The agenda is under construction and will be completed shortly. In the meantime, we will update you on the new speakers and presentation scheduled.
University of Strathclyde - CMAC
Reader in Pharmaceutical Product Engineering
Traditional methods of developing drug products for a new active pharmaceutical ingredient are time-consuming, costly and often inflexible. The selection of the right excipients in tablets and process conditions are crucially important as they can impact manufacturability, performance and stability of the drug product. Formulation optimisation studies are conducted to identify a robust formulation that can meet manufacturability criteria (e.g. flowability, tensile strength) while fulfilling the desired performance targets, e.g. release of > 80% of the drug in less than 30 min. This is a multidimensional problem with a high degree of interdependence between raw material attributes, process parameters, and drug product properties. These complex relationships cannot be fully captured by first principle models and it is not feasible, in a reasonable time, to experimentally investigate these multidimensional formulation (type of excipient, concentration, drug loading) and process parameter (e.g. compression force, dwell time) spaces following traditional experimental planning and methods. This talk will present a high-throughput, data-intensive micro-scale tablet development system that can automatically prepare and measure powder, and produce and test single tablets. By employing robots, the system combines an automated dosing unit, a dedicated powder transportation unit, near-infrared spectroscopy for evaluating powder blend homogeneity, the STYL'One Nano compaction simulator, and an automated testing system for measuring tablet properties. The data is automatically structured and fed into a database for the development of a hybrid system of models, including mechanistic and data-driven approaches, to predict critical powder blend (e.g. flowability) and tablet attributes (tensile strength, porosity) from raw material properties. This talk will further discuss the combination of hybrid modelling approaches with model-based optimisation and the micro-scale tablet development system. This approach significantly reduces hands-on-lab time (> 80%), material, and waste, offering significant potential for accelerated and sustainable drug product development.
Capping is a common defect that can occur during the manufacturing of pharmaceutical tablets. It refers to the separation of one or both cups of biconvex tablets. Despite being recognized since the early development of the tableting process in the 19th century, capping is still not fully understood and remains challenging to predict.
In this presentation, we will discuss and attempt to comprehend the impact of process parameters on capping. Additionally, we will explore the product properties that can aid in predicting capping occurrences.
University of Bordeaux
Jan Henrik FINKE
University of Braunschweig
Division Head Pharma and Bioparticle Technology
Challenges of incompatible APIs or the combination of different dissolution profiles in one dosage form, moisture sensitivity of APIs, or engineering needs for advanced solid dosage forms (e.g. oral osmotic systems) make the development of multiple compartment tablets attractive. However, when the number of compartments in a tablet is elevated, challenges towards formulation and manufacturing multiply and new challenges such as layer separation in bilayer tablets or loss of mechanical integrity in press-coated tablets arise.
In this presentation, the effects of process parameter combinations and formulation properties on interfacial strength in bilayer tablets and porosity distribution in press-coated tablets will be elucidated. The deformation behaviour of the different compartments plays a vital role and will be evaluated toward the understanding of the structural and mechanical properties of the resulting multi compartment tablets and the implication towards their application performance will be discussed.
The development of a quality pharmaceutical tablet product is a complex process. Successful design of tablet formulation requires a clear understanding of mechanical properties of APIs, excipients, and their mixtures. Owning to the level of complexity, tablet development has been largely empirical. Consequently, a significant amount of active pharmaceutical ingredient (API) and a long time is required before identifying a scalable tablet formulation by a trial-and-error approach. However, problems still frequently occur during commercial manufacturing. There is a need for a material-sparing tool for characterizing compression properties of powders in order to improve the efficiency of tablet development in the pharmaceutical industry. With the aid of a compaction simulator, it is possible to systematically characterize APIs and formulations using little material, enabling an expedited and material-sparing development of quality tablet formulation. The ability of compaction simulation to predict success or failure of a prototype tablet formulation during commercial manufacturing has been well recognized. This talk will focus on the use of a compaction simulator as a tool to determine fundamental physical properties of powders, e.g., plasticity of powders and true density, which is an essential element for developing a materials database to enable digital tablet formulation design.
University of Minnesota
Professor & Associate Department Head
With the ever-growing pressure to get new therapies to patients faster, predictive modeling and simulation tools are increasingly recognized as critical enabling technologies for accelerating drug product development. In the development of oral solid dosage forms, predictive modeling and simulation tools of the manufacturing processes can enhance process understanding, save on API supply, improve product quality, and reduce or eliminate many of the bottlenecks associated with empirical methods.
Each API has its own set of unique physical and chemical properties that can affect the success of product formulations and manufacturing routes. Because of this, the manufacturing process for solid dosage forms need to be thoroughly understood. Determining robust formulations and processes for a given compound requires a deep understanding of material science and powder behavior.
This presentation will cover aspects of:
Thermo Fisher Scientific - Global
Senior Director, Science and Innovation
Janssen, Pharmaceutical Companies of Johnson & Johnson
Nowadays there is an increased focus on patient centric drug development. Therefore, formulations typically contain a higher active pharmaceutical ingredient (API) load to reduce the pill burden. At these elevated concentrations formulation properties and process capabilities are typically dictated by API characteristics. So, it is key for a formulator to weigh-in on the active ingredient selection to be able to deliver a robust production process.
This work shows how a STYL’One compaction simulator can be used to guide API grade selection to facilitate formulation development and tableting operation. A case study is presented which demonstrates the use of a compaction simulator to classify sticking propensity of different API qualities as pure compounds as well as in compression mixtures. Finally, the impact of API attributes on the processability of the final formulation is shown.
Time to market and limited quantities of API are pressing aspects in early drug product development. By combining computer aided formulation concepts, with a systematic and scientific based working pattern, both aspects can be addressed successfully. The presentation discusses the benefits of such an approach.
Project Manager Technical Service
Lonza recently established an early phase clinical manufacturing (EPCM) facility designed to quickly advance molecules to the clinic by enabling flexible and data-driven development and clinical manufacturing. Tablets containing spray dried dispersions (SDDs) for bioavailability enhancement are a common dosage form manufactured in EPCM. However, SDD tablets can be challenging to manufacture successfully “right first time” on a rotary tablet press due to the unique physicochemical properties of each SDD. Therefore, successful clinical manufacturing of SDD tablets has traditionally relied on conducting a ‘demonstration batch’ prior to clinical manufacturing to set processing parameters and avoid risks such as deviations and low yields. To reduce the time, resource, and material constraints, we have evaluated the STYL’One Evo compaction simulator as a time- and material-sparing alternative to a demonstration batch. By performing matching studies on the compaction simulator during demonstration batches and collecting data during EPCM batches a comparison of the two methodologies was evaluated. In the presentation the capability of the STYL’One Evo to be used as a predictive tool for clinical manufactures will be discussed.
Senior Engineer in solid dosage and bioavailability
Head of Innovation & Formulation
MEGGLE uses the STYL’One compaction simulator for performance studies or product development, monitoring the direct compression product portfolio and alternative DC excipients.
In our contribution at the STYL’One User Group we will give you an insight in MEGGLE’s systematic approach to analyse the special group of direct compressible Co-Processed Excipients (CPE) according to the UPS chapter 1062.
Data will be shown, how the STYL’One helps to better understand and compare this excipients and gives valuable information about performance and application fields. The direct comparison of CPEs with the corresponding admixtures is mandatory. Showing at least one superior attribute compared to the physical admixture required by definition for those group of excipients and needs systematic evaluation.
The purpose of this activity was to evaluate the impact, of using a new processed Drug Substance (DS), on the final product Critical Quality Attribute.
This activity therefore consisted in:
Oral delivery of active pharmaceutical ingredients (APIs) is highly desirable for patient convenience, cost, and throughput relative to other oral image presentations. However, the physical and mechanical properties of many APIs may result in challenging quality attributes, including poor tablet strength and a propensity for tablet defects such as cracking and chipping. This effect is exacerbated when high API loadings are required to deliver smaller, commercially competitive images. We present an approach to mitigate poor compaction properties of these materials via tab-in-tab, also known as press-coating or compression-coating, processing. By confining API within an inner tablet core, an outer tablet shell with more desirable mechanical properties can serve to protect the weak inner core. We demonstrate a proof-of-concept tab-in-tab formulation design for a poorly compressing API utilizing the STYL’One Evo WipCon compaction simulator which enables higher API loading compared to a traditional formulation approach with significantly improved tablet robustness for further downstream handling. This approach also enables the use of functional components for the outer shell, allowing for robust controlled and modified release formulations which can often provide an in vivo biopharmaceutic performance enhancement for many classes of APIs.
Compaction simulation allows tablets formulation development and understanding of compression process in a material sparing way. In the present case study, tablet formulation showed tendency to lamination. Compaction simulation trials on a STYL’One Nano aimed at understanding how compression parameters like compression force and compression speed influence the lamination occurrence were performed. The trials lead to successful identification of air entrapment as the cause of lamination. The troubleshooting consisted in examining alternative tablets formulations and setting up compression parameters that would lead to defect free tablets. Finally, a set of trials to determine pre-compression and upper punch penetration settings to be used for manufacture of this product were successfully determined. The use of a compaction simulator contributed to robust formulation and process development without excessive material spending.
The study aimed to learn more about tablets disintegration behaviour and complex interrelationships between raw material properties, process settings and resulted tablet properties.
Globally, tablets remain the preferred oral solid dosage form because of its high stability, easy handling and easy dosing. Moreover, tableting by direct compression is a fast and “simple” process to produce a high amount of tablets. However, direct compression of powders is in many cases not straightforward, since most of the powders do not exhibit preferred powder/particle characteristics to obtain proper powder compacts, which might result in tablet deficiencies (e.g. tablet capping and lamination). Consequently, intensive and time-consuming formulation and/or process development is required (e.g. intermediate granulation step to improve powder quality).
Via spray drying, solid particles are formed by atomizing a liquid feed in a drying chamber. Therefore, particle shape/size can be adjusted by applying varying process parameters (e.g. nozzle type, atomization gas, inlet air temperature, inlet airflow). This implies that spray drying can be used as particle engineering technology to target specific particle and powder characteristics.
Powder characteristics which are of importance to obtain proper powder compacts are mainly (i) powder flowability and (ii) powder compressibility. Proper powder flowability is required to result in an adequate die filling, which is critical to obtain a robust compaction process (i.e. low tablet mass variation). Moreover, powder flowability is correlated to the particle size distribution (since – in general – larger particles result in better powder flow) and to particle shape.
Furthermore, sufficient powder compactability is required to result in proper bonding, and so, in good tablets. Powder compactability can also be influenced by particle shape (wrinkled vs. inflated particles) and by particle size (small particles have a larger specific surface area compared to larger particles).
Current study shows the ability to obtain the required powder characteristics via spray drying to directly result in feasible powder properties for tableting via direct compression.
Bi-layer tableting introduces additional parameters to be considered in formulation development and tablet press adjustment and therefore insides into compression characteristics are required even more compared to mono-layer tablet development process. One parameter to be investigated is the tamping force of the first layer. This parameter not only influences the filling of the second layer but also the interfacial strength of the bilayer tablet which is the base for the overall mechanical tablet stability during coating and transport. Examples of bi-layer tamping force investigations on the STYL’One Evo and rotary tablet presses of the KORSCH Innovation Center Lab will be presented and the daily challenges of bi-layer manufacturing companies explained.
The production of tablets containing viable microorganisms is of particular importance for the effective administration of probiotic microorganisms. Previous studies have investigated the influence of formulation and compression stress in particular, and have linked deformation mechanisms to cell damage. The question of how other process parameters affect the survival of microorganisms during tableting remains open. Especially for industrial scale production, the speed of tableting is of crucial importance. Using a Styl’One Evo, the influence of dwell time and consolidation time on the survival of fluidized bed granulated yeast cells and on the physical-mechanical tablet properties was investigated and related to formulation-specific deformation characteristics.
University of Braunschweig
University of Lille
This study developed a material sparing approach for process development using a compaction simulator and oscillating mill to mimic a roller compactor. Results showed that the compaction simulator and oscillating mill adequately mimicked the roller compactor, saving material and time during process development.
Nanjing Haiwei Pharmaceutical Technologies
Mannitol is the first intention excipient choice for API’s with stability problems in final drug formulations. Mannitol is not hygroscopic, presents a high chemical stability and is considered as compatible with almost all drugs. Texturized mannitol powders have been developed specifically for direct compression processing, enabling the easy tableting. However, whatever the process and parameters used to produce directly compressible mannitol, and whatever the compactibility of this mannitol, lamination (usually described as capping by formulators) is observed at high tablet production speed on industrial equipment, particularly when producing convex tablets.
Mannitol behavior is evolving with the tableting speed. This capping appears only at high tableting speed and the necessity to study this phenomenon on industrial rotary press has been a drag for a long time. Rotary tablet press simulators STYLCAM and STYL'One Evo made it possible to test numerous mannitol powders mimicking high speed production and finally, to understand how the mannitol structure interferes with the observed capping phenomenon. A new directly compressible mannitol, PEARLITOL® 200 GT, was developed. Studies with sitagliptin as drug model demonstrated that delaying the apparition of capping presents huge interests in tablet formulation, by decreasing the tablet size by one third thanks to an API ratio increase of fifty per cent, and in tablet production, by increasing the production yield by fifty percent.
University of Bonn
Professor for Pharmaceutical Technology
Mesoporous silica offers an easy way to transform liquids into solids, due to high loading capacities for liquid or dissolved active ingredients. The incorporation of these materials via various techniques such as the incipient wetness impregnation method results in free-flowing powders, which also exhibit enhanced dissolution properties for poorly water-soluble APIs.
However, the compression of both unloaded and loaded mesoporous silica bulk material into tablets is challenging, due to high elastic recovery and poor/non-existing binding capacity. This becomes even more critical when high drug loads are to be achieved and the fraction of additional excipients in the final tablet formulation needs to be kept at a minimum.
The aim of our study was to investigate mechanism of compression and tabletability dependent on the liquid load factor of the silicate and type of filler/binder in binary tableting mixtures. To this end Vivapur 101®, FlowLac 90®, Pearlitol 200 SD® and anhydrous Tricalciumcitrate were selected and mixed with Syloid XDP 3050® at varying liquid load factors. Compaction characteristics were analysed using the StylOne Classic 105 ML®.
Results indicate an optimal liquid load factor to obtain a stable compression process and acceptable tensile strength of the compacts. Furthermore, strong binding capacity and high plasticity of the diluents were identified as a key component for successful high liquid load silica formulations of up to 35-40% (V/V).
Good news! You can still present your work at the next User Group meeting with a poster. Click below to read the "call for poster".
(*Transportation to Lyon and dinner costs courtesy of MEDELPHARM)
(*Transportation to Lyon and dinner costs courtesy of MEDELPHARM)