Six years of progress in the oral biopharmaceutics area - a summary from the IMI OrBiTo project.
rnäs H Abstract OrBiTo was a precompetitive collaboration focused on the development of the next generation of Oral Biopharmaceutics Tools. The consortium included world leading scientists from nine universities, one regulatory agency, one non-profit research organisation, three small/medium sized specialist technology companies together with thirteen pharmaceutical companies. The goal of the OrBiTo project was to deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This goal was achieved through novel prospective investigations to define new methodologies ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 21, 2020 Category: Drugs & Pharmacology Authors: Abrahamsson B, McAllister M, Augustijns P, Zane P, Butler J, Holm R, Langguth P, Lindahl A, Müllertz A, Pepin X, Rostami-Hodjegan A, Sjögren E, Berntsson M, Lennernäs H Tags: Eur J Pharm Biopharm Source Type: research

Inhalable Formulations of Rifampicin by Spray Drying of Supersaturated Aqueous Solutions.
Abstract Tuberculosis is still one of the leading causes of death from a single infectious agent (i.e. Mycobacterium tuberculosis). First line therapy includes per oral administration of high doses of rifampicin over several months and is often times accompanied by the occurrence of unwanted side effects that might limit the patient's adherence to the therapy. Thus, local antibiotic treatment at the site of infection i.e. the lungs is desirable. Amongst other approaches, spray drying of solutions of rifampicin has been shown as suitable method to produce respirable dry powders. In this work, we present inhalable f...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 21, 2020 Category: Drugs & Pharmacology Authors: Berkenfeld K, McConville JT, Lamprecht A Tags: Eur J Pharm Biopharm Source Type: research

Exploration of temperature and shelf-life dependency of the therapeutically available Insulin Detemir.
CONCLUSIONS: These findings are critical to our understanding of the behaviour of this particular clinically relevant drug, as it will allow the development of future generations of peptide-based therapies with greater clinical efficacy. PMID: 32446962 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 21, 2020 Category: Drugs & Pharmacology Authors: Beji O, Gillis RB, Dinu V, Jiwani SI, Gyasi-Antwi P, Fisk ID, Meal A, Morgan PS, Harding SE, Huang S, Agugini G, Fedele F, Adams GG Tags: Eur J Pharm Biopharm Source Type: research

Preclinical challenges for developing long acting intravitreal medicines.
Abstract The majority of blinding conditions arise due to chronic pathologies in the retina. During the last two decades, antibody-based medicines administered by intravitreal injection directly into the back of the eye have revolutionised the treatment of chronic retinal diseases characterised by uncontrolled blood vessel growth, e.g. wet age-related macular degeneration (wAMD), diabetic retinopathy (DR) and choroidal neovascularisation. Although intravitreal injections have become a commonly performed ophthalmic procedure that provides a reproducible dose to maximise drug exposure in the back of the eye, there i...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 20, 2020 Category: Drugs & Pharmacology Authors: Awwad S, Henein C, Ibeanu N, Khaw PT, Brocchini S Tags: Eur J Pharm Biopharm Source Type: research

Influence of the Porosity of Cushioning Excipients on the Compaction of Coated Multi-Particulates.
This study was designed to investigate the impact of porous pellets as cushioning agent without issues related to segregation while tableting. Different drying techniques were applied to produce microcrystalline cellulose (MCC) pellets with various porosities. Sodium chloride was also added to the pellet formulation as a pore forming agent to generate a porous skeleton after production and aqueous extraction. The pellets fabricated were characterized for their porosity, crushing strength and yield pressure. Tablets were prepared using unlubricated pellets and their tensile strengths determined. Blends containing polymer-co...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 20, 2020 Category: Drugs & Pharmacology Authors: Elsergany RN, Wah Chan L, Wan Sia Heng P Tags: Eur J Pharm Biopharm Source Type: research

Real-time monitoring of multi-layered film coating processes using Raman spectroscopy.
Abstract Raman spectroscopy was used as an in-line PAT tool to predict the applied coating mass of three different coating layers on caffeine cores. The different coating suspensions contained titanium dioxide in the anatase and rutile modification and iron oxide as Raman markers. Partial least squares-regression (PLSR) and multivariate curve resolution-alternating least squares (MCR-ALS) were used for multivariate analysis. The acquired Raman spectra were correlated to the applied coating mass. MCR-ALS models were built and applied offline, while PLS-regression was implemented in the coating process to enable a r...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 20, 2020 Category: Drugs & Pharmacology Authors: Radtke J, Kleinebudde P Tags: Eur J Pharm Biopharm Source Type: research

Controlled Polysorbate 20 Hydrolysis - A new Approach to Assess the Impact of Polysorbate 20 Degradation on Biopharmaceutical Product Quality in Shortened Time.
Abstract Hydrolysis of polysorbate in biopharmaceutical liquid formulations upon long-term storage represents a risk factor, since reduction of the intact surfactant concentration may compromise protein stability. Moreover, accumulation of polysorbate degradation products is associated with the formation of particulates potentially affecting drug product stability and quality. These effects are conventionally assessed by real-time end-of-shelf life studies constituting an integral yet lengthy process of formulation development. To accelerate this procedure, we describe here a powerful tool to conduct shake stress ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 20, 2020 Category: Drugs & Pharmacology Authors: Graf T, Abstiens K, Wedekind F, Elger C, Markus H, Wurth C, Leiss M Tags: Eur J Pharm Biopharm Source Type: research

Artificial neural networks applied to quality-by-design: From formulation development to clinical outcome.
In this study, the application of Artificial Neural Networks (ANNs) in the QbD-based development of a test drug product is presented, where material specifications are defined and correlated with its performance in vivo. Along with other process parameters, drug particle size distribution (PSD) was identified as a critical material attribute and a three-tier specification was needed. An ANN was built with only five hidden nodes in one hidden layer, using hyperbolic tangent functions, and was validated using a random holdback of 33% of the dataset. The model led to significant and valid prediction formulas for the three res...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 19, 2020 Category: Drugs & Pharmacology Authors: Simões MF, Silva G, Pinto AC, Fonseca M, Silva NE, Pinto RMA, Simões S Tags: Eur J Pharm Biopharm Source Type: research

Design and development of a novel fused filament fabrication (FFF) 3D printed diffusion cell with UV imaging capabilities to characterise permeation in pharmaceutical formulations.
Abstract The present work aimed at designing and developing a novel 3D printed diffusion cell capable of UV imaging using the fused filament fabrication (FFF) method. UV imaging has proven to be very versatile in the area of pharmaceutics giving insights into various phenomena including the dissolution behaviour of dosage forms, intrinsic dissolution rates and the drug precipitation processes. A 3D printed diffusion cell in similitude of a Franz cell was successful printed using polylactic acid (PLA) filaments equipped with quartz for the imaging area. A model ibuprofen (IBU) gel formulation was tested by introduc...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 19, 2020 Category: Drugs & Pharmacology Authors: Fazili Z, Ward A, Walton K, Blunt L, Asare-Addo K Tags: Eur J Pharm Biopharm Source Type: research

In vivo Efficacy of a Dry Powder Formulation of Ciprofloxacin-Copper Complex in a Chronic Lung Infection Model of Bioluminescent Pseudomonas aeruginosa.
This study aimed to evaluate the in vivo efficacy of CIP-Cu, prepared as a dry powder, in a chronic lung infection model. The powders were prepared by jet milling (CIP-HCl) and by spray drying (CIP-Cu). A bioluminescent strain of P. aeruginosa (PAO1::p16Slux) was used to prepare bacteria-loaded agar beads that were inoculated intratracheally to rats. The dynamics of the infection were monitored using luminometry. The bacteria/beads ratio was optimized to allow the highest luminescence signal and animal survival for 8 days. The efficacy of the treatment was evaluated by luminometry in addition to the end-point (Day 8) where...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 19, 2020 Category: Drugs & Pharmacology Authors: Tewes F, Bahamondez-Canas TF, Moraga-Espinoza D, Smyth HDC, Watts AB Tags: Eur J Pharm Biopharm Source Type: research

In vitro and in vivo evaluation of organic solvent-free injectable melatonin nanoformulations.
In conclusion, we have developed an organic solvent-free injectable formulation for melatonin by utilizing FDA-approved components, as a safe alternative for facilitating the potential of melatonin against variety of pathological conditions. PMID: 32439308 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 18, 2020 Category: Drugs & Pharmacology Authors: Molska A, Nyman AKG, Sofias AM, Kristiansen KA, Hak S, Widerøe M Tags: Eur J Pharm Biopharm Source Type: research

Fatty acid chain length impacts nanonizing capacity of albumin-fatty acid nanomicelles: Enhanced physicochemical property and cellular delivery of poorly water-soluble drug.
This study aimed to design the ideal nanonizing vehicle for poorly water-soluble model curcumin (CCM) using fattigation-platform nanotechnology, and to investigate the effects of fatty acid salts chain length on nanonizing CCM and its efficient delivery to different cancer cells. HSA-fatty acid conjugates were synthesized by EDC/NHS coupling. Fattigation-platform nanomicelles (NMs), prepared by film hydration, exhibited uniform and spherical morphology, although, each NM varied in particle size, zeta potential, and critical micelle concentration according to the types of fatty acid. Preliminary solubility studies of albumi...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 15, 2020 Category: Drugs & Pharmacology Authors: Park C, Meghani N, Loebenberg R, Cui JH, Cao QR, Lee BJ Tags: Eur J Pharm Biopharm Source Type: research

Investigation of cannabidiol gastro retentive tablets based on regional absorption of cannabinoids in rats.
Abstract The cannabis plant has been widely researched for many therapeutic indications and found to be effective in many chronic conditions such as epilepsy, neuropathic or chronic pain and more. However, biased opinion against compounds of the plant, regulatory as well as compounding challenges have led to very few approved medicinal products. Those formulations which are approved are dosed several times a day, creating an unmet need for controlled release (CR) formulations of cannabinoids. Conventional CR formulations rely on prolonged absorption including the colon. The purpose of this work is to investigate r...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 15, 2020 Category: Drugs & Pharmacology Authors: Izgelov D, Freidman M, Hoffman A Tags: Eur J Pharm Biopharm Source Type: research

The immunogenicity of an anti-EGFR single domain antibody (VHH) is enhanced by misfolded amorphous aggregation but not by heat-aggregation.
Abstract Amorphous aggregates of therapeutic proteins can provoke an unwanted immune response (anti-drug antibodies; ADAs), but counter-examples have led to some controversy. Amorphous aggregates can possess unique biophysical and biochemical attributes depending on both the way they are generated and the protein's biophysical/biochemical properties. Here, we examine the immunogenicity of an anti-EGFR single domain antibody (VHH) in four types of amorphous aggregates: two heat-aggregated VHH incubated at 65 °C (VHH-65) and 95 °C (VHH-95), a misfolded VHH isolated from the insoluble fraction of the E. coli ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 13, 2020 Category: Drugs & Pharmacology Authors: Kibria MG, Akazawa-Ogawa Y, Rahman N, Hagihara Y, Kuroda Y Tags: Eur J Pharm Biopharm Source Type: research

Modulation of protein release from penta-block copolymer microspheres.
This study highlighted the potential of this penta-block polymer where the PEO block mass ratio influence clearly the Tg and consequently the microsphere structure and the release behavior at 37°C. The (1:1) mixture was a starting point but could be finely tuned to control the protein release. PMID: 32416135 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 13, 2020 Category: Drugs & Pharmacology Authors: Le MQ, Gimel JC, Garric X, Nguyen-Pham TQ, Paniagua C, Riou J, Venier-Julienne MC Tags: Eur J Pharm Biopharm Source Type: research

Nose-to-brain drug delivery system with ligand/cell-penetrating peptide-modified polymeric nano-micelles for intracerebral gliomas.
In this study, to develop tumor-selective novel polymeric micelles, mixed micelles consisting of Tat-conjugated polymer micelles and stearoyl-modified bombesin (Bom/PEG-PCL-Tat) were designed. The GRPR selectivity, cellular uptake, and cytotoxicity in C6 glioma cells as well as the intracerebral drug distribution and therapeutic efficacy of Bom/PEG-PCL-Tat mixed micelles after intranasal administration in C6 glioma orthotropic grafted rats were evaluated. Selective cellular uptake and marked cytotoxic effects against GRPR-expressing C6 glioma cells were observed, as well as C6 tumor tissue-specific accumulation in vivo. Ra...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 5, 2020 Category: Drugs & Pharmacology Authors: Kanazawa T, Taki H, Okada H Tags: Eur J Pharm Biopharm Source Type: research

A head-to-head Caco-2 assay comparison of the mechanisms of action of the intestinal permeation enhancers: SNAC and sodium caprate (C10).
In conclusion, FD4 permeability increases in monolayers in response to C10 were in the range of concentrations that altered end-point cytotoxicity and HCA parameters. For SNAC, while HCA parameters were also altered in a similar overall pattern as C10, they did not lead to increased paracellular flux. These assays show that both agents are primarily surfactants, but C10 has additional TJ-opening effects. While these in vitro assays illucidate their epithelial mechanism of action, clinical experience suggests that they over-estimate their toxicology in the dynamic intestinal environment. PMID: 32387703 [PubMed - as sup...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 5, 2020 Category: Drugs & Pharmacology Authors: Twarog C, Liu K, O'Brien PJ, Dawson KA, Fattal E, Illel B, Brayden DJ Tags: Eur J Pharm Biopharm Source Type: research

Novel Approach for Overcoming the Stability Challenges of Lipid-Based Excipients. Part 3: Application of Polyglycerol Esters of Fatty Acids for the next generation of solid lipid nanoparticles.
Abstract Solid lipid nanoparticles (SLN) are an advantageous carrier system for the delivery of lipophilic active pharmaceutical ingredients (APIs). The use of SLN has been limited due to stability issues attributed to the unstable solid state of the lipid matrix. A novel approach for overcoming this problem is the application of polyglycerol ester of fatty acids (PGFAs) as lipid matrices with stable solid state. PG2-C18 full, a PGFA molecule, was used to develop SLN loaded with dexamethasone as a model API. Dexamethasone-loaded SLN were manufactured via melt-emulsification and high pressure homogenization in the ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 5, 2020 Category: Drugs & Pharmacology Authors: Corzo C, Meindl C, Lochmann D, Reyer S, Salar-Behzadi S Tags: Eur J Pharm Biopharm Source Type: research

Scintigraphic evaluation of the in vivo performance of dry-coated delayed-release tablets in humans.
Abstract We characterized the gastrointestinal (GI) transit and drug release characteristics of dry-coated delayed-release tablets under both prandial states in humans using a gamma scintigraphy approach. We also estimated the onset time of drug release from the dry-coated tablets after dissolution of the outer layer in a clinical study, and compared findings with those of in vitro release testing. The dry-coated tablets used in this study were composed of a core containing radiolabeled resin (111-Indium) and a gel forming outer layer made of polyethylene oxide and polyethylene glycol. The dry-coated tablets were ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 4, 2020 Category: Drugs & Pharmacology Authors: Kambayashi A, Sako K, Kondo H Tags: Eur J Pharm Biopharm Source Type: research

Lipid-encapsulated oral therapeutic peptide vaccines reduce tumour growth in an orthotopic mouse model of colorectal cancer.
Abstract The aim of this study was to develop an oral vaccine that could be used to treat colorectal cancer. Oral vaccines are technically challenging to develop due to the harsh gastric environment but have numerous benefits including high patient acceptability and the potential to stimulate local mucosal immune responses. Therapeutic vaccines are being investigated as options to treat cancer and the generation of local mucosal immunity may be of benefit in the treatment of gastrointestinal cancers. Novel oral vaccines consisting of a long tumour peptide and the TLR2 (Toll-like receptor 2) ligand Pam2Cys, formula...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 4, 2020 Category: Drugs & Pharmacology Authors: Naciute M, Niemi V, Kemp RA, Hook S Tags: Eur J Pharm Biopharm Source Type: research

Spray drying of API nanosuspensions: Importance of drying temperature, type and content of matrix former and particle size for successful formulation and process development.
Abstract Active pharmaceutical ingredient (API) nanosuspensions from naproxen (Nap) and itraconazole (Itra) stabilized with Kollidon®VA64 (KVA) and sodium dodecyl sulfate (SDS) were produced in two different size classes each by wet media milling. These API nanosuspensions were spray dried with lactose, trehalose and sucrose as matrix formers in different proportions and at different drying temperatures (Toutlet). Toutlet as well as the API content significantly influenced the redispersibility of the API nanoparticles. It could be shown that these two parameters are related to each other, with an increasing AP...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 3, 2020 Category: Drugs & Pharmacology Authors: Czyz S, Wewers M, Henrik Finke J, Kwade A, van Eerdenbrugh B, Juhnke M, Bunjes H Tags: Eur J Pharm Biopharm Source Type: research

Lipid-mimicking peptide decorates erythrocyte membrane for active delivery to engrafted MDA-MB-231 breast tumour.
This study reports a new method for liposome decoration as an alternative to chemical conjugation. PMID: 32376370 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 3, 2020 Category: Drugs & Pharmacology Authors: Fan X, Xu H, Zhao F, Song J, Jin Y, Zhang C, Wu G Tags: Eur J Pharm Biopharm Source Type: research

Comparison of induction methods for supersaturation: amorphous dissolution versus solvent shift.
This study develops and compares a small-scale non-sink amorphous dissolution method to a solvent shift method as induction methods for supersaturation of the model drugs albendazole, felodipine and tadalafil with respect to the maximum dissolved drug concentration, and the solid form of the precipitate. The study also investigates the effect of pre-dispersed precipitation inhibitors (hydroxypropyl methyl cellulose (HPMC) or polyvinylpyrrolidone (PVP)) on tadalafil supersaturation induced by both amorphous dissolution and solvent shift with respect to maximum dissolved drug concentration, precipitation rate and solid form ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 3, 2020 Category: Drugs & Pharmacology Authors: Plum J, Bavnhøj CG, Eliasen JN, Rades T, Müllertz A Tags: Eur J Pharm Biopharm Source Type: research

Pegfilgrastim (PEG-G-CSF) induces anti-PEG IgM in a dose dependent manner and causes the accelerated blood clearance (ABC) phenomenon upon repeated administration in mice.
Abstract Pegfilgrastimis a recombinant PEGylated human granulocyte colony-stimulating factor (G-CSF) analog filgrastim (trade names Neulasta® or G-Lasta®) that stimulates the production of white blood cells (neutrophils). It is employed as an alternative to filgrastim (G-CSF) for chemotherapy-induced neutropenia in patients due to its longer half-life. In clinical settings, PEG-G-CSF is administered to cancer patients via both the s.c. and i.v. routes. In a murine study, we showed that, regardless of administration route, initial doses of PEG-G-CSF above 0.06 mg/kg elicited anti-PEG immune response in a do...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 3, 2020 Category: Drugs & Pharmacology Authors: Elsadek NE, Lila ASA, Emam SE, Shimizu T, Takata H, Ando H, Ishima Y, Ishida T Tags: Eur J Pharm Biopharm Source Type: research

Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery.
h A Abstract The lipophilic character of peptides can be tremendously improved by hydrophobic ion pairing (HIP) with counterions to be efficiently incorporated into lipid-based nanocarriers (NCs). Herein, HIPs of exenatide with the cationic surfactant tetraheptylammonium bromide (THA) and the anionic surfactant sodium docusate (DOC) were formed to increase its lipophilicity. These HIPs were incorporated into lipid based NCs comprising 41% Capmul MCM, 15% Captex 355, 40% Cremophor RH and 4% propylene glycol. Exenatide-THA NCs showed a log D lipophilic phase (LPh)/release medium (RM) of 2.29 and 1.92, whereas the lo...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 1, 2020 Category: Drugs & Pharmacology Authors: Ismail R, Nhu Quynh Phan T, Laffleur F, Csoka I, Bernkop-Schnürch A Tags: Eur J Pharm Biopharm Source Type: research

A Physiologically-based Drug Absorption Modeling for Orally Disintegrating Tablets.
Abstract The aim of this research was to simulate oral pharmacokinetic (PK) profiles of atorvastatin from orally disintegrating tablets (ODTs) dosed without water ingestion in fasted humans. The in vitro dissolution profiles of three different formulations of ODTs were evaluated with fasted state biorelevant media using a paddle dissolution apparatus, and the results were coupled with an in silico model to simulate the in vivo oral PK profiles of ODTs following administration to humans. Since the dissolution rates of the ODTs in the intestinal medium (FaSSIF-V2) were highly affected by pre-exposure of the tablets ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 1, 2020 Category: Drugs & Pharmacology Authors: Kambayashi A, Kiyota T Tags: Eur J Pharm Biopharm Source Type: research

Tracking the physical stability of fluorescent-labeled mAbs under physiologic invitro conditions in human serum and PBS.
Abstract In recent years, the stability of biotherapeutics in vivo has received increasing attention. Assessing the stability of biotherapeutics in serum may support the selection of adequate molecule candidates. In our study, we compared the physical stability of 8 different monoclonal antibodies (mAbs) in phosphate-buffered saline (PBS) and human serum. mAbs were Alexa Fluor 488-labeled and characterized with respect to fragmentation, aggregation, and proteinaceous particle formation. Samples were analyzed using size-exclusion chromatography, light obscuration, and flow imaging. In addition, novel methods such a...
Source: European Journal of Pharmaceutics and Biopharmaceutics - May 1, 2020 Category: Drugs & Pharmacology Authors: Schuster J, Mahler HC, Koulov A, Joerg S, Racher A, Huwyler J, Detampel P, Mathaes R Tags: Eur J Pharm Biopharm Source Type: research

Inhaled aerosol dose distribution between proximal bronchi and lung periphery.
Abstract Modern inhaled drug discovery programs assess dose delivery to proximal and distal airways using rudimentary imaging indices, where relative deposition is estimated by generically defined 'central' and 'peripheral' lung regions. Utilizing recent data linking the proximal airway topology to a characteristic pattern of aerosol lung deposition, we provide a direct measure of dose distribution between the proximal bronchi and the distal lung. We analyzed scintigraphic lung images of twelve asthma patients following inhalation of 1.5-, 3- and 6-µm monodisperse drug particles at breathing flows of 30- and...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 30, 2020 Category: Drugs & Pharmacology Authors: Verbanck S, Biddiscombe MF, Usmani OS Tags: Eur J Pharm Biopharm Source Type: research

Determination of ice interface temperature, sublimation rate and the dried product resistance, and its application in the assessment of microcollapse using through-vial impedance spectroscopy.
In this study, a pair of copper foil electrodes was attached to the external surface of a Type I glass tubing vial, of nominal capacity 10 mL and containing 3.5 g of an aqueous solution of 5%w/v lactose, and the impedance spectrum of the vial and contents recorded during a lyophilization cycle. The cycle included a temperature ramp in the primary drying stage in order to induce a collapse event in the dry layer. Using the peak in the dielectric loss spectrum, associated with the dielectric relaxation of ice, methods were developed to predict the sublimation rate and the ice interface temperature at the sublimation front,...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 27, 2020 Category: Drugs & Pharmacology Authors: Jeeraruangrattana Y, Smith G, Polygalov E, Ermolina I Tags: Eur J Pharm Biopharm Source Type: research

Acceptability of an Orodispersible Film Compared to Syrup in Neonates and Infants: A Randomized Controlled Trial.
e H Abstract OBJECTIVES: Reliable pediatric pharmacotherapy in all age groups requires the availability of age-appropriate drug administration. Orodispersible films (ODF) are a promising pediatric oral dosage form. ODFs would meet relevant targets: one dosage form matching the full range of pediatric patients, a minimum of non-toxic excipients, a stable drug formulation easily to be produced. However, there is a lack of reliable data on ODFś acceptability, swallowability and palatability, especially in young children. The primary objective was to demonstrate non-inferiority in acceptability of a drug-free ODF in ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 26, 2020 Category: Drugs & Pharmacology Authors: Klingmann V, Emanuel Pohly C, Meissner T, Mayatepek E, Möltner A, Flunkert K, Breitkreutz J, Martin Bosse H Tags: Eur J Pharm Biopharm Source Type: research

Xylan in drug delivery: A review of its engineered structures and biomedical applications.
ira E Abstract Xylan, an abundant biopolymer mainly extracted from plants and algae, is commonly studied for textile, food and biomedical applications. In this review, different approaches to obtain xylan-based products for drug delivery purposes were described. Investigations about xylan-based films, micro- and nanostructure, with the ability or not to swell (hydrogels), developed for biomedical applications, were summarized. Furthermore, a section on colon drug delivery and the methods that have been developed for the evaluation of these systems were presented. PMID: 32339636 [PubMed - as supplied by publis...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 24, 2020 Category: Drugs & Pharmacology Authors: Cartaxo da Costa Urtiga S, Rodrigues Marcelino H, Sócrates Tabosa do Egito E, Eleamen Oliveira E Tags: Eur J Pharm Biopharm Source Type: research

Self-dispersing formulations for the delivery of poorly soluble drugs - miscibility of phosphatidylcholines with oils and fats.
s H Abstract The presented study aimed to develop self-dispersing drug delivery systems based on natural phospholipids. A comprehensive investigation on miscibility was therefore carried out on mixtures containing one or two phosphatidylcholines as emulsifying excipients, ethanol 96% as co-solvent and different oils and fats. The soybean diacyl phosphatidylcholines Phospholipon90G and LipoidS75 as well as the monoacyl phosphatidylcholine LipoidSLPC80 were investigated for their maximum incorporation in the different lipids. Homogeneity and stability of the mixtures were determined according to their macroscopic ap...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 24, 2020 Category: Drugs & Pharmacology Authors: Grüne L, Bunjes H Tags: Eur J Pharm Biopharm Source Type: research

Lipid-polymer hybrid nanoparticles carrying linezolid improve treatment of methicillin-resistant Staphylococcus aureus (MRSA) harbored inside bone cells and biofilms.
In this study, we developed a lipid-polymer hybrid nanoparticle loading the antibiotic linezolid (LIN-LPN), and focused on evaluating if this new nanoantibiotic can achieve significant in vitro activities against these intracellular and biofilm-embedded MRSA. The optimal LIN-LPN formulation demonstrated both high linezolid payload (12.0% by weight of nanoparticles) and controlled release characteristics (gradually released the entrapped antibiotic in 120 h). Although it achieved lower activities against bacteria including USA300-0114, CDC-587, RP-62A in planktonic form, it was substantially superior against the intracellul...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 23, 2020 Category: Drugs & Pharmacology Authors: Guo P, Buttaro BA, Xue HY, Tran NT, Wong HL Tags: Eur J Pharm Biopharm Source Type: research

High Frequency Acoustic Nebulization for Pulmonary Delivery of Antibiotic Alternatives Against Staphylococcus aureus.
Abstract The increasing prevalence of multidrug resistant bacteria has warranted the search for new antimicrobial agents as existing antibiotics lose their potency. Among these, bacteriophage therapy, as well as the administration of specific bacteriolysis agents, i.e., lytic enzymes, have emerged as attractive alternatives. Nebulizers offer the possibility for delivering these therapeutics directly to the lung, which is particularly advantageous as a non-invasive and direct route to treat bacterial lung infections. Nevertheless, nebulizers can often result in significant degradation of the bacteriophage or protei...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 18, 2020 Category: Drugs & Pharmacology Authors: Marqus S, Lee L, Istivan T, Kyung Chang RY, Dekiwadia C, Chan HK, Yeo LY Tags: Eur J Pharm Biopharm Source Type: research

Potential drug delivery nanosystems for improving tumor penetration.
Abstract Nanosystems, as one of the most important drug delivery systems, play a crucial rule in tumor therapy. However, the deep tumor penetration is retarded by the tumor physiological factors and nanomedicine properties. In this review, we firstly elaborate the factors which impact tumor penetration, including the tumor physiological factors and nanomedicine properties. Then, the latest and potential drug delivery nanosystems for improving tumor penetration are summarized and analyzed in detail. Moreover, recent combination therapies for improving penetration are described to enhance penetration. Finally, we su...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 17, 2020 Category: Drugs & Pharmacology Authors: Peng F, Li R, Zhang F, Qin L, Ling G, Zhang P Tags: Eur J Pharm Biopharm Source Type: research

Biogenic silver nanoparticles: in vitro and in vivo antitumor activity in bladder cancer.
Bispo de Jesus M Abstract ladder cancer is the fifth most common disease in the United States, and the treatment and alternatives for patients have not changed in the last decades. Silver nanoparticles (AgNP) have been used in the treatment of various cancer, mainly because of the antineoplastic activity; however, their use and the molecular mechanisms towards bladder cancer still unexplored. Therefore, this work aims to evaluate in vitro and in vivo the antitumoral mechanisms of biogenic silver nanoparticles synthesized from Fusarium sp. First, AgNP showed cytotoxicity in a dose- and time-response relationship, ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 17, 2020 Category: Drugs & Pharmacology Authors: Alberto Bandeira Ferreira L, Garcia-Fossa F, Radaic A, Durán N, José Fávaro W, Bispo de Jesus M Tags: Eur J Pharm Biopharm Source Type: research

A Semi-Theoretical Model for Simulating the Temporal Evolution of Moisture-Temperature During Industrial Fluidized Bed Granulation.
This study has demonstrated the capabilities of simple process models as a practical approach to predict time-wise evolution of bed moisture-temperature profiles in industrial FBG modeling, while also pointing out their limitations. PMID: 32304867 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 15, 2020 Category: Drugs & Pharmacology Authors: Amini H, He X, Tseng YC, Kucuk G, Schwabe R, Schultz L, Maus M, Schröder D, Rajniak P, Bilgili E Tags: Eur J Pharm Biopharm Source Type: research

A study on the impact of HPMC viscosity grade and proportion on the functional properties of co-freeze-dried mannitol-HPMC cushioning excipients for compacted MUPS.
This study was designed to systematically investigate the impact of 3 factors, hydroxylpropyl methyl cellulose (HPMC) viscosity grade, mannitol to HPMC ratio and particle size fraction on the functional properties of freeze-dried (FD) mannitol-HPMC cushioning excipients produced for multi-unit pellet system tableting. Based on the results, the investigated formulation variables were significant in determining the functional properties of the FD-mannitol-HPMC cushioning excipients. Among the formulations, FD-mannitol-HPMC F4M (3:1 ratio) excipients exhibited the best cushioning performance. It was postulated that the protec...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 14, 2020 Category: Drugs & Pharmacology Authors: Ru Shan Siow C, Wan Sia Heng P, Wah Chan L Tags: Eur J Pharm Biopharm Source Type: research

Gastro-protective protein-silica nanoparticles formulation for oral drug delivery: in vitro release, cytotoxicity and mitochondrial activity.
itz F Abstract Our contribution aims to provide an efficient solution to one of the major challenges of oral delivery of gastro-sensitive drugs, namely preventing their premature release and degradation in the gastric fluid in order to maximize the absorption in the small intestine. Our results show that a pH-responsive protein, i.e., succinylated β-lactoglobulin (BL), together with the key attributes of mesoporous silica nanoparticles (MSNs), can synergetically reduce the release of the gastro-sensitive drug, omeprazole (OMP), in acidic pH and enhance the dissolution in intestinal pH conditions. Two families...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 14, 2020 Category: Drugs & Pharmacology Authors: Juère E, Del Favero G, Masse F, Marko D, Popat A, Florek J, Caillard R, Kleitz F Tags: Eur J Pharm Biopharm Source Type: research

Establishment of a clinically relevant specification for dissolution testing using physiologically based pharmacokinetic (PBPK) modeling approaches.
In conclusion, a CRS was established with the BE simulation by using the verified PBPK model, in order to detect and reject non-BE batches of drug products. The establishment of the CRS is useful for a quality control and finding optimal formulation to accomplish target PK behavior, safety, and efficacy. PMID: 32298756 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 13, 2020 Category: Drugs & Pharmacology Authors: Kato T, Nakagawa H, Mikkaichi T, Miyano T, Ando S, Matsumoto Y Tags: Eur J Pharm Biopharm Source Type: research

Preclinical evaluation of new formulation concepts for abiraterone acetate bioavailability enhancement based on the inhibition of pH-induced precipitation.
; Canová N, Šíma M, Slanař O, Štěpánek F Abstract Abiraterone acetate is a potent drug used for the treatment of metastatic castration resistant prostate cancer. However, currently marketed product containing crystalline abiraterone acetate exhibits strong positive food effect which results in strict dosing regimen. In the present work, a rational approach towards design of novel abiraterone acetate formulations that would allow increased bioavailability on a fasting stomach and thus decreased food effect is presented. Precipitation experiments in biorelevant media were designe...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 13, 2020 Category: Drugs & Pharmacology Authors: Boleslavská T, Světlík S, Žvátora P, Bosák J, Dammer O, Beránek J, Kozlík P, Křížek T, Kutinová Canová N, Šíma M, Slanař O, Štěpánek F Tags: Eur J Pharm Biopharm Source Type: research

Effect of supersaturation on absorption of indomethacin and tadalafil in a single pass intestinal perfusion rat model, in the absence and presence of a precipitation inhibitor.
z A Abstract The effect of the degree of supersaturation (DS) on absorption of the model drugs indomethacin and tadalafil was elucidated in a single-pass intestinal perfusion (SPIP) model in rats. In addition, the performance of the precipitation inhibitor (PI) hydroxypropylmethylcellulose (HPMC) was evaluated when added at a concentration of 0.1% (w/v) to fasted state simulated intestinal fluid (FaSSIF and FaSSIFHPMC) used as perfusion medium. A supersaturated state was created by a solvent shift method where indomethacin or tadalafil dissolved in dimethyl sulfoxide (DMSO) were administered to a segment of the sm...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 13, 2020 Category: Drugs & Pharmacology Authors: Strindberg S, Plum J, Bay Stie M, Lau Christiansen M, Hagner Nielsen L, Rades T, Müllertz A Tags: Eur J Pharm Biopharm Source Type: research

European Paediatric Formulation Initiative Workshop Report: Improving the Administration of Oral Liquid Medicines in Paediatrics using Dosing Syringes and Enteral Accessories.
Abstract Accurate dosing of the right medicine to the right patient is a key element of safe and efficacious pharmacotherapy, yet prone to technical challenges and human error when dosing involves the administration of small volumes of liquid medicines. For this reason, the topic has gained increased attention over the last decade from multiple stakeholder parties e.g. academia, hospital pharmacy, the medical device and pharmaceutical industry, and regulatory agencies. It is now well acknowledged that spoons and cups are not suitable for the measurement of small volumes of oral liquid medicines and that syringes a...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 11, 2020 Category: Drugs & Pharmacology Authors: Walsh J, van Riet-Nales D, Hermans E, de Vries R, Hilton G, Blowers P, Salunke S Tags: Eur J Pharm Biopharm Source Type: research

Hydrophobic ion pairing (HIP) of (poly)peptide drugs: Benefits and drawbacks of different preparation methods.
In this study, different HIP methods were compared with each other. Hydrophobic complexes were formed between bovine serum albumin (BSA) and either dodecyl sulfate, cetyl trimethylammonium or 1,2-dipalmitoyl-sn-glycero-3-phosphate applying the organic solvent-free method, Bligh-Dyer method and biphasic metathesis reaction either with ethyl acetate or chloroform as organic phase. Complex formation efficiency was determined. Hydrophobicity of the obtained complexes was characterized by their apparent partition coefficient between 1-butanol and water. The highest complex formation efficiency was achieved with the Bligh-Dyer m...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 11, 2020 Category: Drugs & Pharmacology Authors: Wibel R, David Friedl J, Zaichik S, Bernkop-Schnürch A Tags: Eur J Pharm Biopharm Source Type: research

Protein stability during nebulization: mind the collection step!
In conclusion, aerosol samplers interfere with protein stability; this impact depends both on the samplers and the protein, highlighting the importance of using the same collection device throughout the aerosol development process. PMID: 32289493 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 11, 2020 Category: Drugs & Pharmacology Authors: Bodier-Montagutelli E, Respaud R, Perret G, Baptista L, Duquenne P, Heuzé-Vourc'h N, Vecellio L Tags: Eur J Pharm Biopharm Source Type: research

Supporting the use of sildenafil infusions in paediatric and neonatal intensive care - a compatibility study.
CONCLUSIONS: This research provides support and information to clinicians looking to co-administer sildenafil with other IV medicines thus removing the requirement to subject their patients to multiple intravenous cannula insertion points where IV access is restricted. ARTICLE TWEET: New evidence to support administration of sildenafil infusions in #PedsICU and #nicu- collaboration between @RCSIPharBioMol@FionaSOBrien1 and @OLCHCrumlin @RCSI_Irl @MoninneHowlett #CHI. PMID: 32289494 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutics and Biopharmaceutics)
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 11, 2020 Category: Drugs & Pharmacology Authors: AlSalman A, Howlett M, Breatnach C, Kelly H, O'Brien F Tags: Eur J Pharm Biopharm Source Type: research

Electrospun Nimodipine-loaded fibers for nerve regeneration: development and in vitro performance.
l;der K Abstract Nimodipine is a 1,4-Dihydropyridine type calcium antagonist routinely used to control blood pressure and reduce the risk of secondary ischemia after aneurismal subarachnoid hemorrhage. Additionally, Nimodipine has unique neuroprotective properties. With respect to brain related applications, the full potential of the desired local effect can often not be realized after systemic administration due to systemic side effects. Therefore, it was our aim to develop a biodegradable drug delivery system for the local controlled release of the drug inside the brain. As a suitable and biodegradable system we...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 10, 2020 Category: Drugs & Pharmacology Authors: Zech J, Leisz S, Göttel B, Syrowatka F, Greiner A, Strauss C, Knolle W, Scheller C, Mäder K Tags: Eur J Pharm Biopharm Source Type: research

Design and in vitro characterization of multistage silicon-PLGA budesonide particles for inflammatory bowel disease.
Abstract Inflammatory bowel disease (IBD) affects a confined area of the intestine and, therefore, administration of drugs via oral route is preferable. However, obstacles such as changes in the pH along gastrointestinal tract (GIT), enzymatic activity, and intraluminal pressure may cause low drug availability in the target tissue when delivered orally. Previous studies have pointed out the benefits of using micron-sized particles for targeting inflamed intestinal mucosa and nanoparticles for delivery of anti-inflammatory agents to the affected epithelial cells. We hypothesized that by combining the benefits of mi...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 10, 2020 Category: Drugs & Pharmacology Authors: Leonard F, Srinivasan S, Liu X, Collnot EM, Ferrari M, Lehr CM, Godin B Tags: Eur J Pharm Biopharm Source Type: research

Binding of excipients is a poor predictor for aggregation kinetics of biopharmaceutical proteins.
Abstract One of the major challenges in formulation development of biopharmaceuticals is improving long-term storage stability, which is often achieved by addition of excipients to the final formulation. Finding the optimal excipient for a given protein is usually done using a trial-and-error approach, due to the lack of general understanding of how excipients work for a particular protein. Previously, preferential interactions (binding or exclusion) of excipients with proteins were postulated as a mechanism explaining diversity in the stabilisation effects. Weak preferential binding is however difficult to quanti...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 10, 2020 Category: Drugs & Pharmacology Authors: Zalar M, Svilenov HL, Golovanov AP Tags: Eur J Pharm Biopharm Source Type: research

What is the fate of multi-lamellar liposomes of controlled size, charge and elasticity in artificial and animal skin?
Abstract Multi-lamellar liposomes (MLLs), prepared by shearing a lamellar phase composed of lipids (phosphatidylcholine) and surfactant (Tween 80®), were designed to control their size, charge and elasticity, the key parameters known to influence liposomes penetration through skin. Their size was tuned by the water content of the sheared lamellar phase, and by the surfactant-to-lipid ratio as was their elasticity. Their charge was varied by the incorporation of DPPG and DOTAP to confer a high negative or positive zeta potential, respectively. Couples of MLLs differing solely in one physicochemical parameter, t...
Source: European Journal of Pharmaceutics and Biopharmaceutics - April 7, 2020 Category: Drugs & Pharmacology Authors: Touti G, Noun M, Guimberteau F, Lecomte S, Faure C Tags: Eur J Pharm Biopharm Source Type: research