Gastrointestinal diseases and their impact on drug solubility: Ulcerative Colitis.
Abstract For poorly soluble compounds, drug product performance in patients with Ulcerative Colitis (UC) compared to healthy subjects can be affected due to differences in drug solubility in GI fluids. A risk assessment tool was developed to identify compounds with a high risk of altered solubility in the GI fluids of UC patients. Pathophysiological changes impacting on the composition of GI fluids in UC patients were considered and UC biorelevant media representative of the stomach, intestine and colon were developed based on alteration of biorelevant media based on healthy subjects and literature data using a De...
Source: European Journal of Pharmaceutical Sciences - July 6, 2020 Category: Drugs & Pharmacology Authors: Effinger A, M O'Driscoll C, McAllister M, Fotaki N Tags: Eur J Pharm Sci Source Type: research

Gastrointestinal diseases and their impact on drug solubility: Celiac disease.
Abstract The aim of this study was to develop an in vitro tool for predicting drug solubility and dissolution in intestinal fluids of patients with Celiac disease (CED). Biorelevant media for patients with CED were developed based on published information and a Design of Experiment (DoE) approach. The CED biorelevant media were characterised according to their surface tension, osmolality, dynamic viscosity and buffer capacity. By performing solubility studies of six drugs with different physicochemical properties in CED media, we aimed to identify drugs at high risk of altered luminal solubility in CED patients. I...
Source: European Journal of Pharmaceutical Sciences - July 6, 2020 Category: Drugs & Pharmacology Authors: Effinger A, O'Driscoll CM, McAllister M, Fotaki N Tags: Eur J Pharm Sci Source Type: research

Development of nimesulide amorphous solid dispersions via supercritical anti-solvent process for dissolution enhancement.
Abstract Formulating amorphous solid dispersions (ASDs) is one of the most promising strategies to overcome solubility limitations in drug development. In this work, development of nimesulide (NIM) ASDs via supercritical anti-solvent (SAS) process was proposed, where the mixtures of dichloromethane (DCM) and methanol (MeOH) were selected as the liquid solvent, and the mixtures of hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) were the dispersing materials. The effects of NIM/HPMC/PVP (w/w/w) ratio and DCM/MeOH (v/v) ratio on particle solid-state properties were investigated to identify success...
Source: European Journal of Pharmaceutical Sciences - July 6, 2020 Category: Drugs & Pharmacology Authors: Liu G, Gong L, Zhang J, Wu Z, Deng H, Deng S Tags: Eur J Pharm Sci Source Type: research

Molecular Dynamic Simulations of Human Purinergic Receptor Subtype P2  × 7 Bonded to Potent Inhibitors.
Molecular Dynamic Simulations of Human Purinergic Receptor Subtype P2 × 7 Bonded to Potent Inhibitors. Eur J Pharm Sci. 2020 Jul 03;:105454 Authors: Santos EG, Faria RX, Rodrigues CR, Bello ML Abstract Among the members of purinergic receptors, the family P2X of ionotropic proteins has the ion channel subtype P2 × 7 that show in studies to be an important molecular target for new drugs. The activity of human P2 × 7 receptor (hP2 × 7r) in the body, due to its pro-inflammatory function, can trigger physiological disorders related to chronic inflammatory processes,...
Source: European Journal of Pharmaceutical Sciences - July 3, 2020 Category: Drugs & Pharmacology Authors: Santos EG, Faria RX, Rodrigues CR, Bello ML Tags: Eur J Pharm Sci Source Type: research

Design, synthesis and biological evaluation of water-soluble phenytoin prodrugs considering the substrate recognition ability of human carboxylesterase 1.
In this study, design, synthesis and evaluation of water-soluble phenytoin prodrugs were performed with consideration of the substrate recognition ability of hCES1. The phenytoin prodrugs were synthesized in two steps without column chromatography. It was confirmed that all prodrugs are efficiently converted to phenytoin in a human liver microsome (HLM) solution (up to 54.6 nmol/mg protein/min). Although some of the prodrugs were degraded in strongly basic solution, the solubility of all prodrugs was greater than that of phenytoin in buffer solutions at pH 7.4 and 8.3. Among the synthesized phenytoin prodrugs, the 3,3-dime...
Source: European Journal of Pharmaceutical Sciences - July 3, 2020 Category: Drugs & Pharmacology Authors: Takahashi M, Lee YJ, Kanayama T, Kondo Y, Nishio K, Mukai K, Haba M, Hosokawa M Tags: Eur J Pharm Sci Source Type: research

Exploring impact of supersaturated lipid-based drug delivery systems of celecoxib on in vitro permeation across Permeapad Ⓡ membrane and in vivo absorption.
This study has shown that by using two cell-free PermeapadⓇ permeation models coupled with rat-adapted gastro-intestinal conditions, bio-predictive in vitro tools can be developed to be reflective of in vivo scenarios. With further optimization, such models could be successfully used in pharmaceutical industry settings to rapidly screen various prototype formulations prior to animal studies. PMID: 32622980 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - July 2, 2020 Category: Drugs & Pharmacology Authors: Ilie AR, Griffin BT, Brandl M, Bauer-Brandl A, Jacobsen AC, Vertzoni M, Kuentz M, Kolakovic R, Holm R Tags: Eur J Pharm Sci Source Type: research

Targeting SLC7A11 specifically suppresses the progression of colorectal cancer stem cells via inducing ferroptosis.
Abstract Recent studies have revealed the critical roles of ferroptosis in different physiological and pathological processes, however, its effects on the progression of colorectal cancer stem cells (CSCs) are still unclear. Here, we found that colorectal CSCs exhibited a remarkably lower level of reactive oxygen species (ROS), a higher level of cysteine, glutathione and SLC7A11 compared to colorectal cancer cells. Knockout of SLC7A11 increased the ROS level and reduced the levels of cysteine and glutathione, subsequently attenuating the viability of colorectal CSCs. Erastin, an inhibitor of SLC7A11, was found to ...
Source: European Journal of Pharmaceutical Sciences - July 1, 2020 Category: Drugs & Pharmacology Authors: Xu X, Zhang X, Wei C, Zheng D, Lu X, Yang Y, Luo A, Zhang K, Duan X, Wang Y Tags: Eur J Pharm Sci Source Type: research

Dose Investigation of Imrecoxib in Patients with Renal Insufficiency Based on Modelling and Simulation.
Conclusion A PPK model of imrecoxib and its two metabolites is presented. The renal insufficiency regimen should be reduced to '75 mg q12h' or '50 mg q8h'. PMID: 32621967 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - July 1, 2020 Category: Drugs & Pharmacology Authors: Li Y, Wang J, Huang J, Yu J, Wang Y, Tan H, Zhang H, Yang G, Pei Q Tags: Eur J Pharm Sci Source Type: research

Population pharmacokinetics and dosing regimen optimization of tacrolimus in Chinese lung transplant recipients.
Abstract We aimed to (i) develop a population pharmacokinetic model of tacrolimus in Chinese lung transplant recipients and (ii) propose model-based dosing regimens for individualized treatment. We obtained 807 tacrolimus steady-state whole blood concentrations from 52 lung transplant patients and genotyped CYP3A5*3. Population pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. Monte Carlo simulations were employed to determine the initial dosing regimens. Tacrolimus pharmacokinetics was described by a one-compartment model with first-order absorption and elimination processes. In CYP3A...
Source: European Journal of Pharmaceutical Sciences - July 1, 2020 Category: Drugs & Pharmacology Authors: Cai X, Song H, Jiao Z, Yang H, Zhu M, Wang C, Wei D, Shi L, Wu B, Chen J Tags: Eur J Pharm Sci Source Type: research

Phosphatidylserine (PS)- and phosphatidylglycerol-(PG)-enriched mixed micelles (MM): a new nano-drug delivery system with anti-inflammatory potential?
r K Abstract Phosphatidylserine (PS) and phosphatidylglycerol (PG) are naturally occurring phospholipids (PL) with intrinsic anti-inflammatory properties. The therapeutic potential of PS and PG has not been extensively explored and the main focus had been directed towards PS- and PG-liposomes. In order to increase the formulation options, we explored whether mixed micelles (MM) could be an alternative to liposomes. Potential advantages of MM are their thermodynamic stability, small size and ease of manufacture. DOPS- and DOPG-enriched MM were obtained via a co-precipitation technique and physicochemical characteri...
Source: European Journal of Pharmaceutical Sciences - July 1, 2020 Category: Drugs & Pharmacology Authors: Klein ME, Rieckmann M, Lucas H, Meister A, Loppnow H, Mäder K Tags: Eur J Pharm Sci Source Type: research

Biopharmaceutical characterization of rebamipide: the role of mucus binding in regional-dependent intestinal permeability.
In this study, we aimed to elucidate biopharmaceutical characteristics of the anti-ulcer drug rebamipide, with special emphasis on the influence of gastrointestinal (GI) mucus on rebamipide segmental-dependent permeability and absorption. Experimental studies and physiologically-based pharmacokinetic (GastroPlusTM) simulations were used to elucidate segmental-dependent absorption and pharmacokinetic (PK) profile, accounting for various drug properties, including solubility/dissolution limitations, regional-dependent drug affinity to mucus and membrane permeability, as well as physiological factors such as regional-pH diffe...
Source: European Journal of Pharmaceutical Sciences - June 29, 2020 Category: Drugs & Pharmacology Authors: Markovic M, Zur M, Dahan A, Cvijić S Tags: Eur J Pharm Sci Source Type: research

Celecoxib substituted biotinylated poly(amidoamine) G3 dendrimer as potential treatment for temozolomide resistant glioma therapy and anti-nematode agent.
Abstract Glioblastoma multiforme (GBM) is a one of the most widely diagnosed and difficult to treat type of central nervous system tumors. Resection combined with radiotherapy and temozolomide (TMZ) chemotherapy prolongs patients' survival only for 12 - 15 months after diagnosis. Moreover, many patients develop TMZ resistance, thus important is search for a new therapy regimes including targeted drug delivery. Most types of GBM reveal increased expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2), that are considered as valuable therapeutic target. In these studies, the anti-tumor prope...
Source: European Journal of Pharmaceutical Sciences - June 29, 2020 Category: Drugs & Pharmacology Authors: Uram Ł, Markowicz J, Misiorek M, Filipowicz-Rachwał A, Wołowiec S, Wałajtys-Rode E Tags: Eur J Pharm Sci Source Type: research

Curcumin loaded nanostructured lipid carriers for enhanced skin retained topical delivery: optimization, scale-up, in-vitro characterization and assessment of ex-vivo skin deposition.
The objective of the present study was to improve the permeation of poorly soluble curcumin into topical skin layers for the treatment of chronic inflammatory disorder psoriasis and microbial mediated acne vulgaris. Hot emulsification followed by probe sonication method was employed for the preparation of the curcumin loaded NLC. Further, in-vitro and ex-vivo characterization was performed for designed NLC. The designed NLC showed a mean particle size 96.2 ± 0.9 nm, entrapment efficiency of 70.5 ± 1.65% and zeta potential of -15.2 ± 0.566 mV. Curcumin-NLC showed extended in-vitro release up to 48 hours...
Source: European Journal of Pharmaceutical Sciences - June 26, 2020 Category: Drugs & Pharmacology Authors: Rapalli VK, Kaul V, Waghule T, Gorantla S, Sharma S, Roy A, Dubey SK, Singhvi G Tags: Eur J Pharm Sci Source Type: research

A Proposed Pediatric Biopharmaceutical Classification System for Medications for Chronic Diseases in Children.
The objective of this study was to provisionally classify oral liquid formulations of extemporaneously prepared drugs at our institution into an age-appropriate BCS class after elimination of any duplicate listing when matched with the most current World Health Organization's Essential Medicines List for Children available at the time of this study and other published studies that may have reported BCS classification of drugs used as extemporaneous oral liquid formulations in children to treat chronic or rare diseases. A total of 96 orally administered extemporaneously compounded liquid formulations were included in this c...
Source: European Journal of Pharmaceutical Sciences - June 26, 2020 Category: Drugs & Pharmacology Authors: Bhatt-Mehta V, Hammoud H, Amidon GL Tags: Eur J Pharm Sci Source Type: research

Glibenclamide transfer across the perfused human placenta is determined by albumin binding not transporter activity.
This study investigated the role of drug transporters and protein binding in the transfer of the antidiabetic drug glibenclamide across the human placental syncytiotrophoblast using placental perfusion experiments and computational modelling. In the absence of albumin, placental glibenclamide uptake from the fetal circulation was not affected by competitive inhibition with bromosulphothalein (BSP), indicating that OATP2B1 does not mediate placental glibenclamide uptake from the fetus. In the presence of maternal and fetal albumin, BSP increased placental glibenclamide uptake from the fetal circulation by displacing glibenc...
Source: European Journal of Pharmaceutical Sciences - June 24, 2020 Category: Drugs & Pharmacology Authors: Lofthouse EM, Cleal JK, Hudson G, Lewis RM, Sengers BG Tags: Eur J Pharm Sci Source Type: research

The effects of fluoroalkyl chain length and density on siRNA delivery of bioreducible poly(amido amine)s.
Abstract Fluorination is an attractive strategy for the improvement of transfection efficiency of nucleic acid delivery vectors. Bioreducible poly(amido amine)s (bPAAs) are an important class of biomaterials exhibited to effectively deliver multiple nucleic acids. However, still, the effects of fluoroalkyl chain length and density of bPAA on siRNA delivery are unveiled. Here, we synthesized bPAAs and grafted with different chain lengths and densities of fluorocarbon compounds. Furthermore, we prepared a library of complexes of fluorinated bPAA and siRNA, and investigated the effects of fluorination on the siRNA de...
Source: European Journal of Pharmaceutical Sciences - June 23, 2020 Category: Drugs & Pharmacology Authors: Chen G, Wang Y, Ullah A, Huai Y, Xu Y Tags: Eur J Pharm Sci Source Type: research

Investigating the Skin Penetration and Wound Healing Properties of Niosomal Pentoxifylline Cream.
In this study, PTX-niosomes were prepared and characterized. Niosomes with Zavg of 150, 200, and 300 nm were incorporated into the base cold cream. In-vitro release of PTX from these formulations was obtained between 70 -100%. Ex-vivo penetration/retention studies showed that niosomal formulations (F6 and F7) increased penetration of PTX by 1.8 and 1.2 times, respectively in comparison with the PTX-conventional cream. Retention of PTX from both niosomal creams was about 2 times higher than the PTX-conventional cream. In -vivo studies on the full-thickness wound in BALB/c mice showed that PTX-niosomal creams shortened the d...
Source: European Journal of Pharmaceutical Sciences - June 23, 2020 Category: Drugs & Pharmacology Authors: Aghajani A, Kazemi T, Enayati-Fard R, Amiri FT, Narenji M Tags: Eur J Pharm Sci Source Type: research

Improved antibacterial efficiency of inhaled thiamphenicol dry powders: Mathematical modelling of in vitro dissolution kinetic and in vitro antibacterial efficacy.
This study characterized the effect of the dissolution rate of TAP dry powders on in vitro antibacterial activity against MRSA, and an enhanced antibacterial activity of TAP was observed with an increase in the dissolution rate of TAP from the dry powders at certain concentration ranges. PMID: 32590123 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - June 23, 2020 Category: Drugs & Pharmacology Authors: Wang J, Grégoire N, Marchand S, Kutter JP, Mu H, Moodley A, Couet W, Yang M Tags: Eur J Pharm Sci Source Type: research

Nanocrystal dispersion of DK-I-56-1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: formulation approach toward improved in vivo performance.
Nanocrystal dispersion of DK-I-56-1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: formulation approach toward improved in vivo performance. Eur J Pharm Sci. 2020 Jun 18;:105432 Authors: Mitrović JR, Divović B, Knutson DE, Đoković JB, Vulić PJ, Randjelović DV, Dobričić VD, Čalija BR, Cook JM, Savić MM, Savić SD Abstract DK-I-56-1 (7-methoxy-2-(4-methoxy-d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one), a recently developed deuterated pyrazoloquinolinone, has been recognized as a lead candidate for treatment of various neuropsychiatric disorders...
Source: European Journal of Pharmaceutical Sciences - June 18, 2020 Category: Drugs & Pharmacology Authors: Mitrović JR, Divović B, Knutson DE, Đoković JB, Vulić PJ, Randjelović DV, Dobričić VD, Čalija BR, Cook JM, Savić MM, Savić SD Tags: Eur J Pharm Sci Source Type: research

Cross linking of poly (vinyl alcohol) films under acidic and thermal stress.
Abstract Poly (vinyl alcohol), PVA, a commonly used excipient to coat tablets, forms insoluble films in the presence of acids and thermal stress. This may lead to drug products failing to meet dissolution specifications over time. Studies were conducted to understand the effect of acid strength, processing conditions, and storage stress on the mechanism of insoluble film formation using PVA and Opadry® II as model systems. Aqueous cast films, prepared by incorporating hydrochloric acid (HCl) into the coating solutions or exposing pre-cast "as is" films to HCl vapors, were used as surrogates to develo...
Source: European Journal of Pharmaceutical Sciences - June 17, 2020 Category: Drugs & Pharmacology Authors: Desai SD, Kundu I, P NS, Crull GB, Pan D, Zhao J, Shah RP, Venkatesh C, Vig B, Varia SA, Badawy SIF, Desikan S, Bhutani H Tags: Eur J Pharm Sci Source Type: research

Identification of solubility-limited absorption of oral anticancer drugs using PBPK modeling based on rat PK and its relevance to human.
SA Abstract Solubility is one of the key parameters that is optimized during drug discovery to ensure sufficient drug concentration in systemic circulation and to achieve the desired pharmacological response. We recently reported the application of PBPK analysis of early clinical pharmacokinetic data to identify drugs whose absorption are truly limited by solubility. In this work, we selected ten anticancer drugs that exhibit poor in vitro solubility to explore the utility of this approach to identify solubility-limited absorption based on rat pharmacokinetic data and compare the findings to human data. Oral rat ...
Source: European Journal of Pharmaceutical Sciences - June 17, 2020 Category: Drugs & Pharmacology Authors: Fink C, Lecomte M, Badolo L, Wagner K, Mäder K, Peters SA Tags: Eur J Pharm Sci Source Type: research

Temperature and Solvent Facilitated Extrusion Based 3D Printing for Pharmaceuticals.
This reported approach offers significant advantages compared to other 3DP technologies: simplification of pre-product, the use of a moderate temperature range, a minimal drying period, and avoiding the use of mechanically complicated machinery. In the future, we envisage the use of this low-cost and facile approach to fabricate small batches of bespoke tablets. PMID: 32562691 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - June 17, 2020 Category: Drugs & Pharmacology Authors: Dores F, Kuźmińska M, Soares C, Bohus M, Shiverington L, Habashy R, Pereira BC, Peak M, Isreb A, Alhnan MA Tags: Eur J Pharm Sci Source Type: research

Design and characterization of dual responsive mesoporous silica nanoparticles for breast cancer targeted therapy.
Abstract The main reason for limited efficacy of anticancer drug is the poor accretion of administered amount of drug within the tumor. Here, chitosan folate capped dual responsive mesoporous silica nanoparticles (MSNs) which can actively target cancer cells, and provide burst release of loaded anticancer drug within tumor cells and ultimately leading to improved therapeutic efficacy were synthesized. MSNs were synthesized using most economic silica source, sodium silicate. Doxorubicin (DOX) was loaded within the pores of MSNs and these drug loaded MSNs were first reacted with cystamine dihydrochloride followed by...
Source: European Journal of Pharmaceutical Sciences - June 15, 2020 Category: Drugs & Pharmacology Authors: Bhavsar DB, Patel V, Sawant KK Tags: Eur J Pharm Sci Source Type: research

Improving the dissolution of a water-insoluble orphan drug through a fused deposition modelling 3-dimensional printing technology approach.
IMPROVING THE DISSOLUTION OF A WATER-INSOLUBLE ORPHAN DRUG THROUGH A FUSED DEPOSITION MODELLING 3-DIMENSIONAL PRINTING TECHNOLOGY APPROACH. Eur J Pharm Sci. 2020 Jun 13;:105426 Authors: Saydam M, Takka S Abstract Lennox-Gastaut Syndrome (LGS) is a rare form of childhood epilepsy. Rufinamide is an orphan drug indicated for the treatment of LGS. Three-Dimensional Printing (3DP) is a process in which solid objects are created based on a digital file by adding materials layer by layer. Fused deposition modelling (FDM) is a 3DP technique with the advantages of solid dispersion systems and the ability to us...
Source: European Journal of Pharmaceutical Sciences - June 13, 2020 Category: Drugs & Pharmacology Authors: Saydam M, Takka S Tags: Eur J Pharm Sci Source Type: research

Glutamine chelation governs the selective inhibition of Staphylococcus aureus and Salmonella typhi growth by cis-dichloro-bis(8-quinolinolato)zirconium(IV): Theory and Experiment.
, Cerda SDG Abstract Quinolone-based Schiff base zirconium(IV) complex was studied as potential bacterial inhibitor against Gram-positive Staphylococcus aureus and Gram-negative Salmonella typhi growth, showing that the interaction of the complex with L-glutamine which presents in the membrane of wall leads cell death, and the mode of bacterial interaction was analyzed theoretically by DFT. Furthermore, the interaction of different amino acid residues L-alanine, D-alanine, L-lysine and D-glutamine with the metal complex through UV-vis docking studies was conducted observing that D-glutamine interacts efficiently a...
Source: European Journal of Pharmaceutical Sciences - June 13, 2020 Category: Drugs & Pharmacology Authors: Narayanan J, Hernández JG, Aguilar CAH, Rodríguez MM, Cerda SDG Tags: Eur J Pharm Sci Source Type: research

Therapeutic effects of mangiferin on sepsis-associated acute lung and kidney injuries via the downregulation of vascular permeability and protection of inflammatory and oxidative damages.
CONCLUSIONS: The downregulation of vascular permeability and protection of inflammatory and oxidative damages by MF may be used as treatment targets for sepsis-associated acute lung and kidney injuries. PMID: 32540472 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - June 12, 2020 Category: Drugs & Pharmacology Authors: Zhang D, Han S, Zhou Y, Qi B, Wang X Tags: Eur J Pharm Sci Source Type: research

In vitro release of hydrophobic drugs by oleogel rods with biocompatible gelators.
CONCLUSIONS: Oleogel based rods can provide extended release of many hydrophobic drugs. Solubility of drugs in the gels are affected by gelator type, which suggests some interaction between the drug and the gelling agent. Drug dissolution, diffusion, binding as well as tortuosity due to the formation of voids must be considered to model drug release. PMID: 32535213 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - June 11, 2020 Category: Drugs & Pharmacology Authors: Macoon R, Robey M, Chauhan A Tags: Eur J Pharm Sci Source Type: research

An insight into the therapeutic applications of coumarin compounds and their mechanisms of action.
In conclusion, the coumarin class of phytomolecules has a lot of potential to be used as drugs for various diseases. Much work is needed to bring them at the stage of clinical trials for further approval. There is a lot of hope for this unexplored area of translational research. PMID: 32534193 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - June 10, 2020 Category: Drugs & Pharmacology Authors: Garg SS, Gupta J, Sharma S, Sahu DD Tags: Eur J Pharm Sci Source Type: research

Absorption, Distribution, Metabolism, Excretion (ADME), Drug-drug interaction potential and Prediction of Human Pharmacokinetics of SUVN-G3031, a Novel Histamine 3 Receptor (H3R) inverse agonist in Clinical development for the treatment of Narcolepsy.
Abstract SUVN-G3031 is a potent and selective inverse agonist of Histmine-3 (H3) receptor that is being investigated for the treatment of narcolepsy. SUVN-G3031 has high passive permeability, not a substrate for P-glycoprotein, has high plasma unbound fractions and was equally distributed between blood and plasma. Major routes of metabolism in vitro were cyclization (Metabolite A) in microsomes and dealkylation (Metabolite D) in hepatocytes. Intrinsic clearance in liver microsomes and hepatocytes was low as monitored by metabolite formation approach. CYP3A4 and MAO-A were the major enzymes involved in the formatio...
Source: European Journal of Pharmaceutical Sciences - June 10, 2020 Category: Drugs & Pharmacology Authors: Nirogi R, Bhyrapuneni G, Muddana NR, Manoharan A, Shinde AK, Mohammed AR, Padala NP, Ajjala DR, Subramanian R, Palacharla VRC Tags: Eur J Pharm Sci Source Type: research

Exploring membrane proteins of Leishmania major to design a new multi-epitope vaccine using immunoinformatics approach.
Abstract Leishmaniasis is one of the major global endemic diseases. Among all the different forms of the disease, cutaneous leishmaniasis has the highest prevalence worldwide. Treatment with current drugs has not had a significant effect on the improvement of the disease. An attempt to replace an appropriate vaccine that can stimulate host cellular immunity and induce the response of Major histocompatibility complex I (MHCI) and Major histocompatibility complex II (MHCII) against Leishmania is essential. Vaccine production remains a challenge despite the use of different antigens for vaccination against Leishmania...
Source: European Journal of Pharmaceutical Sciences - June 10, 2020 Category: Drugs & Pharmacology Authors: Rabienia M, Roudbari Z, Ghanbariasad A, Abdollahi A, Mohammadi E, Mortazavidehkordi N, Farjadfar A Tags: Eur J Pharm Sci Source Type: research

Pharmacokinetics of tedizolid, sutezolid, and sutezolid-M1 in non-human primates.
The objective of the current study was to determine if NHPs can also be used to reliably predict the exposure of tedizolid, sutezolid, and its biologically active metabolite sutezolid-M1 in humans. The prodrug tedizolid phosphate and sutezolid were administered orally to NHPs either once or twice daily for up to eight days. The activity moieties, tedizolid, and sutezolid showed linear pharmacokinetics and respective concentration-time profiles could be described by one-compartment body models with first-order elimination. One additional metabolite compartment with first-order elimination was found appropriate to capture th...
Source: European Journal of Pharmaceutical Sciences - June 9, 2020 Category: Drugs & Pharmacology Authors: Kim S, Scanga CA, Miranda Silva C, Zimmerman M, Causgrove C, Stein B, Dartois V, Peloquin CA, Graham E, Louie A, Flynn JL, Schmidt S, Drusano GL Tags: Eur J Pharm Sci Source Type: research

The role of pH and dose/solubility ratio on cocrystal dissolution, drug supersaturation and precipitation.
edo N Abstract Cocrystals that are more soluble than the constituent drug, generate supersaturation levels during dissolution and are predisposed to conversion to the less soluble drug. Drug release studies during cocrystal dissolution generally compare several cocrystals and their crystal structures. However, the influence of drug dose and solubility in different dissolution media has been scarcely reported. The present study aims to investigate how drug dose/solubility ratio (Do=Cdose/Sdrug), cocrystal solubility advantage over drug (SA=Scocrystal/Sdrug), and dissolution media affect cocrystal dissolution-drug s...
Source: European Journal of Pharmaceutical Sciences - June 9, 2020 Category: Drugs & Pharmacology Authors: Machado TC, Kuminek G, Cardoso SG, Rodríguez-Hornedo N Tags: Eur J Pharm Sci Source Type: research

Species differences in the drug-drug interaction between atorvastatin and cyclosporine: In vivo study using a stable isotope-IV method in rats and dogs.
In conclusion, PK analysis on the DDI between ATV and CsA in rats and dogs clearly demonstarted the factors to cause species differences in the extent of DDI. This type of quantitative analysis of DDIs in both small and large animals can be a great help to predict the extent of DDI in humans in the clinical study. PMID: 32512140 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - June 5, 2020 Category: Drugs & Pharmacology Authors: Minami K, Higashino H, Kataoka M, Yamashita S Tags: Eur J Pharm Sci Source Type: research

Vesicular elastic liposomes for transdermal delivery of rifampicin: In-vitro, in-vivo and in silico GastroPlusTM prediction studies.
This study investigated enhanced bioavailability and sustained delivery of transdermally delivered rifampicin (RIF) in elastic liposomes (ELs). F3, F5, and F7 were optimized formulations comprising of 200, 140 and 80 mg of tween 80, respectively, and Phospholipon® 90G (300 mg). They were optimized based on in vitro and ex vivo parameters. Using the Franz diffusion cell, an ex vivo study was conducted by utilizing the rat skin for permeation profiles. Also, pharmacokinetic parameters, mechanistic evaluation of penetration, and histopathological investigation were conducted in the rat model for complete dynamic evaluatio...
Source: European Journal of Pharmaceutical Sciences - June 4, 2020 Category: Drugs & Pharmacology Authors: Hussain A, Altamimi MA, Alshehri S, Imam SS, Singh SK Tags: Eur J Pharm Sci Source Type: research

Electroporation-enhanced transdermal drug delivery: effects of logP, pKa, solubility and penetration time.
Abstract Electroporation is an important physical technique to improve drug transdermal delivery, although its mechanism remains unclear. Here, some types of polar drugs, including aspirin, diclofenac sodium, metformin hydrochloride, ibuprofen and zidovudine, were used as the model drugs for the exploration of electroporation mechanisms. Electroporation had great influences on the structure of stratum corneum to improve the cumulative permeability due to the formation of pores maintaining for at least 2 h, depending on the power and time, and then the permeation gradually recovered to the normal value after 12 h. ...
Source: European Journal of Pharmaceutical Sciences - June 4, 2020 Category: Drugs & Pharmacology Authors: Chen X, Zhu L, Li R, Pang L, Zhu S, Ma J, Du L Tags: Eur J Pharm Sci Source Type: research

Drug Delivery Systems Based on Nanoparticles and Related Nanostuctures.
Abstract A new approach to drug design based on nanoparticles and related nanostructures for effective drug delivery, is of great importance in future medical treatment, especially for cancer therapy. Nanomaterials hold tremendous potential for increasing the efficiency of drug delivery, with a high degree of biocompatibility. Additionally, for biomedical applications, they must be biodegradable, have prolonged circulation half-life, not tend to aggregate or cause an inflammatory response in the body and to be cost-effective. The efficacy of such structures is highly dependent on their chemical properties as well ...
Source: European Journal of Pharmaceutical Sciences - June 4, 2020 Category: Drugs & Pharmacology Authors: Nikezić AV, Bondžić AM, Vasić VM Tags: Eur J Pharm Sci Source Type: research

Antileishmanial activity of the chalcone derivative LQFM064 associated with reduced fluidity in the parasite membrane as assessed by EPR spectroscopy.
nso A Abstract A novel chalcone derivative, LQFM064, demonstrated antileishmanial activity against Leishmania (L.) amazonensis, with an IC50 value of ∼10 μM for the promastigote form. Electron paramagnetic resonance (EPR) spectroscopy of a spin-labeled stearic acid incorporated in the plasma membrane of L. amazonensis promastigotes revealed that after 2 h of treatment with LQFM064, the parasite showed remarkable reductions in membrane fluidity. The features of the altered EPR spectra were similar to those reported for the erythrocyte membrane, which was suggested to be due to the cross-linking of oxidized h...
Source: European Journal of Pharmaceutical Sciences - June 3, 2020 Category: Drugs & Pharmacology Authors: Alonso L, Menegatti R, Gomes RS, Dorta ML, Luzin RM, Lião LM, Alonso A Tags: Eur J Pharm Sci Source Type: research

Understanding Breast cancer: from conventional therapies to repurposed drugs.
e N Abstract Breast cancer is the most common cancer among women and is considered a developed country disease. Moreover, is a heterogenous disease, existing different types and stages of breast cancer development, therefore, better understanding of cancer biology, helps to improve the development of therapies. The conventional treatments accessible after diagnosis, have the main goal of controlling the disease, by improving survival. In more advance stages the aim is to prolong life and symptom palliation care. Surgery, radiation therapy and chemotherapy are the main options available, which must be adapted to ea...
Source: European Journal of Pharmaceutical Sciences - June 3, 2020 Category: Drugs & Pharmacology Authors: Costa B, Amorim I, Gärtner F, Vale N Tags: Eur J Pharm Sci Source Type: research

Fine grade engineered microcrystalline cellulose excipients for direct compaction: Assessing suitability of different dry coating processes.
e; RN Abstract Recent work showed that contrary to conventional wisdom, fine surface engineered excipients outperform their larger counterparts in blends of highly loaded blends of cohesive drug powders in terms of their packing, flowability and tablet tensile strength. Here, two continuous devices, fluid-energy mill (FEM) and conical mill (Comil), are compared with LabRAM, a batch device used in previous work, for nano-silica dry coating of microcrystalline cellulose (MCC) excipients, 20 and 30 μm. Coated MCCs from all three devices had higher bulk densities and flow function coefficients (FFCs) compared with ...
Source: European Journal of Pharmaceutical Sciences - June 2, 2020 Category: Drugs & Pharmacology Authors: Chen L, He Z, Kunnath K, Zheng K, Kim S, Davé RN Tags: Eur J Pharm Sci Source Type: research

A new acetylcholinesterase allosteric site responsible for binding voluminous negatively charged molecules - the role in the mechanism of AChE inhibition.
ć GV Abstract Acetylcholinesterase (AChE) inhibitors are important in the treatment of neurodegenerative diseases. Two inhibitors, 12-tungstosilicic acid (WSiA) and 12-tungstophosphoric acid (WPA), which have polyoxometalate (POM) type structure, have been shown to inhibit AChE activity in nM concentration. Circular dichroism and tryptophan fluorescence spectroscopy demonstrated that the AChE inhibition was not accompanied by significant changes in the secondary structure of the enzyme. The molecular docking approach has revealed a new allosteric binding site, termed β-allosteric site (β-AS), which is c...
Source: European Journal of Pharmaceutical Sciences - May 31, 2020 Category: Drugs & Pharmacology Authors: Bondžić AM, Lazarević-Pašti TD, Leskovac AR, Petrović SŽ, Čolović MB, Parac-Vogt TN, Janjić GV Tags: Eur J Pharm Sci Source Type: research

Pyrazinamide alleviates rifampin-induced steatohepatitis in mice by regulating the activities of cholesterol-activated 7 α-hydroxylase and lipoprotein lipase.
Pyrazinamide alleviates rifampin-induced steatohepatitis in mice by regulating the activities of cholesterol-activated 7α-hydroxylase and lipoprotein lipase. Eur J Pharm Sci. 2020 May 31;:105402 Authors: Tan W, Zhao K, Xiang J, Zhou X, Cao F, Song W, Liu Q, Zhang X, Li X, Tan Z Abstract The combination of rifampin and pyrazinamide is commonly used in the clinical treatment of tuberculosis, but its safety needs to be further clarified. Mice were intragastric administration of rifampin 300 mg/kg, pyrazinamide 625 mg/kg, rifampin 300 mg/kg plus pyrazinamide 625 mg/kg. The results showed that rifamp...
Source: European Journal of Pharmaceutical Sciences - May 31, 2020 Category: Drugs & Pharmacology Authors: Tan W, Zhao K, Xiang J, Zhou X, Cao F, Song W, Liu Q, Zhang X, Li X, Tan Z Tags: Eur J Pharm Sci Source Type: research

Temperature: an overlooked factor in tablet disintegration.
Abstract Disintegration is the first event in the bioavailability cascade after the ingestion of immediate release tablets. Although the influence of various physico-chemical parameters of media on tablet disintegration has been investigated in depth, the role of temperature has received much less attention. Probing the effect of temperature on disintegration is important in order to understand if previous in vitro studies conducted at room temperature can be related to those performed at body temperature. Moreover, from a biorelevant point of view, a tablet could be co-ingested with a cold or hot drink, inducing ...
Source: European Journal of Pharmaceutical Sciences - May 30, 2020 Category: Drugs & Pharmacology Authors: Basaleh S, Bisharat L, Cespi M, Berardi A Tags: Eur J Pharm Sci Source Type: research

Lipid-core nanocapsules containing simvastatin improve the cognitive impairment induced by obesity and hypercholesterolemia in adult rats.
This study aimed to develop and characterize lipid-core nanocapsules (LNC) containing SV (SV-LNC) or LV (LV-LNC), evaluating the effects of SV-LNC in an animal model of cognitive deficit. The formulations SV-LNC and LV-LNC presented a particle average size around 200 nm, a low-polydispersity index, and negative zeta potential. Analysis of differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy showed that there is no reaction among LNC components: LV was crystallized in the suspensions, and SV was molecularly dispersed. The encapsulation efficiency of ...
Source: European Journal of Pharmaceutical Sciences - May 30, 2020 Category: Drugs & Pharmacology Authors: Lorenzoni R, Davies S, Cordenonsi LM, Viçosa JADS, Mezzomo NJ, de Oliveira AL, Carmo GMD, Raffin RP, Alves OL, Vaucher RA, Rech VC Tags: Eur J Pharm Sci Source Type: research

Acoustically-driven drug delivery to maxillary sinuses: Aero-acoustic analysis.
Abstract This paper investigates the effect of aero-acoustic parameters on the efficiency of acoustically-driven drug delivery (ADD) to human maxillary sinus (MS). To be more specific, the effect of the frequency, amplitude at the acoustic excitation, and the inlet mean flow rate on the efficiency of ADD to the MS is studied. Direct computational aero-acoustics, using a validated computational fluid dynamics (CFD) model, has been utilised to carry out the parametric study. The transport pattern of the particles (drugs) in the presence of an external acoustic field has been investigated through the discrete phase m...
Source: European Journal of Pharmaceutical Sciences - May 30, 2020 Category: Drugs & Pharmacology Authors: Pourmehran O, Cazzolato B, Tian Z, Arjomandi M Tags: Eur J Pharm Sci Source Type: research

Drug delivery to solid tumors with heterogeneous microvascular networks: Novel insights from image-based numerical modeling.
This study examines how tumor-related parameters including the necrotic core size and tumor size, and also drug-related parameters drug dosage, binding affinity of drug, and drug degradation can affect the delivery of the drug to solid tumors. Results indicate that concentration of drug are high in the tumor, low in normal tissue, and remarkably low in the necrotic core. Results also offer a treatment of tumors with smaller necrotic core. Tumor size, which implies the tumor progression, has a considerable impact on treatment outcomes, so to be more effective, treatment should be applied at a specific size of tumor. It is d...
Source: European Journal of Pharmaceutical Sciences - May 30, 2020 Category: Drugs & Pharmacology Authors: Kashkooli FM, Soltani M, Hamedi MH Tags: Eur J Pharm Sci Source Type: research

Identification of functional epitopes of structural proteins and in-silico designing of dual acting multiepitope anti-tick vaccine against emerging Crimean-Congo hemorrhagic fever virus.
Abstract Recurrent outbreaks of Crimean-Congo hemorrhagic fever (CCHF) virus infection in different parts of world are a major global health concern. The CCHF viral infection is associated with severe hemorrhagic fevers and mortality up to 40%. More than 30 countries in Asia, Europe and Africa are affected with CCHF infection. Prevention of infection through vaccine becomes more important when no effective antiviral and associated therapies are available. Further ticks play a crucial role in maintenance and transmission of CCHFV. Therefore, the control of transmission by ticks is warranted for ultimate prevention ...
Source: European Journal of Pharmaceutical Sciences - May 29, 2020 Category: Drugs & Pharmacology Authors: Shrivastava N, Verma A, Dash DPK Tags: Eur J Pharm Sci Source Type: research

Fluorescent probes for the dual investigation of MRP2 and OATP1B1 function and drug interactions.
os É, Özvegy-Laczka C Abstract Detoxification in hepatocytes is a strictly controlled process, in which the governed action of membrane transporters involved in the uptake and efflux of potentially dangerous molecules has a crucial role. Major transporters of hepatic clearance belong to the ABC (ATP Binding Cassette) and Solute Carrier (SLC) protein families. Organic anion-transporting polypeptide OATP1B1 (encoded by the SLCO1B1 gene) is exclusively expressed in the sinusoidal membrane of hepatocytes, where it mediates the cellular uptake of bile acids, bilirubin, and also that of various drugs. The re...
Source: European Journal of Pharmaceutical Sciences - May 28, 2020 Category: Drugs & Pharmacology Authors: Székely V, Patik I, Ungvári O, Telbisz Á, Szakács G, Bakos É, Özvegy-Laczka C Tags: Eur J Pharm Sci Source Type: research

Gellan gum-based hydrogel containing nanocapsules for vaginal indole-3-carbinol delivery in trichomoniasis treatment.
In this study, design, formulation, and evaluation of a vaginal hydrogel containing I3C-loaded nanocapsules for the treatment of trichomoniasis have been investigated. Nanocapsules of Eudragit® RS100 and rosehip oil containing I3C (NC-I3C) were prepared by interfacial deposition of preformed polymer method. In vitro evaluations showed that free I3C (IC50 = 3.36 µg/mL) was able to reduce the trophozoites viability at higher concentrations (3.13 and 6.25 µg/mL), while nanoencapsulation (IC50 = 2.09 µg/mL) reduced the viability at all concentrations evaluated. Comparing free and nanoencapsulated ...
Source: European Journal of Pharmaceutical Sciences - May 27, 2020 Category: Drugs & Pharmacology Authors: Osmari BF, Giuliani LM, Reolon JB, Rigo GV, Tasca T, Cruz L Tags: Eur J Pharm Sci Source Type: research

The Global Bioequivalence Harmonisation Initiative: Report of EUFEPS/AAPS Third Conference.
This report summarizes the extensive discussions that led to better understanding of the similarities and differences across the major regulatory agencies on these topics and paved the way for future international harmonization. PMID: 32473200 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - May 27, 2020 Category: Drugs & Pharmacology Authors: Mehta M, Blume H, Beuerle G, Tampal N, Schug B, Potthast H, Jiang W, Wilson C Tags: Eur J Pharm Sci Source Type: research

Pharmacokinetic and bioequivalence study of new S-1 capsule in Chinese cancer patients.
In conclusion, the newly developed generic S-1 showed similar pharmacokinetics to those of an original brand-name S-1 in cancer patients, thereby indicating bioequivalence. Furthermore, both treatments were well tolerated, suggesting that the cost-effective generic S-1 should be considered as a feasible option when treating patients. PMID: 32470574 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - May 26, 2020 Category: Drugs & Pharmacology Authors: Chen Y, Jiang Y, Qu J, Wang Q, Bai Y, Shi J, Shi Y, Chen X, Yang N, Heng J, Li K Tags: Eur J Pharm Sci Source Type: research