Focused on the science
of solubility
ISP offers ingredients and process technology
services for the greatest formulation
challenge facing the industry today.
It has been estimated that 40-60% of drugs in
development
have poor bioavailability due to low aqueous solubility.
This percentage is likely to increase in the
future with
increased use of combinatorial chemistry in drug
discovery
targeting lipophilic receptors. Poor bioavailability
results in
increased development times, decreased efficacy,
increased
inter- and intra-patient variability and side
effects, and higher
dosages that reduce patient compliance and increase
cost.
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"When properly formulated,
solid dispersions have excellent shelf-life
stability, and dramatically enhanced drug
solubility and bioavailability."
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The ability to improve drug solubility and, hence,
bioavailability through formulation and process
technology is critical to improving the efficacy
and safety of a drug product and to reducing its
cost. At ISP, drug solubility is being addressed
using the organisation’s expertise in material
science and its broad portfolio of ingredients
as the foundation for activities ranging from
employing traditional formulation technologies
to working with emerging ones.
Ingredient technologies
Since no single solution applies to all active
pharmaceutical
ingredients (APIs), ISP offers a broad range of
ingredients that
enable the development of poorly soluble drugs
(see table). One
such solution is Polyplasdone Crospovidone. Studies
by ISP have
shown that this disintegrant improves the dissolution
of poorly
soluble drugs in tablet formulations in a way
not possible with
other disintegrant technologies. Its high surface
area combined
with unique chemistry result in high interfacial
activity and
enhanced drug dissolution.
Another option pertains to cyclodextrins. ISP
offers a wide
range of cyclodextrin products for forming inclusion
complexes
with poorly soluble drug actives. The resulting
cyclodextrin
drug complex has improved solubility and thus
enhanced drug
bioavailability. The company provides cyclodextrins
suitable for
formulation of solid, liquid and parenteral dosage
forms.
Solid experience
Solid dispersions have been gaining momentum as
a technology to improve drug solubility and enhance
drug bioavailability. They are molecular (thermodynamically
stable solid solutions) and/or colloidal (kinetically
stable solid suspensions) dispersions of the amorphous
API in a polymeric matrix.
While formulations of solid dispersions have
been known to improve drug bioavailability since
the 1960s, the technology began to receive much
greater attention in the late 1990s as a means
to address current development challenges.
When properly formulated and processed, the result
is a solid
dispersion formulation with excellent shelf-life
stability. It also
has dramatically enhanced drug solubility and
bioavailability,
which can often be an order of magnitude greater
than that of
the purely crystalline drug form. Currently, there
are five
commercial products based on solid dispersion
technology.
ISP has years of experience with respect to the
formulation
of stable solid dispersions with enhanced bioavailability,
having worked with over 100 different actives.
Its Plasdone
K-29/32 Povidone and Plasdone S-630 Copovidone
are highly
effective polymeric dispersants and stabilising
agents used in
solid dispersion formulations.
Solid dispersions are most practically and most
commonly produced in the laboratory through to
commercial scale by either spray-drying or melt-extrusion
processes. With many years of spray-drying expertise
and a GMP spray-drying facility, the organisation
helps
to develop solid dispersion formulations from
feasibility
through clinical supply. In alliance with Coperion
in
Stuttgart, Germany, a market leader in extrusion
equipment,
ISP is also working on advancing hot-melt extrusion
(HME)
technology for the pharmaceuticals market.
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