Comparing freeze drying and spray drying of interleukins using model protein CXCL8 and its variants.

Spray-dried products, such as synthetic peptides and hormones, have already been approved by the U.S. Food and Drug Agency and the European Medicines Agency, while spray-dried antibodies or interleukins, are not yet available on the market.

Barriers and potential solutions in the recruitment and retention of older patients in clinical trials-lessons learned from six large multicentre randomized controlled trials.

Background: older people remain underrepresented in clinical trials, and evidence generated in younger populations cannot always be generalized to older patients.

Objective: to identify key barriers and to discuss solutions to specific issues affecting recruitment and retention of older participants in clinical trials based on experience gained from six current European randomised controlled trials (RCTs) focusing on older people.

Methods: a multidisciplinary group of experts including representatives of the six RCTs held two networking conferences and compiled lists of potential barriers and solutions.

Impact of simulated lung fluid components on the solubility of inhaled drugs and predicted in vivo performance.

Orally inhaled products (OIPs) are gaining increased attention, as pulmonary delivery is a preferred route for the treatment of various diseases. Yet, the field of inhalation biopharmaceutics is still in development phase. For a successful correlation between various in vitro data obtained during formulation characterization and in vivo performance, it is necessary to understand the impact of parameters such as solubility and dissolution of drugs.

Spray-Congealing and Wet-Sieving as Alternative Processes for Engineering of Inhalation Carrier Particles: Comparison of Surface Properties, Blending and In Vitro Performance.

Purpose: Traditionally, α-lactose monohydrate is the carrier of choice in dry powder inhaler (DPI) formulations. Nonetheless, other sugars, such as D-mannitol, have emerged as potential alternatives. Herein, we explored different particle engineering processes to produce D-mannitol carriers for inhaled delivery.

Novel polyester-based thermoplastic elastomers for 3D-printed long-acting drug delivery applications.

To improve patient compliance and personalised drug delivery, long-acting drug delivery devices (LADDDs), such as implants and inserts, greatly benefit from a customisation in their shape through the emerging 3D-printing technology, since their production usually follows a one-size-fits-most approach. The use of 3D-printing for LADDDs, however, is mainly limited by the shortage of flawlessly 3D-printable, yet biocompatible materials. The present study tackles this issue by introducing a novel, non-biodegradable material, namely a polyester-based thermoplastic elastomer (TPC) - a multi-block copolymer containing alternating semi-crystalline polybutylene terephthalate hard segments and poly-ether-terephthalate amorphous soft segments.

Understanding Carrier Performance in Low-Dose Dry Powder Inhalation: An In VitroIn Silico Approach.

The use of physiologically based pharmacokinetic (PBPK) models to support drug product development has become increasingly popular. The in vitro characterization of the materials of the formulation provides valuable descriptors for the in silico prediction of the drug's pharmacokinetic profile. Thus, the application of an in vitroin silico framework can be decisive towards the prediction of the in vivo performance of a new medicine.

Modeling the coating layer thickness in a pharmaceutical coating process.

Although mechanistic numerical simulations can offer great insights into a process, they are limited with respect to resolved process time. While statistical models provide long-term predictability, determining the underlying probability distributions is often challenging. In this work, detailed CFD-DEM simulations of a pharmaceutical Wurster coating process for microspheres are used to evaluate the input parameters for a novel Monte-Carlo simulation approach.

Polyethylene oxide matrix tablet swelling evolution: The impact of molecular mass and tablet composition.

This article describes the designing of matrix tablets composed of polyethylene oxides (PEOs) with relative molecular masses of 1 × 106, 2 × 106, and 4 × 106. Percolation thresholds were determined for all of the selected PEO formulations (18, 16, and 12 %, m/m), taking into consideration excipients and tablet surface area which significantly increased the percolation threshold. Moreover, the robustness of the gel layer in PEO matrix tablets was evaluated by magnetic resonance imaging under various mechanical stresses (no flow, 12 mL min-1, and 64 mL-1 of medium flow).

Investigation into powder tribo-charging of pharmaceuticals. Part II: Sensitivity to relative humidity.

Environmental conditions can have a profound impact on the bulk behaviour of pharmaceutical powders, including their tribo-charging tendency. Typically, high relative humidity (RH) has been associated to a reduction in the electrostatic charge of the material. However, the occurrence of charge mitigation seems to be related to the quantity of water molecules at the powder surface, which depends on intrinsic material attributes (i.

Performance Evaluation of a High-Precision Low-Dose Powder Feeder.

Highly potent active pharmaceutical ingredients (APIs) and low-dose excipients, or excipients with very low density, are notoriously hard to feed with currently available commercial technology. The micro-feeder system presented in this work is capable of feeding low-dose rates of powders with different particle sizes and flow properties. Two different grades of lactose, di-calcium phosphate, croscarmellose sodium, silicon dioxide, a spray-dried intermediate, and an active ingredient were studied to vary material properties to test performance of the system.

Investigation into powder tribo-charging of pharmaceuticals. Part I: Process-induced charge via twin-screw feeding.

Powder feeding is a crucial unit operation in continuous manufacturing (CM) of pharmaceutical products. Twin-screw feeders are typically employed to ensure the accurate mass flow of pharmaceutical materials throughout the production process. Here, contact and separation of particles can give rise to electrostatic charges, affecting feeder performance and final product quality.

High-Molecular-Weight Hypromellose from Three Different Suppliers: Effects of Compression Speed, Tableting Equipment, and Moisture on the Compaction.

Use of higher tableting speeds is gaining increasing importance for pharmaceutical industry. There is a profound lack of new studies of mechanical properties of hypromellose, and none of them evaluate different suppliers. Thus, the objective of this study was to investigate flow and compaction properties of different grades of hypromellose (type 2208) from three different suppliers, with particular focus on the effect of the compression speed.

Novel Cleaning-in-Place Strategies for Pharmaceutical Hot Melt Extrusion.

To avoid any type of cross-contamination, residue-free production equipment is of utmost importance in the pharmaceutical industry. The equipment cleaning for continuous processes such as hot melt extrusion (HME), which has recently gained popularity in pharmaceutical applications, necessitates extensive manual labour and costs. The present work tackles the HME cleaning issue by investigating two cleaning strategies following the extrusion of polymeric formulations of a hormonal drug and for a sustained release formulation of a poorly soluble drug.

End-Point Prediction of Granule Moisture in a ConsiGma™-25 Segmented Fluid Bed Dryer.

Continuously operated pharmaceutical manufacturing lines often consist of a wet granulation unit operation, followed by a (semi-) continuous dryer. The operating conditions of the dryer are crucial for obtaining a desired final granule moisture. Commercially available dryers lack of a thorough online measurement of granule moisture during the drying process.

Filling of lactose-based formulations in a tamping-pin capsule filler.

We studied three lactose-based formulations in terms of bulk powder properties and capsule-filling behavior in a tamping-pin capsule filling system, to which several mechanical adaptions were made for process optimization in light of future continuous production. The model formulations were thoroughly characterized and filled into size 1 capsules according a well-defined design of experiments (DoE). Overall, the three entirely different formulations were successfully filled within the selected design space.

Polyelectrolyte-surfactant-complex nanoparticles as a delivery platform for poorly soluble drugs: A case study of ibuprofen loaded cetylpyridinium-alginate system.

Previously, we reported on the surfactant cetylpyridinium chloride (CPC) as a crosslinker of alginate for the formation of stable polyelectrolyte-surfactant-complex nanoparticles. Here, we evaluate this system for increased solubility of a poorly soluble drug. The aim was to use CPC for solubilisation of ibuprofen and to use the micellar associates formed for alginate complexation and nanoparticle formation.

Controlled-Release from High-Loaded Reservoir-Type Systems-A Case Study of Ethylene-Vinyl Acetate and Progesterone.

Reservoir systems (drug-loaded core surrounded by drug-free membrane) provide long-term controlled drug release. This is especially beneficial for drug delivery to specific body regions including the vagina. In this study, we investigated the potential of reservoir systems to provide high drug release rates over several weeks.

Mechanistic modelling of fluid bed granulation, Part II: Eased process development via degree of wetness.

The performance of a fluid bed granulator was investigated through experimental and numerical study to develop a stand-alone fluid bed granulation model. The single-compartment model proposed in part I (for agglomeration modeling) was extended to account for i) evaporation of freely-flowing droplets, and ii) particle drying. This model enables us to predict the granule liquid content and temperature besides the granule size.

Feasibility of rapidly assessing reactive impurities mediated excipient incompatibility using a new method: A case study of famotidine-PEG system.

The present work demonstrates the utility of temperature controlled set up with pressurized headspace oxygen as an approach to effectively reduce the time required for solid-state drug-excipient compatibility study. To illustrate the utility, the incompatibility of polyethylene glycol (PEG) and polyethylene oxide (PEO) with Famotidine (Fam) was shown. Owing to thermal and oxidative stress, polyethylene ether moieties of PEG generated reactive impurities, resulting in the degradation of Fam.

PVP-HO Complex as a New Stressor for the Accelerated Oxidation Study of Pharmaceutical Solids.

Reactive impurities, such as hydrogen peroxide in excipients, raise a great concern over the chemical stability of pharmaceutical products. Traditional screening methods of spiking impurities into solid drug-excipient mixtures oversimplify the micro-environment and the physical state of such impurities in real dosage form. This can lead to an inaccurate prediction of the long-term product stability.

Understanding the motion of hard-shell capsules in dry powder inhalers.

The delivery of small drug particles from a dry powder inhaler (DPI) into the patient's peripheral airways requires the dispersion of the powder. In DPIs that contain a rotating pierced capsule, the capsule's motion is paramount to powder dispersion. Previous studies have simplified the capsule motion in an Aerolizer® inhaler as a constant rotation around a fixed center.

Ensuring tablet quality via model-based control of a continuous direct compaction process.

Switching from batch to continuous pharmaceutical production offers several advantages, such as an increased productivity, a steady product quality, and decreased costs. This paper presents a control strategy for direct compaction on a continuous tablet production line consisting of two feeders, one blender, and a tablet press (TP). A data-driven, linear modeling approach is applied in order to develop a Smith predictor for active pharmaceutical ingredient concentration control and a model predictive controller responsible for the TP hopper level.

Study of the capsule-filling dosator process via calibrated DEM simulations.

Capsule filling is frequently accomplished via the dosator process. Controlling the main quality attributes, i.e.

Solid-State Reactivity of Mechano-Activated Simvastatin: Atypical Relation to Powder Crystallinity.

The present study investigated the impact of solid-state disorders generated during milling on the chemical reactivity of simvastatin. An amorphous and a partially crystalline simvastatin powders were generated via cryomilling simvastatin crystals for either 90 or 10 min, respectively. The thoroughly characterized milled powders were stored at 40°C/75% RH, in open and closed containers.