title: Impact of the digital revolution on the future of pharmaceutical formulation science.
abstract: The ongoing digital revolution is no longer limited to the application of apps on the smart phone for daily needs but starts to affect also our professional life in formulation science. The software platform F-CAD (Formulation-Computer Aided Design) of CINCAP can be used to develop and test in silico capsule and tablet formulations. Such an approach allows the pharmaceutical industry to adopt the workflow of the automotive and aircraft industry. Thus, the first prototype of the drug delivery vehicle is prepared virtually by mimicking the composition (particle size distribution of the active drug substance and of the excipients within the tablet) and the process such as direct compression to obtain a defined porosity. The software is based on a cellular automaton (CA) process mimicking the dissolution profile of the capsule or tablet formulation. To take account of the type of dissolution equipment and all SOPs (Standard Operation Procedures) such as a single punch press to manufacture the tablet, a calibration of the F-CAD dissolution profile of the virtual tablet is needed. Thus, the virtual tablet becomes a copy of the real tablet. This statement is valid for all tablets manufactured within the same formulation design space. For this reason, it is important to define already for Clinical Phase I the formulation design space and to work only within this formulation design space consisting of the composition and the processes during all the Clinical Phases. Thus, it is not recommended to start with a simple capsule formulation as service dosage form and to change later to a market ready tablet formulation. The availability of F-CAD is a necessary, but not a sufficient condition to implement the workflow of the automotive and aircraft industry for developing and testing drug delivery vehicles. For a successful implementation of the new workflow, a harmonization of the equipment and the processes between the development and manufacturing departments is a must. In this context, the clinical samples for Clinical Phases I and II should be prepared with a mechanical simulator of the high-speed rotary press used for large batches for Clinical Phases III & IV. If not, the problem of working practically and virtually in different formulation design spaces will remain causing worldwide annually billion of $ losses according to the study of Benson and MacCabe. The harmonization of equipment and processes needs a close cooperation between the industrial pharmacist and the pharmaceutical engineer. In addition, Virtual Equipment Simulators (VESs) of small and large scale equipment for training and computer assisted scale-up would be desirable. A lean and intelligent management information and documentation system will improve the connectivity between the different work stations. Thus, in future, it may be possible to rent at low costs F-CAD as an IT (Information Technology) platform based on a cloud computing solution. By the adoption of the workflow of the automotive and aircraft industry significant savings, a reduced time to market, a lower attrition rate, and a much higher quality of the final marketed dosage form can be achieved.
authors.affiliation: Institute for innovation in Industrial Pharmacy, IFIIP GmbH, Kreuzackerweg 12, CH-4148 Pfeffingen, Switzerland; Department of Pharmaceutical Sciences, University of Basel, WRO 1060, Mattenstrasse 28, CH-4058 Basel, Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Leuenberger
authors.affiliation: Amificas Inc., 195 Stillwater Drive, Oviedo, FL 32765, USA; Nanoscience and Technology Center, Department of Physics, University of Central Florida, 12424 Research Parkway, Suite 428, Orlando, FL 32826, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Leuenberger
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D002986:Clinical Trials as Topic; D003201:Computers; D004338:Drug Combinations; D055808:Drug Discovery; D016568:Drugs, Generic; D006801:Humans; D008962:Models, Theoretical; D010599:Pharmacokinetics; D013678:Technology, Pharmaceutical / Q000191:economics / Q000379:methods; D013810:Therapeutic Equivalency
chemical_list: D004338:Drug Combinations; D016568:Drugs, Generic