| dc.description.abstract | The science of powders in the pharmaceutical industry is a specialised field and the
particle size of a powder may influence its bulk performance, its tabletting properties
and handling. During the synthesis process of an API, the crystal form is dependent
on the solvent being used in the final stage of recrystallisation. Usually, the particle
size is too large for use as is, in which case milling would be the next step in the
production line-up. Milling of APIs can result in polymorphic phase transformations,
contamination, and costly product losses through dust. The understanding of the
physico-chemical properties of a given API is critical during the pre-development
phases of dosage forms.
This study investigated the feasibility of particle size reduction of nevirapine through
rapid crystallisation (metastable, intermediary form IV), followed by desolvation and a
subsequent phase transformation. The powder obtained by this novel method was
characterised and compared with commercially available, nevirapine powder. The
following properties of the two nevirapine powders were investigated: 1) Particles
size and size distribution, 2) Particle shape and surface, 3) Powder flowability,
using angle of repose, critical orifice diameter, Carr’s compressibility index and the
Hausner ratio, and 4) Solubility and dissolution rate. Tablets were also
manufactured during this study by means of wet granulation from the two nevirapine
powders. The tablets were subjected to the following tablet tests: 1) Friability, 2)
Crushing strength/hardness, 3) Disintegration, 4) Dissolution, and 5) Weight
variation.
Based on the results obtained from the powder and tablet studies, the following
conclusions were reached. Nevirapine raw material may be suitable for tablet
manufacturing, either through direct compression, or through a method involving
processing prior to tablet compression, i.e. granulation. Novel nevirapine powder
posed flowability problems and would only be suitable for use if its flow properties
could be improved by a granulation process. However, novel nevirapine powder may be the preferred API, due to its properties that could aid the dissolution of the
final product. The results have shown that those tablets that had been produced
from the novel nevirapine powder had several advantages over those, produced
from the nevirapine raw material, such as better mechanical strength and dissolution
properties.
This study showed that small changes in the powder characteristics could
significantly affect its subsequent processing. The change in the powder properties
of nevirapine had proven this statement. There were significant differences in the
flowabilities and solubilities of the two nevirapine powders, as well as between their
respective tablet properties. Novel nevirapine powder had poor flowability, while
offering better solubility values. Its poor flowability rendered the production of tablets
by direct compression practically impossible. The tablets produced from the novel
nevirapine powder showed advantageous properties.
Further studies are, however, recommended in order to improve the flowability of the
fine, novel, nevirapine powder and to further establish its promising potential to
produce effective tablets without prior milling, as is currently being practiced. | en_US |
