Excipients: Their Role in Rational Formulation Design - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 82

substance and can have an influence on its modes of deactivation. 90
Excipients are thus still regarded as an enigma: '' . . . they do not treat a
disease, but the drug industry cannot do without them''. 91
Apart from substances that have been carried over from prior process-
ing stages, e.g. salts, the reasons for adding excipients are manifold, as are
also their chemical origins. The latter can be classified as follows:
(i) Natural products, including polymers and derivatives.
(ii) Synthetic polymers and chemically modified polymers.
(iii) Natural products, modified with synthetic polymers.
(iv) Small molecules.
(v) Natural products, chemically modified with small molecules.
A short selection of less well-known excipients, their chemical groups and
applications is given in Table 1. A more exhaustive compilation can be
found in Apte and Ogwu. 89
Many of the more recently reported excipient additives are subjects of
patents or patent applications and have not been tested for general clinical
use. However, the literature contains frequent references to ''new'' excipi-
ents. Usually they are not new in the chemical sense, but only in their
claimed application field. For instance, erythritol, a well-studied poly-
hydroxy compound (PHC), has recently been reported as a ''... new,
multipurpose excipient''. 92 As regards FDA-approved freeze-drying excipi-
ents, the list is depressingly short. It consists mainly of mono- and disaccha-
rides, some amino acids and a few simple peptides. This is in a sense curious
because some very efficient in vivo lyoprotectants, biosynthesised by many
organisms to counter the stresses of drying either by freezing or drought, are
diverse and manifold. We shall return to this subject later.
7.2 Attributes and Requirements
In pharmaceutical freeze-drying operations, excipients fulfil several func-
tions. These include:
pH buffering.
Ensuring isotonicity of the reconstituted solution at point of use, e.g.
saline solution.
In-process chemical protection (lyoprotectants) of the bioactive
component.
Long-term chemical stability of the dried product.
Improved mechanical strength (bulking) of the freeze-dried cake;
prevent powdering.