Formulation of minitablets with personalised dissolution profile by fluid-bed granulation ofdrug nanosuspensions.

Transforming poorly soluble active pharmaceutical ingredients (APIs) into a nanoparticulate form is a proven way of improving their dissolution characteristics. The preparation of API nanosuspensions is commonly achieved by wet-stirred media milling. The challenge lies in converting the nanosuspension into a solid dosage form without compromising its re-dispersibility.

Liposomal Copermeation Assay Reveals Unexpected Membrane Interactions of Commonly Prescribed Drugs.

The permeation of small molecules across biological membranes is a crucial process that lies at the heart of life. Permeation is involved not only in the maintenance of homeostasis at the cell level but also in the absorption and biodistribution of pharmacologically active substances throughout the human body. Membranes are formed by phospholipid bilayers that represent an energy barrier for permeating molecules.

Manufacturing process transfer to a 30 kg/h continuous direct compression line with real-time composition monitoring.

Transferring an existing marketed pharmaceutical product from batch to continuous manufacturing (CM) without changes in regulatory registration is a challenging task in the pharmaceutical industry. Continuous manufacturing can provide an increased production rate and better equipment utilisation while retaining key quality attributes of the final product. Continuous manufacturing necessitates the monitoring of critical quality attributes in real time by appropriate process analytical tools such as near infra-red (NIR) probes.

Imiquimod nanocrystal-loaded dissolving microneedles prepared by DLP printing.

The utilization of 3D printing- digital light processing (DLP) technique, for the direct fabrication of microneedles encounters the problem of drug solubility in printing resin, especially if it is predominantly composed of water. The possible solution how to ensure ideal belonging of drug and water-based printing resin is its pre-formulation in nanosuspension such as nanocrystals. This study investigates the feasibility of this approach on a resin containing nanocrystals of imiquimod (IMQ), an active used in (pre)cancerous skin conditions, well known for its problematic solubility and bioavailability.

Light-Responsive Hydrogel Microcrawlers, Powered and Steered with Spatially Homogeneous Illumination.

Sub-millimeter untethered locomoting robots hold promise to radically change multiple areas of human activity such as microfabrication/assembly or health care. To overcome the associated hurdles of such a degree of robot miniaturization, radically new approaches are being adopted, often relying on soft actuating polymeric materials. Here, we present light-driven, crawling microrobots that locomote by a single degree of freedom actuation of their light-responsive tail section.

Inhibition of mevalonate pathway by macrophage-specific delivery of atorvastatin prevents their pro-inflammatory polarisation.

Adjustment of the cellular metabolism of pro-inflammatory macrophages is essential for their bactericidal function; however, it underlies the development of many human diseases if induced chronically. Therefore, intervention of macrophage metabolic polarisation has been recognised as a potent strategy for their treatment. Although many small-molecule inhibitors affecting macrophage metabolism have been identified, their in vivo administration requires a tool for macrophage-specific delivery to limit their potential side effects.

Rapid screening of ternary amorphous formulations by a spray drying robot.

Spray drying is commonly used for producing amorphous solid dispersions to improve drug solubility. The development of such formulations typically relies on comprehensive excipient and composition screening, which requires the preparation of many spray-dried powder samples. This is both labour-intensive and time-consuming when carried out manually.

Magnetic Yeast Glucan Particles for Antibody-Free Separation of Viable Macrophages from .

Currently available methods for cell separation are generally based on fluorescent labeling using either endogenously expressed fluorescent markers or the binding of antibodies or antibody mimetics to surface antigenic epitopes. However, such modification of the target cells represents potential contamination by non-native proteins, which may affect further cell response and be outright undesirable in applications, such as cell expansion for diagnostic or therapeutic applications, including immunotherapy. We present a label- and antibody-free method for separating macrophages from living based on their ability to preferentially phagocytose whole yeast glucan particles (GPs).

Utility of texture analysis for objective quantitative ex vivo assessment of meningioma consistency: method proposal and validation.

Background: Tumor consistency is considered to be a critical factor for the surgical removal of meningiomas and its preoperative assessment is intensively studied. A significant drawback in the research of predictive methods is the lack of a clear shared definition of tumor consistency, with most authors resorting to subjective binary classification labeling the samples as "soft" and "hard." This classification is highly observer-dependent and its discrete nature fails to capture the fine nuances in tumor consistency.

Nanoformulations for dermal delivery of imiquimod: The race of "soft" against "hard".

Imiquimod (IMQ) is an immunostimulating agent used in the treatment of basal cell carcinoma and actinic keratosis. Due to its low solubility and poor skin bioavailability, the dermal formulation of IMQ remains challenging. In analogy to tyre compounds used in Formula 1 racing, we compare four types of nanosystems belonging to three groups: (i) "hard" nanoparticles in the form of IMQ nanocrystals, (ii) "intermediate" nanoparticles in the form of liposomes and lipid nanocapsules, and (iii) "soft" nanoparticles in the form of a nanoemulsion based on oleic acid.

Accelerated reactive dissolution model of drug release from long-acting injectable formulations.

Long-acting injectable formulations represent a rapidly emerging category of drug delivery systems that offer several advantages compared to orally administered medicines. Rather than having to frequently swallow tablets, the medication is administered to the patient by intramuscular or subcutaneous injection of a nanoparticle suspension that forms a local depot from which the drug is steadily released over a period of several weeks or months. The benefits of this approach include improved medication compliance, reduced fluctuations of drug plasma level, or the suppression of gastrointestinal tract irritation.

Azobisisobutyronitrile loaded on mesoporous silica particles: A new stressor for solid-state oxidative forced degradation studies.

A new approach for testing drug sensitivity to autooxidative degradation in the solid state is demonstrated in this work. A novel solid-state form of stressing agent for autooxidation has been proposed, based on azobisisobutyronitrile loaded into mesoporous silica carrier particles. The new solid-state form of the stressing agent was applied in degradation studies of two active pharmaceutical ingredients: bisoprolol and abiraterone acetate.

Computational Prodrug Design Methodology for Liposome Formulability Enhancement of Small-Molecule APIs.

Encapsulation into liposomes is a formulation strategy that can improve efficacy and reduce side effects of active pharmaceutical ingredients (APIs) that exhibit poor biodistribution or pharmacokinetics when administered alone. However, many APIs are unsuitable for liposomal formulations intended for parenteral administration due to their inherent physicochemical properties─lipid bilayer permeability and water-lipid equilibrium partitioning coefficient. Too high permeability results in premature leakage from liposomes, while too low permeability means the API is not able to pass across biological barriers.

Serum and lymph pharmacokinetics of nilotinib delivered by yeast glucan particles per os.

Nilotinib is a selective tyrosine-kinase inhibitor approved for the treatment of chronic myeloid leukemia. It is poorly soluble in aqueous media and has a low oral bioavailability. Nilotinib encapsulation into yeast glucan particles (GPs) was investigated in this work as a means of increasing bioavailability.

Surprising efficacy twist of two established cytostatics revealed by a-la-carte 3D cell spheroid preparation protocol.

Three-dimensional cell culture systems are increasingly used for biological and anticancer drug screening as they mimic the structure and microenvironment of tumors more closely than conventional two-dimensional cell models. In this study, the growth kinetics of colon adenocarcinoma-derived spheroids (HT-29 cell line) cultivated in liquid marble micro-bioreactors and nonadherent PDMS-coated well plates was investigated in detail and enabled precise control of the spheroid size by the seed cell density and cultivation time. The therapeutic effect of 5-fluorouracil and irinotecan hydrochloride in 2D monolayer cell culture and 3D tumor spheroids revealed an unexpected twist in their efficacy due to different ability to penetrate through 3D microtissue.

Pharmaceutical Product Characterization and Manufacturability of Surfactant-Enriched Oil Marbles with Abiraterone Acetate.

The present study investigates the physicochemical properties and stability of a novel lipid-based formulation-surfactant-enriched oil marbles containing abiraterone acetate. While the biopharmaceutical performance of this formulation has been reported recently, this study aims to fill the gap between a promising in vivo performance and industrial applicability. A series of techniques were employed to assess the solid-state characteristics of oil marble cores along with their physicochemical properties upon stability testing.

Surface stabilization determines macrophage uptake, cytotoxicity, and bioactivity of curcumin nanocrystals.

Pharmaceutical nanocrystals represent a promising new formulation that combines the benefits of bulk crystalline materials and colloidal nanoparticles. To be applied in vivo, nanocrystals must meet several criteria, namely colloidal stability in physiological media, non-toxicity to healthy cells, avoidance of macrophage clearance, and bioactivity in the target tissue. In the present work, curcumin, a naturally occurring poorly water-soluble molecule with a broad spectrum of bioactivity has been considered a candidate substance for preparing pharmaceutical nanocrystals.

Model-Based Evaluation of Drying Kinetics and Solvent Diffusion in Pharmaceutical Thin Film Coatings.

Purpose: Fluid-bed coating processes make it possible to manufacture pharmaceutical products with tuneable properties. The choice of polymer type and coating thickness provides control over the drug release characteristics, and multi-layer pellet coatings can combine several active ingredients or achieve tailored drug release profiles. However, the fluid-bed coating is a parametrically sensitive process due to the simultaneous occurrence of polymer solution spraying and solvent evaporation.

Antibiotic depot system with radiofrequency controlled drug release.

Drug depot systems have traditionally relied on the spontaneous dissolution and diffusion of drugs or prodrugs from a reservoir with constant exposure to the surrounding physiological fluids. While this is appropriate for clinical scenarios that require constant plasma concentration of the drug over time, there are also situations where multiple bursts of the drug at well-defined time intervals are preferred. This work presents a drug depot system that enables repeated on-demand release of antibiotics in precise doses, controlled by an external radiofrequency magnetic field.

Multilobed Magnetic Liposomes Enable Remotely Controlled Collection, Transport, and Delivery of Membrane-Soluble Cargos to Vesicles and Cells.

Lipid bilayers are the basic structural components of all living systems, forming the membranes of cells, sub-cellular organelles, and extracellular vesicles. A class of man-made lipidic vesicles called multilobed magnetic liposomes (MMLs) is reported in this work; these MMLs possess a previously unattained combination of features owing to their unique multilobe structure and composition. MMLs consist of a central cluster of lipid-coated magnetic iron oxide nanoparticles that lend them a magnetophoretic velocity comparable to the most efficient living microswimmers.

Evaluation of β-glucan particles as dual-function carriers for poorly soluble drugs.

Yeast glucan particles are porous polysaccharide cell walls extracted from Saccharomyces cerevisiae. Being mildly immunogenic, they are efficiently phagocytosed and have therefore been proposed as possible vehicles for drug delivery. Using curcumin as a model poorly water-soluble drug, a systematic comparison of three different physical loading methods - incipient wetness impregnation, slurry evaporation, and spray drying - was carried out and their influence on the particle morphology, encapsulation efficiency, amorphous drug content and release kinetics was evaluated.

Drug loading to mesoporous silica carriers by solvent evaporation: A comparative study of amorphization capacity and release kinetics.

The sorption of poorly aqueous soluble active pharmaceutical ingredients (API) to mesoporous silica carriers is an increasingly common formulation strategy for dissolution rate enhancement for this challenging group of substances. However, the success of this approach for a particular API depends on an array of factors including the properties of the porous carrier, the loading method, or the attempted mass fraction of the API. At present, there is no established methodology for the rational selection of these parameters.

Validity of cycloheximide chylomicron flow blocking method for the evaluation of lymphatic transport of drugs.

Background And Purpose: Lymphatic transport of drugs after oral administration is an important mechanism for absorption of highly lipophilic compounds. Direct measurement in lymph duct cannulated animals is the gold standard method, but non-invasive cycloheximide chylomicron flow blocking method has gained popularity recently. However, concerns about its reliability have been raised.

Friction-directed self-assembly of Janus lithographic microgels into anisotropic 2D structures.

We present a method for creating ordered 2D structures with material anisotropy from self-assembling micro-sized hydrogel particles (microgels). Microgel platelets of polygonal shapes (hexagon, square, and rhombus), obtained by a continuous scalable lithographic process, are suspended in an aqueous environment and sediment on an inclined plane. As a consequence of gravitational pull, they slide over the plane.