Evaluation of rheological properties of wet mass without microcrystalline cellulose for preparation of pellets by extrusion/spheronization process

Abstract

To study pellet formulation containing no microcrystalline cellulose (MCC) prepared by extrusion-pheronization process and to study the rheological properties of wet mass for preparation of the pellets. The pellet formulations composed of 0.25-2.0% w/w of the formulation aids, i.e. sodium carboxymethyl cellulose (NaCMC 1180), methylcellulose (Methocel A-15 (MC 15)), hydroxyethyl cellulose (HEC 4000), hydroxypropyl cellulose low-substituted (HPC-L (HPC-L)) or hydroxypropyl methylcellulose (Methocel E15 LV (HPMC E15)); model substances, i.e. lactose, dibasic calcium phosphate (CaHPO[subscript 4]), propranolol hydrochloride or ibuprofen; and liquid binders, i.e. water or 50% w/w ethanol. The rheological properties, in terms of the instantaneous compliance (J[subscript 0]), storage modulus (G'), loss modulus (G") and loss tangent (tan [delta]) of the wet mass were measured using a controlled stress rheometer. The results showed that lactose pellets could be prepared with 0.5-1.0% w/w of NaCMC1180, MC 15 or HPMC E15. Propranolol hydrochloride pellets could be prepared with 1.0-2.0% w/w MC 15, while ibuprofen pellets could be prepared with 4.0-8.0% w/w MC 15. It was not possible to prepare CaHPO[subscript 4] pellets because too high pressure was required for extruding the wet mass. There appeared to be an optimum rheological property of the wet mass that could produce lactose pellets. The tan[delta] values of 0.07-0.49 were required for the wet mass granulated with either water or 50% ethanol in order to obtain the pellets. The rheological properties of the wet mass, however, were varied with the formulation variables, i.e. type and amount of the formulation aids, model substances and liquid binders. The formulation in this study may be applied for drugs which are incompatible with MCC and/or are degraded when exposed to high level of moisture as well as for pellets with high-drug loading. The approach of evaluation of rheological properties by the controlled stress rheometer may be useful in quality control of the wet mass for pellets preparation by extrusion-spheronization process.