title: Review of bilayer tablet technology.
abstract: Therapeutic strategies based on oral delivery of bilayer (and multilayer) tablets are gaining more acceptance among brand and generic products due to a confluence of factors including advanced delivery strategies, patient compliance and combination therapy. Successful manufacturing of these ever more complex systems needs to overcome a series of challenges from formulation design to tablet press monitoring and control. This article provides an overview of the state-of-the-art of bilayer tablet technology, highlighting the main benefits of this type of oral dosage forms while providing a description of current challenges and advances toward improving manufacturing practices and product quality. Several aspects relevant to bilayer tablet manufacturing are addressed including material properties, lubrication, layer ordering, layer thickness, layer weight control, as well as first and final compression forces. A section is also devoted to bilayer tablet characterization that present additional complexities associated with interfaces between layers. The available features of the manufacturing equipment for bilayer tablet production are also described indicating the different strategies for sensing and controls offered by bilayer tablet press manufacturers. Finally, a roadmap for bilayer tablet manufacturing is advanced as a guideline to formulation design and selection of process parameters and equipment.
authors.affiliation: Bristol-Myers and Squibb Company, Drug Product Science and Technology, New Brunswick, NJ, USA.
authors.forename: Admassu
authors.initials: A
authors.lastname: Abebe
authors.affiliation: Boehringer Ingelheim Company, Pharmaceutical Development, Ridgefield, CT, USA. Electronic address: ilgaz.akseli@boehringer-ingelheim.com.
authors.forename: Ilgaz
authors.initials: I
authors.lastname: Akseli
authors.affiliation: Bristol-Myers and Squibb Company, Drug Product Science and Technology, New Brunswick, NJ, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Sprockel
authors.affiliation: Bristol-Myers and Squibb Company, Drug Product Science and Technology, New Brunswick, NJ, USA.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Kottala
authors.affiliation: Department of Mechanical and Aerospace Engineering, Rutgers University, Piscataway, NJ, USA.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Cuitiño
mesh_terms: D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D016503:Drug Delivery Systems; D004867:Equipment Design; D005079:Excipients / Q000737:chemistry; D017408:Guidelines as Topic; D006801:Humans; D055118:Medication Adherence; D011312:Pressure; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D005079:Excipients; D013607:Tablets
keywords: Bilayer tablet manufacturing; Delamination; Interfacial strength; Layered tablets; Tablet compression