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Theself-assembly of block copolymers in solution leads to micellarstructures with various morphologies. One way to modify the morphologyof these micelles is to blend the block copolymer with a homopolymercorresponding to the core-forming block. Although the self-assemblyof blends of amorphous homopolymers and block polymers has been extensivelystudied, there are few examples of solution self-assembly of blendsof a core-crystalline block copolymer with a semicrystalline homopolymer.Here we describe a systematic study of the assembly in decane of blendsof a polyferrocenylsilane-block-polyisoprene sample(PFS48-b-PI264) with two differentPFS homopolymer samples (PFS50and PFS20). Weexamine the structures formed as a function of blend composition andcompare them to the structures formed from the individual components.PFS48-b-PI264itself formslong cylindrical micelles, while the two homopolymer samples formstacks of lamellar crystals. Self-assembly of block copolymer mixturesleads to structures with an elongated planar core and fiber-like protrusionsfrom the ends. The details of the structure vary in an interestingand systematic way as the ratio of homopolymer/block copolymer isincreased, with important differences seen for the PFS50 and PFS20homopolymer samples. This study demonstrates that cocrystallizationplays a crucial role in determining the structures formed from thesemixtures. [ABSTRACT FROM AUTHOR]

Background: The STarT Back Screening Tool (SBT) is recommended to provide risk-stratified care in low back pain (LBP), yet its predictive value is moderate for disability and low for pain severity. Assessment of human assumed central sensitisation (HACS) in conjunction with the SBT may improve its predictive accuracy., Objectives: To examine whether assessment of HACS in acute LBP improves the predictive accuracy of the SBT for LBP recovery at six months in people with acute non-specific LBP., Design: A prospective longitudinal study., Method: Data were drawn from the UPWaRD study. One hundred and twenty people with acute non-specific LBP were recruited from the community. Baseline measures included SBT risk status, nociceptive flexor withdrawal reflex, pressure and heat pain thresholds and conditioned pain modulation. Primary outcome was the presence of LBP (pain numeric rating scale ≥1 and Roland Morris Disability Questionnaire score ≥3) at six-month follow-up. Regression coefficients were penalised using the least absolute shrinkage and selection operator technique to select predictor variables. Internal validation was performed using ten-fold cross-validation., Results/findings: SBT risk status alone did not predict the presence of LBP at six months (area under receiver operating characteristic curve [AUC] = 0.58). Adding measures of HACS to the SBT did not improve discrimination for whether LBP was present at six months (AUC = 0.59)., Conclusions: This study confirmed the suboptimal predictive accuracy of the SBT, administered during acute LBP, for LBP recovery at six months. Assessment of HACS in acute LBP does not improve the predictive accuracy of the SBT., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Itraconazole is a drug used in veterinary medicine for the treatment of different varieties of dermatophytosis at doses between 3-5 mg/kg/day in cats. Nevertheless, in Spain, it is only available in the market as a 52 mL suspension at 10 mg/mL. The lack of alternative formulations, which provide sufficient formulation to cover the treatment of large animals or allow the treatment of a group of them, can be overcome with compounding. For this purpose, it has to be considered that itraconazole is a weak base, class II compound, according to the Biopharmaceutics Classification System, that can precipitate when reaching the duodenum. The aim of this work is to develop alternative oral formulations of itraconazole for the treatment of dermatophytosis. Several oral compounds of itraconazole were prepared and compared, in terms of dissolution rate, permeability, and stability, in order to provide alternatives to the medicine commercialized. The most promising formulation contained hydroxypropyl methylcellulose and β-cyclodextrin. This combination of excipients was capable of dissolving the same concentration as the reference product and delaying the precipitation of itraconazole upon leaving the stomach. Moreover, the intestinal permeability of itraconazole was increased more than two-fold.

The purpose of this study was to predict the in vivo bioequivalence (BE) outcome of valsartan (VALS, BCS class IV) from three oral-fixed combination products with hydrochlorothiazide (HCTZ, BCS class III) ( Co-Diovan ® Forte as reference and two generic formulations in development) by conducting in vivo predictive dissolution with a gastrointestinal simulator (GIS) and a physiologically based biopharmaceutic model (PBBM). In the first BE study, the HCTZ failed, but the VALS 90% CI of Cmax and the AUC were within the acceptance limits, while, in the second BE study, the HCTZ 90% CI of Cmax and the AUC were within the acceptance limits, but the VALS failed. As both drugs belong to different BCS classes, their limiting factors for absorption are different. On the other hand, the gastrointestinal variables affected by the formulation excipients have a distinct impact on their in vivo exposures. Dissolution tests of the three products were performed in a GIS, and a PBBM was constructed for VALS by incorporating in the mathematical model of the in vitro-in vivo correlation (IVIVC) the gastrointestinal variables affected by the excipients, namely, VALS permeability and GI transit time. VALS permeability in presence of the formulation excipients was characterized using the in situ perfusion method in rats, and the impact of the excipients on the GI transit times was estimated from the HCTZ's in vivo results. The model was able to fit the in vivo BE results with a good prediction error. This study contributes to the field by showing the usefulness of PBBM in establishing in vitro-in vivo relationships incorporating not only dissolution data but also other gastrointestinal critical variables that affect drug exposure in BCS class IV compounds.

Background: Currently, there is ongoing research in the pharmaceutical technology field to develop innovative drug delivery systems with improved therapeutic efficacy., Objectives: Although there is a high need for new drug molecules, most scientists focus on the advancement of novel pharmaceutical formulations since the present excipients lack important properties such as low release rate leading to repeated dosing. Aside from this, pharmaceutical technologists aim to develop drug formulations that can target specific organs and tissues, lowering the possibility of adverse effects., Methods: This review aims to cover the different polymer-based gel types, the development and characterization methods, as well as applications thereof. Finally, the recent advancements and future perspectives focusing on radiolabeled gels will be addressed., Results: In the last decades, polymer based pharmaceutical gels have shown attractive properties and therefore have raised the attention of pharmaceutical scientists. Gels are either chemically or physically cross-linked networks that can absorb fluids such as water (hydrogels), oil (organogels) and even air(aerogels). A variety of polymers, either synthetic or natural, have been employed as components for the gels. Stimuli-responsive gels based on stimuli-sensitive polymers are among the most studied gel class of last years., Conclusion: The use of polymer-based gels as drug delivery systems would be beneficial for targeting numerous diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Radiolabeled trastuzumab (TRZ) loaded solid lipid nanoparticles (SLNs) were prepared by high shear homogenization and sonication techniques. The apoptosis mechanism of TRZ-SLNs was studied only with the MCF-7 cell line, while the cytotoxicity and cell binding capacity were investigated using breast cancer cells (MCF-7 and MDA-MB-231) and the human keratinocyte cell line (HaCaT). The particle sizes of TRZ-SLNs were found to be below 100 nm, and they possessed a negative charge. The high radiolabeling efficiency and good radiolabeling stability in saline and a cell culture medium were obtained in the results of radiolabeling studies. According to the in vitro studies, TRZ-SLNs were found to be biocompatible, and they effectively induced apoptosis in MCF-7 cells. After the parenteral injection of TRZ-SLNs into rats, a sustained release profile in blood circulation was achieved compared with free drug solution by the evaluation of pharmacokinetic parameters. As a conclusion, the study reveals that Technetium-99m ( 99m Tc radiolabeled) TRZ loaded SLN formulations could be promising theranostic agents based on their characterization profiles, in vitro cellular uptake and apoptosis induction capacity, and in vivo pharmacokinetic profiles., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The main aim of this work is the biopharmaceutical characterization of a new hybrid benzodiazepine-dihydropyridine derivative, JM-20, derived with potent anti-ischemic and neuroprotective effects. In this study, the p K a and the pH-solubility profile were experimentally determined. Additionally, effective intestinal permeability was measured using three in vitro epithelial cell lines (MDCK, MDCK-MDR1 and Caco-2) and an in situ closed-loop intestinal perfusion technique. The results indicate that JM-20 is more soluble at acidic pH (9.18 ± 0.16); however, the Dose number (Do) was greater than 1, suggesting that it is a low-solubility compound. The permeability values obtained with in vitro cell lines as well as with the in situ perfusion method show that JM-20 is a highly permeable compound (Caco-2 value 3.8 × 10 -5 ). The presence of an absorption carrier-mediated transport mechanism was also demonstrated, as well as the efflux effect of P-glycoprotein on the permeability values. Finally, JM-20 was provisionally classified as class 2 according to the biopharmaceutical classification system (BCS) due to its high intestinal permeability and low solubility. The potential good oral absorption of this compound could be limited by its solubility.

One of the main obstacles in neurological disease treatment is the presence of the blood-brain barrier. New predictive high-throughput screening tools are essential to avoid costly failures in the advanced phases of development and to contribute to the 3 Rs policy. The objective of this work was to jointly develop a new in vitro system coupled with a physiological-based pharmacokinetic (PBPK) model able to predict brain concentration levels of different drugs in rats. Data from in vitro tests with three different cells lines (MDCK, MDCK-MDR1 and hCMEC/D3) were used together with PK parameters and three scaling factors for adjusting the model predictions to the brain and plasma profiles of six model drugs. Later, preliminary quantitative structure-property relationships (QSPRs) were constructed between the scaling factors and the lipophilicity of drugs. The predictability of the model was evaluated by internal validation. It was concluded that the PBPK model, incorporating the barrier resistance to transport, the disposition within the brain and the drug-brain binding combined with MDCK data, provided the best predictions for passive diffusion and carrier-mediated transported drugs, while in the other cell lines, active transport influence can bias predictions.