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TABLETING
DIRECT COMPRESSION
CO-PROCESSED LACTOSE
TOSE
Technical brochure
Cellactose 80
MEGGLE co-processed lactose grades
for direct compression: Cellactose 80
Direct compression (DC) tablet manufacture is a popular choice Alpha-lactose monohydrate and cellulose powder are functional
because it provides the least complex, most cost effective process excipients used in oral solid dosage forms. Both are naturally
to produce tablets compared to other tablet manufacturing derived and well-established for use in the pharmaceutical industry.
approaches. Manufacturers can blend APIs with excipients and In an effort to create synergistic functional performance, such
compress, making dosage forms simple to produce [1, 2]. as improved compactability and mixing characteristics, co-spray-
drying was used to integrate alpha-lactose monohydrate and
DC technology and the use of modern tableting equipment require cellulose powder into a monoparticulate system. Cellactose80
that excipients and APIs form a compactable mixture with was developed to provide the flow and compaction properties
excellent flowability and low particle segregation tendency [3]. necessary for direct compression tableting. Cellactose80
comprises 75% alpha-lactose monohydrate and 25% powdered
In the pharmaceutical industry, lactose is one of the most cellulose, both maintaining their individual chemical identities.
commonly used excipients; however, like many other excipients,
lactose may not be suitable for direct compression without
modification due to insufficient powder flow or/and compaction
properties (Figure 1).
Lactose performance
Flowability/compressability
High
WG DC
Powder flow
WGDG
Low Powder compressability High
The raw materials used to produce Cellactose80, alpha-lactose Cellactose80 is designed for direct compression tableting and
monohydrate and cellulose powder, meet Ph.Eur., USP-NF, and JP may be used in other formulation applications such as dry granu-
monograph requirements. Since no chemical modifications result lation and capsule filling. In comparison with a corresponding
during co-processing and individual chemical identities are physical blend of the individual components, Cellactose80
maintained, Cellactose80 can be considered as a physical blend provides improved compactability, superior flowability, and
of alpha-lactose monohydrate and cellulose powder. In addition, increased adherence capacity, which reduces segregation
a Cellactose80 drug master file (DMF) is available during FDA tendencies typical of simple powder blends. Due to improved
(Food and Drug Administration) drug product submission review blending characteristics and increased adherence capacity,
and approval. Specifications and regulatory documents can be Cellactose80 is ideal for low-dose formulations. Cellactose80s
downloaded from www.meggle-pharma.com. superior compaction properties increases tablet hardness in high-
dose formulations as well. For low-dose or high-dose applications,
Our pharma-dedicated production facility in Wasserburg, Germany Cellactose80 maximizes formulation development flexibility.
is certified according to DIN ISO 9001:2008, has implemented
cGMP according to the Joint IPEC-PQG Good Manufacturing
Practices Guide for Pharmaceutical Excipients, and USP General Direct compression
Information Chapter <1078>. The Wasserburg facility demonstrates Low dosage formulations
MEGGLEs complete lactose production capability range, High dosage formulations
including sieving, milling, agglomeration, spray-drying, and
co-processing. Additionally, MEGGLE is a member of IPEC
(International Pharmaceutical Excipients Council).
Figure 2 shows typical laser diffraction particle size distribution Figure 3 depicts the specified PSD range and typical average
data for Cellactose80. Cellactose80 possesses a narrow PSD values by air jet sieving. These parameters are constantly
that is effective in preparing homogenous powder blends, monitored through in-process-control (IPC) testing and are part
a prerequisite in achieving good tablet quality. of the Cellactose80 particle size distribution specification.
Typical particle size distribution (Laser diffraction) Typical particle size distribution (Laser diffraction)
Cellactose 80 co-processed grade, cumulative PSD Cellactose 80 co-processed grade, distribution density
Cumulative distribution Q3(x)/% Distribution density q3lg(x)
100 2.0
90 1.8
80 1.6
70 1.4
60 1.2
50 1.0
40 0.8
30 0.6
20 0.4
10 0.2
0 0
1 10 100 1000 1 10 100 1000
Particle size (m) Particle size (m)
Figure 2: Typical cumulative PSD and distribution density of MEGGLEs Cellactose80. Analyzed by Sympatec/Helos & Rodos particle size analyzer.
Figure 3: Specified PSDs for Cellactose80 by air jet sieve in bold letters. Typical values
obtained from a permanent in-process-control are shown for orientation.
Batch-to-batch consistency for all lactose products can be attributed Cellactose80 exhibits moderate moisture uptake under high
to MEGGLEs long history and experience in lactose manufacture, relative humidity conditions due to the cellulose powder influence
and broad technical expertise. Constant in-process and final on the observed equilibrium moisture content (Figure 5).
product testing ensures consistency and quality (Figure 4).
Batch-to-batch consistency particle size distribution co-processed lactose Sorption isotherm (Dynamic vapor sorption at 20C)
Cellactose 80 Cellactose80
Passing through 100 Weight change (%)
sieve (%) 6.0
80
5.0
60 4.0
40 3.0
20 2.0
1.0
0
Particle size (m) < 32 < 160 < 250 0.0
Specified NMT 20 % 35 65 % NLT 80 % 0 20 40 60 80 100
Mean IPC value (%) 6.5 53.9 92.5 Relative humidity (%)
SD (%) 1.4 3.3 2.3 Sorption Desorption
Particle size distribution batch-to-batch consistency of Cellactose 80 by air-jet-sieving. Data obtained from
Figure 4: Cellactose
a permanent
80 particle (IPC)
in-process-control size distribution batch-to-batch
of subsequent consistency
batches over by air of
a time period jet 12
sieve analysis.
months. Figure 5: Sorption-desorption isotherm of Cellactose80.
Data obtained from a permanent in-process-control (IPC) of subsequent batches over 12 months.
20 Poor flow
15 Moderate flow
10 Good flow
Figure 8: Flowability index of Cellactose80 and its corresponding physical blend. Smaller Figure 9: Flowability/processability related parameters of Cellactose80.
values indicate better flowability.
0
0 10 20 30 40
Compaction force (kN)
Tablet press: IMA Styl`one 105ML, Tablets: 11.3 mm, 500 mg
Figure 10: Tablet hardness profile for Cellactose80 compared to a physical blend of the individual
Cellactose80 FlowLac90 + powdered cellulose 75:25
components and Tablettose80 (granulated lactose). Tablets were produced using a tablet press: IMA Styl`one
Tablettose80 + powdered cellulose 75:25 Tablettose80 fittet with 11.3 mm punches. Average tablet weight was targeted at 500 mg.
1.5
100
1.0
50
0.5
0 0.0
0 5 10 15 0 4 1 2 3
Compaction force (kN) Tenslile strength (N/mm2)
Cellactose80 Tablet press: Korsch EK 0, Tablets: 8 mm, 240 mg Cellactose80 Tablettose80 + powdered cellulose 75:25
Figure 11: Tablet hardness profile for tablets comprising 69% Vitamin C, 30% Cellactose80, and 1% Figure 12: Friability of tablets produced with either Cellactose80 or its corresponding physical blend.
Compritol 888. Tablets were produced by Korsch EK 0 tablet press fitted with 8 mm punches. Average tablet
weight was targeted at 240 mg.
MEGGLE Consultant
MEGGLE Group Wasserburg Phone +49807173476 MEGGLE warrants that its products conform to MEGGLEs written specification and makes no other expressed
or implied warrantees or representations. For any specific usage, the determination of suitability of use or
BG Excipients & Technology Fax +49807173320
application of MEGGLE products is the sole responsibility of the user. The determination of the use, application,
Megglestrasse 612 service.pharma@meggle.de and compliance of this product with regard to any national, regional, or local laws and/or regulations is the
83512 Wasserburg www.meggle-pharma.com sole responsibility of the user, and MEGGLE makes no representation with regards to same. Nothing herein shall
Germany be construed as a recommendation or license to use the product or any information that conflicts with any
patent or intellectual property of MEGGLE or others and any such determination of use is the sole responsibility
of the user. MEGGLE US 03-27-2014 Sai