title: Evaluation of the performance characteristics of bilayer tablets: Part I. Impact of material properties and process parameters on the strength of bilayer tablets.
abstract: Bilayer tableting technology has gained popularity in recent times, as bilayer tablets offer several advantages over conventional tablets. There is a dearth of knowledge on the impact of material properties and process conditions on the performance of bilayer tablets. This paper takes a statistical approach to develop a model that will determine the effect of the material properties and bilayer compression process parameters on the bonding strength and mode of breakage of bilayer tablets. Experiments were carried out at pilot scale to simulate the commercial manufacturing conditions. As part of this endeavor, a seven-factor half-fraction factorial (2(7-1)) design was executed to study the effect of bilayer tablet compression process factors on the bonding strength of bilayer tablets. Factors studied in this work include: material properties (plastic and brittle), layer ratio, dwell time, layer sequence, first- and second-layer forces, and lubricant concentration. Bilayer tablets manufactured in this study were tested using the axial tester, as it considers both the interfacial and individual layer bonding strengths. Responses of the experiments were analyzed using PROC GLM of SAS (SAS Institute Inc, Cary, North Carolina). A model was fit using all the responses to determine the significant interactions (p < 0.05). The results of this study indicated that nature of materials played a critical role on the strength of bilayer compacts and also on mode of fracture. Bilayer tablets made with brittle materials in both the layers are strongest, and fracture occurred in the first layer indicating that interface is stronger than layers. Significant interactions were observed between the selected factors and these results will provide an insight into the interplay of material properties, process parameters, and lubricant concentration on the bonding strength and mode of breakage of bilayer tablets.
authors.affiliation: Bristol-Myers Squibb Co, Drug Product Science and Technology, New Brunswick, New Jersey 08903, USA. niranjan.kottala@bms.com
authors.forename: Niranjan
authors.initials: N
authors.lastname: Kottala
authors.forename: Admassu
authors.initials: A
authors.lastname: Abebe
authors.forename: Omar
authors.initials: O
authors.lastname: Sprockel
authors.forename: James
authors.initials: J
authors.lastname: Bergum
authors.forename: Faranak
authors.initials: F
authors.lastname: Nikfar
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Cuitiño
mesh_terms: D005079:Excipients / Q000737:chemistry; D054327:Lubricants / Q000737:chemistry; D008962:Models, Theoretical; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D013718:Tensile Strength
chemical_list: D005079:Excipients; D054327:Lubricants; D013607:Tablets