltitol have good workability for
production of sugar free pastilles. The
wet granulates are sieved, dried and
depositing as well as for plastic
correct sweetness can be obtained
possibly ground prior to compressing
moulding.
using maltitol syrup as sole sweetener.
the tablets. In dry granulation,
Other types of products containing
Texture, transparency, gloss and
powdered components are typically
active ingredients such as
storage stability are key properties.
mixed prior to a compaction also
dextromethorphan, diphenhydramine
Gum arabic pastilles formulated with
called pre-compression that yield
or pseudoephedrine can be found in
maltitol syrup have excellent storage
hard slugs which are then ground
chewy format. These products provide
stability and better controlled water
and sieved before addition of other
pleasant-tasting cough suppressant
pick-up and retention. This also means
ingredients and final compression.
which chew out smoothly and
that maltitol prevents gums from
Direct compression is now
dissolve away in the mouth. Similar
becoming sticky or brittle as often
considered as the simplest and the
products also contain antacids,
occurs with traditional sugar based
most economical process to produce
calcium supplements or antibacterial
pastilles. Sugar free pastilles are
tablets. This process requires only
preparation and provide soft-chew
normally deposited in moulding starch
two steps that are the mixing of all
dosage form in almost soft nougat
and dried under standard conditions.
the ingredients and the compression
consistency. The preparation and the
Tablets are amongst the most
of this mixture. Excipients when
equipment are similar to those of
frequently employed delivery forms for
intended for direct compression must
classical chewy candies. Sugar-free
most of the medicinal preparation. This
fulfil a certain number of properties.
formulations are as well used.
situation can be explained by the fact
They should have a high flowability.
Gelatine and gum arabic starchthat these dosage forms allow a good
They should have a high
deposited gum products are useful bases
accuracy of dosage of the active
compressibility and a good
for medicated confectionery. Typical
component of the medicinal
pressure/hardness profile. They
products contain actives from Table III,
formulation. Medicated forms of tablets
should be compatible with all types
however the high temperature process and
are usually applied to deliver salts and
of active ingredients and not interfere
the stoving may cause significant losses of
actives, such as vitamins (Table IV).
with their biological availability, they
volatile materials. Mainly base ingredients
Tablets can be manufactured
also should be stable against ageing,
are manufactured from sugar, glucose
using three main processes, wet
air moisture and heat. They should
syrup, gum arabic, gum tragacanth, pectin,
granulation, dry granulation and direct
be colourless and tasteless and
agars, starches, actives, colours and
compression. In wet granulation,
provide a pleasant mouth feeling.
flavours.
components are typically mixed and
Excipients can be characterised
As for hard boiled candy,
according to their function
sugar free formulations of gum
during the formulation as,
Figure 1 - Relative sweetness of polyols compared to sucrose
product are more and more
for instance, binders, fillers,
developed. A wide range of
glidants, lubricants and
maltitol syrups is now available
eventually flavours,
with contents from 50% to 90%
sweeteners and dyes.
of maltitol. For sugar free gelatine
Filling and binding is often
gums with taste and sensorial
provided by the same
properties equivalent to
material. Sucrose, lactose,
conventional gums, a maltitol
dextrose, mannitol or
syrup containing 75% of maltitol
sorbitol are commonly
is a possible product to replace
used compression fillers.
all the sugar. It has almost 90%
When necessary other
of the sweetness of sucrose and
binders such as
therefore the addition of intense
pregelatinised starches or
PHARMACEUTICALS

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the manufacturing process consists


of softening the gum base by
Indication
heating it between 50C and 70C
in a mixer equipped with slow
Sore throat relief, throat infections
turning blades. Glucose syrup is then
and anaesthetic
added together with powdered sugar
Cough relief
(liquid sorbitol and powdered
Cough and cold relief
sorbitol respectively in the case of a
Sore throat relief
sugar-free formulation). Softeners
Cough relief
and flavours are then added. The
Cough relief
warm mass is transferred from the
Cough, cold and sore throat relief
mixer onto slow moving cooling
Cough and sore throat relief
belts which are bathed in current of
cool air. The mass is then extruded
Cough and sore throat relief
and rolled out to the right thickness
Cough relief
prior to be cut in single pieces. The
Cough relief
chewing gum is then moved to a
Cough, cold and sore throat relief
conditioning room and is coated
after a few days of maturing. The
active ingredient is generally
micro-crystalline cellulose are used to
incorporated into the gum base,
hold the structure of the dosage
however it is also possible to add
forms.
the drug during the coating process
Tablets are certainly the
if it is unstable under the
medicated confectionery dosage Figure 2 - Hardness of tablets vs. sorbitol particle size distribution
conditions of the
form that is using the most sugar
manufacturing process.
free formulations. Compressible
Granulation and
grades of mannitol and sorbitol
compression method similar
are available to produce hard
to that used for tablets have
tablets. Surface area, melting
also been developed for
point, degree of crystallinity,
producing chewing gum. This
crystal morphology, surface
granulation method is
geometry and texture are very
particularly suitable for active
important characteristics of
ingredients that exhibit poor
sorbitol powder that influence
release profiles.
compressional behaviour. In
Many factors can affect the
addition, the particle size
release of drugs formulated in
distribution has to be adapted
chewing gums. The most
according to the crystal
important of these factors being
morphology for optimum
the chewing time, the chewing
performance (Figure 2). Finally good
rate, the solubility of the drug and the
natural and synthetic resins such as
flowability, as expressed by Carr index in
composition of the chewing gum.
polyvinyl acetate, fats, emulsifiers, waxes,
Table V, is very important for tabletting to
antioxidants, fillers
provide uniform tablets weight which is
and flavouring agents.
Table IV - Typical application of tablets and lozenges
essential for a uniform active dosage
The elastomers
distribution.
provide elasticity and
Indication
Active ingredient
Friability of sorbitol tablets, even when
cohesion to the
compressed at low pressure, is very low.
chewing gum
Nasal decongestion, catarrh and
Ammonium chloride
Additionally to the nature and the dosage
blocked sinuses
whereas the resins
of the active substance, other factors such
act as mastication
Vitamin C supplements and
Ascorbic acid
as lubricant level, mixing time, flavour and
cold relief
substances and
colour type or tablet shape will also
binding agents
Bronchial catarrh, cough and
Capsicin
influence the properties of the compressed
cold relief
between the
tablets.
elastomers and the
Mouth and throat infection,
Dequalinium chloride
Chewing gum is a potentially useful
pharyngitis
fillers. The elastomers
mean of administering drugs. As an oral
are important for the
Sore throat
Domiphen bromide
mucosal drug delivery system it offers
balance between
Cough relief and decongestant
Eucalyptus oil
several advantages. For the
elasticity and
Cough and sore throat relief,
Menthol
administration of drugs intended to
plasticity. The
decongestant
treat or prevent local diseases of the
sweetening agents
Cough, cold and sore throat relief
Methyl salicylate
mouth, it offers the possibility of
can be based either
Nasal congestion, catarrh and
Phenylephrine hydrochloride
releasing active substances in a
on sugar or on
blocked sinuses
controlled manner over extended times
polyols. Most of the
Sore throat relief
Potassium chlorate
thereby providing a prolonged
medicated chewing
Sore throat relief
Terebene
therapeutic effect. It can be particularly
gums are now sugar
Cough and sore throat relief,
Thymol
useful for the systemic delivery of drugs
free and mainly
decongestant
which are susceptible to metabolism in
sweetened with
Throat irritation, pharyngitis and
Tyrothricin
the gut wall or the liver. Additionally,
sorbitol and intense
laryngitis
active substances that are formulated in
sweeteners.
chewing gum are delivered in the
The first step of
Table III - Typical application of gums

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gastrointestinal
tract either
Active ingredient
dissolved or
suspended in
Benzalkonium
saliva and are
thus present in a
Cinnamic acid
readily bioCodeine phosphate
available form.
Camphor
The formulation
Camphorated opium lind
of a chewing gum is
Acetic acid
always based on the
Guaicol
gum base, see typical
Guaiphesin
formulation of a
Fluorinated chewing
Halogenated phenols
gum in Table VI.
Ipecacuanha liquid extract
Other added
Papaverine hydrochloride
components typically
Terpineol
include sweetening
agents, flavour and
aromas. The gum
base can consist of a complex mixture of
elastomers either natural or synthetic such
as polyisobutylene or styrene-butadiene,

PHARMACEUTICALS

Figure 3 - Release of drugs vs. water solubility

Europe it is not permitted to make


medicinal claims unless a medicine licence
is obtained. All the raw materials have to be
identified and checked according to the
relevant monographs and the processes
have to meet the requirements of the
c-GMP's. Additionally, a complete clinical
study has to be performed in order to
guaranty the activity of the drug.

REFERENCES

LACHMAN, L.; LIEBERMAN, H.A.; RICHARDSON,


G.Medicated Candies, Drug and Cosmetic
Industry 1966, 99 (1-3)
CUMMINGS, C.S. Sugar Confectionery
Manufacture 258-279
ROMER RASSING, M. Drugs and the
Pharmaceutical Sciences 1996, 74,
319-357
ALEXANDER, R.J. Cereal Foods World
1998, 43, 386-387

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Although it is quite
medicated chewing
Table V - Flowability of sorbitol
difficult to design
gum. A reduction of
according to particle size distribution
clinical trials for
the particle size of
chewing gum
the drug before its
Fine
Medium Coarse
formulated drugs, it
addition to the gum
Carr Index 20.6
20
15
has been reported
base can be used to
that a minimum
retard the release.
chewing time of 30
Finer particles can be
minutes should be used to be able to
more tightly embedded into the gum base
extrapolate the ordinary use of chewing
and their contact with saliva can therefore
gum. The rate at which a patient chews
be delayed. Another sustained release
the gum also affects the release of the
formulation possibility is the binding of a
drug. The average chewing rate is
drug to an ion exchange resin to decrease
normally about one chew every second,
the release. This is the well known example
although, it has been shown that slower
of Nicorette for which nicotine is
chewing rates give significantly lower
complexed to a methacrylic acid polymer.
drug release. The release of water
Different coating agents such as
soluble drugs (at least 100 g/l) is
polyvinylpyrrolidone and cellulose
generally about 75% or more during the
derivatives have also been used to obtain
first 5 minutes of chewing. When the
prolonged release. Embedding a drug in a
water solubility of a drug is lower, the
hydrophobic matrix consisting of lecithin
release of this drug decreases accordingly
and synthetic waxes is also reported.
(Figure 3) and not more that 5% release
Although pharmaceutical confectionery
can be expected for a drug
products are
that exhibit solubility lower Table VI - Composition
manufactured according
than 3 g/l.
to processed resembling
of a commercially available
The rapid release of
those of food products,
medicated chewing gum
drugs with high water
they must be strictly
solubility from a
complying with
Ingredients
Percentage
conventional chewing gum
pharmaceutical rules both
Gum base
52.6
might become a drawback
for ethical or OTC
Paraffin oil
3.4
when a sustained release
products. Full
Sorbitol
40.8
of the active ingredient is
documentation and
Mannitol
0.9
targeted. Only few
validation are required to
Saccharin
0.1
methods have been
obtain a product licence
Aromas
2.1
reported up to now to
from the national
Sodium fluoride
0.1
slow down the release of
authorities when any
the drug from the
medical claim is made. In

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