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A REVIEW ON CO-PROCESSED EXCIPIENTS: A NOVEL APPROACH IN
FORMULATION DEVELOPMENT
Patil Atul1*; Kundu Subrata2; Srinivasan Ganga3
Shri JJT University, Rajasthan1
VerGo Pharma Research Laboratories Pvt. Ltd, Goa2
Vivekananda College of Pharmacy, Mumbai University3
ABSTRACT:
Co-processed excipients help to overcome the deficiencies occurring with the use of general
grade excipients. The co-processed excipients retain favourable attributes, and are
supplemented with new ones. As the chemical change is absent, they are considered to retain
the “GRAS” (Generally Regarded as Safe) status. Co-processed excipients are believed to
bring a drastic change in the field of pharmaceutical Research.
Keywords: Co-processing, Adjuvant, excipients, Novel drug delivery system.
INTRODUCTION:
In recent years scientists have found out
that single-component excipients do not
always provide the requisite performance
to allow certain active pharmaceutical
ingredients to be formulated or
manufactured. Hence formulation
scientists have worked on combination of
excipients to overcome the deficiencies
occurring with the use of general grade
excipients.
There is considerable activity in the
development of new and innovative
excipients. Excipient Innovations include
excipients for orally disintegrating tablets
and controlled-release formulations. New
technologies are being evaluated to
increase the amount or rate of absorption
of drugs with new excipients. In the future,
the application of nanotechnology may be
evaluated for developing novel excipients
for new therapeutic solutions.
Co-Processed Excipients Enhanced
Performance [1]
- Combination (“intimate” mixtures)
of established excipients that
possess performance advantages
and improvements: increased
surface area, improved flow,
compaction, etc.
- Covalent bonds usually not formed
- High-functionality excipients
(perform multiple functions)
- Produced using specialized
manufacturing process: high shear
dispersion, granulation, spray
drying, melt extrusion
- One or more components may be
formed in situ
*Corresponding Author
Patil Atul
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- Appropriate for monograph
consideration in the United States
Pharmacopeia/National Formulary
- Several listed in FDA Inactive
Ingredient Database
- May create new intellectual
property
Combination excipients are of two types:
physical mixtures and co-processed
excipients. [2]
A co-processed excipient is a
combination of two or more excipients
having physically modified their properties
in a manner not achievable by simple
physical mixing, and without significant
change in the chemical properties. Co-
processed microcrystalline cellulose and
calcium carbonate were the first co-
processed excipients (1980). It was
followed by Cellactose (Meggle Corp.,
Wasserburg, Germany) in 1990, [3]
which
is a co-processed combination of cellulose
and lactose. Later, silicified
microcrystalline cellulose (SMCC), which
is the most widely used co-processed
excipient was developed using the same
technique and many more in the recent
years. [4]
Excipients:
Pharmaceutical excipients are substances
other than the API which have been
appropriately evaluated for safety and are
intentionally included in a drug delivery
system. For example, excipients can:
Aid in the processing of the drug
delivery system during its manufacture,
Protect, support or enhance stability,
bioavailability or patient acceptability,
Assist in product identification, or
Enhance any other attribute of the
overall safety, effectiveness or delivery
of the drug during storage or use.
Types of Excipients
1. Standard Excipients
Standard excipients are defined as
compendial or non-compendial substances
that are neither mixed excipients nor co-
processed excipients. They may contain
other components including concomitant
components, residual processing aids
and/or additives.
2. Mixed Excipients
A mixed excipient is defined as a simple
physical mixture of two or more
compendial or non-compendial excipients
produced by means of a low- to medium-
shear process where the individual
components are mixed but remain as
discrete chemical entities, i.e. the nature of
the components is not chemically
changed,. Mixed excipients may be either
solid or liquid.
3. Co-processed Excipients
A co-processed excipient is a combination
of two or more compendial or non-
compendial excipients designed to
physically modify their properties in a
manner not achievable by simple physical
mixing, and without significant chemical
change. Many different co-processing
methods may be used, including standard
unit operations such as granulation, spray
drying, melt extrusion, milling etc. The
choice for a specific application will
depend on the materials used, their form
(e.g. whether dry powders or liquid) and
the specific physical properties desired.
Likewise the ratios of the components may
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vary depending on the desired
performance. [5]
Co-processing is a novel concept in which
the excipient functionality is altered by
retaining the favorable attributes and
supplementing with newer-ones. This is
achieved by processing the parent
excipient with another excipient. This
allows production of high-functionality
excipients which can be of a greater
importance to the formulator. The high
functionality can be in terms of improved
process ability such as flow properties,
compressibility, content uniformity,
dilution potential, and lubricant sensitivity,
or improved performance such as
disintegration and dissolution profile. [6]
Need For Co-Processed Excipients:
It has been found that less than 20 per cent
of pharmaceutical materials can be
compressed directly into tablets due to lack
of flow, cohesion properties and
lubrication. Therefore, they must be
blended with other directly compressible
ingredients to manufacture satisfactory
tablets. In the development of directly
compressible granules by the modification
of a single substance, Co-processing
involves interaction of two or more
excipients at the sub-particle level, aimed
at providing a synergy of functionality
improvements, as well as masking the
undesirable properties of the individual
excipients. The composite particles or
co‐processed multi‐component‐based
excipients are introduced to achieve better
powder characteristics and tableting
properties than a single substance or the
physical mixture.
The availability of a large number of
excipients for co-processing provides a
plethora of opportunities to produce tailor
made „„designer excipients‟‟ catering to
specific functionality requirements.[7]
The
combination of excipients chosen for co-
processing should complement each other
to mask the undesirable properties of
individual excipients and at the same time,
retain or improve the desired properties of
excipients. For example, if a substance
used as a filler–binder has a low
disintegration property, it can be co-
processed with another excipient that has
good wetting properties and high porosity
because these attributes will increase the
water intake, which will aid and increase
the disintegration of the tablets.[8]
Difference between physical mixtures
and co-processed excipients
Physical mixtures, as the name suggests,
are simple admixtures of two or more
excipients typically produced by short
duration low-shear processing. They may
be either liquids or solids and are generally
used for convenience rather than for
facilitating the manufacturing process or
improving the resultant pharmaceutical
product. [9]
Co-processed excipients are combinations
of two or more excipients that possess
performance advantages that cannot be
achieved using a physical admixture of the
same combination of excipients. Typically
they are produced using some form of
specialized manufacturing process. The
performance benefits relate to the
manufacture or performance of the
finished pharmaceutical product. [9]
Co-
processed excipients are appropriate for
consideration as new monographs because
one or more of the components may be
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formed in situ, or the component may not
be isolated prior to co-processing [6]
PROCESS OF DEVELOPING CO-
PROCESSED EXCIPIENTS:
The actual process of developing a co-
processed excipient involves the following
steps:
1. Identification of the group of
excipients to be co-processed: This is
done by taking material characteristics and
functionality requirements into
consideration.
2. Selection of proportion of various
excipients
3. Assessing the particle size: This is
important because, Post processing the
particle size of the latter depends on its
initial particle size.
4. Selecting a suitable process of drying:
processes such as spray- or flash drying
are employed
5. Optimizing the process (because even
this can contribute to functionality
variations. [6]
Figure 1: Demonstrating the co-processing technology
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Considering material characteristics in
co-processing:
Material science plays an important role in
altering the physical and mechanical
characteristics of a material, especially
with regard to its compression and flow
behaviour. [10]
Materials can be classified
as elastic, plastic, or brittle materials by
virtue of their response to applied forces.
Pharmaceutical materials exhibit all three
types of behavior, with one type being the
predominant response. This makes it
difficult to demarcate which property is
good for compressibility. Co-processing is
generally conducted with one excipient
that is plastic and another that is brittle.
Scientists have experimented to make co-
processed excipients by utilizing large
amount of brittle material and a small
amount of plastic material, as exemplified
by Cellactose (Meggle Corp.) in which
75% lactose (brittle material) is co-
processed with 25% cellulose (plastic
material).[11]
This combination prevents
the storage of too much elastic energy
during compression, which results in a
small amount of stress relaxation and a
reduced tendency of capping and
lamination.[12]
However, examples of the
other extreme also exist (e.g., SMCC has a
large amount of MCC [plastic material]
and a small amount of silicon dioxide
[brittle material]).[13]
A combination of
plastic and brittle materials is necessary for
optimum tableting performance. Hence,
co-processing these two kinds of materials
produces a synergistic effect, in terms of
compressibility, by selectively overcoming
the disadvantages. These types of
combinations help in improving
functionalities such as compaction
performance, flow properties, strain-rate
sensitivity, lubricant sensitivity or
sensitivity to moisture, or reduced
hornification. [14]
Advantages of co-processed excipients
1. Improved flow properties:
Controlled particle-size distribution and
optimum particle size ensures superior
flow properties of co-processed excipients
without the need of using glidant. Consider
the volumetric flow properties of SMCC
(silicified micro crystalline cellulose) were
studied in comparison with MCC. The
particle-size range of co-processed and
parent excipients was similar but the flow
of co-processed excipients was better than
the flow of simple physical mixtures. [15]
A
comparison of the flow properties of
Cellactose and lactose was also performed.
Cellactose was found to have better flow
characteristics than lactose or a mixture of
cellulose and lactose. The spray-dried
product had a spherical shape and even
surfaces, which also improved the flow
properties. [16]
2. Improved compressibility:
Co-processed excipients have been used
mainly in direct-compression tableting
because in this process there is a net
increase in the flow properties and
compressibility profiles and the excipient
formed is a filler–binder. The pressure–
hardness relation of co-processed
excipients, when plotted and compared
with simple physical mixtures, showed a
marked improvement in the
compressibility profile. The
compressibility performance of excipients
such Cellactose [17]
, SMCC [18]
, and
Ludipress have been reported to be
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superior to the simple physical mixtures of
their constituent excipients. SMCC
retained its compaction properties even at
high compression forces, yielding tablets
of good hardness. [19]
MCC, however, lost
its compaction properties. Although direct
compression seems to be the method of
choice for pharmaceutical manufacturing,
wet granulation is still preferred because it
has the potential advantages of increasing
flow properties and compressibility when
an extra granular binder is introduced, and
it achieves a better content uniformity in
case of low-dose drugs. Excipients such as
MCC lose compressibility upon the
addition of water, a phenomenon called
quasi hornification. This property is
improved, however, when it is co-
processed into SMCC.
3. Better Dilution potential:
Dilution potential is the ability of the
excipient to retain its compressibility even
when diluted with another material. Most
active drug substances are poorly
compressible, and as a result, excipients
must have better compressibility properties
to retain good compaction even when
diluted with a poorly compressible agent.
Cellactose is shown to have a higher
dilution potential than a physical mixture
of its constituent excipients. [20]
4. Fill weight variation:
In general, materials for direct
compression tend to show high fill-weight
variations as a result of poor flow
properties, but co-processed excipients,
when compared with simple mixtures or
parent materials, have been shown to have
fewer fill-weight variation problems. The
primary reason for this phenomenon is the
impregnation of one particle into the
matrix of another, which reduces the rough
particle surfaces and creates a near-optimal
size distribution, causing better flow
properties. Fill-weight variation was
studied with various machine speeds for
SMCC and MCC, and SMCC showed less
fill-weight variation than MCC. [21]
5. Reduced lubricant sensitivity
Most co-processed products consist of a
relatively large amount of brittle material
such as α-lactose monohydrate and a
smaller amount of plastic material such as
cellulose that is fixed between or on the
particles of the brittle material. The plastic
material provides good bonding properties
because it creates a continuous matrix with
a large surface for bonding. The large
amount of brittle material provides low
lubricant sensitivity because it prevents the
formation of a coherent lubricant network
by forming newly exposed surfaces upon
compression, thus breaking up the
lubricant network. [22]
Other advantages:
(a) Pharmaceutical manufacturers have
the option of using a single excipient
with multiple functional properties,
thereby reducing the number of
excipients.
(b) Improved organoleptic properties
such as those in Avicel CE-15 (FMC
Corp., Philadelphia, PA), which is a
co-processed excipient of MCC, and
guar gum were shown to have
distinctive advantages in chewable
tablets in terms of reduced grittiness,
reduced tooth packing, minimal
chalkiness, better mouth feel, and
improved overall palatability in
inventory.
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(c) Overall product cost decreases
because of improved functionality
and fewer test requirements
compared with individual excipients.
(d) Co-processed excipients can be used
to develop tailor-made designer
excipients. This can be helpful in
reducing the time required to
develop formulations.
(e) Co-processed excipients can be used
as proprietary combinations, and in-
house formularies can be maintained
by pharmaceutical companies could
help in developing a formulation that
is difficult to reproduce and provides
benefits in terms of intellectual
property rights. [23]
Limitations of co-processed excipients:
Major limitation of co-processed excipient
mixture is that the ratio of the excipients in
a mixture is fixed and in developing a new
formulation, a fixed ratio of the excipients
may not be an optimum choice for the API
and the dose per tablet under development.
Co-processed adjuvant lacks the official
acceptance in pharmacopoeia. For this
reason, a combination filler/binder will not
be accepted by the pharmaceutical industry
until it exhibits significant advantages in
the tablet compaction when compared to
the physical mixtures of the excipients.
Although the spray-crystallized dextrose-
maltose (Emdex) and compressible sugar
are co-processed products, they are
commonly considered as single
components and are official in USP/NF.
CO-PROCESSED DIRECTLY
COMPRESSIBLE ADJUVANTS
Ludipress:
Ludipress, a co-processed product, consists
of 93.4% α- lactose monohydrate, 3.2%
polyvinyl pyrrolidone (Kollidon 30) and
3.4% crospovidone (Kollidon CL). [24]
It
consists of lactose powder coated with
polyvinyl pyrrolidone and crospovidone.
At low compression force Ludipress gives
harder tablets but the addition of glidant
and disintegrant is needed. It is reported
that binding capacity of Ludipress was
higher than that of microcrystalline
cellulose. The dilution potential was high
(up to 70%) when aspirin was used a
model drug [25]
. The binding property of
Ludipress, both un-lubricated and
lubricated with 1% magnesium stearate
was found to be much better than
corresponding physical mixture. The
disintegration time of Ludipress containing
tablets remained unchanged at about 100
MPa compaction pressure while significant
prolongation was observed with
Cellactose. Ludipress exhibited highest
flow ability followed by Cellactose,
Tablettose, Fast Flo lactose and anhydrous
lactose as demonstrated by lower static and
dynamic angles of repose than the other
excipients. The values of compressibility
could be ranked from maximum to
minimum in the following order:
Tablettose, Cellactose, Ludipress and Fast
Flow lactose. Fragmentation propensity
was from maximum to minimum in
Tablettose, Cellactose, Ludipress and Fast-
Flo lactose. [26]
Cellactose:
Cellactose is a co-processed product
consisting α-lactose monohydrate (75%)
and cellulose (25%). Apart from good flow
ability, it has good compatibility. [27]
The
compatibility is attributed to a synergetic
effect of consolidation by fragmentation of
lactose and plastic deformation of
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cellulose. Because the lactose covers the
cellulose fibers, moisture sorption is much
lower than that of microcrystalline
cellulose alone. Armstrong et al. pointed
that Cellactose exhibit the dual
consolidation behavior since it contains a
fragmenting component (Lactose) and a
substance that consolidates primarily by
plastic deformation (Cellulose). It was
reported that the Cellactose exhibited
better compressibility compared to
Ludipress, Fast Flo lactose, Tablettose, Di-
pac and anhydrous lactose.[28]
Belda and
Mielck found that due to co-processing
Cellactose exhibited enhanced crushing
strength compared to the powder mixtures
each containing 25% w/w Avicel PH-101
or Elcema P-100 and 75% w/w Tablettose
or lactose (100#). Casal derrey et al
reported that the Cellactose tablets
prepared at a compression pressure that
largely eliminated macro pores had better
mechanical properties but much poorer
disintegration than tablets of the other
blends having similar composition, particle
size, and true density at the same punch
pressure. Authors further reported that the
tensile strength and disintegration time of
Cellactose tablets decreased rapidly as the
compression pressure is reduced.
Goheland Jogani prepared and evaluated
co-processed directly compressible
adjuvant containing lactose and
microcrystalline cellulose using starch as a
binder. The percentage fines, Carr‟s index
of the agglomerates as well as friability
and tensile strength of the tablets were
affected by the ratio of lactose to
microcrystalline cellulose and percentage
of starch in binder solution. A product
containing lactose: microcrystalline
cellulose (9:1) and 1% starch paste
exhibited satisfactory flow,
compressibility and friability. Tablets of
diltiazem hydrochloride and
acetaminophen prepared using the co-
processed excipients exhibited satisfactory
tableting properties. Gohel et al. prepared
and evaluated co-processed diluents
containing lactose and microcrystalline
cellulose using a 23 factorial design. Ratio
of lactose to MCC (75: 25 and 85:15), type
of binder (hydroxypropyl methylcellulose
or dextrin) and binder concentration (1 or
1.5%) were studied as independent
variables. The results revealed that the
lactose: microcrystalline cellulose ratio
75:25 and dextrin as a binder are better
than the ratio of 85:15 and
hydroxypropylmethylcellulose as a binder.
The tableting properties of the developed
adjuvant were ascertained using diltiazem
HCl as a model drug. Gohel and Jogani
prepared co-processed directly
compressible adjuvant containing lactose
and microcrystalline cellulose using melt
granulation technique. Gohel et al
demonstrated use of factorial design in
development of directly compressible
adjuvant of desired characteristics
consisting of lactose, dicalcium phosphate
and microcrystalline cellulose.
Pharmatose DCL 40
It is a co-processed product consisting of
95% β-lactose and 5% anhydrous lactitol.
Due to spherical shape and favorable
particle size, it exhibits good flow ability.
It has high dilution potential than other
lactose based products due to better
binding property. It has very low water
uptake at high humidity. [29]
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Prosolv
It is co-processed silicified
microcrystalline cellulose. It consists of
98% microcrystalline cellulose and 2%
colloidal silicone dioxide. The
manufacturer claim better flow ability and
compressibility compared to Emcocel and
Avicel PH 101 or physical mixture of
MCC with colloidal silicone dioxide.
Allen reported that Prosolv containing
tablets were significantly robust than those
produced from regular cellulose by wet
granulation. In the presence of magnesium
stearate (0.5%), tablets prepared with
Prosolv maintained tensile strength
profiles, whereas the tensile strength of
regular cellulose was significantly
affected. Author further Prosolv containing
tablets were significantly robust than those
produced from regular cellulose by wet
granulation. In the presence of magnesium
stearate (0.5%), tablets prepared with
Prosolv maintained tensile strength
profiles, whereas the tensile strength of
regular cellulose was significantly
affected. Author further reported that
Prosolv is about 20% more compactable
than regular cellulose. Fraser et al reported
that silicified microcrystalline cellulose
has some improvement in flow but
considerably enhanced mechanical
properties. Lahdenpera et al. demonstrated
that Silicified microcrystalline cellulose is
useful to prepare tablet containing poorly
compressible ingredients by direct
compression. The silicification affects the
moisture sorption and the packing during
tapping as well as the particle deformation
during tableting. Prosolv showed slight
increase in the tensile strength but marked
increase in the disintegration time of the
tablets compared to Avicel. It was
demonstrated that the co-processing of
microcrystalline cellulose with colloidal
silicone dioxide has no significant
contribution on the tablet strength of
lubricated tablets containing the physical
mixture of microcrystalline cellulose and
colloidal silicone dioxide. [30]
StarLac:
Starlac is a co-processed excipient consists
of lactose monohydrate and maize starch
produced by spray drying. The advantage
of Starlac are its good flow ability
depending on the spray-drying process, an
acceptable crushing force due to its lactose
content, its rapid disintegration depending
on starch. Gohel and Jogani demonstrated
use of multiple linear regressions in
development of co-processed lactose and
starch. Authors concluded that as the
lactose/starch ratio increased Carr‟s index
of the adjuvant and crushing strength of
the tablets increased while friability
decreased. Percentage of starch paste has
inverse effect on the friability. [31]
REGULATORY PERSPECTIVE:
In the light of the fact that a chemical
change is absent during processing, co-
processed excipients can be considered to
retain the generally regarded as safe
(GRAS) status if the parent excipients are
GRAS certified by the regulatory agencies,
then co-processed excipients are also .This
reduces the requirement for additional
toxicological studies as mandatory for a
new chemical entity seeking regulatory
approval. [31]
A very limited number of co-
processed excipients are included in
pharmacopoeial monographs.
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• Microcrystalline Cellulose and
Carboxymethylcellulose Sodium
(USNF) – aka Dispersible Cellulose BP
• Compressible Sugar (USNF) (BP)
• Various acrylate dispersions (Truly co-
processed) (USNF and Ph.Eur)
However the majority of commercially
available co- processed excipients are not
described in a major pharmacopoeia. For
any „new‟ excipient regulatory agencies
should be looking for a safety assessment,
However in the case of co-processed
excipients the components, the
manufacturing process and component
combination are not novel, The only novel
parameters are the physical form and the
functionality. Therefore it should not be
necessary to perform a full toxicological
assessment, It should be possible to
provide data to „bridge‟ to the safety data
of the components, However the bridging
assessment needs to be fully justified by
demonstrating that the co-processing
process does not create a change of
regulatory significance. The absence of
significant chemical change should be
demonstrated using suitable techniques
including:
• Scanning Electron Microscopy
• Pyncnometry
• FT-IR
• 13
C NMR
• X ray diffraction
• Viscosity measurements
• Differential Scanning Calorimetry
The Regulation of Excipients
New excipients are only approved
throughout the world when they are
included in new drug applications. A
separate independent regulatory review
system would greatly enhance the use of
new excipients.
Excipients regulation:
- No independent regulatory
approval process exists for new
excipients
- New excipients are only approved
within a new drug application
approval
- New excipients need supporting
safety data; testing strategy
developed on a case by case Basis;
large investment for safety studies
- Drug product manufacturers are
reluctant to use new excipients;
they generally rely on excipients
already used in approved drug
products
IPEC-Americas have submitted a proposal
for Excipient Master File, analogous to
Drug Master File, to the Food and Drug
Administration. This document is intended
to provide a standard format for submitting
excipient safety and manufacturing
information to regulatory agencies, and
includes provisions for co-processed
excipients also. The major obstacle to the
success of co-processed excipients in the
marketplace is their non-inclusion in
official monographs. The mixture of
excipients was presented as a topic to the
National Formulary and was assigned a
priority on the basis of its use in marketed
dosage forms in which processing
provided added functional value to the
excipient mixture. Although spray-
crystallized dextrose-maltose (EMDEX1,
J. Rettenmaier & Sohne GmbH & Co. KG,
Germany) and compressible sugars are co-
processed, they are commonly considered
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as single components and are listed as such
in the United States Pharmacopeia, while
the third edition of the Handbook of
Pharmaceutical Excipients has listed
SMCC as a separate excipient .[1]
Japan Master File Guideline: (enforced
as of April 1st, 2005) [1]
DMF plus Japanese QOS
J DMF consists of open and closed part,
like EU DMFs e-CTD format accepted
Categories of JMFs:
I - API /intermediates used for drugs*
II - New excipients
III - Medical devices
IV - Others (packaging etc.)
European Excipient Master Files
In contrast to Japan, Canada and the US, in
Europe, for materials, where a Certificate
of Suitability is not available, confidential
information needed to support the drug
product filing by a pharmaceutical
manufacturer must be supplied directly to
the drug manufacturer e.g. by using
confidentiality agreements. IPEC Europe
Initiative on Excipient Master Files has
been implemented to meet the need, create
awareness with the EU stakeholders and
authorities (mission statement). [32]
COMMERCIAL STATUS:
Co-processed excipients are widely
available in the market for a wide
spectrum of purposes. Majority of these
are produced mainly by spray drying.
Ludipress is produced by fluidized-bed
granulation, while Di-Pac (American
Sugar Co., New York, U.S.) involves
mini-granulation of sugar crystals glued
together with amorphous dextrin. Some of
the co-processed excipients which are
commercially available in the present
scenario and their brief details are
mentioned in the following table no. 1.
Table No. 1. Commercially available co-processed excipients
Trade name Manufacturer Components Added
advantage
Regulatory
status
IID
limits
Ludipress® BASF Lactose
PVP
Low
hydroscopicity
Good
flowability
Constant tablet
weight
NA 50.73
mg
Ludiflash BASF Mannitol-90%
Crospovidone-5%
Polyvinyl acetate-5%
Fast
disintegration
for Oral
Dispersible
Tablets
NA NA
Avicel® CE- 15 FMC
Biopolymer
MCC
Guar
Less grittiness,
improved tablet
palatability
NA NA
Avicel® RC-581
Avicel® RC-591
FMC
Biopolymer
MCC
Sodium CMC
Viscosity
modifier,
NF, Ph
Eur.
160 mg
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Avicel® CL-611 thixotropic
characteristics,
Heat and Freeze
thaw stable,
long self life
stability,
lengthly
hydration times
eliminated,
stable at pH
range 4-11
Pharmatose®
DCL 40
DMV ß-lactose
Lactitol
High
Compressibility
Low lubricant
sensitivity
NA NA
StarLac® Meggle α-Lactose MH
Maize Starch
Good
flowability
USP-NF,
Ph Eur.
NA
ProSolv® JRS MCC
Silicon Dioxide
Better flow, less
sensitivity to
wet granulation,
better tablet
hardness
NF 536.349
mg
Di-Pac® Domino Sucrose
Maltodextrin
For direct
compression,
NF NA
StarCap 1500® Colorcon Maize starch
Pregel Starch
Tablet
disintegration
and
dissolution
independent of
pH
USP,
Ph Eur, JP
482.0
mg
Xylitab® Danisco Xylitol
Sodium CMC
Directly
compressible
NA NA
Celocal® FMC
Biopolymer
MCC
Calcium sulfate
Directly
compressible
NA NA
Vitacel® VE-
650
FMC
Biopolymer
MCC
Calcium carbonate
Direct
compression,
encapsulation
NA NA
LustreClearTM FMC
Biopolymer
MCC
Carrageenan
Efficient Tablet
coating with
short hydration
time prior to
coating and the
first drying time
NA NA
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Formaxx® Merck KGaA Calcium carbonate
Sorbitol
High
compressibility,
excellent taste
masking, free
flow, superior
content
uniformity,
controlled
particle size
distribution
NA NA
PharmaburstTM SPI pharma Carbohydrate
system, made from
compendia
ingredients
High
compactibility,
high loading in
small tablets,
smooth mouth
feel, rapid
disintegration
NA 671.13
mg
AdvantoseTM
FS 95
SPI pharma Fructose
Corn Starch
Excellent flow,
good
compressibility,
tablets hold
shape well and
easily chewable.
NA NA
MicroceLac
100
Meggle α-Lactose MH
MCC
Good
flowability
USP-NF,
Ph Eur, JP
614.2
mg
EffersodaTM SPI Pharma Sodium
BiCarbonate-88%
Sodium Carbonate-
12%
Improve the
stability of the
Effervescent
product
NA NA
Sorbcel M® Blanver Mannitol +
Polyethylene glycol
+
Polyvinylpyrrolidone
+ Citric Acid +
Sodium Bicarbonate.
Effervescent
excipients,
Homogeneous
and stable mix
of excipients
that dissolves
completely and
rapidly,
resulting in a
clear solution
free of insoluble
residues.
NA NA
Sorbcel E® Blanver Sorbitol + Mannitol
+
Polyvinylpyrrolidone
+ Citric Acid +
Sodium Bicarbonate.
NA NA
Fujicalin® Fuji Chemical DCP Anhydrous -Directly
compressible,
-High
USP-NF,
Ph Eur, JP
850.0
mg
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exceptional
flow
-Rapid
disintegration
Neusilin® Fuji Chemical Amorphous
Magnesium
Aluminometasilicate
-Oils and
extracts to
powder
-Improve flow
-Anti caking
-Improve
Compressibility
-To make Solid
dispersion
USP/NF
JP
NA
F-Melt ® Fuji Chemical Carbohydrate,
Disintegrant, DCP
etc
(Total 5 ingredients)
-Directly
compressible
-Oral
disintegrating
time less than
30 seconds
-Highly
flowable with
minimum or no
sticking/capping
US type IV
DMF filed
on 2007
NA
Sepitrap 80® Seppic Polysorbate 80 -Improves the
bioavailability
of APIs with
low solubility
-It can be used
in direct
compression
processes.
NA NA
Sepitrap 4000® Seppic Ethoxylated
hydrogenated castor
oil
NA NA
TAP -400® Pharmatrans Processed Tartaric
acid pellets
As a acidic core
for drug
delivery
technologies
NA NA
Conclusion:
At present no regulatory mechanism exists
in which a new excipient can be assessed
entirely for safety and quality. Therefore,
the pharmaceutical industry has been
reluctant to use new excipients, which in
turn could prevent the advancement of
pharmaceutical technology. The
implementation of a global DMF system to
handle confidential information for
excipients may support efforts for an
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independent acknowledgement and review
system for new excipients.
New excipients could be evaluated with a
base set of data for general acceptance
similar to the programs established by the
Flavour and Extract Manufacturers
Association for flavour ingredients and the
Cosmetic Ingredient Review for cosmetic
ingredients. However, the use of a new
excipient still would be subject to final
approval as part of a drug product, and
specific-use information would be supplied
with the drug product submission.
Co-Processed excipients certainly have a
role in pharmaceutical innovation. They
can be custom designed to possess specific
characteristics and functionality for
specific applications. Co-Processing does
create a new entity. But demonstration of
the lack of significant chemical change
should allow entry to market much faster
(and more cost effectively) than with a
truly novel chemical or biological
excipient.
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