Vol 3, Issue 1, 2021 (20-25)
http://journal.unpad.ac.id/idjp
*Corresponding author,
e-mail : i.sopyan@unpad.ac.id (I. Sopyan)
https://doi.org/10.24198/idjp.v3i1.34038
© 2021 I. Sopyan et al
Mini Review : SeDem System as a Tool to Characterize Excipients in Solid Dosage Form
Iyan Sopyan
*
, Rizka Guntina Khairunisa
Department of Pharmaceutics and Technology of Pharmacy, Faculty of Pharmacy Universitas
Padjadjaran, Jl. Raya Bandung Sumedang Km.21, Sumedang, Indonesia 45363
Received: 13 Feb 2021, Revised: 8 March 2021, Accepted: 16 March 2021, Published: 20 March
2021
ABSTRACT
SeDem System is a new system that can be applied in solid dosage form preformulation
studies of medicines. It has parameters to evaluate critical quality attributes of materials
that have an impact on final drug product’s quality. SeDeM studies could be used as a
method for identifying the best excipient and calculating the maximum amount of
excipient required for formulation. SeDeM method can providing formulation with the
lowest amount of excipients as it combines the Active Pharmaceutical Ingredients (API)
with only one excipient and the standard formula of lubricants, thus avoiding the used of
unnecessary excipients, such as diluents, binders and agglutinants. The information given
by the SeDeM system contributes to a quality by drug design development.
Keywords: SeDeM System, Excipients
1. Introduction
In recent years, several technologies are
available to produce solid dosage forms. One is
the direct compression method. This method
offers a number of advantages such as fewer
manufacturing steps, eliminating heat and
humidity processes, simplified validation, and
improving drug stability. The things that need
to be addressed that can determine the success
of the direct printing process are the
characteristics of mixed pre-compression
powders, such as flowability and
compressibility. In most cases, excipients have
higher concentrations than active
pharmaceutical ingredients (APIs). As a result,
excipients contribute critically to the
processing, stability, safety and performance of
drugs. The quality and effectiveness of the drug
depends largely on how the excipient works.
This requires appropriate flowability, adequate
compactibility, a homogeneous mixing process
without drug segregation, good physical and
chemical stability including chemical drug
compatibility. Most of the available excipients
are now less well and less suitable for achieving
the desired set of functions 1.
Therefore, research to identify the most suitable
excipients and calculate the exact number of
excipients required for direct compression of
the API is indispensable. SeDeM has many
advantages, such as identifying the best
excipient, creating a formulation requiring the
lowest excipient, minimizing the variation of
the type of excipients required in the formula so
as to streamline the excipients used, such as
diluents, binders and agglutins. the quality of
SeDem is governed by ICH (International
Harmonization Conference) Q8 2.
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2. SeDeM System
SeDeM is a system that is used to select the
excipients used for the delivery of solid dosage
forms for several solid parameters3. SeDeM is
a new system for preformulation and excipient
formulation studies for the manufacture of
drugs, especially in solid dosage forms. This
existing system is an innovative new tool that
the concept of Quality by Design is regulated
by ICH Q8. This system gives information
related to the excipient can be forged directly
or not based on the existing parameters 4.
SeDeM is a process that can be used to
determine the reproduction capabilities of APIs
and Excipients. In addition, it can be used as a
guide to incorporate less-compressed drugs
with suitable materials followed by SeDeM can
be used to determine a bad API latch 5.
3. SeDeM Parameters
There are 12 parameters in SeDem system to be
identified : bulk density (Da), interparticle
porosity (Ie), particle size (%Pf), Carr index
(IC), cohesion index (Icd), Hausner ratio (IH),
angle of repose (a), tapped density (Dc),
flowability (tn), loss on drying (%LoD),
hygroscopicity (%H) and homogeneity index
(Iq). Validated experimental methods and
processes determine these parameters for
fitting into SeDeM diagram method and
analyzed to discover the suitability of the
powder for direct compression. Therefore,
SeDeM diagram method could be described as
a mathematical and graphical representation of
powder characteristic parameters for
discovering direct compression suitability of
various API and excipients 6, 7.
Angle of Repose
Break angle (h). The rest angle of a powder
solid is determined by the funnel method. The
weighted solid powder is inserted into the
funnel and then knocked. Measured the height
of the powder that fell so that the end of the
funnel fitted with the top of the powder. The
powder flows freely down through the funnel.
After which the powder diameter is measured
and measured also angle istanyah according to
the formula:
tan θ = h / r,
where h is the height and r is the radius 8.
Bulk density and tapped density
Mass density. Both bulk density (LBD) and
bulk density (TBD) density are determined.
The powder of a preparation inserted into a
measuring cup is attached to a device and
shakes its purpose to prevent clots from
occurring. then determined and calculated the
difference of initial volume and final volume.
The tap continues until no volume change is
recorded. LBD and TBD are calculated.
LBD = Powder weight / packing volume
TBD = Powder weight / volume tapped packing 8.
Compressibility index and Hausner's ratio
This following formula used to determine the
compressibility index of granules:
Carr's compressibility index (Carr's index)
(IC%) = [(TBD − LBD) × 100]/TBD
Hausner's ratio = (IH) Tapped density/Bulk density
Inter-particle porosity
The powder porosity of the drug is measured
using the following formula:
Ie = Dc-Da/Dc X Da
Carr index (IC %)
It computed from Da and Dc using this
equation :
IC = (Dc-Da/Dc) x 100
Cohesion index (Icd)
The cohesion index is determined by directly
printing the drug powder using the enteric
press. After that, the hardness of the tablet is
determined and the mean hardness is calculated
9.
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Flow ability
The flow rate that suitable with the method
determined as the time for a fixed amount of
powder to flow through the glass tunnel with
0.85 cm orifice diameter. It was expressed in
seconds and tenths of a second per 100 grams
of sample. The mean value of three
determinations always being taken 9.
Table 1: SeDeM System For Pharmaceutical Excipients
No
Parameter
Lactose
Monohydrate
9
Lactose
SD
9
Microcrystalline
Cellulose
13
Maize
Starch
13
1
Parametric
index (IP)
0.50
0.50
0.58
0.56
2
Parametric
profile index
(IPP)
6,.01
7.18
5.80
5.46
3
Good
compression
index
5.72
6.83
5.52
5.20
Loss on drying (%HR)
The powder was dried in a convection oven at
105 ° C ± 2 ° C until a constant weight was
obtained 9.
Hygroscopicity (%H)
The hygroscopicity determined by calculate the
increase in sample weight after being kept in a
humidifier 9.
Percentage of particles measuring
The particle size was calculated by means of a
test such as a strainer and then observed a
powder that passed through a sieve with a size
of 0.05 mm 9.
Homogeneity index (Iθ)
Homogeneity index is used to determine
particle size using filter test. The measurement
of the 100 g powder is shaken for 10 minutes.
The filter size used is: 0.355, 0.212, 0.100 and
0.05 mm 9.
Parameter Index (IP) defined as the limit that
can be accepeted for indexes to detemine if the
product is suitable to be processed by direct
compression. IP calculated using this formula:
Parameter Index (IP) = (n^o P ≥5)/(n^o Pt)
Where :
N0P ≥ 5 = the number of parameters where the
value is equal to or higher than 5
N0Pt = the total number of parameter that being
studied.
The acceptability limit of IP should meet the
value of 0,5.
Parameter Profile Index (IPP) defined as the
average (r) of all parameters, or the value of the
parameters calculated. The acceptability limit
of IPP (r) should meet the value of 5.
Good Compressibility Index (IGC) Formula = IPP x f
Where :
f = Reliability factor = (Polygon area )/(Circle area)
The reliability factor (f) explain that the more
parameters included means the increasing of
reliability of the method. The acceptability
limit of IGC should meet the value of 5.
Lactose SD is the choice of excipient for
masking poor flow property of drug substances.
SeDeM method helps to predict the aptitude of
I. Sopyan et al / Indo J Pharm 3 (2021) 20-25
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excipients to obtain orodispersible tablets and
their suitability for direct compression and
based on the result lactose SD is recommended
to be used in the formulation.
Application of SeDem System
SeDeM system has numerous application. It
could be applied to determine whether an API
is suitabile to be manufactured by direct
compression technology, based on the profile
of SeDem diagram. Furthermore, this method
could be applied to characterize an active
pharmaceutical ingredient in powder form, and
quality control of batches of a single API and
excipient used in direct compression method2.
Table 2. Three parameters of disgregability in SeDeM ODT system.
Factors
Parameter
Limit value
(Minute)
Radius
Disgregability
Effervescence
0-5 (minutes)
10-0
Disintegration Time with disk
(DCD)
0-3 (minutes)
10-0
Disintegration Time without disc
0-3 (minutes)
10-0
Beside that, SeDeM system could be used to
determine the amount of excipient required for
the compression of an API that is not suitable
for direct compression method2.
There are 12 parameters that measured in the
SeDeM method system. To meet the
qualification or acceptance of formulation for
direct compression, the parametric index for the
formula were interpreted in the form of
numerical results of the radius (r) and then
described in a diagram called SeDeM Diagram.
The parametric profile value for the results of
the radius should be more than 5. This value
means that material is suitable for direct
compression method2.
The SeDeM system is also used to prove the
reproducibility of manufacturing between
batches of the same powdered raw material.
The utilization of SeDeM Diagrams in each
batch can measure the degree of similarity or
difference between the same API based on
established parameters thus can determine its
worthiness for direct compression method2.
SeDeM method is also applied to differentiate
the excipient in the same chemical group and
same functional type, but different in physical
characteristics. The physical characteristics of
an API for direct compression will determine
their use in a drug formulation2.
There is a new model of SeDeM system, called
SeDeM-ODT. This method used for
developing tablet by direct compression
method that can orally disintegrate (orally
disintegration tablet, ODT). SeDeM-ODT can
provides the Index of Good Compressibility &
Bucodispersibility (IGCB index) acquired from
the previous SeDeM method. SeDeM-ODT
model which has IGCB index concist of 6
factors. The index simultanously indicates if
these tablets are suitable as bucodispersible
tablet which can be disintegrated in < 3
minutes. There is new factor, disgregability has
3 parameters that impact the parameter 2.
In the past decade, the focus of interest is to
develop the ODTs by trying different solutions
to improve the formulation. Therefore, some
excipient manufacturers started producing
“superdisintegrants” which can be effectivelly
used to reach the ODT’s parameters. Moreover,
there are many known techniques and methods
that used to prepare such pharmaceutical forms,
such as freeze-drying, molding, lyophilization
and direct compression11.
I. Sopyan et al / Indo J Pharm 3 (2021) 20-25
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Direct compression is the most used method to
manufacture ODTs. This method has a high
efficiency and great variety of excipients and
tablet manufacturing. The most critical step of
ODT formulation process is the selection of
superdisintegrant and determination of its
concentration12. So, the advantage of SeDeM
and SeDeM-ODT are it is efficient in terms of
time and cost effective for both preformulation
and formulation stage.
4. Conclusion
SeDeM system method could be used as a tools
for knowing the parameters of materials for
preformulations. By measuring the 12
parameters offered in the SeDeM system
method, it can identify the most suitable
excipient, calculate the maximum quantity of
excipient that required in direct compression of
API which is having poor flow, provide
formulation with the minimum quantity of
excipients so the use of unnecessary excipients
such as binders, agglutinants and diluents could
be avoided. This system can also be used as a
quality control tool to study the reproducibility
between batchs of API and excipients, based on
the 12 parameters offered in the SeDeM
Diagram.
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