Chatchawalsaisin, Jittima; (1998) The influence of hydrophilic and hydrophobic additives on the formation and drug release from pellets prepared by extrusion/spheronization. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The preparation of pharmaceutical pellets by the process of extrusion and spheronization usually relies on microcrystalline cellulose as a basic ingredient. The addition of other additives could influence the performance of the formulation of pellets, especially if an attempt is made to control the drug release from the pellets. The aim of this study was to investigate the influence of hydrophilic and hydrophobic additives on the ability to prepare spherical pellets by this process and on the characterization of in vitro drug release from the pellets produced. The study was carried out with the use of a ram extruder and a conventional spheronizer. The ability to form spherical pellets and the optimum quantity of binder liquid required were assessed by characterization of the extrusion force and the final product, in terms of size, size distribution, shape, density and porosity. An investigation of the extrudate diameter and the surface roughness of the extrudate and pellets was included for certain formulations. The influence of the additive on the in vitro drug release from pellets was assessed by the application of the statistical moment analysis. Spherical pellets containing paracetamol could be prepared by the addition of a wide range of potential drug release-controlling additives including the hydrophilic additives: 1-16% chitosan and/or 1-16% sodium alginate, 3% methylcellulose, 3% hydroxypropyl methylcellulose and 30% pregelatinized starch, and the hydrophobic additives: 30% methylcellulose, 15% solid of the aqueous dispersions of methylcellulose and acrylate co-polymers, 30-60% glyceryl monostearate, 30% cetyl alcohol and 30% carnauba wax. Pellets containing diclofenac sodium, ibuprofen, and indomethacin were also successfully formed with glyceryl monostearate at levels of 30-60%. For diclofenac sodium, glyceryl monostearate could fully replace microcrystalline cellulose in the formulation. Different glyceride-based waxes were also shown to form satisfactorily spherical pellets containing diclofenac sodium at a level of 30%. The presence of the additives in the formulations of pellets did influence the characteristics of the product and the in vitro drug release. It was not, however, possible to ensure sufficient retardation of drug release to provide a controlled release matrix pellet. This appeared to be in some way related to the fact that some additives caused the pellets to disintegrate when added to fluid. Identification of the mechanism of the control of drug release also provided an insight into the way the additives influenced the formulation.

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