title: Influence of MCC II fraction and storage conditions on pellet properties.
abstract: Microcrystalline cellulose II (MCC II)--a polymorph of commonly used MCC I--was introduced as new pelletization aid in wet-extrusion/spheronization leading to fast disintegrating pellets. Previous investigations suggested that pellet properties were influenced by the fraction of MCC II. Furthermore, it is unknown whether the storage conditions can affect the disintegration behavior. Therefore, the effects of MCC II fraction and the storage conditions on several pellet properties were investigated. MCC II-based pellets were prepared of pure MCC II or binary mixtures containing 10-50% (steps of 10%) MCC II as pelletization aid and theophylline, chloramphenicol or lactose. The pellets were characterized by their aspect ratio, equivalent diameter, water content, tensile strength, porosity as well as shrinking, and disintegration behavior and drug release according to their MCC II fraction. Furthermore, the pellets were stored at different relative humidities (0-97%rh), and the influence on their disintegration and drug release was investigated. With increasing MCC II fraction, the pellets became lager in size, decreased their porosity, and required higher water contents for spheronization. Moreover, the disintegration time increased and the disintegration itself was incomplete. Furthermore, the storage conditions had an impact on the disintegration properties of MCC II-based pellets. The disintegrating was affected irreversibly after storage at high humidity (80-97%rh) resulting in a slow drug release. Therefore, MCC II-based pellets need to be stored below 80%rh to secure a fast disintegration. A better knowledge of the properties of MCC II-based pellets was obtained providing a basis for a successful manufacturing and adequate storage of MCC II-based pellets prepared by extrusion/spheronization.
authors.affiliation: Heinrich-Heine-University, Duesseldorf, Germany. Electronic address: cornelia.krueger@hhu.de.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Krueger
authors.forename: Markus
authors.initials: M
authors.lastname: Thommes
authors.forename: Peter
authors.initials: P
authors.lastname: Kleinebudde
mesh_terms: D002482:Cellulose / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002701:Chloramphenicol / Q000737:chemistry; D016503:Drug Delivery Systems; D004343:Drug Implants / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D006813:Humidity; D007700:Kinetics; D007785:Lactose / Q000737:chemistry; D010316:Particle Size; D016062:Porosity; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D013718:Tensile Strength; D013806:Theophylline / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D004343:Drug Implants; D005079:Excipients; D014867:Water; D002701:Chloramphenicol; D002482:Cellulose; D013806:Theophylline; D007785:Lactose; C109691:microcrystalline cellulose
keywords: Disintegration; Extrusion; MCC II; Pellet; Relative humidity; Spheronization