Chemistry Reference
In-Depth Information
system may have to be modi
ed if spray drying is used to make larger quantities. If the
API is poorly soluble in many solvents, this may limit the solvents and polymers
available for a speci
c screen. If the API exhibits low solubility in all commonly used
organic solvents, melt experiments may be a better option.
It is also useful to prepare the amorphous form of the API for comparison with
the dispersions produced in the screen. A variety of methods are available to produce
amorphous material and the methods chosen will depend on the properties of the
crystalline material. Methods to produce the amorphous form include melt quench,
grinding, and solvent methods (crash precipitation, rotary evaporation, lyophilization,
and spray drying) [3]. Once amorphous material is produced, characterization can
include the techniques shown in Table 3.1. Solubility in water, biorelevant media,
and organic solvents would also be helpful for comparison with the crystalline material
and to determine supersaturation levels.
Once these data are obtained for the API material, they will be used to help plan the
dispersion screen and determine speci
c parameters for experiments.
Most polymer properties can be obtained from
literature references or from the vendor. Considerations when selecting a polymer may
include molecular weight, glass transition temperature, hydrophilic/hydrophobic prop-
erties, hydrogen bond donors/acceptors, solubility parameter, pH
3.2.1.2 Polymer Properties
le,
thermal stability, water uptake, and monomer levels. Some of these properties are
compiled in Chapter 14 and Appendix A. Other considerations that will be speci
-
solubility pro
cto
the dispersion system include solubility and/or miscibility of the drug in the polymer,
degree of supersaturation during dissolution, and prevention of API crystallization from the
solid or solution. Additional properties may be important for the method of manufacture,
as outlined in Chapters 9 and 10 for spray drying and melt extrusion, respectively.
3.2.2 Screening Considerations
A number of factors need to be determined for each project that are dependent on the
properties of the molecule, the stage of development (early versus late), and the
development/formulation plan. These factors will help de
ne the goals and scope of
the dispersion screen. The following sections will outline some of the parameters to
consider for the screen, such as polymer selection, API and polymer composition, and
use of a surfactant.
There are a number of approaches that can be used
when choosing polymers for a screen, and some of these are summarized in Table 3.2. It
is obvious that a wide variety of methods have been reported for
3.2.2.1 Polymer Selection
finding the best
combination of API and polymer. Some methods are straightforward for narrowing the
list of polymers, such as an empirical approach using only common polymers [4] or using
polymers speci
c to melt extrusion. Other methods attempt to choose polymers based on
simple tests of miscibility, such as information obtained from differential scanning
calorimetry (DSC) (
T
g
,
T
m
, and
T
c
)[5
7] or calculation of solubility parameters [8].
Interactions between components are also considered from simple hydrogen bonding
-
