Sponsored by

Solubilization
Solutions
Tackling current and emerging
bioavailability challenges

A supplement to

EUROPE AND NORTH AMERICA

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Editorial

Inside...
Round Table
4
Open Alliance to Provide
Bioavailability Solutions
An industry round table with Catalent and BASF

Collaborative work can lead to innovation

Dear Reader,
In drug development, the majority
of new chemical entities are
lipophilic and/or poorly soluble.
New actives often fail during
development due to these
challenging properties. The
solubilization of actives is therefore
an important approach towards
improving the bioavailability of
a drug molecule in an accepted
dosage form.
In this special issue, BASF would like to open up a discussion
about solubilization challenges and innovative solutions, focusing
on both products and cost-effective production technologies,
such as hot-melt extrusion and spray drying. Because innovation
is always the result of many, companies such as Catalent, Bend
Research and Johnson & Johnson have also contributed with their
expertise on this topic.
True to its legacy of innovation, BASF continues to develop new
innovative solubilizers, such as Soluplus. Thus, together with
our established portfolio of Kolliphor solubilizers and Kollisolv
cosolvents, we offer a versatile toolbox capable of coping with
the many solubilization challenges facing our industry. This, in
combination with our SoluHTS screening robot, enables the
industry to screen and identify the most suitable solubilization
excipients faster, thereby shortening their product development
time.

Formulation
5
Solid Dispersions by Hot-Melt Extrusion
The advantages and disadvangages of
hot-melt extrusion in solid dispersion formulations
Industry Rebranding
8
Lipophilic Excipients
Streamlining the structure, nomenclature
and functionality of excipients
Case Study
10 Bioavailability Enhancement
A Soluplus case study of itraconazole
New Solubilization Strategies
12 Lipid-Based Formulations
A Johnson & Johnson viewpoint
Spray Drying
13 Fundamental Approaches to Performance,
Stability and Manufacture
Bend Research on optimizing spray-drying approaches
Trends
15 Addressing the Solubility Challenge
A Q&A with Karl Kolter, Head of Pharmaceutical
Excipients R&D at BASF

In the end, there is no single way out of the maze of

pharmaceutical development. However, the use of new
technologies and innovative products may get us out quicker.

2012 Advanstar Communications Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical including by photocopy, recording, or information storage
and retrieval without permission in writing from the publisher. Authorization to photocopy items for internal/educational or personal use, or the internal/educational or personal use of specic clients is granted by Advanstar Communications Inc. for libraries and other users registered with the Copyright Clearance Center, 222 Rosewood Dr. Danvers,
MA 01923, 978.750.8400 fax 978.646.8700 or visit http://www.copyright.com online. For uses beyond those listed above,
please direct your written request to Permission Dept. fax 440.756.5255 or email: mcannon@advanstar.com.

Dr. Ralf Fink

Vice-President of Global Marketing,
BASF Pharma Ingredients & Services

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Disclaimer: The views and opinions expressed by the participants of this supplement do not
necessarily reect the views and opinions of Advanstar Communications, publisher of Pharmaceutical Technology and Pharmaceutical Technology Europe.

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Open
Alliance

Below left to right: Ian Muir, Catalent, and Martin Widmann, BASF.

A round table with Catalent and BASF on their new

collaboration to provide bioavailability solutions
In early 2012, BASF and Catalent formed an open alliance aimed at
providing solutions for bioavailability. To understand the details of the
collaboration and its goals, we spoke to representatives at each company.
Participating in the round table were: Martin Widmann, Senior VicePresident of Pharma Ingredients & Services at BASF and Ian Muir, PhD,
President of Modified Release Technologies at Catalent.
Q. Can you explain what each company is contributing to the alliance and
how the collaboration functions?
Widmann: BASF and Catalent have complementary offerings and
knowledge that address the same customer needs: the enhancement
of solubility and bioavailability of poorly soluble drugs. BASF has the
broadest portfolio of solubilizers in the industry.
Muir: Together, we will build efficiencies for our customers along
the value chain from formulation development and ingredient selection
through manufacturing process selection to the finished dosage form
bringing more products and better treatments faster to the market.
Catalent has 75 years of heritage enhancing bioavailability with our Softgel
technology and has recently expanded its OptiMeltTM hot-melt extrusion
capabilities in the US and its Schorndorf, Germany, facility.
Q. The collaboration joins two companies with formulation development
and manufacturing expertise. How does the collaboration go beyond a
traditional supply relationship? What is meant by an open alliance?
Widmann: Open means that both partners have joined forces on
a nonexclusive basis, because we think that this is the most efficient
approach to the market and one that maximizes the reach of both
companies. The idea is to provide support in excipient selection for a
particular customer need and to provide access to Catalents formulation
and manufacturing experts and leading drug delivery technologies.
Muir: Catalent wants to keep full flexibility in the choice of excipients
for its customers, and the open alliance arrangement ensures that
customers are not limited to the excipient portfolio of one supplier.
The major advantage of the BASF portfolio is the access to its different
chemistries, which makes matching to optimize solubility all the more
likely. The open alliance will provide customers with formulation expertise
across BASF and Catalent and in turn offer seamless bioavailability
enhancement solutions from molecule to market.
Q. The alliance was specifically formed to respond to client problems in
resolving problems of bioavailability of BCS Class II and IV poorly soluble
compounds. What are the potential solutions that can be used to resolve
these challenges from an excipient and technology perspective?
Muir: Catalent is the leading industry partner in the development
and formulation of drugs, biologics and consumer health products and
a world leader in drug delivery technology. Bioavailability enhancement
can be addressed through multiple approaches, including optimizing the
API, formulation, processing technology, and/or drug delivery dosage

form. Our technologies range from OptiFormTM high throughput screening

to Softgel technology and OptiMeltTM hot-melt extrusion to highly
differentiated controlled release tableting technologies such as OSDrC
OptiDoseTM.
Widmann: Our Kolliphor range of products, including poloxamers,
hydrogenated castor oil, TPGS and others offers a wide variety of
properties that match the physicochemical properties of active
ingredients. The latest innovation in this field is Soluplus, which won the
Silver CPhI Innovation Award in 2010.
Q. Hot-melt extrusion is one potential solution for resolving bioavailability
issues. Can you provide details on the companies expertise in this area?
Widmann: BASF is a recognized world-leading manufacturer and
innovator of pharmaceutical excipients. We offer a line of polymers
designed specifically to increase solubility in general and for use with
hot-melt extrusion in particular. We have significant investments year on
year in the development of pharmaceutical excipients because we believe
that todays formulation challenges can not be solved with yesterdays
excipients. Furthermore, BASF has decades of experience in the hot-melt
extrusion technology in plastics as well as in pharmaceutical applications.
Muir: Catalent is the world-leading solubility solutions provider,
with Softgel and OptiMeltTM hot-melt extrusion. Its capabilities range
from development, formulation, pilot, commercial manufacturing to
differentiated drug delivery on a global scale.

Q. Will BASF and Catalent staff jointly work on a project for a given client?
Muir: Catalent will cooperate with BASF to optimize solubility from
excipient selection, formulation, process technology to drug delivery and
dosage form for customers desiring an integrated approach. By providing
our customers with the option of working with a team of experts across
our companies, we will increase efficiencies for them from development
to scale-up to commercial, hence enabling them to deliver more products
to market.
Widmann: Nobody knows our products better than we do. This
know-how in the application of our excipients is brought into the alliance
by training and supporting the Catalent formulation experts. Where
appropriate, experts of both companies will work together on customer
projects to find optimal solutions.
Q. What feedback have you received since the collaboration began?
Widmann: The announcement generated a lot of interest in the market
because every formulator is concerned about the solubility challenge.
Muir: Not only in the market, but also internally, everybody is excited
about the opportunity to jointly cover the whole pharmaceutical value
chain from excipients to finished drugs.

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Solid Dispersions by
Hot-Melt Extrusion
The advantages and disadvantages of hot-melt
extrusion in solid dispersion formulations
Andreas Gryczke, BASF

Solid dispersions represent a promising formulation approach for

overcoming todays major challenge in pharmaceutical formulation
development: poorly soluble and poorly permeable active
pharmaceutical ingredients (APIs). Solid dispersions can be obtained
using different processes; however, hot-melt extrusion (HME) is
extremely suitable for this purpose. One major advantage is the
fact that no solvents are required; this avoids residual amounts of
solvent and the accompanying stability risks during the shelf life of the
formulation (see Figure 1).
A solid dispersion is defined as a formulation of poorly soluble
compounds as solid dispersions might lead to particle size reduction,
improved wetting, reduced agglomeration, changes in the physical
state of the drug and possibly dispersion on a molecular level,
according to the physical state of the solid dispersion. This will depend
on the physicochemical properties of the carrier and the drug, the
drug-carrier interactions and the preparation method (1).
This definition points to some of the success factors of a solid
dispersion. The miscibility between the API and the carrier, often an
amorphous polymer, has to be defined. The polymer has to act as
a solvent for the API to immobilize it within a molecular dispersion.
This can be achieved by a high glass transition temperature (i.e., high
viscosity and low cold flow) but this usually leads to a kinetically
stabilized system only.
Any disturbing factor such as a slightly increased temperature
or moisture can enhance flexibility in the solid dispersion and can
accelerate migration of the drug; this in turn leads to nuclei formation
and possible re-crystallization of the previously amorphous drug. A
better solution is to utilize interactions such as hydrogen bonding
between the API and the polymer to immobilize and stabilize the API in
its molecular dispersion. Such systems are thermodynamically stable
and are called solid glassy solutions.
In addition to a solid glassy solution, the API can be amorphously
suspended in small clusters in the carrier, which can be kinetically
stabilized. This is called an amorphous glass suspension (see Figure
2). If the API is a crystalline suspension in the amorphous carrier, the
system is called a crystalline glass suspension. Such systems appear
stable because the crystalline state is the energetically favored state.
Solid glassy solutions and amorphous glass suspensions enhance the
dissolution rate of the API by providing it in a non-crystalline form. In
this way energy is applied to the API to bring it to a higher energy state

Figure 1: Hot-melt extrusion is an efficient processing method

for obtaining solid dispersions.
Weakly soluble
crystalline API
Amorphous
polymer
solvent

Solid dispersion
of API in polymer

Hot-Melt Extrusion
Extruder

Figure 2: Solid dispersions based on amorphous polymeric

carriers.

Glass suspension

Glass solution

API

Crystalline

Matrix
(polymer)

Amorphous

Amorphous

Amorphous

Very stable

Only kinetically stabilized

(oversaturation)

Stable (drug below

saturation solubility)

System
stability

Amorphous

Molecularly dispersed

Figure 3: Energy brings the API from the crystalline to the

amorphous state and to separate single molecules.

Energy

E1

E2

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One can utilize interactions

such as hydrogen bonding
between the API and the
polymer to immobilize
and stabilize the API in its
molecular dispersion.
Figure 4 shows the relevant parameters that determine the stability
of a solid dispersion. It also describes the second challenge faced
when formulating a solid dispersion: stabilization of the released API by
avoiding a re-crystallization in the gastro-intestinal tract. Soluplus was
developed as a polymeric amorphous carrier to stabilize the API when
molecularly dispersed in the Soluplus matrix by its lipophilic structural
elements.
However, Soluplus was also developed as a polymeric emulsifier
to keep the API in a dissolved state after its release into the
gastro-intestinal fluids. If this were not the case, the API would
likely precipitate out from its supersaturated state. In some cases,
precipitation cannot be fully avoided, but Soluplus and other polymers
such as Kollidon VA 64 can sufficiently slow down the precipitation
process, thus allowing sufficient absorption of the API into the
blood stream. This approach, when the API is released fast into
supersaturation and starts to precipitate out, is known as the jumpand-parachute effect. The important parameter is the precipitation
rate after supersaturation is reached.

Figure 4: Main parameters that determine the success of solid

dispersions (solid glassy solutions).
Storate stability
Advantage (+)

Disadvantage (-)

Hot-melt extrusion is a recognized process for the manufacture of

solid dispersions and innovative new dosage forms. It is an established
process that has been used in the plastics and food industries since
the 1930s. In the 1980s, BASF SE was the first to apply the melt
extrusion process based on polymers with high glass transition
temperatures (such as polyvinylpyrrolidones) to pharmaceuticals (2).
Extruders for pharmaceutical use have been designed and adapted
for mixing drugs with carriers in various dosage forms. The significant
difference between extruders for thermoplastics and pharmaceutical
applications is the equipment used, and hence, the contact surface,
which must meet regulatory requirements. The contact parts of the
extruders used in pharmaceuticals must not be reactive nor may
they release components into the product. The extruder equipment
is specially configured to fulfill all cleaning and validation standards
applicable to the pharmaceutical industry.
The use of extruders in the pharmaceutical industry cannot be seen
as a niche application. Figure 5 demonstrates four fields of versatility
of the technology. Not all the benefits available, however, have been
realized to date.
In principle, an extruder consists of barrels enclosing single or twin
screws that transport and, subsequently, force the melt through a die,
giving it a particular shape. The barrel can be heated to the desired

Tg of matrix
Compatibility matrix / API

Stable dissolution rate

Parameters of relevance
Matrix dissolution rate
Matrix solubilizing
capability
Matrix amphiphilicity
Use of solubilizers

Time

Figure 5: The four fields of versatility of hot-melt extrusion

technology in the pharmaceutical industry.
Dosage form

Application
Bioavailability enhancement
Controlled release
Sustained release
Safer medication
abuse deterrent, reduced side
effects

Direct shaping (calender)

Granules and spheres
also for powders

Films and patches

Injection moulding

Formulation

Process

Broad excipient range available

Reduced number of ingredients for
formulation

High throughput
exible in terms of time or scale

Continuous quality monitoring

Precise energy utilization
Small footprint

Figure 6: From poor API solubility to a final formulation.

Crystalline
drug

Hot-melt extrusion

Parameters of relevance

Interaction matrix / API

Dissolved drug

where the crystal lattice energy is overcome. Figure 3 illustrates this

fact. Because the API is in a higher energy state when amorphous, it
tends to re-crystallize.

Hot-melt
extrusion

Solid solution
extrudate

Tablets

+ Tem.
+ Polymer

Polymer matrix acts as a solid solvent for drug molecules

In the ideal case, the drug is molecularly dissolved in the polymer
Enhanced rate of dissolution and solubility of drug molecules compared to the
crystalline form

temperature. Due to the external heat and shear provided by the

screws, the polymer is plasticized and its viscosity reduced. Hot-melt
extrusion is a typical continuous process, because the extruder is fed
at one side and the extruded material exits from the other side. This
makes it even more attractive for pharmaceuticals (3). The hot-melt
extrusion process comprises the steps melting, mixing and shaping.

Advantages of hot-melt extrusion in detail

Within the pharmaceutical industry, hot-melt extrusion has been used
for various purposes, such as:
Enhancing the dissolution rate and bioavailability of a drug
Controlling or modifying drug release

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Figure 7: Opportunities and advantages of hot-melt extrusion.

Solid Dispersion

Crystalline, amorphous or molecularly dispersed

Can enhance solubility and hence bioavailability
Controlled release matrix systems

Temperature

Temperature can be set low if required for stability

Can be set high if required for melting API

Mixing

High dispersive mixing capability

Efcient and reproducible mixing due to positive
mixing prinicple
Shear can be set very mild

Continuous for adjustable batch volumes

Reduced number of process steps
No solvents required

Process

e-

lim

ite

Volume-limited

Dissolving of
drug in polymer
Tm API

Degra

No dissolving of
drug in polymer

datio

n-limit

ed

qu

Determines cost
efciency

To
r

Volume-specic feed loading VSFL [mg/cm3*rev]

Figure 8: Process parameter chart.

Minimum volume-specic feed load

Temperature [C]

Taste masking
Stabilizing the API
Parenteral depots and topical delivery systems.
Once developed, hot-melt extrusion is a reliable and robust process
offering benefits in cost-efficiency. Compared to other processes for
the production of solid solutions, it is far less complex, because the
manufacturing of such dosage forms requires only a few steps and
avoids the use of organic solvents (Figure 6).
Hot-melt extrusion also has advantages over solvent-based methods
of forming solid solution and dispersions (Figure 7):
No need to handle explosive solvents
Absence of residual solvents
Continuous processing possible
Possibility of continuous processing
Fewer process steps
High product density
Non-dusty pellets (e.g., for highly active ingredients formulations)
Small-scale equipment
Non-aqueous process.

clear that only an optimized formulation together with an optimized

process set-up will yield the best product.
Besides the parameters such as screw speed and feed rate, which
can be adjusted during the extrusion process, screw configuration is
a major parameter. Screw design is not often optimized although it
plays a major role in determining product quality. Screw configuration
basically determines the shear stress. It also strongly influences
the residence time distribution. BASFs second edition of the HME
compendium provides more information on the design of screws in
co-rotating twin screw extruders. Here, the functionality of different
screw segments is explained in detail.
The new HME compendium also shows how to determine residence
time distribution and how to read it. It provides a guide for process
analysis and for developing better process understanding.
BASF has also developed a process parameter chart that enables
the whole extrusion process with all its influencing variables to be
included. The advantages of the new process parameter chart are:
It displays technical aspects.
It also displays the economic effects of changes made in process
design.
It is scale-independent and can be used in scale-up procedures.
The proposed process parameter chart is shown in Figure 8. It is a
XY-diagram, displaying the volume-specific feed load (VSFL) versus the
extrusion temperature (mean barrel temperature).
Throughput triggers cost. The throughput in an extruder can
be either torque-limited or volume-limited. In Figure 8, one curve
represents the determined maximum achievable VSFL values at the
limit of the extruder. The vertical line indicates the process boundary.
Only the position on the temperature axis is relevant for reading the
line; the line height does not matter. Each VSFL value to the left of the
line is limited by the maximum torque of the extruder (configuration),
while each VSFL value to the right of the line is limited by maximum
intake (volume). The vertical dotted line on the right indicates the
process boundary given by the maximum allowable temperature,
which can be determined by the degradation points of either the active
substance or any non-active ingredient in the processed formulation.
The design space can be filled with contour lines of extrusion system
parameters such as mean residence time for better process analysis.
More information on the process parameter chart and its use can be
found in BASFs new HME compendium (see below).

References
1. S. Janssens and G. Van den Mooter, JPP 2009, 61: 15711586, DOI 10.1211/
jpp/61.12.0001
2. H. H. Grtz et al., EP 0240904 B1
3. C. Leuner and J. Dressman, Eur. J. Pharm. Biopharm. 50, 47-60 (2000).

Hot-Melt Extrusion with

BASF Pharma Polymers
Extrusion Compendium
K. Kolter, M. Karl, A. Gryczke

Download for free the new edition of the

hot-melt extrusion compendium at:
www.innovate-excipients.basf.com

Process understanding and process design

To develop the melt extrusion process in an appropriate manner it is
important to have tools to characterize and analyze the process. It is

Pharma Ingredients & Services.

Welcome to more opportunities.

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Rebranding
Lipophilic Excipients
Streamlining the structure, nomenclature
and functionality of excipients
Shaukat Ali and Nina Karpynec, BASF

the complexity of such formulations is increasing and often two or

more solubilizers and/or cosolvents are required to develop stable and
Solubilizers play an important role in dissolving poorly soluble
efficacious formulations with enhanced bioavailability (1).
molecules. As the number of poorly soluble lipophilic and/or
As pharmaceutical manufacturers develop generic and new
hydrophobic molecules increaseswhether as brick dusts or waxy
molecules that require high-quality, functional excipients, they seek
substancesthe industry is struggling to identify the appropriate
support from excipient manufacturers. Indeed, the pharmaceutical
lipophilic excipients (surfactants, solubilizers, solvents or polymers)
industry relies on excipient manufacturers to design and produce
that can be used to develop such poorly soluble formulations into solid
excipients that are appropriate to the envisaged dosage form and API.
dosages and other forms of pharmaceutical products. Furthermore,
This is a complex undertaking made all the more difficult because
of the number of different names that
Table I: Kolliphor grades.
manufacturers use for their excipients.
Kolliphor
However, several excipient manufacturers
are now streamlining the structure,
Previous name
Rebranded name
Monograph name
nomenclature and functionality of their
Polyoxyl 35 castor oil (USP-NF), Macrogolglycerol
Cremophor EL/P
Kolliphor EL/P
excipients, including solubilizers.
ricinoleate 35 (EP)
Such rebranding has been used in other
Polyoxyl 40 hydrogenated castor oil (USP-NF),
Kolliphor RH40
Cremophor RH40
industries to reduce complexity and to
Macrogolglycerol hydroxystearate 40 (EP)
promote products on the merits of their
Polyoxyl 15 hydroxystearate (USP-NF), Macrogol
performances and qualities, ideally without
Kolliphor HS15
Solutol HS15
15 hydroxystearate (EP)
undermining the old brands. This is now
Kolliphor P407
Poloxamer 407 (USP-NF, EP, JP)
Lutrol F127
occurring among excipient manufacturers,
Kolliphor micro 127
Poloxamer 407 (USP-NF, EP, JP)
Lutrol micro 127
particularly those that carry lipophilic
excipients, including BASF, as well as
Kolliphor P188
Poloxamer 188 (USP-NF, EP, JP)
Lutrol F68
other companies. Many companies have

Kolliphor P188
Poloxamer 188 (USP-NF, EP, JP)
Lutrol micro 68
used branding and rebranding to either

Kolliphor P338
Poloxamer P338 (USP-NF, EP)
Lutrol F108
introduce new products or reintroduce
Kolliphor P237
Poloxamer P237 (USP-NF, EP)
Lutrol F87
an old product under a single prefix to
simplify identification. In the case of BASF,
Polysorbate 20 (USP-NF, EP)
Polysorbate 20 PH
Kolliphor PS 20
Cremophor, Solutol, Lutrol and other
Polysorbate 80 (USP-NF, EP)
Polysorbate 80PH
Kolliphor PS 80
solubilizers will become part of the Kolliphor
Vitamin E Polyethylene glycol succinate (USP-NF)
Speziol TPGS Pharma Kolliphor TPGS
brand family.
Kolliphor SLS 1216
Sodium lauryl sulfate (USP-NF, EP, JP)
Speziol V95G
The basis for rebranding with the same
Kolliphor SLS
Sodium lauryl sulfate (USP-NF, EP, JP)
Texapon K12 G PH
prefix is to identify molecules by structures,
functions and the applications of choice;
Kolliphor SLS Fine
Sodium lauryl sulfate (USP-NF, EP, JP)
Texapon K12 P PH
enable the companys brand products

Kolliphor CS 12
Macrogol cetostearyl ether 12 (EP)
Eumulgin B1 PH
to be recognized; and to differentiate
Polyoxyl 20 cetostearyl ether (USP-NF), Macrogol
pharmaceutical excipients from other grades.
Eumulgin B2 PH
Kolliphor CS 20
cetostearyl ether 20 (EP)
Rebranding is a tedious and time-consuming
Kolliphor CSS
Sodium cetostearyl sulphate (EP)
Lanette E PH
process, and in some instances adds
Kolliphor CS A
Cetostearyl alcohol (Type A), Emulsifying (EP)
Lanette N PH
complexity if the functionality of the molecule
is not well defined.
Kolliphor CS B
Cetostearyl alcohol (Type B), Emulsifying (EP)
Lanette 20 PH
Here, we provide a synopsis of how we

Kolliphor CSL
Not monographed
Lanette SX PH
have
undertaken the process of rebranding
Polysorbate 60 (USP-NF, EP, JP)
Polysorbate 60
Kolliphor PS 60
our solubilizers for pharmaceutical

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applications. With a few exceptions, we have

tried to preserve some of the characters
from the old product brand name to avoid
confusion and to allow scientists to easily
recognize them. The surfactants and
solubilizers, as well as related products,
have been categorized under four umbrella
rebranding subgroups:
Kolliphor: For amphiphilic substances
such as ionic and non-ionic surfactants,
solubilizers and emulsifying agents, as
shown in Table I.
Kollisolv: For solvents such as
medium-chain triglycerides, propylene
glycol, liquid polyethylene glycols and liquid
poloxamers, as shown in Table II.
Kolliwax: This name was coined to
represent consistency factors, such
as those in fatty acids, alcohols and
glycerides, as shown in Table III.
Kollicream: The name was chosen to
represent emollients such as fatty acid
esters and special fatty alcohols, as shown
in Table IV.

Table II: Kollisov grades.

Kollisov
Previous name

Rebranded name

Monograph name

Propylene glycol

Kollisov PG

Propylene glycol (USP-NF, EP, JP)

Lutrol E 300

Kollisov PEG 300

Polyethylene glycol (USP-NF), Macrogol (EP),

Macrogol 300 (JP)

Lutrol E 400

Kollisov PEG 400

Polyethylene glycol (USP-NF), Macrogol (EP),

Macrogol 400 (JP)

Lutrol L44

Kollisov P124

Poloxamer 124 (USP-NF, EP, JP)

Myritol 312 PH

Kollisov MCT 60

Medium-chain triglyceride (USP-NF), Triglycerides

medium-chain (EP)

Myritol 318 PH

Kollisov MCT 70

Medium-chain triglyceride (USP-NF), Triglycerides

medium-chain (EP)

Speziol CAP

Kollisov CAP

Not monographed

Speziol G 85% PF

Kollisov G 85

Glycerol 85% (EP)

Speziol G 99.8% PF

Kollisov G 99

Glycerin (USP-NF), glycerol (EP)

Speziol GTA

Triacetin (USP-NF, EP)

Pyrrolidone (EP)

Kollisov GTA

Soluphor P

Kollisov PYR

Table III: Kolliwax grades.

Kolliwax

Conclusion
Rebranding gives us the opportunity to
include other solubilizers and related
excipients based on their chemistry and
functionalities in our four umbrella subgroups.
With continuing interest to increase drug
solubilization, it is our understanding that
this rebranding will reduce the complexity
involved in selecting pharmaceutical-grade
excipients in formulation development. Thus,
this will encourage excipients manufacturers
to adopt a norm to simplify complex product
portfolios.

Previous name

Rebranded name

Cutina GMS V PH

Kolliwax GMS II

Mono- and di- glycerides (USP-NF); Glycerol

monostearate 40-55 (Type II) (EP)

Cutina HR PH

Kolliwax HCO

Hydrogenated castor oil (USP-NF), Castor oil

hydrogenated (EP), hydrogenated oil (JP)

Speziol C 14 Pharma

Kolliwax MA

Myristyl alcohol (USP-NF)

Speziol C 16 Pharma

Kolliwax CA

Cetyl alcohol (USP-NF, EP), Cetanol (JP)

Spezio l D Pharma

Kolliwax CSA 70

Cetostearyl alcohol (EP)

Speziol C16-C18 Pharma

Kolliwax CSA 50

Cetostearyl alcohol (USP-NF, EP, JP)

Speziol C18 Pharma

Reference
1. C.J.H. Porter, C.W. Pouton, J.F. Cuine and W.N.
Charman, Adv. Drug Delivery Rev. 60 (6), 673691
(2008).

Download
your free copy
of BASFs
solubility
enhancement
compendium
at:
www.innovateexcipients.
basf.com

Monograph name

Stearyl alcohol (USP-NF, EP, JP)

Kolliwax SA

Speziol L2SM GF Pharma

Kolliwax S Fine

Stearic acid (USP-NF, JP), Stearic acid 50 (EP)

Speziol L2SM GS Pharma

Kolliwax S

Stearic acid (USP-NF, JP), Stearic acid 50 (EP)

Speziol GDB Pharma

Kolliwax GBD

Glycerol behenate (USP-NF), Glycerol

dibehenate (EP)

Speziol MD Pharma

Kolliwax GMS I

Glycerol monostearate 40-55, Glycerol

monostearate Type I (EP)

Table IV: Kollicream grades.

Kollicream
Previous name

Rebranded name

Cetiol LC PH

Kollicream 3C

Cocoyl caprylocaprate (EP)

Cetiol SN PH

Kollicream CI

Cetostearyl isononanoate (EP)

Kollicream DO

Decyl oleate (EP)

Cetiol V PH

Monograph name

Eutanol G PH

Kollicream OD

Octyldodecanol (USP-NF, EP)

HD Eutanol V PH

Kollicream OA

Oleyl alcohol (USP-NF, EP)

Isopropyl myristate PH

Kollicream IPM

Isopropyl myristate (USP-NF, EP)

Cutina CP PH

Kollicream CP 15

Cetyl palmitate 15 (EP)

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Bioavailability
Enhancement
A Soluplus case study of itraconazole
Thomas Reintjes and Felicitas Guth, BASF
Figure 1: Chemical structure of Soluplus (A) and physical
appearance of the product (B).

Soluplus, a graft copolymer of PEG comprising polyvinyl acetate

and polyvinyl caprolactam (see Figure 1A), was specially designed
to solubilize poorly water-soluble drugs. To guarantee appropriate
processability (e.g., in melt-extrusion applications), the
composition of the polymer was adjusted to optimize its physical
properties. With a low glass-transition temperature of around
70 C, Soluplus can be processed at low temperatures. Soluplus
shows good stability. Its formulations remain stable so that drugs,
especially those that are formulated in an amorphous state, do
not show recrystallization. In addition to these compositionrelated properties, the physical appearance of Soluplus has been
optimized. Using a special drying process, Soluplus is formulated
as free-flowing granules (see Figure 1B) that allow high feed rates
and dust-free handling during the feeding process. At the same
time the granules can easily be blended with most API crystals
without showing segregation in subsequent process steps.
The unique chemical structure of Soluplus enables it to interact
with a large variety of chemical substances to form watersoluble complexes. Soluplus is therefore considered suitable
for increasing the bioavailability of many active pharmaceutical
ingredients (APIs) that otherwise suffer from low solubility, which
is a common attribute of most new chemical entities. In a previous
study, it was shown that the bioavailability of fenofibrate, danazol
and itraconazole was significantly increased when the drugs were
formulated in a solid dispersion with Soluplus via a melt-extrusion
process (1) .

HO
O
O
O

N
l

HO

Figure 2: DSC thermograms show no crystalline itraconazole for

the Soluplus formulation (red). Interpretation for Sempera was
impossible due to overlaid peaks.
6.0
5.0
Sempera

Heat - Flow (W/g)

A solid solution

4.0

Itraconazole - Soluplus extrudate

Itraconazole crystaline

3.0
2.0
1.0
0.0

Case study
Although the above mentioned study demonstrated the enhanced
bioavailability of the investigated drugs, it also compared drug
formulations with Soluplus using only the crystalline form of
the API. However, the crystalline form is not an ideal benchmark
for comparison, considering that it is not optimized and is not
expected to show comparable biovavailability.
Therefore, a new case study was performed by selecting the
marketed formulation of a poorly-soluble drug (itraconazole) that
had already been optimized with regard to the bioavailabity of the
formulated API (2).
Sempera is a formulation of itraconazole that contains sucrose,
corn starch, hypromellose and PEG 20,000 in addition to the API
(3). The product was used as a benchmark and compared with

-1.0
-50

50

100

150

200

Temperature (C)

a Soluplus-based itraconazole extrudate. The melt-extruded

formulation (20% itraconazole, 80% Soluplus was prepared with
a 16 mm twin-screw extruder (Polylab, Thermo-Fisher, Germany)
at 160 C, 200 rpm and a feed rate of 1000 g/h. Before the
formulations were compared in-vivo, characterization of certain
properties was performed.
Differential scanning calorimetry (DSC) analysis showed
the absence of any crystalline substances in the Soluplus
formulation (see Figure 2). Itraconazole in Sempera seemed

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Figure 3: Dissolution study of itraconazole formulations (USP

<711> paddle, 700 ml SGF). In both cases, a massive oversaturation
could be achieved compared to the crystalline drug.

Drug release (%)

100

Itraconazole crystaline

90

Itraconazole - Soluplus extrudate

80

Sempera

70
60
50
40
30
20
10
0
0

30

60

90

120

Time (min)

Figure 4: Plasma level profiles in beagle dogs after

administration of the different itraconazole formulations. The
highest bioavailability was found for the Soluplus formulation.
1000

Plasma level (ng/mL)

from in-vitro dissolution tests and in-vivo plasma concentrations

did not really correlate; the observed effect was much higher for
the Soluplus-based extrudate. The corresponding area under the
curve (AUC 0-72 h ) increased more than two-fold compared to the
Sempera formulation (8.503 ng*h/mL versus 18.558 ng*h/mL).

900

Itraconazole crystaline

800

Sempera

700

Itraconazole - Soluplus extrudate

A new case study was

performed by selecting
the marketed formulation
of a poorly-soluble drug
that had already been
optimized with regard to
the bioavailability of the
formulated API.

600
500

Conclusion

400
300
200
100
0
0

10

20

30

40

50

60

70

80

Time (h)

mainly amorphous, but an interpretation of the thermograms was

impossible due to superimposed peaks from other excipients
(PEG, sucrose).
Dissolution studies with the two formulations in simulated
gastric fluid (USP) showed comparable dissolution profiles and a
strong oversaturation of the drug in the release medium in both
cases (see Figure 3).
For the in-vivo study, each of the formulations was given to
five beagle dogs in the form of an individually filled hard gelatin
capsule that contained a dose of 10 mg of itraconazole per
kg of body weight. Blood samples were taken at predefined
sampling times and itraconazole plasma levels were analyzed by a
chromatographic method.
The test formulations were tolerated well and there were no
clinical findings. Both formulations, Sempera and Soluplus
extrudates, achieved a strong increase in bioavailability, compared
with crystalline itraconazole (see Figure 4). However, the results

This case study confirms the results obtained from previous

studies and demonstrates once more that it is possible to achieve
a significant increase in oral bioavailability with a Soluplus
formulation. Furthermore, the tested melt-extruded formulation
was very easy to formulate and performed significantly better
than the more complex marketed formulation. It is the authors
opinion therefore that Soluplus can therefore help to bring
promising new chemical entities to the market and shorten
development times by an easy and fast formulation process via
melt extrusion.

References
1. M. Linn et al., Soluplus as an Effective Absorption
Enhancer of Poorly Soluble Drugs In Vitro and In
Vivo, Eur. J. Pharm. Sci., 45, 336343 (2012).
2. F. Guth et al., Bioavailability Enhancement of Itraconazole
with Solid Solutions Based on Soluplus, presented at the
39th Annual Meeting and Exposition of the Controlled
Release Society (CRS), Quebc City, Canada 2012.
3. Rote Liste online, available at www.rote-liste.
de/Online, accessed July 20, 2012.

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Lipid-Based Formulations
A new solubilization technology
Wei-Guo Dai, Janssen Research and Development, Johnson & Johnson

Background
Development of viable dosage forms for poorly water-soluble
compounds continues to be a significant challenge for formulation
scientists, and insufficient bioavailability of such compounds may
result in development delays or failures. Various solubilization
techniquessuch as using surfactants, co-solvents or cyclodextrins,
and adjusting the formulation pHhave been developed, but these
conventional techniques are not always effective in achieving
the desirable solubility enhancement for an increasing amount of
difficult-to-formulate compounds. Recently, several new solubilization
technologies have been developed. This article focuses on one
potential solution: lipid-based formulations.
Several commercial successes, including Sandimmune and
Neroal(Cyclosporine A), Norvir (Ritonavir) and Fortovase
(Saquinavir), have drawn industry interest to this approach. In principle,
one dissolves the lipohilic drug in oil, emulsifies the oil phase in water
and maintains the drug in the solubilized state in the gastrointestinal
tract until absorption has occurred. Often, the lipid formulation is
designed in a way to generate and maintain a supersaturated drug
concentration in vivo for improved oral absorption. In some cases
nanoparticulate emulsions are formed. Excipients play a crucial role in
the formulation performance.
A crucial criterion of the excipient is its solubilization capacity.
The excipient or excipient blend must be able to fully solubilize the
entire drug dose, preferably in a volume of a single oral dosage. This
is often achieved by careful screening of appropriate oils, co-solvents
and surfactants. Both long-and medium-chain triglyceride oils with
different degrees of saturation have been extensively investigated for
the design of lipid-based formulations. Co-solvents also have been
used to help dissolve the drug or a large amount of the hydrophilic
surfactant in the formulations (e.g., ethanol, propylene glycol and
polyethylene glycol). Surfactants with a relatively high hydrophilic/
liphophilic balance are often needed to provide a good dispersing/
self-emulsifying performance. For example, polysorbates, Cremophor
(now Kolliphor EL/RH40) and Solutol HS15 (now Kolliphor HS15) are
used due to their relatively low toxicity and excellent performance.
In addition to the solubilization capacity, excipients in lipidbased formulations must maintain the drug in the solubilized state
in the gastrointestinal tract, preferably in supersaturable high
concentration, until absorption has occurred. Therefore, excipient
typecomposition and excipientdrug ratio are key factors.
For supersaturable lipid-based formulations, the metastable
supersaturated drug concentration has to be maintained for a time
period sufficient for adsorption before drug precipitation occurs. This

is often achieved by temporary inhibition of drug precipitation using

excipients as precipitation inhibitors (e.g., cellulose derivatives and
vinyl polymers have been studied as precipitation inhibitors). Such
polymers include hydroxypropyl methylcellulose (HPMC), methyl
cellulose, hydroxypropyl cellulose, hypromellose acetate succinate,
polyvinylpyrrolidone (PVP), polyvinyl alcohol, and vinylpyrrolidone/
vinylacetate copolymers. The studies showed that HPMC and PVP
were effective at prolonging the supersaturable drug concentration for
significantly improved bioavailability.
Despite lipid-based formulation efforts, the success of commercial
products is limited to a few APIs. The effect of excipients on the
bioavailability of lipid-based formulations is highly complex; the in vivo
performance of such formulations is poorly predictable. Furthermore,
excipients with both acceptable toxic profile and high solubilization
capacity for lipophilic drugs are limited. Very often, a large amount
of surfactants and co-solvents are needed to achieve the targeted
dose level and to form stable microemulsions. Such a large quantity of
excipients may raise safety concerns or compromise shelf-life stability.

Future outlook
The success of novel solubilization techniques such as lipid-based
formulation has been demonstrated with the launch of commercial
products targeting poorly water-soluble products. However,
challenges remain with these difficult-to-formulate compounds,
especially those with high dose requirements. Future efforts may
involve exploring and developing new excipients for high-dose
drug formulations. For example, new oils with high solubilization
capacity are needed to dissolve more lipophic drugs in a lipid-based
formulation. In addition, it may be worth exploring combining widely
used excipients in formulation screening to produce a synergistic
effect for an optimized product performance. Using high throughput
and automation techniques, scientists can screen rapidly thousands of
excipient combinations in various formulations using small quantities
of compoundssomething that is difficult to do manually.
Another key aspect of excipient selection in new solubilization
technologies is the structure-property correlation in the formulation.
Current excipient selection is often empirical or semi-empirical.
The interaction of excipients with drug in the formulation is poorly
understood and development of the in vitroin vivo correlation remains
an obstacle to new solubilization technology. With more understanding
of interactions of the drug with excipients in the formulation and the
drug/excipients with the gastrointestinal tract environment, it could be
possible to establish a structure-property correlation.
Read more, including a look at solid dispersion, on PharmTech.com/BASF

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Spray Drying of
Amorphous Dispersions
Fundamental approaches to
performance, stability and manufacture
Contributed by Bend Research

Reversible Heat Flow [W/g]

Spray drying is a key process

for manufacturing amorphous
Figure 1: Spray drying process and key amorphous dispersion attributes.
dispersions because of its
breadth of applicability.
The Product
The Process
The wide range of potential
DSC Analysis
0.10
atomization techniques and
Nozzle
Homogeneous,
stable,
SDD
Hot Drying Gas,
0.08
controllable drying kinetics
amorphous dispersion
Recycled
Feed Solution:
Solvent Vapor
0.06
Drug is dissolved with
Physical mixture
enables amorphous spraypolymer in a common
0.04
organic solvent
dried dispersions (SDDs) to be
Polymer only
0.02
Drying Chamber:
produced from a wide variety
Amorphous drug
The solution is spraydried using a scalable
0.00
of active pharmaceutical
0
20
40
60
80
100 120 140
process
Temperature [C]
ingredients (APIs). Moreover,
Good Dispersion
spray drying is a continuous,
Bioavailability Enhancement
Increased dissolution rate
efficient, and well-characterized
Poor Dispersion
Increased dissoved drug
Crystalline Drug
process that can be easily
Sustainment of supersaturation
scaled up from development
Time
(min)
SDD,
to pilot to production scale.
Nitrogen,
Solvent Vapor
Oral Dosage Forms
The use of spray drying for
Tablets
pharmaceutical applications is
SDD:
Capsules
The resulting powder is a homogenous,
important because amorphous
stable, amorphous dispersion suitable for
Powder in bottle
incorporation into oral dosage forms such
dispersions are key delivery
Controlled-release
as tablets and capsules.
or modied-release
technologies for increasing the
dosage forms
30 microns
solubility of BCS Class II and IV
drugs, which represent more
can be efficiently optimized to achieve the desired performance
than 50% of the compounds in pharmaceutical company pipelines.
attributes of the dispersion (1). The process space is then selected to
Bend Research, a leader in the production of amorphous dispersions
provide a robust manufacturing window.
for pharmaceutical applications, has devoted a substantial amount of
work to the application of fundamental engineering principles to the
Stability
spray drying of amorphous dispersions. Application of fundamental
Physical stability during spray drying is maintained through the rapid
knowledge has made it possible to obtain spray-dried amorphous
drying kinetics of high-surface-area droplets. Rapid quenching of
dispersions with the desired stability and performance attributes,
droplets to achieve a low mobility state, facilitated by use of a high-Tg
smooth process scale-up, and downstream manufacturability. An
polymer, is critical to achieving an amorphous dispersion. Atomization
overview of the process and product is shown in Figure 1.
and drying conditions are both optimized to ensure a reproducible,
Performance
robust process that achieves a molecular dispersion and promotes
The spray drying process is amenable to the manufacture of amorphous
physical stability during in-process hold times.
dispersions across a wide range of API physicochemical properties.
Manufacture
Mechanistic understanding of the dissolution mechanism is critical
The spray drying process is broadly applicable to a large number of
during formulation selection. Dissolution of the primary solid dispersion
APIs and formulation approaches. Multiple spray solvents can be
particle to free drug or high-activity drug species is necessary to
successfully used, simplifying the formulation of many drug and polymer
enchance the bioavailability of the amorphous solid.
combinations.
To increase the efficiency and robustness of formulation selection,
Fundamental understanding of the spray drying process requires defiguidance maps are used that account for key API properties related to
nition of a control volume to identify the key physical situation. Mapping
physical stability and performance. Drug loading and polymer selection
Exo Down

70

[CPD] [g/mL]

60
50
40
30
20
10

30

60

90

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the process from

droplet formation to
Figure 2: Overview of droplet-to-particle history.
particle formation,
Pressure Nozzle
Feed Solution
as shown in Figure 2,
Msoln, Tsoln, Pnozzle
Hot Drying Gas,
is critical to accurate
Recycled Solvent Vapor
prediction of the
Pressure
Mgas, Tin, Tcond
impact of process
Nozzle
variables on final
particle attributes.
Fluent Modeling Output
Initial Solution
CONTROL
By matching the conTemperature Contours
Particle Tracks
Droplet
10 sec
VOLUME
ditions encountered
during the dropletto-particle history,
the critical-to-quality
product attributes
Drying Chamber
Hot Drying Gas
Pchamber
can be achieved,
Contacts Droplet
independent of
process scale.
Residence Time
10 to 60 sec
A rational flowchart methodology
Skinned Droplet
Wet droplet
Skinned droplet
10 sec
based on this fundaDry particle
SDD,
mental knowledge
Nitrogen,
can be applied to
Solvent Vapor
optimize the spray
Dried SDD Particle
Tout
1 sec
drying process,
focusing on two core
processes: atomization and drying (see
Figure 3) (2).
Figure 3: Process development flowchart.
Numerous atomiFORMULATION
DEFINE:
PROCESS
INPUT
zation techniques
can be employed to
manufacture specific
PRODUCT ANALYSIS
ITERATE
particles sizes for
DRYING
THERMODEVELOPMENT
PROCESS
ATOMIZATION
KINETICS
DYNAMICS
WORK
CONSTRANTS
applications such as
oral solubilization (10
to 100 m) and engineered particles for
inhalation (1 to 5 m).
200
Engineering correla0.12
180
tions are combined
D90 = 150
160
0.1
with an experi140
120
mental approach.
80
D50 = 90
70
0.08
60
100
Experiments are
50
40
80
30
conducted to select
20
60
10
D10 = 40
0.06
0
40
target droplet-size
20
distributions through
0.04
0
changes in atom130
180
230
280
80
80
100
120
Atomization Liquid Pressure [PSI]
izer geometry and
T (C)
operating conditions
to achieve the target
parameters and their impact on performance, manufacture, and
operating ranges and final particle size.
stability. The process is easily scaled and is applicable to with a wide
Drying conditions are selected based on physical-stability constraints
variety of APIs.
and the desired morphology or density of particles. Process parameters
are correlated to particle attributes, serving as a basis for scale-up.
-6

385
370
355
340
325

-2

310
295

Stability screen
Stability production
Solvent screen

Desired product properties

Ready for Transfer

No code Operating

Process Conditions

Target Droplet Size

(As Required)

Conditions
Nozzle
Tool
Stand:

Tout (C)

Specic Drying Ratio

(Mgas)/(Msoln)

Inlet temperature

Droplet Diameter [m]

Drying gas owrate

in

Conclusions
Use of engineering fundamentals in the spray drying process
for amorphous dispersions allows understanding of key process

References
1. D.T. Friesen et al., Mol. Pharm. 5 (6), 9031144 (2008).
2. D.E. Dobry et al., J. Pharm. Innov. 4 (3), 133142 (2009).

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Addressing the
Solubility Challenge
A Q&A with Karl Kolter, PhD, Head of Pharmaceutical Excipients R&D, BASF
Q. Excipients add important
functionality to a formulation. With
respect to solubility improvement
specifically, how can excipients
be used to improve solubility and
therefore bioavailability? Can
you provide examples in terms of
the functionality and the type of
excipients that may be used?
A. Solubility and speed of
dissolution can be influenced by
various excipients. Here, I would
distinguish between excipients
that act directly on the active and
those, such as disintegrants, that simply ensure quick disintegration
of the dosage forms. The first class is represented by wetting agents,
solubilizers, protective colloids, adsorbents and so forth. All of these
can contribute to improved dissolution, the strongest effect coming
from solubilizers. Solubilizers are typically surfactants of a relatively
low molecular weight, such as Polysorbate 80, Kolliphor EL (formerly
Cremophor EL) and many other ethoxylated materials. With the
launch of Soluplus in 2009, the first polymeric solubilizer appeared on
the market offering new opportunities, particularly for tablets.

Q. What are the key properties of an excipient to determine whether

it will be an effective solubilizing agent? What type of pharmacodynamic
and pharmacokinetic data is used to evaluate solubility and
bioavailability, and what is the influence of the excipient on these levels?
A. The main prerequisites for a solubilizer/bioavailability enhancer
are that it is capable of overcoming the crystal lattice energy of a drug
and that it can be delivered into the aqueous fluids of the GI-tract.
Taking into account that the ideal excipient has to act as a bridge
between the high lipophilicity of the poorly soluble active and the high
hydrophilicity of aqueous fluids, it should be amphiphilic.
At the end of the day, in-vitro dissolution studies must be
accompanied by in-vivo studies in animals or humans to reveal
whether improved dissolution really leads to enhanced bioavailability.
To give you an example of what excipients can generate: a Soluplusitraconazole formulation resulted in 25-fold higher bioavailability than
itraconazole alone and outperformed the marketed drug by a factor of
2.3. This shows the potential associated with unique excipients.
Q. What type of predictive tools can be used to evaluate the optimal
levels or type of excipient(s) to be used in a formulation with respect to
bioavailability enhancement?
A. There are screening methods available which can be used to
find the best solubilizer for a particular active such as the solubilizing

power in aqueous solution and the solid solution capacity. These tests,
which are described in detail in the BASF booklet Hot-Melt Extrusion
Compendium determine how much drug can be dissolved either
in the aqueous or solid phase, which is mainly the polymer. From
the results of these tests, a preliminary formulation can be derived
which of course needs to be further optimized not only regarding
performance but also processing.
Q. What role can excipients play with respect to certain
technologies such as hot-melt extrusion, as an approach in resolving
solubility challenges? Do they facilitate the formation of the solid
dispersion? Can the excipient also facilitate processing in a hotmelt extrusion process? Can you offer specific examples of either
application?
A. For the preparation of solid dispersions or solid solutions, two
technologies have become popular so far: hot-melt extrusion and
spray drying with organic solvents. These are completely different
from a processing point of view and also have different requirements.
For hot-melt extrusion, a low glass-transition temperature
and low melt viscosity enable processing at lower temperatures
to be carried out, thus avoiding drug degradation. Soluplus for
instance was developed especially for hot-melt extrusion and fulfills
this target profile ideally. There is no other material that runs so
smoothly on an extruder and that is able to take up so much poorly
soluble active.
Q. Poor solubility is an obvious barrier to advancing potentially
efficacious drug candidates. Looking into the future of solubilization,
what key technologies are currently being employed and which are
being evaluated for further development? What role will excipients play
in those efforts?
A. Hot-melt extrusion is currently in the stage of becoming a
mature technology in pharma; however, this process can still be
modified further to obtain even better results. Furthermore, new
solubilizers with unique properties need to be developed so that
all kinds of poorly soluble actives can be addressed. The area of
nanoformulations, for example, has not been fully explored.
However, one of the biggest hurdles facing industry is the regulatory
issue of using a new excipient. There is some reluctance to use a
new excipient for the first time. A Novel Excipients Consortium of
pharmaceutical companies and excipient suppliers has just been
created with the specific aim of paving the road for new excipients.
To use the words of Martin Luther King, I have a dream that one day
excipients will have their own approval process. This achievement
would remove the risks from pharmaceutical companies and their drug
approvals, speed up drug development, innovate formulations, and
ultimately improve treatments.

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