4 Granules, powders, dry
syrups and lyophilisates
4.1 Size of formulations and amounts used
The formulations were developed on a laboratory scale.
Normally the amounts used were those required for a trial of 50 – 500 g.
Larger batches, e.g. in fluidized-bed granulation, were only resorted to in
exceptional cases.
4.2 M ethods of granulation
The granules were mostly produced by traditional means, i.e. moistening,
screening, drying, and again scree- ning. Fluidized-bed granulation was
resorted to only in exceptional cases in view of the amounts needed.
4.3 Assessment of the properties of the granules
Most of the cases concerned granu- les that were suspended in water
before the administration. Conse- quently, the properties of the suspen-
sion thus formed were assessed. The parameters that attracted most atten-
tion were the relative sediment volume volume of sediment total
volume and the redispersability. See Chapter 5.3 for details on the sus-
pensions.
4.4 Formulations
The formulations in this chapter have been arranged in alphabetical order of
their active substances.
BASF Fine Chemicals Generic Drug Formulations 1998
5 Liquid preparations
5.1 Size of formulations and amounts used
The formulations were developed on a laboratory scale.
The batches were of 50 –1,000 g size.
5.2 Solubilization of insoluble active substances
In order to solubilize insoluble lypophil- ic or hydrophobic active substances
in an aqueous medium, BASF Phar- maceutical Excipients offer several
possibilities and mechanisms.
A Microemulsions Cremophor RH 40, Cremophor EL,
and Solutol HS 15 act as surface- active solubilizers in water and
form the structures of micelles. The micelle that envelops the active
substance is so small that it is in- visible or perhaps visible in the
form of an opalescence.
Typical fields of application are oil- soluble vitamins, antimycotics of
the miconazole type, mouth disin- fectants, e.g. hexiditin, and ether-
ian oils or fragrances.
Solutol HS 15 is recommended for parenteral use of this solubilizing
system and has been specially developed for this purpose.
B Formation of complexing compounds
The soluble Kollidon products form reversible complexes with many
hydrophobic active substances, and clear solutions in water are
thus obtained. This may be affec- ted by the molecular weight. The
longer the chains or the higher the K-value of the Kollidon type, the
stronger is the solubility effect and thus the greater the solubility that
can be obtained by the active sub- stance. In practice, this effect was
mostly exploited for the solubiliza- tion of antibiotics in human and
veterinary medicine. Details are given in the book “Kollidon –
Polyvinylpyrrolidone for the phar- maceutical industry”.
There are also restrictions on the use of this auxiliary in human pa-
renterals. It is laid down in many countries that the K-value must not
exceed 18, and there is also a re- striction on the amount to be used
for each dose administered in intramuscular application.
C Hydrophilization Active substances can also be
solubilized by Lutrol F 68 in addi- tion to the Cremophor and Kollidon
products. The mechanism is pro- bably based, for the most part, on
the principle of hydrophilization. Micelle formation is certainly of
minor significance, if it exists at all.
5.3 Stabilizing suspensions
