Chemistry of Pectin and Its Pharmaceutical Uses: A Review

206 206 206 206 206 Chemistry of Pectin and Its Pharmaceutical Uses : A Review
Abstract
Pectin, a naturally occurring polysaccharide, has in recent years
gained increasingly in importance. The benefits of natural pectin are
also more and more appreciated by scientists and consumer due to
its biodegradability. Pectin is the methylated ester of polygalacturonic
acid. It is commercially extracted from citrus peels and apple
pomace under mildly acidic conditions. Pectins are divided into two
major groups on the basis of their degree of esterification. The
association of pectin chains leads to the formation of the three-
dimensional networks that is to gel formation. The pectin, by itself
or by its gelling properties, was employed in pharmaceutical
industry, health promotion and treatment. It has been used
potentially as a carrier for drug delivery to the gastrointestinal tract,
such as matrix tablets, gel beads, film-coated dose form. This
review will discuss the important chemistry and general properties
of pectin, and its gel formation mechanism and properties. The
example of the pharmaceutical uses of pectin will be given.
Chemistry of Pectin and Its
Pharmaceutical Uses : A Review
Pornsak Sriamornsak
Pornsak Sriamornsak 207 207 207 207 207
Introduction
Pectin is a naturally occurring biopolymer that is finding
increasing applications in the pharmaceutical and biotechnology
industry. It has been used successfully for many years in the food
and beverage industry as a thickening agent, a gelling agent and a
colloidal stabiliser. Pectin also has several unique properties that
have enabled it to be used as a matrix for the entrapment and/or
delivery of a variety of drugs, proteins and cells. This review will
first describe the source and production, chemical structure and
general properties of pectin. The methods of gel formation and
properties of the gels will then be discussed. Finally, some examples
of the pharmaceutical uses of pectin will be given.
Chemistry of pectin
Source and production
Pectin is a complex mixture of polysaccharides that makes up
about one third of the cell wall dry substance of higher plants. Much
smaller proportions of these substances are found in the cell walls of
grasses. The highest concentrations of pectin are found in the middle
lamella of cell wall, with a gradual decrease as one passes through
the primary wall toward the plasma membrane (Kertesz, 1951).
Although pectin occurs commonly in most of the plant tissues, the
number of sources that may be used for the commercial
manufacture of pectins is very limited. Because the ability of pectins
to form gel depends on the molecular size and degree of
esterification (DE), the pectin from different sources does not have
the same gelling ability due to variations in these parameters.
Therefore, detection of a large quantity of pectin in a fruit alone is
not in itself enough to qualify that fruit as a source of commercial
pectin (Thakur et al., 1997). At present, commercial pectins are
almost exclusively derived from citrus peel or apple pomace, both
by-products from juice (or cider) manufacturing. Apple pomace
contains 10-15% of pectin on a dry matter basis. Citrus peel
contains of 20-30% (May, 1990). From an application point of
view, citrus and apple pectins are largely equivalent. Citrus pectins
are light cream or light tan in colour; apple pectins are often darker.
Alternative sources include sugarbeet waste from sugar
manufacturing, sunflower heads (seeds used for edible oil), and
mango waste (Rolin, 1993).
Commercially, pectin is extracted by treating the raw material
with hot dilute mineral acid at pH about 2. The precise length of
extraction time varies with raw material, the type of pectin desired,
and from one manufacturer to another. The hot pectin extract is
separated from the solid residue as efficiently as possible. This is
not easy since the solids are by now soft and the liquid phase are
viscous. The viscosity increases with pectin concentration and
molecular weight. There is a compromise between efficient
extraction and solids separation and operating cost. The pectin
extract may be further clarified by filtration through a filter aid. The
clarified extract is then concentrated under vacuum. Powdered pectin
can be produced by mixing the concentrated liquid from either apple
or citrus with an alcohol (usually isopropanol). The pectin is
separated as a stringy gelatinous mass, which is pressed and washed
to remove the mother liquor, dried and ground.
This process yields pectin of around 70% esterification (or
methoxylation). To produce other types, some of the ester groups
must be hydrolysed. This is commonly carried out by the action of
acid, either before or during a prolonged extraction, in the
concentrated liquid, or in alcoholic slurry before separation and
drying. This process can produce a range of calcium reactive low
methoxyl pectins. Hydrolysis using ammonia results in the
conversion of some of the ester groups into amide groups,
producing amidated low methoxyl pectins (May, 1990).
Chemical structure
Pectin is an essentially linear polysaccharide. Like most other
plant polysaccharides, it is both polydisperse and polymolecular and
its composition varies with the source and the conditions applied
during isolation. In any sample of pectin, parameters such as the
molecular weight or the content of particular subunits will differ from
molecule to molecule.
The composition and structure of pectin are still not completely
understood although pectin was discovered over 200 years ago.
The structure of pectin is very difficult to determine because pectin
can change during isolation from plants, storage, and processing of
plant material (Novoselskaya et al., 2000). In addition, impurities
can accompany the main components. At present, pectin is thought
to consist mainly of D-galacturonic acid (GalA) units (Mukhiddinov
et al., 2000), joined in chains by means of -(1-4) glycosidic
linkage. These uronic acids have carboxyl groups, some of which
are naturally present as methyl esters and others which are
commercially treated with ammonia to produce carboxamide groups
(Fig. 1).
Fig. 1 (a) A repeating segment of pectin molecule and functional
groups: (b) carboxyl; (c) ester; (d) amide in pectin chain.
Pectin contains from a few hundred to about 1000 saccharide
units in a chain-like configuration; this corresponds to average
molecular weights from about 50,000 to 150,000 daltons. Large
differences may exist between samples and between molecules
within a sample, and estimates may differ between methods of
measurement.
In addition to the galacturonan segments shown in Fig. 1,
neutral sugars are also present. Rhamnose (Rha) is a minor
component of the pectin backbone and introduces a kink into the
straight chain (Fig. 2) and other neutral sugars such as arabinose,
galactose and xylose occur in the side chains (Oakenful, 1991). A
chain of several hundred -(1-4)-bonded GalA units with a varied
DE is a typical fragment.
The X-ray fibre diffraction studies showed that the galacturonan
segments in sodium pectate form helixes with three subunits per turn
and an identity period of 1.31 nm. The conformation of GalA units
as determined by NMR spectroscopy is
4
C
1
(Rees & Wright, 1971).
Calculations indicate that the helix is probably right-handed (Rees
& Wright 1971; Walkinshaw & Arnott, 1981a). Walkinshaw &
Arnott (1981a,b) indicated that X-ray fibre diffraction patterns of
sodium and calcium pectates, pectic acids, and pectinic acids show
the same helix structure, but the ways in which these helixes were
arranged relative to each other in the crystals seemed to differ. They
suggested that helical pectinic acid molecules pack in a parallel
arrangement, whereas the pectates pack as corrugated sheets of
antiparallel helixes.
Fig. 2 Schematic diagram showing how rhamnose (Rha) insertions
cause kinking of galacturonic acid (GalA) chain; S =neutral
sugars (adaptedfrom Sriamornsak, 2002).
Degree of esterification
The polygalacturonic acid chain is partly esterified with methyl
groups and the free acid groups may be partly or fully neutralised
with sodium, potassium or ammonium ions. The ratio of esterified
GalA groups to total GalA groups is termed as the DE. Pectin might
be formed initially in a highly esterified form, undergoing some
deesterification after they have been inserted into the cell wall or
middle lamella. There can be a wide range of DEs dependent on
species, tissue, and maturity. In general, tissue pectins range from
60 to 90% DE. It seems that the distribution of free carboxyl groups
along the pectin chains is somewhat regular, and the free carboxyl
groups are largely isolated from one another (DeVries et al., 1986).
The pectin classes based on the DE are high methoxyl (HM)
pectins, and the low methoxyl (LM) pectins which are either the
conventionally demethylated or the amidated molecule. DEs values
for commercial HM-pectins typically range from 60 to 75% and
those for LM-pectins range from 20 to 40%. These two groups of
pectin gel by different mechanisms. HM-pectin requires a minimum
amount of soluble solids and a pH within a narrow range, around
3.0, in order to form gels. HM-pectin gels are thermally reversible.
In general, HM-pectins are hot water soluble and often contain a
dispersion agent such as dextrose to prevent lumping. LM-pectins
produce gels independent of sugar content. They also are not as
sensitive to pH as the HM-pectins are. LM-pectins require the
presence of a controlled amount of calcium or other divalent cations
for gelation.
General properties of pectin
Pectins are soluble in pure water. Monovalent cation (alkali
metal) salts of pectinic and pectic acids are usually soluble in water;
di- and trivalent cations salts are weakly soluble or insoluble. Dry
powdered pectin, when added to water, has a tendency to hydrate
very rapidly, forming clumps. These crumps consist of semidry
packets of pectin contained in an envelope of highly hydrated outer
coating. Further solubilisation of such crumps is very slow. Clump
formation can be prevented by dry mixing pectin powder with
water-soluble carrier material or by the use of pectin having
improved dispersibility through special treatment during
manufacturing (Rolin, 1993; Hercules Incorporated, 1999).
Dilute pectin solutions are Newtonian but at a moderate
concentration, they exhibit the non-Newtonian, pseudoplastic
behaviour characteristics. As with solubility, the viscosity of a pectin
solution is related to the molecular weight, DE, concentration of the
preparation, and the pH and presence of counterions in the
solution. Viscosity, solubility, and gelation are generally related. For
example, factors that increase gel strength will increase the tendency
to gel, decrease solubility, and increase viscosity, and vice versa.
These properties of pectins are a function of their structure, which is
that of a linear polyanion (polycarboxylate). As such, monovalent
cation salts of pectins are highly ionised in solution, and the
distribution of ionic charges along the molecule tends to keep it in an
extended form by reason of coulombic repulsion (Paoletti, 1986).
Furthermore, this same coulombic repulsion between the
carboxylate anions prevents aggregation of the polymer chains. (The
number of negative charges is, of course, determined by the DE.) In
addition, each polysaccharide chain, and especially each
carboxylate group, will be highly hydrated. Solutions of monovalent
salts of pectins exhibit stable viscosity because each polymer chain
is hydrated, extended, and independent.
As the pH is lowered, ionisation of the carboxylate groups is
suppressed, and this results in a reduction in hydration of the
carboxylic acid groups. As a result of reduced ionisation, the
polysaccharide molecules no longer repel each other over their
entire length, and as a result, they can associate and form a gel.
Apparent pK-values (pH at 50% dissociation) vary with the DE of
the pectin (Plaschina et al., 1978); a 65% DE pectin has an
apparent pK of 3.55, while a 0% DE pectic acid has an apparent
pK of 4.10. However, pectins with increasingly greater degrees of
methylation will gel at somewhat higher pH, because they have fewer
carboxylate anions at any given pH.
Dissolved pectins are decomposed spontaneously by
deesterification as well as by depolymerisation; the rate of this
decomposition depends on pH, on water activity, and on the
temperature. In general, maximum stability is found at pH 4. The
presence of sugar in the pectin solution has a certain protective
effect while elevated temperatures increase the rate of degradation.
At low pH-values and elevated temperatures degradation due to
hydrolysis of glycosidic linkages is observed. Deesterification is also
favoured by low pH. By deesterification a HM-pectin becomes
slower setting or gradually adapts LM-pectin characteristics. At
near-to-neutral pH (5-6), HM-pectin is stable at room temperature
only. As the temperature (or pH) increases, a so-called -
elimination starts which results in chain cleavage and very rapid loss
of viscosity and gelling properties. LM-pectins show a somewhat
better stability at these conditions. At alkaline pH-values pectin is
rapidly deesterified and degraded even at room temperature (Rolin,
1993).
Powdered HM-pectins slowly lose their ability to form gels if
stored under humid or warm conditions while LM-pectins are more
stable and loss should not be significant after one year storage at
room temperature (Hercules Incorporated, 1999).
Gel formation properties of pectin
The most important use of pectin is based on its ability to form
gels. HM-pectin forms gels with sugar and acid. This can be seen as
a partial dehydration of the pectin molecule to a degree where it is in
a state between fully dissolved and precipitated. The particular
structure of pectin imposes some specific constraints. HM-pectin,
unlike LM-pectin, does not contain sufficient acid groups to gel or
precipitate with calcium ions, although other ions such as aluminium
or copper cause precipitation under certain conditions. It has been
suggested by Oakenfull (1991) that hydrogen bonding and
hydrophobic interactions are important forces in the aggregation of
pectin molecules. Gel formation is caused by hydrogen bonding
between free carboxyl groups on the pectin molecules and also
between the hydroxyl groups of neighbouring molecules. In a
neutral or only slightly acid dispersion of pectin molecules, most of
the unesterified carboxyl groups are present as partially ionised salts.
Those that are ionised produce a negative charge on the molecule,
which together with the hydroxyl groups causes it to attract layers
of water. The repulsive forces between these groups, due to their
negative charge, can be sufficiently strong to prevent the formation
of a pectin network. When acid is added, the carboxyl ions are
converted to mostly unionised carboxylic acid groups. This decrease
in the number of negative charges not only lowers the attraction
between pectin and water molecules, but also lowers the repulsive
forces between pectin molecules. Sugar further decreases
hydration of the pectin by competing for water. These conditions
decrease the ability of pectin to stay in a dispersed state. When
cooled, the unstable dispersing of less hydrated pectin forms a gel,
a continuous network of pectin holding the aqueous solution. The
rate at which gel formation takes place is also affected by the
degree of esterification. A higher DE causes more rapid setting.
Rapid-set pectins (i.e. pectin with a DE of above 72%) also gel at
lower soluble solids and higher levels than slow-set pectins (i.e. pectin
with a DE of 58-65%).
LM-pectins require the presence of divalent cations (usually
calcium) for proper gel formation. The mechanism of LM-pectin
gelation relies mainly on the well-known egg-box model (Grant
et al., 1973). The mechanism involves junction zones created by the
ordered, side-by-side associations of galacturonans, whereby
specific sequences of GalA monomer in parallel or adjacent chains
are linked intermolecularly through electrostatic and ionic bonding
of carboxyl groups (Fig. 3).
It is generally accepted that the junctions consist of dimers in 2
1
helical symmetry, similar to the 2
1
model proposed for alginates
(Axelos & Thibault, 1991). The oxygen atoms of the hydroxyl
groups, the ring oxygen atoms, and the bridging oxygen atoms of
the component sugar units participate in the bonding process through
their free-electron pairs (Kohn, 1987). The life of the junction
depends on the strength of the electrostatic bonds. The bonds are
stable when there are at least seven consecutive carboxyl groups on
the interior of each participating chain (Powell et al., 1982). The
occurrence of methyl ester groups in the primary backbone limits
the extent of such junction zones leading to formation of the gel.
Other models for LM-pectin gelation (e.g. 3
2
helical model) have
been proposed (Walkinshaw & Arnott, 1981a,b), but they are
currently unconfirmed by experimentation. Nevertheless, all
LM-pectin gels seem to develop similar, if not identical, junction
zones (Filippov et al., 1988).
Furthermore, amidation increases or improves the gelling
ability of LM-pectin: amidated pectins need less calcium to gel and
are less prone to precipitation at high calcium levels (May, 1990).
Fig. 3 Schematic representation of calcium binding to
polygalactoronate sequences: egg box dimer and egg-box
cavity (adapted from Axelos & Thibault, 1991).
Fig. 4 Model for the gelation of amidated LM-pectins showing ionic
interactions between galacturonic acid residues and
hydrogen bonding between amidated galacturonic acid
residues (adapted from Sriamornsak, 2002).
The gel structure is a net-like formation of cross-linked pectin
molecules. The cross-linkages formed by ionic bonds between the
carboxyls are strong and produce a rather brittle, less elastic than
those formed by hydrogen bonding as in regular pectin. With
pectins of lower DE, there is an increasing probability for the
formation of cross-links with a given amount of calcium. As the
number of reactive carboxyl groups that can form a salt bridge
increases, the greater the chances are that the bridge will be formed.
Furthermore, because of the larger amount of charged groups,
de-esterified molecules are straighter than the esterified ones, so
they will be more likely to form calcium linkages (Thibault &
Rinaudo, 1985).
Racape and coworkers (1989) suggested that the gelation of
amidated pectins could not be explained by the egg-box model
alone, as blocks of amide groups along the chain promote
association through hydrogen bonding. As expected for any
polymer, the lower the molecular weight, the weaker the gel. Fig. 4
illustrated the model for gelation of amidated LM-pectins.
The amount of LM-pectin required for the formation of such
gel decreases with the DE. The strengths of such ionic bonded gels
are strongly dependent on the DE. Monovalent ions such as
sodium, which can also react with free carboxyl groups, can affect
gel formation because they decrease the cross-linking reaction of
calcium and improve the solubility of LM-pectin in the presence of
calcium (Axelos, 1990). Although sugar is not essential for gel
formation with LM-pectins, the presence of small amounts (10-20%)
of sugar tends to decrease syneresis and adds desirable firmness of
these gels (Christensen, 1986). When some sugar is present, the
amount of calcium required to form gel is reduced. High
concentrations of sugar (60% or higher) interfere with gel formation
because the dehydration of the sugar favours hydrogen bonding and
decreases cross-linking by divalent ion forces.
Pharmaceutical uses of pectin
Pectin has applications in the pharmaceutical industry. Pectin
favaorably influences cholesterol levels in blood. It has been
reported to help reduce blood cholesterol in a wide variety of
subjects and experimental conditions as comprehensively reviewed
(Sriamornsak, 2001). Consumption of at least 6 g/day of pectin is
necessary to have a significant effect in cholesterol reduction.
Amounts less than 6 g/day of pectin are not effective (Ginter et al.,
1979). Mietinnen & Tarplia (1977) reported a 13% reduction in
serum cholesterol within 2 weeks of treatment.
Pectin acts as a natural prophylactic substance against
poisoning with toxic cations. It has been shown to be effective in
removing lead and mercury from the gastrointestinal tract and
respiratory organs (Kohn, 1982). When injected intravenously,
pectin shortens the coagulation time of drawn blood, thus being useful
in controlling hemorrhage or local bleeding (Joseph, 1956). Pectin
and combinations of pectin with other colloids have been used
extensively to treat diarrheal diseases, especially in infants and
children. Although a bactericidal action of pectin has been proposed
to explain the effectiveness of pectin treating diarrhea, most
experimental results do not support this theory. However, some
evidence suggests that under certain in-vitro conditions, pectin may
have a light antimicrobial action toward Echerichia coli (Thakur
et al., 1997).
Pectin reduces rate of digestion by immobilising food
components in the intestine. This results in less absorption of food.
The thickness of the pectin layer influences the absorption by
prohibiting contact between the intestinal enzyme and the food, thus
reducing the latters availability (Wilson & Dietschy, 1974; Dunaif
& Schneeman, 1981; Flourie et al., 1984). Due to its large water-
binding capacity, pectin gives a feeling of satiety, thus reducing food
consumption. Experiments showed a prolongation of the gastric
emptying half-time from 23 to 50 minutes of a meal fortified with
pectin (Holt et al., 1979). These attributes of pectin are used in the
treatment of disorders related to overeating (Di Lorenzo et al., 1988).
Pectin hydrogels have been used in tablet formulations as a
binding agent (Slany et al., 1981a,b) and have been used in
controlled-release matrix tablet formulations (Krusteva et al., 1990;
Naggar et al., 1992). Recently, Sungthongjeen et al. (1999) have
investigated HM-pectins for their potential value in controlled-
release matrix formulations. The application of a binary polymer
system, i.e. HM-pectin and hydroxypropyl methylcellulose, in drug
release rate modulation for oral administration was studied by Kim
& Fassihi (1997a,b,c). Pectin beads prepared by the ionotropic
gelation method (Aydin & Akbuga, 1996) were used as a sustained
release drug delivery system. However, the use of these beads has
some drawbacks due to their rapid in-vitro release. By changing
the DE of LM-pectin, Sriamornsak & Nunthanid (1998) modified
the drug release pattern from calcium pectinate gel beads.
Since pectin can react with calcium ions, calcium pectinate has
been investigated as an insoluble hydrophilic coating for sustained
release delivery by interfacial complexation process (Sriamornsak
1996; Sriamornsak et al., 1997a,b). The spherical pellets, which
contain calcium acetate, were prepared using an extrusion-
spheronisation method and then coated in a pectin solution. An
insoluble and uniform coating of calcium pectinate gel was formed
around the pellets. The use of pectin to develop other oral
controlled release drug delivery systems has been reported by some
authors (Table 1).
Pectin has a promising pharmaceutical uses and is presently
considered as a carrier material in colon-specific drug delivery
systems (for systemic action or a topical treatment of diseases such
as ulcerative colitis, Crohns disease, colon carcinomas), as
indicated by the large number of studies published over the last few
years (Table 2). The potential of pectin or its salt as a carrier for
colonic drug delivery was first demonstrated by two studies, i.e.
Ashford et al. (1993) and Rubinstein et al. (1993). The rationale for
this is that pectin and calcium pectinate will be degraded by colonic
pectinolytic enzymes (Englyst et al., 1987), but will retard drug
release in the upper gastrointestinal tract due to its insolubility and
because it is not degraded by gastric or intestinal enzymes (Sandberg
et al., 1983). Rubinstein et al. (1992) demonstrated that
pectin-degrading bacteria, Klebsiella oxytoca, could adhere to
a film casted of low methoxylated pectin. The ability of the bacteria
to adhere to the films, however, was not correlated with their
ability to degrade pectin. When the dissolution of pectin matrix
tablets was analysed with and without K. oxytoca, a significant
retardation in the dissolution rate was observed in the presence of
K. oxytoca, suggesting the formation of a biofilm on the matrix or
sedimentation of insoluble pectin salts.
Pectin is an interesting candidate for pharmaceutical use, e.g.
as a carrier of a variety of drugs for controlled release applications.
Many techniques have been used to manufacture the pectin-based
delivery systems, especially ionotropic gelation and gel coating. These
simple techniques, together with the very safe toxicity profile, make
pectin an exciting and promising excipient for the pharmaceutical
industry for present and future applications.
Dose form
Tablets
Tablets
Tablets
Tablets
Tablets
Gel beads
Gel beads
Gel beads
Gel beads
Pellets
Particulates
Microspheres
Coated
pellets
Table 1 Controlled release formulation using pectin.
Types of pectin
Pure and standardised
pectin
HM-pectin
HM-pectin
HM-pectin (pure
and standardised)
HM-pectin
LM-pectin
LM-pectin
(amidated)
LM-pectin
(amidated)
LM-pectin
LM-pectin
LM-pectin
LM-pectin
LM-pectin
(amidated and
non-amidated)
Application
Binding agents and delayed
drug release
Monolithic bioerodible system
Sustained release properties of
direct compression tablets
Hydrogel matrix system
Direct compression of the
mixture of HM-pectin and
HPMC
Pectin beads prepared by
ionotropic gelatin
Sustained release drug
delivery using calcium
pectinate gel beads
In-vitro and in-vivo studies
of pectin hydrogel beads
A crosslinked calcium-
alginate-pectinate-cellulose
acetophthalate gel spheres.
Calcium petinate or calcium
alginate-pectinate prepared
by ionotropic gelation
Alginate-pectin-polylysine
system
Pectin-based microspheres
prepared by emulsification
technique
Insoluble calcium pectinate gel
coating for sustained release
delivery prepared by
interfacial complexation
References
Slany et al.,1981a,b
Krusteva et al., 1990
Naggar et al., 1992
Sungthongjeen et al.,
1999
Kim and Fassihi,
1997a,b,c
Aydin and Akbuga,
1996
Sriamornsak and
Nunthanid, 1998,
1999
Munjeri et al., 1998;
Musabayane et al.,
2000
Pillay et al., 2002
Pillay and Fassihi,
1999
Liu and Krisnan,
1999
Esposito et al.,
2001;Wong et al.,
2002
Sriamornsak et al.,
1997a,b
HM-pectin =high methoxy pectin; LM-pectin =low methoxy pectin.
Table 2 Colon-specific drug delivery using pectin.
Dose form
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Tablets
Gel beads
Gel beads
Film coated
tablets
Film coated
tablets
Film coated
tablets
Film coated
tablets
Capsule
with plug
Types of pectin
Calcium pectinate
HM-pectin
HM-pectin and
LM-pectin
Calcium pectinate
HM-pectin and
LM-pectin
HM-pectin
Amidated LM-
pectin and calcium
salt of pectin
LM-pectin
(amidated)
LM-pectin
(amidated)
HM-pectin
HM-pectin or
LM-pectin
HM-pectin
HM-pectin
LM-pectin
Application
Compression of calcium
pectinate (matrix system)
Compression coat
Matrix system
Matrix system and
compression coat
Direct compression of HM-
pectin or LM-pectin alone
or combined with MCC
Compression coated with
HM-pectin/ethylcellulose
mixtures
Direct compression of
amidated or calcium of
pectin alone or incorporated
with ethylcellolose
Formation of a chitosan
polyelectrolyte complex
around calcium pectinate
beads
Calcium pectinate gel beads
for protein delivery
Coating with mixtures of
HM-pectin and
ethylcellulose aqueous
dispersion
Coating with HM-pectin
or LM-pectin combined
with commercially
aqueous polymer dispersion
Coating with HM-pectin or
HM-pectin/chitosan mixtures
Coating with mixtures of HM-
pectin/chitosan/HPMC
Direct compression of pectin/
pectinase-plug
References
Rubinstein et al.,
1993
Ashford et al., 1993
Ashford et al., 1994
Rubinstein and Radai,
1995
Kim et al., 1998
Semde et al., 1999
Ahrabi et al., 2000
Munjeri et al., 1997
Sriamornsak, 1998,
1999
Wakerly et al., 1997;
Macleod et al., 1997
Semde et al., 1998,
2000a,b
Fernandezhervas and
Fell, 1998; Macleod
et al., 1999a
Macleod et al.,
1999b
Krogel and
Bodmeier, 1999
HM-pectin =high methoxy pectin; LM-pectin =low methoxy pectin; HPMC =
hydroxypropyl methylcellculose.
Conclusion
The chemistry and gel-forming characteristics of pectin have
enabled this naturally occurring biopolymer to be used in
pharmaceutical industry, health promotion and treatment. It has also
been used potentially in pharmaceutical preparation and drug
formulation as a carrier of a wide variety of biologically active agents,
not only for sustained release applications but also as a carrier for
targeting drugs to the colon for either local treatment or systemic
action. By selection of the appropriate type of pectin, gelation
conditions, added excipients, and coating agents, the dosage forms
of various morphology and characteristics can be fabricated. As
research and development continues with delivery system using
pectin, we expect to see many innovative and exciting applications
in the future.
References
Ahrabi, S.F., et al. (2000). Development of pectin matrix tablets for colonic
delivery of model drug ropivacaine. European Journal of Pharma
ceutical Sciences, 10, pp. 43-52.
Ashford, M., et al. (1993). An evaluation of pectin as a carrier for drug
targeting to the colon. Journal of Controlled Release, 26,
pp. 213-220.
Ashford, M., et al. (1994). Studies on pectin formulations for colonic drug
delivery. Journal of Controlled Release, 30, pp. 225-232.
Axelos, M.A.V. (1990). Ion complexation of biopolymers: Macromolecular
structure and viscoelastic properties of gels. Macromolecular
Symposia, 39, pp. 323-328.
Axelos, M.A.V. and Thibault, J.F. (1991). The chemistry of low-methoxyl
pectin gelation. In The chemistry and technology of pectin, ed.
R.H. Walter. (New York: Academic Press)
Aydin, Z. and Akbuga, J . (1996). Preparation and evaluation of pectin beads.
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