Powder characteristics and tabletting of nevirapine prepared by a novel process : a solubility and stability study

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.