Reprocessing of Microcrystalline Cellulose Spheres with High Drug Concentrations

Abstract

Spherical dosage forms have been reported to be an efficient and effective method for delivering drugs into the body and controlling their dissolution rate. Substantial work has been conducted in these laboratories to delineate the role of microcrystalline cellulose in the extrusion-spheronization method of manufacturing.⁽¹⁾ O'Connor determined and reported the advantages of using microcrystalline cellulose as the matrix ingredient in the extrusion-spheronization process; however, he reported that with simple formulations, using only water as the granulating agent, drug loading above 50% was at best difficult.⁽²⁾ Later work conducted by Funck et al examined the incorporation of adjuvant binders such as hydroxypropyl cellulose, carbotner and starch, to enhance binding capacity and increase drug concentrations to 80%.⁽³⁾

Because of Funck's work, it was decided to examine the only commercially available MCC product coprocessed with a binder. Although three grades of Avice® MCC:CMC are marketed, it was decided that only the RC-591 grade would be examined for its reprocessing characteristics. As more companies turn toward sustained release technology to extend patent protection or afford a novelty to marketing, high drug loaded (80%+) spheres will become the norm rather than the exception. Since no process yields 100% or guarantees outcomes, there will always be some quantity of spheres that are either too large or too small or where an entire batch must be reprocessed. On the basis of earlier work performed in these laboratories,⁽⁴⁾ it was decided to examine the milling and soaking methods of reprocessing spheres. With the presence of a binder, it was uncertain if the previously reported outcomes for reprocessing would be the same.