Computational Support to Explore Ternary Solid Dispersions of Challenging Drugs Using Coformer and Hydroxypropyl Cellulose.

A majority of drugs marketed in amorphous formulations have a good glass-forming ability, while compounds less stable in the amorphous state still pose a formulation challenge. This work explores ternary solid dispersions of two model drugs with a polymer (i.e.

Scattered and transmitted light as surrogates for activated carbon residual in advanced wastewater treatment processes: Investigating the influence of particle size.

The use of powdered activated carbon (PAC) is a common process in advanced wastewater treatment to remove micropollutants. Retention and separation of PAC is essential as PAC loaded with micropollutants should not be released into the environment. Determining the activated carbon (AC) residual in the effluent poses a challenge, as there is currently no on-line measurement method.

Ten years of the manufacturing classification system: a review of literature applications and an extension of the framework to continuous manufacture.

The MCS initiative was first introduced in 2013. Since then, two MCS papers have been published: the first proposing a structured approach to consider the impact of drug substance physical properties on manufacturability and the second outlining real world examples of MCS principles. By 2023, both publications had been extensively cited by over 240 publications.

Modeling-based Approach Towards Quality by Design for a Telescoped Process.

A telescoped, two-step synthesis was investigated by applying Quality by Design principles. A kinetic model consisting of 12 individual reactions was successfully established to describe the synthesis and side reactions. The resulting model predicts the effects of changes in process parameters on total yield and quality.

How Technical Innovations May Help to Prevent Drug Shortages in Switzerland.

In this work, we investigated the technical feasibility of 'on-demand' production of selected drugs to cover their demand for a time window of 90 days. We focused on two sub-processes 'automated chemical synthesis' and 'formulation in micropellets'  to enable personalized dosing. The production of drugs 'on-demand' is challenging, important, but also attractive.

Potential of measured relative shifts in collision cross section values for biotransformation studies.

Ion mobility spectrometry-mass spectrometry (IMS-MS) separates gas phase ions due to differences in drift time from which reproducible and analyte-specific collision cross section (CCS) values can be derived. Internally conducted in vitro and in vivo metabolism (biotransformation) studies indicated repetitive shifts in measured CCS values (CCS) between parent drugs and their metabolites. Hence, the purpose of the present article was (i) to investigate if such relative shifts in CCS were biotransformation-specific and (ii) to highlight their potential benefits for biotransformation studies.

Study of Disordered Mesoporous Silica Regarding Intrinsic Compound Affinity to the Carrier and Drug-Accessible Surface Area.

There is increasing research interest in using mesoporous silica for the delivery of poorly water-soluble drugs that are stabilized in a noncrystalline form. Most research has been done on ordered silica, whereas far fewer studies have been published on using nonordered mesoporous silica, and little is known about intrinsic drug affinity to the silica surface. The present mechanistic study uses inverse gas chromatography (IGC) to analyze the surface energies of three different commercially available disordered mesoporous silica grades in the gas phase.

Solving the explainable AI conundrum by bridging clinicians' needs and developers' goals.

Explainable artificial intelligence (XAI) has emerged as a promising solution for addressing the implementation challenges of AI/ML in healthcare. However, little is known about how developers and clinicians interpret XAI and what conflicting goals and requirements they may have. This paper presents the findings of a longitudinal multi-method study involving 112 developers and clinicians co-designing an XAI solution for a clinical decision support system.

Allosteric targeting resolves limitations of earlier LFA-1 directed modalities.

Integrins are a family of cell surface receptors well-recognized for their therapeutic potential in a wide range of diseases. However, the development of integrin targeting medications has been impacted by unexpected downstream effects, reflecting originally unforeseen interference with the bidirectional signalling and cross-communication of integrins. We here selected one of the most severely affected target integrins, the integrin lymphocyte function-associated antigen-1 (LFA-1, αβ, CD11a/CD18), as a prototypic integrin to systematically assess and overcome these known shortcomings.

New Scale-up Technologies for Hydrogenation Reactions in Multipurpose Pharmaceutical Production Plants.

The classical scale-up approach for hydrogenation reaction processes usually includes numerous laboratory- and pilot-scale experiments. With a novel scale-up strategy, a significant number of these experiments may be replaced by modern computational simulations in combination with scale-down experiments. With only a few laboratory-scale experiments and information about the production-scale reactor, a chemical process model is developed.

Relevance of the theoretical critical pore radius in mesoporous silica for fast crystallizing drugs.

Formulation of poorly water-soluble drugs with mesoporous silica has become a thriving field of pharmaceutics. The theoretical critical pore diameter has been introduced as a maximum value below which an undesired drug crystallization is suppressed by spatial confinement. Currently, only few values have been reported and study of fast crystallising drugs is missing especially at relevant storage temperatures.

Mechanistic aspects of drug loading in liquisolid systems with hydrophilic lipid-based mixtures.

Despite the increasing interest in pharmaceutical use of mesoporous silica, there is still only limited knowledge on mechanisms of pore loading and subsequent drug desorption and release. Hence the aim of this work was to address the mechanistic aspects of drug loading into the mesoporous silica pores and to minimise the risk of pore clogging. Hydrophilic solvents (polysorbate 20 and polyethylene glycol 200) with high dissolving capacity for the model drug celecoxib were studied for their surface tension as well as dynamic viscosity by considering hydration.

Primary stability and osseointegration of dental implants in polylactide modified bone - A pilot study in Goettingen minipigs.

The present study aimed to evaluate primary stability (PS) and osseointegration of dental implants in polylactide [70/30 poly(l-lactide-co-d, l-lactide); (PLDLA)] modified bone in 30 Goettingen minipigs. Each animal received three implants per jaw quadrant. In a split-mouth design, one side of the maxilla and mandible was randomly allocated to the experimental treatment (PLDLA applied into the drill hole before implantation), while the contralateral sides served as intraindividual controls (no PLDLA applied).

Chewability testing in the development of a chewable tablet for hyperphosphatemia.

The official Pharmacopeia does not include a test procedure for the in vitro estimation of the chewability of tablets and publications in the scientific literature on this subject are rare. The purpose of this study was to evaluate a number of different test procedures for assessing chewability, starting from standard breaking force and strength testing and progressing to develop new procedures that simulate the actual chewing action on tablets. A further goal was to apply these test procedures to characterize the chewability of the novel phosphate binder PA21 in comparison with a commercially available phosphate binder chewable tablet product based on lanthanum (Fosrenol®) and a chewable tablet product containing calcium (Calcimagon®) - the latter being used as a standard for its very good chewability.