Effect of powder particle and punch type on the physical and compaction properties of tablets

Abstract

The main purpose of developing a dosage form or improving on a current dosage form is to ensure that the active ingredient present in the dosage form reaches the site of pharmacologic action. A dosage form must ensure the stability of the active pharmaceutical ingredient (API) and contribute to the safe and effective treatment of a patient. To provide a suitable dosage form with the aforementioned properties, it is important that the active ingredient and excipients form a coherent unit that provides the necessary properties of an acceptable dosage form. In this study, tablets were compressed using three different particle types, namely dry powders, granules and beads (pellets). It is important to select the optimum particle type when formulating and compressing tablets, because the flow properties and compaction properties depend on the type of particles used to compress the tablets. Two different types of punches were also used to compress tablets, namely 9 mm diameter flat faced and concave punches. These tablets were evaluated with respect to physical properties as well as dissolution behaviour. A fractional factorial design was used to formulate twenty different particle type mixtures (dry powders, granules or beads) differing with respect to filler, binder and disintegrant. The amount of active ingredient (pyridoxine hydrochloride) used in the tablets was kept constant at 20% w/w. The fillers used were Avicel® (microcrystalline cellulose (MCC)) and MicroceLac® (MCC-lactose). The lubricant was magnesium stearate and was kept constant at 0.5% w/w. The disintegrant used was Ac-di-sol® (super-disintegrant) at a concentration level of either 0.5 or 1% w/w. Kollidon® VA 64 was used as binder and at a 1.5% w/w concentration level for bead-containing tablets and either 3 or 5% w/w for granule and dry powder-containing tablet formulations. The particle type mixtures were characterised with respect to angle of repose (AOR), flow rate, critical orifice diameter (COD), % compressibility and Hausner ratio. Flowability was characterised as flow behaviour plays a significant role in tablet compression as well as during the general handling of powders (particulate mixtures). Upon flowability characterisation, each formulation was compressed using both the flat faced and concave punch sets. During the compression process, the weight of the tablets compressed in this study was kept constant at 250 mg. The tablets were evaluated with respect to crushing strength, mass variation, diameter and thickness, friability, disintegration time and dissolution behaviour. The flowability results indicated that the bead formulations exhibited the most promising flow properties of the three particle types used. The granules exhibited the weakest flow properties with inconsistencies observed especially during flow rate characterisation through both the 10 and 15 mm diameter orifices. Granules had irregular shapes with rough surface textures, whereas the bead particles possessed spherical particles with smoother surfaces contributing to better flow properties and therefore would promote fast and effective compression of uniform tablets. All tablet batches evaluated, complied with the specifications as set by the British Pharmacopoeia (BP) regarding mass variation, disintegration time, and friability. However, tablets compressed with dry powder and bead particles exhibited a lower variation in tablet mass than the tablets compressed with the granule particles. There was also a pronounced difference between the average crushing strength values of tablets formulated with Avicel® and those formulated with MicroceLac® as filler. The tablets formulated with MicroceLac® as filler, produced tablets with higher average crushing strength values than the tablets formulated with Avicel® as filler. The dissolution profiles of the different formulations were characterised with regard to mean dissolution time (MDT) and the initial dissolution rate (Idr). Analysis of the dissolution data indicated that all the Avicel®–containing particle type tablets exhibited a burst release with the shortest average MDT values and the fastest average Idr values indicating faster release of the API from these tablet formulations in comparison to the MicroceLac®–containing formulations. All Avicel®–containing formulations showed an average MDT of 12.22 ± 9.406 min and the MicroceLac®–containing formulations showed an average MDT of 23.80 ± 11.441 min. Avicel®–containing formulations exhibited an average Idr value of 4.59 ± 0.444 %.min-1 and MicroceLac®–containing formulations an average Idr value of 3.38 ± 1.305 %.min-1. Regarding tablets containing different particle types, the MicroceLac®–containing granule formulations exhibited markedly longer average MDT values and slower average Idr values. The punch type, however, used to compress the different tablet formulations in this study did not have a significant effect on the results that were obtained. Regardless of the differences, all the tablets exhibited profiles with a 90 – 100 % release of the API within 4 hours. It is clear that the fillers used in this study had a pronounced effect on the physical tablet properties; it also significantly affected the release of the active ingredient from the dosage form significantly. The particle type used to compress the different formulations had an effect on the flowability of the different formulations. It is therefore clear that the particle type and excipients, although considered to be inert, have a prominent influence on the physical properties of tablets as well as an influence on the release of the active ingredient from tablets. It is thus very important to choose the particle type and excipients such as a f iller with great thoroughness and care as it clearly influences the quality of the final dosage form.