Over the last years, hot melt extrusion (HME) has attracted significant interest in the pharmaceutical industry. HME is performed at elevated process temperatures that cause the material to soften or even melt. Thereby, the formation of molecular solid dispersions is possible, given that the formulation and the HME process are carefully designed.
Following the implantation of European regulation with respect to medicinal products for paediatric use, scientist community has to speed up for making medicine available for children by encountering multiple problems of paediatric formulation . Indeed, the taste of oral medicine is one of the most crucial factors influencing adherence to therapeutic regimens and therapeutic outcomes .
Counterfeit medicines have become an increasing issue worldwide, affecting both developing and developed countries. The presence of counterfeit medicines have a wide range of impacts including health, economic and social effects.[1-4] A major source of counterfeit medicines is sales via the Internet where it has been estimated that medicines purchased from Internet sites that conceal their actual physical address are counterfeit in over 50% of cases.
Solid dispersions are an intensively investigated enabling technology to formulate poorly soluble drugs. Many contributions already studied their higher solubility and resulting dissolution rate as well as the challenges at the level of physical stability due to their high intrinsic energy. Whereas the vast majority of these studies focus on the bulk characteristics of the samples, we are convinced that the (often distinct) properties of the sample surface should not be overlooked.
The structural and physical stability of solid dispersions have not been adequately explored during post spray drying manufacturing processes. Solid dispersions are preferentially formulated as solid dosage forms such as tablets and capsules. Formulation parameters of spray drying may lead to differences in physical form and amorphous content of solids in single component systems . However, there is limited understanding on the effect of spray drying processes and formulation variables on drug-polymer mixing in solid dispersions and this limitation also extends to the unit operations such as milling and tabletting. The drug-polymer mixing in solid dispersions was evaluated in two different laboratory spray dryers, the Buchi-mini spray dryer and Pro-C-epT Micro spray dryer (Figure 1). The effect of compression on the structural and the physical stability of the spray dried solid dispersions was investigated as a major scope of this study.
Non-linear Optical Imaging
Non-linear optical imaging is an emerging technique for imaging drugs and dosage forms . Non-linear optical imaging may be used for non-destructive, non-contact imaging of solid drugs and dosage forms. It offers chemical and structural specificity with no requirement for labels, sub-micron spatial resolution (inherent confocal nature), rapid video-rate image acquisition, and the ability to image samples in aqueous environments in situ.
These combined features make non-linear optical imaging unique compared to existing imaging approaches in the pharmaceutical setting and make the technique well suited to a wide range of solid-state formulation and drug delivery analyses. These include imaging chemical and solid-state form distributions in dosage forms, drug release and dosage form digestion, and drug and micro/nanoparticle distribution in tissues and within live cells. While non-linear optical imaging is comparatively well established in the biomedical field, pharmaceutical applications of non-linear optical imaging are much less widely explored.
The production and manufacturing of solid pharmaceutical products is in need of new technologies to ensure a safe and efficient medical therapy. Hot melt extrusion (HME) is a new and innovative technology in the field of pharmaceutics, which aids to overcome numerous limitations of traditional manufacturing techniques. The benefit of HME is three-fold: First, the bioavailability of poorly soluble drugs is significantly increased due to the conversion of the drug from the crystalline into its amorphous state . Recent work showed that HME is even capable of converting a liquid nanosuspension into a solid formulation in a one-step process , thereby avoiding aggregation of nanocrystals. Second, drug release profiles can be specifically tailored (in most cases retarded release of water soluble drugs) via the application of a proper matrix carrier in combination with plasticisers . Third, drug abuse can be prevented due to superior mechanical properties of the final product .
Continuous processing is a promising approach for solid dosage manufacturing. High-shear wet granulation is performed in continuous mode using twin screw granulators (TSG), characterized by a modular screw profile including a sequence of different screw elements with various shapes, orientation and functions. For process engineers it is a challenge to come up with prediction models to establish the relationship between equipment and material attributes, process data and the end-product testing results. If a reliable model is available which is able to predict the quality of the product, it can be inverted to obtain the design space, corresponding to that set of operating conditions required for achieving the target product quality (Figure 1). Such a modelling framework combined with in-process measurements, can provide a good mechanistic insight into the important parameters of continuous
Oral films have gained interest in the last couple of years. Films for oral application offer an interesting new approach for drug administration. Active pharmaceutical ingredients (API) can be implemented in thin-sheeted polymer film matrices. These dosage forms are intended to be placed in mouth to dissolve in the saliva without the need of additional liquid and without swallowing of a solid dosage form.
The inter-tablet coating uniformity is a critical quality attribute in active coating processes. In this project an active coating process is performed in order to produce a fixed dose combination of a sustained release formulation in the tablet core and an immediate release dose in the coating layer. The tablet cores consist of a push-pull osmotic system containing nifedipine as API (Adalat GITS). They are coated with Candesartan cilexetil as a second API. As the inter-tablet coating uniformity is a critical quality attribute to comply with regulatory requirements, the purpose of this work is to enhance the process understanding and to optimize the coating process with regard to the coating uniformity. Besides experimental investigations, PAT tools such as Raman spectroscopy  and terahertz pulsed imaging  have been applied to study this active coating process. In recent years, numerical simulations of coating processes have been gaining interest as analytical tool . The discrete element method (DEM) in particular is suitable to simulate the tablet motion . In this project, both experimental and numerical analysis of an active coating process is combined to investigate the influence of different process parameters with respect to the optimization of the coating uniformity.
Magnetic Resonance Imaging
The use of MRI as a powerful imaging and characterization modality in pharmaceutical dissolution research is now well established . The non-invasive and non-destructive nature of MRI enables the investigation of structural, chemical and dynamical processes in many optically opaque systems at the microscopic level. Spatial maps of water penetration, tablet swelling and dissolution, as well as the mobilization and distribution of drug products can now be quantified and visualized [2,3]. In addition, the hydrodynamics within a USP recommended flow-through dissolution apparatus can also be visualized by MRI . Such comprehensive information is essential in pharmaceutical research for: (i) the correct interpretation of conventional drug dissolution profiles and (ii) the optimal design (QbD) of controlled release formulations.
Lipid-based drug delivery systems have become a popular approach for the delivery of poorly water-soluble drugs. The limitations associated with this formulation strategy have been the drug solubility in the delivery systems and the lack of characterization techniques predicting the in vivo performance. Solid state characterization of the in vitro digestion products has provided new insights that scrutinize current paradigms in the development of lipid-based drug delivery systems.
Formulation of co-amorphous drug systems
Using the amorphous form of a drug, instead of its crystalline counterpart is one way to enhance the bioavailability of poorly water-soluble drugs. However, in order to fully benefit from the solubility advantages of amorphous drugs, one needs to overcome phyisco-chemical limitations including poor physical stability associated with the amorphous form. Co-amorphous drug formulations are a novel and one of the most promising formulation approaches in this context, where the drug in its amorphous form is stabilized through strong intermolecular interactions with its co-amorphous low molecular weight partner molecule.
The major challenge during preformulation is to gain the greatest possible knowledge about candidate drug compounds with minimal use of resources. Therefore, rapid approaches are proposed for identifying critical conditions for existence of various solid forms so that sudden appearance of new forms and unpredictable stability issues can be avoided during later stages of product development.