Physical characterization of HPMC and HEC and investigation of their use as pelletization aids

Abstract

Pelletization of drugs with suitable excipients by extrusion/spheronization is one of the popular approaches in the development of solid dosage forms, especially for extended-release formulations. However, the choice of pelletization aids is limited to the use of microcrystalline cellulose (MCC), which is generally wet massed using water. In the formulation of water-sensitive drugs, however, pelletization excipients which may be wet massed using an organic liquid are desired. In the present study therefore, two cellulose ethers, hydroxypropyl methylcellulose (HPMC) and hydroxyethyl cellulose (HEC), were characterized for their physical properties, such as moisture content, bulk and tapped densities, median particle size and size distribution, surface area and surface morphology, in an attempt to evaluate the feasibility of their use as pelletization aids. Since HPMC and HEC are water-soluble, but insoluble in isopropyl alcohol, the latter was used as the wet massing liquid for pelletization. Microcrystalline cellulose, because of its established uniqueness as a pellet former, was used as the reference material and was also wet massed using isopropyl alcohol for consistency and comparison. Placebo pellets of the three cellulosic excipients, HPMC, HEC and MCC, were prepared by extrusion/spheronization. The placebo pellets were evaluated for their size and size distribution, hardness, friability, bulk and tapped densities and sphericity. Of the three cellulosic excipients, HPMC and MCC produced pellets with the most desirable attributes. In water as the dissolution medium, the HPMC pellets absorbed water and formed a single viscous gel matrix that slowly dissolved. HEC pellets were swollen but intact and slowly eroded, whereas MCC pellets stayed intact without dissolution or erosion. These findings indicate that HPMC will find application in pellet formulations of water-sensitive drugs, as well as in those formulations where water may not be used as wet massing liquid and an organic liquid must be used. It will also be a good choice as a pelletization excipient when complete water-solubility of all the formulation excipients is desired. It may be anticipated that modification of drug release from pelletized formulations may also be achieved by using cellulose ethers of varying viscosity grades and hydration rates.