How Does DSM 34246 (Canobios-BL) Supplementation Impact the Fecal Parameters of Healthy Adult Dogs?

The gastrointestinal (GI) tract is populated by a variety of microbes, which were recently demonstrated to play a major role in both human and animal health [...

3D printed reservoir-like vaginal rings for antibiotic delivery.

Targeting the development of 3D printed reservoir-like vaginal rings (VRs) intended to fulfill the needs of precision medicine, prototypes ensuring prolonged release of metronidazole (MTZ) were preliminary manufactured and tested. Indeed, this drug represents the first-line therapy against bacterial vaginosis, which would especially benefit from convenient as well as easy dose adjustment and from more than 48 h continuous release, thus avoiding barely tolerated and repeated administrations. Starting from a soft thermoplastic elastomer (TPE), hollow ring structures were successfully printed at 190 °C and then extemporaneously filled with drug-loaded, in-situ-crosslinking hydrogel formulations based on alginate (ALG).

Polyvinyl alcohol-based capsule shells manufactured by injection molding as ready-to-use moisture barriers for the development of delivery systems.

In this work, feasibility of injection molding was demonstrated for manufacturing capsule shells. 600 µm-thick prototypes were successfully molded with pharmaceutical-grade low-viscosity polyvinyl alcohols (PVAs), possibly added with a range of different fillers. They showed reproducible weight and thickness (CV < 2 and 5, respectively), compliant behavior upon piercing (holes diameter analogous to the reference), tunable release performance (immediate and pulsatile), and moisture protection capability.

Development of a robotic cluster for automated and scalable cell therapy manufacturing.

Background Aims: The production of commercial autologous cell therapies such as chimeric antigen receptor T cells requires complex manual manufacturing processes. Skilled labor costs and challenges in manufacturing scale-out have contributed to high prices for these products.

Methods: We present a robotic system that uses industry-standard cell therapy manufacturing equipment to automate the steps involved in cell therapy manufacturing.

Development of a multi-component gastroretentive expandable drug delivery system (GREDDS) for personalized administration of metformin.

Objectives: Efficacy and compliance of type II diabetes treatment would greatly benefit from dosage forms providing controlled release of metformin in the upper gastrointestinal tract. In this respect, the feasibility of a new system ensuring stomach-retention and personalized release of this drug at its absorption window for multiple days was investigated.

Methods: The system proposed comprised of a drug-containing core and a viscoelastic umbrella-like skeleton, which were manufactured by melt-casting and 3D printing.

Electrospinning of pullulan-based orodispersible films containing sildenafil.

Feasibility of electrospinning in the manufacturing of sildenafil-containing orodispersible films (ODFs) intended to enhance oxygenation and to reduce pulmonary arterial pressure in pediatric patients was evaluated. Given the targeted subjects, the simplest and safest formulation was chosen, using water as the only solvent and pullulan, a natural polymer, as the sole fiber-forming agent. A systematic characterization in terms of shear and extensional viscosity as well as surface tension of solutions containing different amounts of pullulan and sildenafil was carried out.

Insights into the Safety and Versatility of 4D Printed Intravesical Drug Delivery Systems.

This paper focuses on recent advancements in the development of 4D printed drug delivery systems (DDSs) for the intravesical administration of drugs. By coupling the effectiveness of local treatments with major compliance and long-lasting performance, they would represent a promising innovation for the current treatment of bladder pathologies. Being based on a shape-memory pharmaceutical-grade polyvinyl alcohol (PVA), these DDSs are manufactured in a bulky shape, can be programmed to take on a collapsed one suitable for insertion into a catheter and re-expand inside the target organ, following exposure to biological fluids at body temperature, while releasing their content.

Towards 4D printing in pharmaceutics.

Four-dimensional printing (4DP) is emerging as an innovative research topic. It involves the use of smart materials for three-dimensional printing (3DP) of items that change their shape after production, in a programmed way over time, when exposed to appropriate external non-mechanical (moisture, electric or magnetic fields, UV, temperature, pH or ion composition). In the performance of 4D printed devices, time is involved as the 4th dimension.

Investigation on the use of fused deposition modeling for the production of IR dosage forms containing Timapiprant.

The present work focused on evaluating the feasibility of fused deposition modeling (FDM) in the development of a dosage form containing Timapiprant (TMP), also known as CHF6532, which is a novel active molecule indicated in the potential treatment of eosinophilic asthma upon oral administration. The resulting product could be an alternative, with potential towards personalization, of immediate release (IR) tablets used in the clinical studies. Formulations based on different polymeric carriers were screened, leading to the identification of a polyvinyl alcohol-based one, which turned out acceptable for versatility in terms of active ingredient content, printability and dissolution performance ( capability to meet the dissolution specification set, envisaging >80% of the drug dissolved within 30 min).

Expandable Drug Delivery Systems Based on Shape Memory Polymers: Impact of Film Coating on Mechanical Properties and Release and Recovery Performance.

Retentive drug delivery systems (DDSs) are intended for prolonged residence and release inside hollow muscular organs, to achieve either local or systemic therapeutic goals. Recently, formulations based on shape memory polymers (SMPs) have gained attention in view of their special ability to recover a shape with greater spatial encumbrance at the target organ (e.g.

Evaluation of Newly Designed and Traditional Punches in Manufacturing of Scored ODTs.

To overcome difficulties in splitting, uneven breaking and inconsistent dosing frequently reported with scored tablets, a novel punch was proposed for the manufacturing of easy breakable tablets (EBTs). In this work, the performance of the EBT punch was investigated vs. a ridged one for traditional breakable tablets (TBTs) using a furosemide powder formulation for orally disintegrating tablets (ODTs).

Administration strategies and smart devices for drug release in specific sites of the upper GI tract.

Targeting the release of drugs in specific sites of the upper GI tract would meet local therapeutic goals, improve the bioavailability of specific drugs and help overcoming compliance-related limitations, especially in chronic illnesses of great social/economic impact and involving polytherapies (e.g. Parkinson's and Alzeimer's disease, tubercolosis, malaria, HIV, HCV).

What's next in the use of opacifiers for cosmetic coatings of solid dosage forms? Insights on current titanium dioxide alternatives.

The consolidated use of coatings containing E171 (i.e. titanium dioxide, TiO) as an opacifier has made the white color of the resulting dosage forms a quality standard in the pharmaceutical and dietary supplement fields.

Intravesical drug delivery approaches for improved therapy of urinary bladder diseases.

Diseases of the urinary bladder have high incidence rates and burden healthcare costs. Their pharmacological treatment involves systemic and local drug administration. The latter is generally accomplished through instillation of liquid formulations and requires repeated or long-term catheterization that is associated with discomfort, inflammation and bacterial infections.

Experimental and computational analysis of a pharmaceutical-grade shape memory polymer applied to the development of gastroretentive drug delivery systems.

The present paper aims at developing an integrated experimental/computational approach towards the design of shape memory devices fabricated by hot-processing with potential for use as gastroretentive drug delivery systems (DDSs) and for personalized therapy if 4D printing is involved. The approach was tested on a plasticized poly(vinyl alcohol) (PVA) of pharmaceutical grade, with a glass transition temperature close to that of the human body (i.e.

The Chronotopic™ System for Pulsatile and Colonic Delivery of Active Molecules in the Era of Precision Medicine: Feasibility by 3D Printing via Fused Deposition Modeling (FDM).

The pulsatile-release Chronotopic™ system was conceived of as a drug-containing core surrounded by a coat made of swellable/soluble hydrophilic polymers, the latter being able to provide a programmable lag phase prior to drug liberation. This system was also proposed in a colon-targeting configuration, entailing a gastroresistant film to prevent early interaction of the inner coat with gastric fluids and enabling the attainment of a lag phase matching the small intestinal transit time. Over the years, various multiple-step manufacturing processes have been tested for the fabrication of the Chronotopic™ system in both its configurations.

Shape memory materials and 4D printing in pharmaceutics.

Shape memory materials (SMMs), including alloys and polymers, can be programmed into a temporary configuration and then recover the original shape in which they were processed in response to a triggering external stimulus (e.g. change in temperature or pH, contact with water).

Quality considerations on the pharmaceutical applications of fused deposition modeling 3D printing.

3D printing, and particularly fused deposition modeling (FDM), has rapidly brought the possibility of personalizing drug therapies to the forefront of pharmaceutical research and media attention. Applications for this technology, described in published articles, are expected to grow significantly in 2020. Where are we on this path, and what needs to be done to develop a FDM 2.

A Graphical Review on the Escalation of Fused Deposition Modeling (FDM) 3D Printing in the Pharmaceutical Field.

Fused deposition modeling 3D printing is currently one of the hot topics in pharmaceutics and has shown a 2000% increase in the number of research articles published in the last 5 years. In the prospect of a new era of fused deposition modeling focused on the industrial development of this technique applied to the fabrication of personalized medicines, a conceptual map to move through the evolution of the design of the printed dosage forms/drug delivery systems was conceived and mainly discussed by means of graphical tools.

Oral hydrophilic matrices having non uniform drug distribution for zero-order release: A literature review.

Oral hydrophilic matrices for prolonged release mostly show a decrease in the rate of drug release over time, owing to the increasing length of the diffusional path and progressive reduction of the area at the interface between glassy and rubbery matrix. In addition, burst effect may also occur due to the fraction of drug present on the surface of the system, which is released when the external polymer particles are not fully swollen yet. Different strategies have been attempted in order to address these issues and, ideally, to reach zero-order release.

Evaluation of powder-layering vs. spray-coating techniques in the manufacturing of a swellable/erodible pulsatile delivery system.

A swellable/erodible system for oral time-dependent release, demonstrated to provide consistent pulsatile and colonic delivery performance, has been manufactured through a range of coating techniques to achieve the functional hydroxypropyl methylcellulose (HPMC) layer. Although aqueous spray-coating has long been preferred, the processing times and yields still represent open issues, especially in view of the considerable amount of polymer required to give lag phases of proper duration. To make manufacturing of the delivery system more cost-efficient, different coating modes were thus evaluated, namely top and tangential spray-coating as well as powder-layering, using a fluid bed equipment.

Erodible coatings based on HPMC and cellulase for oral time-controlled release of drugs.

Oral drug delivery systems for time-controlled release, intended for chronotherapy or colon targeting, are often in the form of coated dosage forms provided with swellable/soluble hydrophilic polymer coatings. These are responsible for programmable lag phases prior to release, due to their progressive hydration in the biological fluids. When based on high-viscosity polymers and/or manufactured by press-coating, the performance of functional hydroxypropyl methylcellulose (HPMC) layers was not fully satisfactory.

Non-uniform drug distribution matrix system (NUDDMat) for zero-order release of drugs with different solubility.

A decrease in the drug release rate over time typically affects the performance of hydrophilic matrices for oral prolonged release. To address such an issue, a Non-Uniform Drug Distribution Matrix (NUDDMat) based on hypromellose was proposed and demonstrated to yield zero-order release. The system consisted of 5 overlaid layers, applied by powder layering, having drug concentration decreasing from the inside towards the outside of the matrix according to a descending staircase function.

Lego-Inspired Capsular Devices for the Development of Personalized Dietary Supplements: Proof of Concept With Multimodal Release of Caffeine.

Dietary supplement companies have recently started to focus on the personalization of products and the improvement of the relevant performance. In this respect, a versatile, easy-to-handle capsular delivery platform with customizable content and release kinetics was here proposed and evaluated after filling with caffeine as a model dietary ingredient. In particular, capsular devices comprising 1 to 3 independent inner compartments were attained by Lego-inspired assembly of matching modular units with different wall compositions, manufactured by injection molding and fused deposition modeling 3D printing.

3D printing by fused deposition modeling of single- and multi-compartment hollow systems for oral delivery - A review.

Feasibility of fused deposition modeling in 3D printing of hollow systems intended to convey different formulations for oral administration has recently been investigated. A major advantage of such printed devices is represented by the possibility of separately undertaking the development of the inner core from that of the outer shell, which could also act as a release-controlling barrier. Systems either composed of parts to be filled and assembled after fabrication or fabricated and filled in a single manufacturing process represent the main focus of this review.