pH stimuli-responsive hydrogels from non-cellulosic biopolymers for drug delivery.

Over the past several decades, there has been significant growth in the design and development of more efficient and advanced biomaterials based on non-cellulosic biological macromolecules. In this context, hydrogels based on stimuli-responsive non-cellulosic biological macromolecules have garnered significant attention because of their intrinsic physicochemical properties, biological characteristics, and sustainability. Due to their capacity to adapt to physiological pHs with rapid and reversible changes, several researchers have investigated pH-responsive-based non-cellulosic polymers from various materials.

Pancreatic lipase digestion: The forgotten barrier in oral administration of lipid-based delivery systems?

This review highlights the importance of controlling the digestion process of orally administered lipid-based delivery systems (LBDS) and their performance. Oral LBDS are prone to digestion via pancreatic lipase in the small intestine. Rapid or uncontrolled digestion may cause the loss of delivery system integrity, its structural changes, reduced solubilization capacity and physical stability issues.

Prediction of dissolution performance of uncoated solid oral dosage forms via optical coherence tomography.

Real-time prediction of the dissolution behavior of solid oral dosage forms is an important research topic. Although methods such as Terahertz and Raman can provide measurements that can be linked to the dissolution performance, they typically require a longer time off-line for analysis. In this paper, we present a novel strategy for analyzing uncoated compressed tablets by means of optical coherence tomography (OCT).

Micro-dosing of powders into capsules using a new automated micro-dosing system: effect of powder characteristics and operating conditions on the filling of 0.5 mg-100 mg weights.

Objective: To demonstrate the applicability of a novel micro-dosing system for precisely filling low powder doses (down to a few mg) into capsules along with weighing the filled powder mass accurately.

Methods: Ten commonly used pharmaceutical powders, ranging from cohesive to free-flowing, were selected and filled at three target fill weights (0.5, 1, and 10 mg), to investigate the effect of distinct powder properties on the filling performance.

A multi-step machine learning approach for accelerating QbD-based process development of protein spray drying.

This study proposes a new material-efficient multi-step machine learning (ML) approach for the development of a design space (DS) for spray drying proteins. Typically, a DS is developed by performing a design of experiments (DoE) with the spray dryer and the protein of interest, followed by deriving the DoE models via multi-variate regression. This approach was followed as a benchmark to the ML approach.

On the influence of raw material attributes on process behaviour and product quality in a continuous WET granulation tableting line.

Continuous manufacturing of oral solids is a complex process in which critical material attributes (CMAs), formulation and critical process parameters (CPPs) play a fundamental role. However, assessing their effect on the intermediate and final product's critical quality attributes (CQAs) remains challenging. The aim of this study was to tackle this shortcoming by evaluating the influence of raw material properties and formulation composition on the processability and quality of granules and tablets on a continuous manufacturing line.

Control oriented modeling of twin-screw granulation in the ConsiGma-25 production plant.

ConsiGma-25 is a continuous production plant integrating a twin-screw granulation, fluid bed drying, granule conditioning, and a tableting unit. The particle size distribution (PSD), active pharmaceutical ingredient (API) content, and liquid content of wet granules after twin-screw granulation affect the quality of intermediate and final products. This paper proposes methods for real-time monitoring of these quantities and control-oriented modeling of the granulator.

Applying Material Science Principles to Chemical Stability: Modelling Solid State Autoxidation in Mifepristone Containing Different Degrees of Crystal Disorder.

Ball-milling and harsh manufacturing processes often generate crystal disorder which have practical implications on the physical and chemical stabilities of solid drugs during subsequent storage, transport, and handling. The impact of the physical state of solid drugs, containing different degrees/levels of crystal disorder, on their autoxidative stability under storage has not been widely investigated. This study investigates the impact of differing degrees of crystal disorder on the autoxidation of Mifepristone (MFP) to develop a predictive (semi-empirical) stability model.

A DEM model to evaluate refill strategies of a twin-screw feeder.

Residence time distribution (RTD) modeling has proven to be a valuable tool for material tracking in continuous pharmaceutical processes. Refilling is thoroughly studied in the literature, but the main focus lies on the feed rate disturbances. The impact of the feeders themselves on intermixing of different material batches is often overlooked.

Impact of Different Saccharides on the In-Process Stability of a Protein Drug During Evaporative Drying: From Sessile Droplet Drying to Lab-Scale Spray Drying.

Objectives: Solid biopharmaceutical products can circumvent lower temperature storage and transport and increase remote access with lower carbon emissions and energy consumption. Saccharides are known stabilizers in a solid protein produced via lyophilization and spray drying (SD). Thus, it is essential to understand the interactions between saccharides and proteins and the stabilization mechanism.

Screening Autoxidation Propensities of Drugs in the Solid-State Using PVP and in the Solution State Using N-Methyl Pyrrolidone.

Oxidative degradation of drugs is one of the major routes of drug substance and drug product instability. Among the diverse routes of oxidation, autoxidation is considered to be challenging to predict and control, potentially due to the multi-step mechanism involving free radicals. C-H bond dissociation energy (C-H BDE) is evidenced to be a calculated descriptor shown to predict drug autoxidation.

Assessment of Tribo-charging and Continuous Feeding Performance of Direct Compression Grades of Isomalt and Mannitol Powders.

Tribo-charging is often a root cause of mass flow deviations and powder adhesion during continuous feeding. Thus, it may critically impact product quality. In this study, we characterized the volumetric (split- and pre-blend) feeding behavior and process-induced charge of two direct compression grades of polyols, galenIQ™ 721 (G721) for isomalt and PEARLITOL 200SD (P200SD) for mannitol, under different processing conditions.

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.