PHARMACEUTICAL FOCUS//R&D
The essential element in direct compression Anhydrous lactose is a versatile and proven excipient in diverse operations and manufacturing procedures. It has become an inherent part of excipient combinations and has repeatedly proven its ability to perform in challenging formulations.
M
eggle’s GRAS-listed
diverse, rapidly formed particles
dependent disintegration is insured
anhydrous lactose,
are subsequently classified by
favouring immediate release by rapid
DuraLac is Ph.Eur. JP and
comminution and sieving. Finally,
water imbibition. This is an essential crux
USP NF-monographed.
pharmaceutical anhydrous lactose
for the great majority of new chemical
It is known for its low overall water
grade DuraLac is packed either
entities showing the phenomenon of
content below 0.5 percent with a very
into 25kg carton boxes or 50kg fibre
reduced solubility.
low hygroscopicity of up to 70 percent
drums, both containing aluminium
RH at 25°C, as indicated by differential
laminated in-liners. The shelf life is
vapour-sorption (DVS). This enables
24 months, according to ICH Q1A
easy manageability in production
stability guidelines.
processes in critical climate zones.
Brittle, anhydrous lactose
Anhydrous lactose – a white to off-
preferentially deforms by a compaction
DuraLac was especially designed for direct compression
white, crystalline, odourless powder
mechanism, resulting in a large surface
– has a slightly sweet taste. Morphology
for binding with a rough surface
of anhydrous particles is different to
morphology. Anhydrous crystals
monoclinic sphenoidal crystals of
undergo brittle fracture increasingly
α-lactose monohydrate. Anhydrous
readily and at lower stresses than
lactose granules are remarkably dense,
the monohydrate1. Together with
exchangeability of various commercially
representing agglomerates of micro
plastically deforming components,
available anhydrous lactose grades,
crystals exhibiting a wide irregularity
it may so act as a stable ‘structure-
a rational approach could be helpful
in shape and breaking edges due to
giving element’, leading to synergistic
using drug substances with diverse
its production process. A typical laser
improvements during compaction
solubility, such as Theophylline (7.4g/l),
diffraction particle size distribution (PSD)
processes such as tabletting, slugging
Paracetamol (14g/l) and Diprophylline
exhibits a d50 value of 135 µm (d10 15 µm,
or roller compaction. A typical tablet
(330g/l). All results demonstrated
d90 310 µm), and a specific BETsurface area is found in the range between 0.3 and 0.4 m2/g. Anhydrous lactose appears as α- and ß-anomer. The ß-anomer exhibits higher water solubility and surface wetting.
Improving compaction synergistically
tensile strength of 2.5 N/mm2 for
DID YOU KNOW?
DuraLac placebos can be seen at a corresponding
Meggle offers dual sourcing and its DuraLac is produced in Le Sueur, in the USA in a state-of the art, exclusively pharma-dedicated production site. The site complies with cGMP-standards according to the Joint IPEC-PQG Good Manufacturing Practices Guide for Pharmaceutical Excipients and USP NF General Information Chapter 1078.
DuraLac’s starting material is a
compaction pressure
performance2,3. This makes DuraLac, which alternative in a formulation strategy with
common and can be
expanding flexibility. •
observed at a tablet hardness of 130N for neat anhydrous lactose grades.
Direct compression
DuraLac was especially designed unit operation and shows a robust
on two counter rotating drums at
performance in powder flow during
elevated temperatures. This process
high speed tabletting.
| AUGUST 2017 | P C Review
indicate equivalence of drug release is available locally from Achem, an ideal
for direct compression process
28
to Moore and Flanner, these values
forces up to 400N are
grade, dissolved in water and sprayed
of anhydrous lactose crystals. These
similarity factors of f2 > 50 and, according
of 180MPa. Ejection
compendial α-lactose monohydrate
leads to the spontaneous formation
When considering robustness and
Due to the elevated content of ß-lactose anomer, a fast, less hardness-
REFERENCES: 1. Bolhuis G.K., and Zak T.C., Materials for Direct Compression; Pharmaceutical Powder Compaction technology ed. by Alderborn G. and Nyström C, pp 419, Marcel Dekker, Inc., 1996 2. Moore J.W., and Flanner H.H., Mathematical comparison of dissolution profiles; Pharm. Tech. 20, pp 64-74, 1996 3. Penz F.K., DuraLac ® H: A new, alternative source of anhydrous lactose; APGI Gazette N° 30, pp 16, 2014
Amchem – www.amchem.co.za Meggle – www.meggle-pharma.com