Role of Crystal Disorder and Mechanoactivation in Solid-State Stability of Pharmaceuticals.

Common energy-intensive processes applied in oral solid dosage development, such as milling, sieving, blending, compaction, etc. generate particles with surface and bulk crystal disorder. An intriguing aspect of the generated crystal disorder is its evolution and repercussion on the physical- and chemical stabilities of drugs.

Steady-state modeling of a new continuous API dryer: Reduced-order model and investigation of dryer performance.

In the present study, a reduced-order model is proposed to analyze a novel continuous dryer with an application in the pharmaceutical industry. The model was validated using process data from ibuprofen drying test runs, and the results were in good agreement with the experimental data. The test substance was an ibuprofen paste with an initial LOD of up to 30 w%.

Theoretical and Experimental Investigation of Autoxidation Propensity of Selected Drugs in Solution State.

The C-H bond dissociation energy (BDE) of drug molecules is often used to estimate their relative propensities to undergo autoxidation. BDE calculations based on electronic structures provide a convenient means to estimate the risk for a given compound to degrade via autoxidation. This study aimed to verify the utility of calculated C-H BDEs of a range of drug molecules in predicting their autoxidation propensities, in the solution state.

Mechanoactivation as a Tool to Assess the Autoxidation Propensity of Amorphous Drugs.

Mechanoactivation has attracted considerable attention in the pharmaceutical sciences due to its ability to generate amorphous materials and solid-state synthetic products without the use of solvent. Although some studies have reported drug degradation during milling, no studies have systematically investigated the use of mechanoactivation in predicting drug degradation in the solid state. Thus, this work explores the autoxidation of drugs in the solid state by comilling amorphous mifepristone (MFP):polyvinylpyrrolidone vinyl acetate (PVPVA) and amorphous olanzapine (OLA):PVPVA.

Machine Learning-Enabled NIR Spectroscopy. Part 2: Workflow for Selecting a Subset of Samples from Publicly Accessible Data.

An increasingly large dataset of pharmaceutics disciplines is frequently challenging to comprehend. Since machine learning needs high-quality data sets, the open-source dataset can be a place to start. This work presents a systematic method to choose representative subsamples from the existing research, along with an extensive set of quality measures and a visualization strategy.

Temperature cycling-induced formation of crystalline coatings.

The surface of particles is the hotspot of interaction with their environment and is therefore a major target for particle engineering. Particles with tailored coatings are greatly desired for a range of different applications. Amorphous coatings applied via film coating or microencapsulation have frequently been described in the pharmaceutical context and usually result in homogeneous surfaces.

SEDEX-Self-Emulsifying Delivery Via Hot Melt Extrusion: A Continuous Pilot-Scale Feasibility Study.

The aim of this study was to develop a continuous pilot-scale solidification and characterization of self-emulsifying drug delivery systems (SEDDSs) via hot melt extrusion (HME) using Soluplus and Kollidon VA-64. First, an oil-binding capacity study was performed to estimate the maximal amount of SEDDSs that the polymers could bind. Then, HME was conducted using a Coperion 18 mm ZSK18 pilot plant-scale extruder with split-feeding of polymer and SEDDS in 10, 20, and 30% / SEDDSs was conducted.

Development of a Workflow to Engineer Tailored Microparticles Via Inkjet Printing.

Purpose: New drug development and delivery approaches result in an ever-increasing demand for tailored microparticles with defined sizes and structures. Inkjet printing technologies could be promising new processes to engineer particles with defined characteristics, as they are created to precisely deliver liquid droplets with high uniformity.

Methods: D-mannitol was used as a model compound alone or co-processed with the pore former agent ammonium bicarbonate, and the polymer polyethylene glycol 200.

Machine Learning-Enabled NIR Spectroscopy in Assessing Powder Blend Uniformity: Clear-Up Disparities and Biases Induced by Physical Artefacts.

NIR spectroscopy is a non-destructive characterization tool for the blend uniformity (BU) assessment. However, NIR spectra of powder blends often contain overlapping physical and chemical information of the samples. Deconvoluting the information related to chemical properties from that associated with the physical effects is one of the major objectives of this work.

Continuous Processing of Micropellets via Hot-Melt Extrusion.

Microparticulate drug delivery systems, e.g., micropellets (MPs), are used in a variety of pharmaceutical formulations such as suspensions, injectable systems, and capsules.

Design and Investigation of a Photocatalytic Setup for Efficient Biotransformations Within Recombinant Cyanobacteria in Continuous Flow.

Photo- and biocatalysis show many advantages as more sustainable solutions for the production of fine chemicals. In an effort to combine the benefits and the knowledge of both these areas, a continuous photobiocatalytic setup was designed and optimized to carry out whole-cell biotransformations within cells of the cyanobacterium Synechocystis sp. PCC 6803 expressing the gene of the ene-reductase YqjM from B.

Lipid-based solubilization technology via hot melt extrusion: promises and challenges.

Introduction: Self-emulsifying drug delivery systems (SEDDS) are a promising strategy to improve the oral bioavailability of poorly water-soluble drugs (PWSD). However, poor drug loading capacity and formulation instability are the main setbacks of traditional SEDDS. The use of polymeric precipitation inhibitors was shown to create supersaturable SEDDS with increased drug loads, and their solidification can help to overcome the instability challenge.

Assessment of Diverse Solid-State Accelerated Autoxidation Methods for Droperidol.

The present study aimed to investigate methods for accelerating autoxidation of crystalline drugs in the solid-state that can potentially predict real-time stability. Solid droperidol (DPD) was selected as the model drug. A common free-radical initiator, 2,2'-azobisisobutyronitrile (AIBN), was used to induce autoxidation in solutions.

In-vial printing and drying of biologics as a personalizable approach.

This study addressed the need for a flexible (personalizable) production of biologics, allowing their stabilization in the solid state and processing of small batch volumes. Therefore, inkjet printing into vials followed by a gentle vacuum drying step at ambient temperature was investigated by screening different formulations with a 2-full factorial design of experiments regarding printability. Human Serum Albumin (HSA) was used as a model protein in a wide range of concentrations (5 to 50 mg/ml), with (10 w/v%) and without the surfactant polysorbate 80 (PS80).

Capability of the TFM Approach to Predict Fluidization of Cohesive Powders.

The fluidization behavior of cohesive particles was investigated using an Euler-Euler approach. To do so, a two-fluid model (TFM) platform was developed to account for the cohesivity of particles. Specifically, the kinetic theory of granular flow (KTGF) was modified based on the solid rheology developed by Gu et al.

Commentary on the EMA reflection paper on the pharmaceutical development of medicines for use in the older population.

Older people are often affected by impaired organ and bodily functions resulting in multimorbidity and polypharmacy, turning them into the main user group of many medicines. Very often, medicines have not specifically been developed for older people, causing practical medication problems for them like limited availability of easy to swallow formulations, easy to open packaging and dosing instructions for enteral administration. In 2020, the European Medicines Agency (EMA) published a reflection paper 'Pharmaceutical development of medicines for use in the older population', which discusses how the emerging needs of an ageing European population can be addressed by medicines regulation.

Insights into the Impact of Nanostructural Properties on Powder Tribocharging: The Case of Milled Salbutamol Sulfate.

The impact of the crystallinity of organic solid materials on their tribocharging propensity is well reported. However, no unequivocal explanation about the potential underlying mechanism(s) could be found so far in the literature. This study reports the effect that different degrees of crystalline disorder has on the tribocharging propensity of a small molecular organic material, salbutamol sulfate (SS).

Topologically directed confocal Raman imaging (TD-CRI): Advanced Raman imaging towards compositional and micromeritic profiling of a commercial tablet components.

Particle size distribution (PSD), spatial location and particle cluster size of ingredients, polymorphism, compositional distribution of a pharmaceutical product are few of the most important attributes in establishing the drug release-controlling microstructural and solid state properties that would be used to (re)design or reproduce similar products. There are numerous solid-state techniques available for PSD analysis. Laser diffraction (LD) is mostly used to study PSD of raw materials.

Focusing on powder processing in dry powder inhalation product development, manufacturing and performance.

Dry powder inhalers (DPI) are well established products for the delivery of actives via the pulmonary route. Various DPI products are marketed or developed for the treatment of local lung diseases such as chronic obstructive pulmonary disease (COPD), asthma or cystic fibrosis as well as systemic diseases targeted through inhaled delivery (i.e.

Carrier particle emission and dispersion in transient CFD-DEM simulations of a capsule-based DPI.

The dispersion of carrier-based formulations in capsule-based dry powder inhalers depends on several factors, including the patient's inhalation profile and the motion of capsule within the device. In the present study, coupled computational fluid dynamics and discrete element method simulations of a polydisperse cohesive lactose carrier in an Aerolizer® inhaler were conducted at a constant flow rate of 100 L/min and considering an inhalation profile of asthmatic children between 5 and 17 years approximated from literature data. In relevant high-speed photography experiments, it was observed that the powder was distributed to both capsule ends before being ejected from the capsule.

Development and Validation of a Stability-Indicating UPLC Method for the Determination of Hexoprenaline in Injectable Dosage Form Using AQbD Principles.

A novel and efficient stability-indicating, reverse phase ultra-performance liquid chromatographic (UPLC) analytical method was developed and validated for the determination of hexoprenaline in an injectable dosage form. The development of the method was performed using analytical quality by design (AQbD) principles, which are aligned with the future requirements from the regulatory agencies using AQbD principles. The method was developed by assessing the impact of ion pairing, the chromatographic column, pH and gradient elution.

3D printed ceramics as solid supports for enzyme immobilization: an automated DoE approach for applications in continuous flow.

Unlabelled: In recent years, 3D printing has emerged in the field of chemical engineering as a powerful manufacturing technique to rapidly design and produce tailor-made reaction equipment. In fact, reactors with complex internal geometries can be easily fabricated, optimized and interchanged in order to respond to precise process needs, such as improved mixing and increased surface area. These advantages make them interesting especially for catalytic applications, since customized structured bed reactors can be easily produced.

A Tribute to Professor Saranjit Singh - A Critical Thinker, Innovator, Mentor, and Educator.

This commentary presents contributions and accomplishments of Professor Saranjit Singh, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, India, to pharmaceutical research and education. Prof. Singh completed his successful tenure in October 2021.

Development of a Controlled Continuous Low-Dose Feeding Process.

This paper proposes a feed rate control strategy for a novel volumetric micro-feeder, which can accomplish low-dose feeding of pharmaceutical raw materials with significantly different powder properties. The developed feed-forward control strategy enables a constant feed rate with a minimum deviation from the set-point, even for materials that are typically difficult to accurately feed (e.g.

Continuous mixing technology: Validation of a DEM model.

Continuous powder mixing is an important technology used in the development and manufacturing of solid oral dosage forms. Since critical quality attributes of the final product greatly depend on the performance of the mixing step, an analysis of such a process using the Discrete Element Method (DEM) is of crucial importance. On one hand, the number of expensive experimental runs can be reduced dramatically.