Bilayer tablets offer a number of advan- tages for patients – their unique formu- lation enables the controlled delivery of one or more active pharmaceutical ingredients (APIs) within a single tablet, improving patient compliance and simplifying a medication regimen. By potentially reducing the number of doses needed to treat a patient, as well as improving the release profile of an API and allowing for incompatible APIs to exist in combination, bilayer tablets represent an integral advancement in patient treatment.
The benefits of this formulation ap- proach exist in concert with its chal- lenges: because of the comparatively novel and bespoke nature of these drugs, additional formulation activity is often required to commercialize them. This investment frequently extends to equipment and process optimization, resulting in an array of unique technical challenges. At Abb- Vie, researchers have worked toward mitigating these issues by identifying a range of technology solutions, from tablet delamination to cross-contami- nation layers, layer separation, weight and depth control, and achieving acceptable yields and throughput.
Central to overcoming the challenges associated with bilayer tablet man- ufacturing is significant technical expertise, a strong commercial manu- facturing network, and state-of-the-art equipment and processes. AbbVie is committed to investing in both new technologies and in customizing its equipment to streamline and optimize their manufacturing paradigms, enabling the successful development and commercialization of multiple bilayer tablet products.
Ensuring Optimal Bilayer Tablet Formulation
Bilayer tablets are produced by compressing two disparate formu- lations into a single solid oral tablet while maintaining a physical barrier between each formulation by layering one on top of the other. This enables the controlled delivery of either a single or multiple APIs within an individual tablet. This is particularly beneficial when one of the tablet layers provides an immediate release and the second layer a sustained release delivery.
Producing tablets that confer the desired release profile necessitates a focus on early optimization and sub- sequent scale-up. AbbVie possesses an extensive range of equipment to support both development and com- mercial-scale activities. For early de- velopment activity, AbbVie’s process blends in the 1kg range and scales up for any subsequent development and commercialization work. AbbVie typi- cally produces 8,000 to 20,000 tablets per hour on its development presses, and would scale incrementally to ap- proximately 600,000 tablets per hour at the commercial level.
For customers, the safety and quality compliance practices and standards employed by AbbVie are key. AbbVie consistently performs and delivers in this regard: its Lake County sites are regularly employed as a training site for the FDA, and its global quality system offers unparalleled flexibility for both product development and downstream applications. In addition, the company employs automated data acquisition and analysis capabilities, modern quality control and development labo- ratories, powder containment solutions, and on-site warehousing.
AbbVie’s Bilayer Tablet Manufacturing Capabilities
The timeframe in which AbbVie can scale a therapeutic to commercial production is highly product-depen- dent; generally, the process can take between 1.5 and 3 years. If stability testing and clinical are excluded, commercial manufacturing can likely be achieved within 12-18 months.
AbbVie has extensive experience in the space, with four bilayers in development at its Cork location alone, as well as a multitude of other solid oral dosage programs being run concur- rently across its remaining five facility locations, which span both Europe and North America.
Despite their novel design, bilayer tablets are capable of being produced with the same cleaning standards as other tablet formulations. When manufactured in its commercial GMP facilities, AbbVie’s contract custom- ers’ products adhere to the AbbVie cleaning standards. This includes cleaning recipe and method develop- ment, cleaning verification, and test method transfer and validation.
As a leading pharmaceutical develop- er and manufacturer, AbbVie Contract Manufacturing has experience with bilayer manufacturing for clients at its high-technology solid dose manufacturing plant in Cork, Ireland; Ludwigshafen, Germany; Lake Coun- ty, Illinois; and Barceloneta, Puerto Rico. Contact the experts at AbbVie to discuss your bilayer manufacturing needs at www.abbviecontractmfg. com or at 1-847-938-8524.