A unifying approach to drug-in-polymer solubility prediction: Streamlining experimental workflow and analysis.

This method paper describes currently used experimental methods to predict the drug-in-polymer solubility of amorphous solid dispersions and offers a combined approach for applying the Melting-point-depression method, the Recrystallization method, and the Melting-and-mixing method. It aims to describe and expand on the theoretical basis as well as the analytical methodology of the recently published Melting-and-mixing method. This solubility method relies on determining the relationship between drug loads and the enthalpy of melting and mixing of a crystalline drug in the presence of an amorphous polymer.

Co-release of paclitaxel and encequidar from amorphous solid dispersions increase oral paclitaxel bioavailability in rats.

The oral bioavailability of paclitaxel is limited due to low solubility and high affinity for the P-glycoprotein (P-gp) efflux transporter. Here we hypothesized that maximizing the intestinal paclitaxel levels through apparent solubility enhancement and controlling thesimultaneous release of both paclitaxel and the P-gp inhibitor encequidar from amorphous solid dispersions (ASDs) would increase the oral bioavailability of paclitaxel. ASDs of paclitaxel and encequidar in polyvinylpyrrolidone K30 (PVP-K30), hydroxypropylmethylcellulose 5 (HPMC-5), and hydroxypropylmethylcellulose 4 K (HPMC-4K) were hence prepared by freeze-drying.

Shifting the Focus from Dissolution to Permeation: Introducing the Meso-fluidic Chip for Permeability Assessment (MCPA).

In response to the growing ethical and environmental concerns associated with animal testing, numerous in vitro tools of varying complexity and biorelevance have been developed and adopted in pharmaceutical research and development. In this work, we present one of these tools, i.e.

Towards personalized drug delivery via semi-solid extrusion: Exploring poly(vinyl alcohol-co-vinyl acetate) copolymers for hydrochlorothiazide-loaded films.

The increasing need for personalized drug delivery requires developing systems with tailorable properties. The copolymer poly(vinyl alcohol-co-vinyl acetate) (PVA/PVAc) allows for adjusting the monomer ratio. This study explored the effect of vinyl alcohol (VA) and vinyl acetate (VAc) monomer ratio on the properties of hydrochlorothiazide (HCT) films.

Impact of drug load and polymer molecular weight on the 3D microstructure of printed tablets.

This study investigates the influence of drug load and polymer molecular weight on the structure of tablets three-dimensionally (3D) printed from the binary mixture of prednisolone and hydroxypropyl methylcellulose (HPMC). Three different HPMC grades, (AFFINISOL HPMC HME 15LV, 90 Da (HPMC 15LV); 100LV, 180 Da (HPMC 100LV); 4M, 500 Da (HPMC 4M)), which are suitable for hot-melt extrusion (HME), were used in this study. HME was used to fabricate feedstock material, i.

Increased bioavailability of a P-gp substrate: Co-release of etoposide and zosuquidar from amorphous solid dispersions.

P-glycoprotein (P-gp) inhibitors, like zosuquidar, partly increase oral bioavailability of P-gp substrates, such as etoposide. Here, it was hypothesised that co-release of etoposide and zosuquidar from amorphous solid dispersions (ASDs) may further increase oral etoposide bioavailability. This was envisioned through simultaneous co-release and subsequent spatiotemporal association of etoposide and zosuquidar in the small intestinal lumen.

Co-administration of Intravenous Drugs: Rapidly Troubleshooting the Solid Form Composition of a Precipitate in a Multi-drug Mixture Using On-Site Raman Spectroscopy.

Intravenous drugs are often co-administrated in the same intravenous catheter line due to which compatibility issues, such as complex precipitation processes in the catheter line, may occur. A well-known example that led to several neonatal deaths is the precipitation due to co-administration of ceftriaxone- and calcium-containing solutions. The current study is exploring the applicability of Raman spectroscopy for testing intravenous drug compatibility in hospital settings.

Water-soluble chitosan eases development of mucoadhesive buccal films and wafers for children.

Oromucosal films and wafers are user-friendly solid dosage forms offering easy and convenient administration, as well as rapid or controlled drug delivery. The aim of this study was to develop prednisolone containing child-friendly chitosan-based mucoadhesive films and wafers with a prolonged residence time on the buccal mucosa. Four different chitosan types (different molecular weights, degree of deacetylation (DDA), pattern of deacetylation) were studied for films prepared by solvent-cast-evaporation and wafers by freeze-drying.

A new method to determine drug-polymer solubility through enthalpy of melting and mixing.

In this study, a new method to determine the solubility of crystalline drugs in (amorphous) polymers is proposed. The method utilizes annealing of supersaturated amorphous solid dispersions to achieve equilibrium between dissolved and recrystallized drug. By measuring the enthalpy of melting and mixing (H) of the recrystallized drug, the equilibrium solubility of the drug in the polymer at the annealing temperature is determined.

Exploring a case of incompatibility in a complex regimen containing Plasma-Lyte 148 in the pediatric intensive care.

Background: In the local pediatric intensive care unit, precipitation was observed in the intravenous catheter upon co-administration of four drugs together with the buffered electrolyte solution (Plasma-Lyte 148, Baxter). Co-infusion of incompatible combinations represents a safety concern.

Aims: To reproduce the clinical case of precipitation.

Frequently acquired drugs in neonatal intensive care and their physical compatibility.

Aim: Incompatibility of intravenous drugs is dangerous and therefore undesirable. The aim of this study was to identify the most commonly acquired intravenous drugs in five neonatal intensive care units and test these for compatibility.

Methods: The most frequently acquired drugs in five key hospitals in the South-Eastern district of Norway for 2019 and 2020 served as a proxy for the prevalence of use.

Co-administration of drugs with parenteral nutrition in the neonatal intensive care unit-physical compatibility between three components.

Unlabelled: There is a lack of compatibility data for intravenous therapy to neonatal intensive care unit (NICU) patients, and the purpose of this study was to contribute with documented physical compatibility data to ensure safe co-administration. We selected Numeta G13E, the 3-in-1 parenteral nutrition (PN) used at our NICU, together with the frequently used drugs morphine, dopamine and cefotaxime in two- but also three-component combinations. Incompatibility may lead to particle formation (precipitation) and oil-droplet growth (emulsion destabilisation), both which are undesirable and pose a safety risk to already unstable patients.

Polymers in pharmaceutical additive manufacturing: A balancing act between printability and product performance.

Materials and manufacturing processes share a common purpose of enabling the pharmaceutical product to perform as intended. This review on the role of polymeric materials in additive manufacturing of oral dosage forms, focuses on the interface between the polymer and key stages of the additive manufacturing process, which determine printability. By systematically clarifying and comparing polymer functional roles and properties for a variety of AM technologies, together with current and emerging techniques to characterize these properties, suggestions are provided to stimulate the use of readily available and sometimes underutilized pharmaceutical polymers in additive manufacturing.

Influence of Drug Load on the Printability and Solid-State Properties of 3D-Printed Naproxen-Based Amorphous Solid Dispersion.

Fused deposition modelling-based 3D printing of pharmaceutical products is facing challenges like brittleness and printability of the drug-loaded hot-melt extruded filament feedstock and stabilization of the solid-state form of the drug in the final product. The aim of this study was to investigate the influence of the drug load on printability and physical stability. The poor glass former naproxen (NAP) was hot-melt extruded with Kollidon VA 64 at 10-30% / drug load.

Adjusting the dose in paediatric care: dispersing four different aspirin tablets and taking a proportion.

Objectives: When caring for children in a hospital setting, tablets are often manipulated at the ward to obtain the right dose. One example is manipulation of tablets containing the slightly water-soluble substance aspirin, used in paediatric care as an antiplatelet agent. The evidence base, however, for choosing certain tablet formulations and manipulation methods over others for extraction of proportions is lacking.

Inorganic Nanocarriers for Encapsulation of Natural Antimicrobial Compounds for Potential Food Packaging Application: A Comparative Study.

Design and development of novel inorganic nanocarriers for encapsulation of natural antimicrobial substances for food packaging applications have received great interest during the last years. Natural nanoclays are the most investigated nanocarriers and recently interest has also grown in the synthetically produced porous silica particles. However, these different carrier matrices have not been compared in terms of their loading capability and subsequent release.

Solid lipid nanoparticle-loaded mucoadhesive buccal films - Critical quality attributes and in vitro safety & efficacy.

The objective of this work was to develop and characterize solid lipid nanoparticle (SLN)-loaded mucoadhesive films to reveal their potential as successful drug formulations. SLNs based on lipid (Lipoid S100) and surfactant (polysorbate 80) were prepared using the solvent-injection method, and their properties examined using experimental designs. Further, the marker coumarin 6 (C6) was solubilized in the particles as a model for a lipophilic drug.

Functionalised calcium carbonate as a coformer to stabilize amorphous drugs by mechanochemical activation.

The aim of this study was to investigate the amorphization, physical stability and drug release of a model drug, carvedilol (CAR), when loaded onto functionalised calcium carbonate (FCC) using mechanochemical activation (vibrational ball milling). The solid-state characteristics and physical stability of CAR-FCC samples, prepared at different weight ratios and for different milling times, were determined using differential scanning calorimetry and X-ray powder diffraction. Upon milling CAR-FCC samples containing 50% CAR, amorphization of CAR was observed after 10 min.

Y-Site Physical Compatibility of Numeta G13E with Drugs Frequently Used at Neonatal Intensive Care.

Preterm neonates require parenteral nutrition (PN) in addition to intravenous drug therapy. Due to limited venous access, drugs are often co-administered with PN via the same lumen. If incompatible, precipitation and emulsion destabilization may occur with the consequent risk of embolism and hyper-immune reactions.

Comparing Two Methods of Tablet Manipulation to Adjust the Warfarin Dose in Paediatric Care.

Tablets containing prescribed doses are not always available, and this is of particular importance in paediatric care where suitable age-appropriate formulations are generally lacking. To obtain a child-adjusted dose, tablets are manipulated in several ways; e.g.

Physical stability of an all-in-one parenteral nutrition admixture for preterm infants upon mixing with micronutrients and drugs.

Objectives: The main objective was to investigate Y-site compatibility of intravenous drugs with one standard total parenteral nutrition (TPN) admixture for preterm infants. Since micro-precipitation was observed in the water phase after addition of trace elements, the concentration effect on micro-precipitation formation developed as a sub-goal.

Methods: Seven drugs (ampicillin, ceftazidime, fluconazole, fosphenytoin, furosemide, metronidazole and paracetamol) were mixed in three mixing ratios with one preterm TPN admixture.

Adjusting the dose in paediatric care by dispersing fragments of four different aspirin tablets.

Aim: Tablets can be manipulated in several ways to obtain a fraction as the dose-a practice frequently seen in paediatric care due to lack of suitable formulations. Splitting tablets prior to fragment dispersion in a small volume of liquid is one such method. The objective of this study was to investigate the accuracy and precision of this method.

Mucoadhesive buccal films based on a graft co-polymer - A mucin-retentive hydrogel scaffold.

From a patient-centric perspective, oromucosal drug delivery is highly attractive due to the ease of administration without the need of swallowing, and improved patient safety. The aim of the presented work was to prepare a buccal film using a self-forming micellar drug solubiliser as the film matrix, combining it with a mucoadhesive polymer for an enhanced retention on the buccal mucosa. Specifically, we propose the use of a graft co-polymer (Soluplus®), as a solubiliser and film former, supplemented with polymers with more hydrophilic properties and known mucoadhesive properties; hydroxypropyl methylcellulose (HPMC) or modified hydroxypropyl pea starch (Lycoat®).

Gellan Gum/Laponite Beads for the Modified Release of Drugs: Experimental and Modeling Study of Gastrointestinal Release.

In this study, gellan gum (GG), a natural polysaccharide, was used to fabricate spherical porous beads suitable as sustained drug delivery systems for oral administration. GG was cross-linked with calcium ions to prepare polymeric beads. Rheological studies and preliminary experiments of beads preparation allowed to identify the GG and the CaCl concentrations suitable for obtaining stable and spherical particles.