Minimizing Undesired Side Reactions Induced by Nanoscale Conductive Carbon Enables Stable Cycling of Semi-Solid Li-Ion Full Batteries.

Semi-solid lithium-ion batteries (SSLIBs) based on "slurry-like" electrodes hold great promise to enable low-cost and sustainable energy storage. However, the development of the SSLIBs has long been hindered by the lack of high-performance anodes. Here the origin of low initial Coulombic efficiency (iCE, typically <60%) is elucidated in the graphite-based semi-solid anodes (in the non-flowing mode) and develop rational strategies to minimize the irreversible capacity loss. It is discovered that Ketjen black (KB), a nanoscale conductive additive widely used in SSLIB research, induces severe electrolyte decomposition during battery charge due to its large surface area and abundant surface defects. High iCEs up to 92% are achieved for the semi-solid graphite anodes by replacing KB with other low surface-area, low-defect conductive additives. A semi-solid full battery (LiFePO4 vs graphite, in the non-flowing mode) is further demonstrated with stable cycle performance over 100 cycles at a large areal capacity of 6 mAh cm-2 and a pouch-type semi-solid full cell that remains functional even when it is mechanically abused. This work demystifies the SSLIBs and provides useful physical insights to further improve their performance and durability.

Stable sodium-sulfur electrochemistry enabled by phosphorus-based complexation.

A series of sodium phosphorothioate complexes are shown to have electrochemical properties attractive for sodium-sulfur battery applications across a wide operating temperature range. As cathode materials, they resolve a long-standing issue of cyclic liquid-solid phase transition that causes sluggish reaction kinetics and poor cycling stability in conventional, room-temperature sodium-sulfur batteries. The cathode chemistry yields 80% cyclic retention after 400 cycles at room temperature and a superior low-temperature performance down to -60 °C. Coupled experimental characterization and density functional theory calculations revealed the complex structures and electrochemical reaction mechanisms. The desirable electrochemical properties are attributed to the ability of the complexes to prevent the formation of solid precipitates over a fairly wide range of voltage.

1.89 $ kg-1 Lake-Water-Based Semisolid Electrolytes for Highly Efficient Energy Storage.

Solid electrolytes with fast ion kinetics and superior mechanical properties are critical to electrochemical energy devices; however, how to design low-cost, high-performance solid electrolytes has become a critical challenge in the energy field, and significant progress has not been achieved until now. Here, lake-water-based semisolid electrolytes with a low cost of 1.89 $ kg-1 have been put forward for the purpose of market promotion. By virtue of the palygorskite dopants and lake water source, the electrolytes display satisfying mechanical, electrical, and electrochemical properties as well as economic benefits. The application potential of electrolytes has been demonstrated by employing a polyelectrolyte with ionic conductivity of 0.82 × 10-4 S cm-1 in flexible supercapacitors. The as-assembled devices give a high energy density of 54.72 Wh kg-1 and excellent cycling stability with a capacity retention of 94.8% over 20 000 cycles. The flexibility of devices has been verified through 5000 repetitive bending tests. Our work presents insight into the design of flexible solid electrolytes based on cheap and green raw materials.

Oleogels: Versatile Novel Semi-Solid System for Pharmaceuticals.

Oleogels is a novel semi-solid system, focusing on its composition, formulation, characterization, and diverse pharmaceutical applications. Due to their stability, smoothness, and controlled release qualities, oleogels are frequently utilized in food, cosmetics, and medicinal products. Oleogels are meticulously formulated by combining oleogelators like waxes, fatty acids, ethyl cellulose, and phytosterols with edible oils, leading to a nuanced understanding of their impact on rheological characteristics. They can be characterized by methods like visual inspection, texture analysis, rheological measurements, gelation tests, and microscopy. The applications of oleogels are explored in diverse fields such as nutraceuticals, cosmetics, food, lubricants, and pharmaceutics. Oleogels have applications in topical, transdermal, and ocular drug delivery, showcasing their potential for revolutionizing drug administration. This review aims to enhance the understanding of oleogels, contributing to the evolving landscape of pharmaceutical formulations. Oleogels emerge as a versatile and promising solution, offering substantial potential for innovation in drug delivery and formulation practices.

Tailored Sticky Solutions: 3D-Printed Miconazole Buccal Films for Pediatric Oral Candidiasis.

In this research, 3D-printed antifungal buccal films (BFs) were manufactured as a potential alternative to commercially available antifungal oral gels addressing key considerations such as ease of manufacturing, convenience of administration, enhanced drug efficacy and suitability of paediatric patients. The fabrication process involved the use of a semi-solid extrusion method to create BFs from zein-Poly-Vinyl-Pyrrolidone (zein-PVP) polymer blend, which served as a carrier for drug (miconazole) and taste enhancers. After manufacturing, it was determined that the disintegration time for all films was less than 10 min. However, these films are designed to adhere to buccal tissue, ensuring sustained drug release. Approximately 80% of the miconazole was released gradually over 2 h from the zein/PVP matrix of the 3D printed films. Moreover, a detailed physicochemical characterization including spectroscopic and thermal methods was conducted to assess solid state and thermal stability of film constituents. Mucoadhesive properties and mechanical evaluation were also studied, while permeability studies revealed the extent to which film-loaded miconazole permeates through buccal tissue compared to commercially available oral gel formulation. Histological evaluation of the treated tissues was followed. Furthermore, in vitro antifungal activity was assessed for the developed films and the commercial oral gel. Finally, films underwent a two-month drug stability test to ascertain the suitability of the BFs for clinical application. The results demonstrate that 3D-printed films are a promising alternative for local administration of miconazole in the oral cavity.

Bloch simulator-driven deep recurrent neural network for magnetization transfer contrast MR fingerprinting and CEST imaging.

PURPOSE: To develop a unified deep-learning framework by combining an ultrafast Bloch simulator and a semisolid macromolecular magnetization transfer contrast (MTC) MR fingerprinting (MRF) reconstruction for estimation of MTC effects. METHODS: The Bloch simulator and MRF reconstruction architectures were designed with recurrent neural networks and convolutional neural networks, evaluated with numerical phantoms with known ground truths and cross-linked bovine serum albumin phantoms, and demonstrated in the brain of healthy volunteers at 3 T. In addition, the inherent magnetization-transfer ratio asymmetry effect was evaluated in MTC-MRF, CEST, and relayed nuclear Overhauser enhancement imaging. A test-retest study was performed to evaluate the repeatability of MTC parameters, CEST, and relayed nuclear Overhauser enhancement signals estimated by the unified deep-learning framework. RESULTS: Compared with a conventional Bloch simulation, the deep Bloch simulator for generation of the MTC-MRF dictionary or a training data set reduced the computation time by 181-fold, without compromising MRF profile accuracy. The recurrent neural network-based MRF reconstruction outperformed existing methods in terms of reconstruction accuracy and noise robustness. Using the proposed MTC-MRF framework for tissue-parameter quantification, the test-retest study showed a high degree of repeatability in which the coefficients of variance were less than 7% for all tissue parameters. CONCLUSION: Bloch simulator-driven, deep-learning MTC-MRF can provide robust and repeatable multiple-tissue parameter quantification in a clinically feasible scan time on a 3T scanner.

Semi-solid MT and APTw CEST-MRI predict clinical outcome of patients with glioma early after radiotherapy.

PURPOSE: The purpose of this study was to compare the potential of asymmetry-based (APTwasym ), Lorentzian-fit-based (PeakAreaAPT and MTconst ), and relaxation-compensated (MTRRex APT and MTRRex MT) CEST contrasts of the amide proton transfer (APT) and semi-solid magnetization transfer (ssMT) for early response assessment and prediction of progression-free survival (PFS) in patients with glioma. METHODS: Seventy-two study participants underwent CEST-MRI at 3T from July 2018 to December 2021 in a prospective clinical trial four to 6 wk after the completion of radiotherapy for diffuse glioma. Tumor segmentations were performed on T2w -FLAIR and contrast-enhanced T1w images. Therapy response assessment and determination of PFS were performed according to response assessment in neuro oncology (RANO) criteria using clinical follow-up data with a median observation time of 9.2 mo (range, 1.6-40.8) and compared to CEST MRI metrics. Statistical testing included receiver operating characteristic analyses, Mann-Whitney-U-test, Kaplan-Meier analyses, and logrank-test. RESULTS: MTconst (AUC = 0.79, p < 0.01) showed a stronger association with RANO response assessment compared to PeakAreaAPT (AUC = 0.71, p = 0.02) and MTRRex MT (AUC = 0.71, p = 0.02), and enabled differentiation of participants with pseudoprogression (n = 8) from those with true progression (AUC = 0.79, p = 0.02). Furthermore, MTconst (HR = 3.04, p = 0.01), PeakAreaAPT (HR = 0.39, p = 0.03), and APTwasym (HR = 2.63, p = 0.02) were associated with PFS. MTRRex APT was not associated with any outcome. CONCLUSION: MTconst , PeakAreaAPT, and APTwasym imaging predict clinical outcome by means of progression-free survival. Furthermore, MTconst enables differentiation of radiation-induced pseudoprogression from disease progression. Therefore, the assessed metrics may have synergistic potential for supporting clinical decision making during follow-up of patients with glioma.

Numerical fitting of Extrapolated semisolid Magnetization transfer Reference (NEMR) signals: Improved detection of ischemic stroke.

PURPOSE: To propose a novel Numerical fitting method of the Extrapolated semisolid Magnetization transfer Reference (NEMR) signal for quantifying the CEST effect. THEORY AND METHODS: Modified two-pool Bloch-McConnell equations were used to numerically fit the magnetization transfer (MT) and direct water saturation (DS) signals at far off-resonance frequencies, which was subsequently extrapolated into the frequency range of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) pools. Then the subtraction of the fitted two-pool z-spectrum and the experimentally acquired z-spectrum yielded APT# and NOE# signals mostly free of MT and DS contamination. Several strategies were used to accelerate the NEMR fitting. Furthermore, the proposed NEMR method was compared with the conventional extrapolated semisolid magnetization transfer reference (EMR) and magnetization transfer ratio asymmetry (MTRasym ) methods in simulations and stroke patients. RESULTS: The combination of RF downsampling, MT lineshape look-up table, and conversion of MATLAB code to C code accelerated the NEMR fitting by over 2700-fold. Monte-Carlo simulations showed that NEMR had higher accuracy than EMR and eliminated the requirement of the steady-state condition. In ischemic stroke patients, the NEMR maps at 1 µT removed hypointense artifacts seen on EMR and MTRasym images, and better depicted stroke lesions than EMR. For NEMR, NOE# yielded significantly (p < 0.05) stronger signal contrast between stroke and normal tissues than APT# at 1 µT. CONCLUSION: The proposed NEMR method is suitable for arbitrary saturation settings and can remove MT and DS contamination from the CEST signal for improved detection of ischemic stroke.

Semi-Solid Supramolecular Ionic Network Electrolytes Formed by Zwitterionic Liquids and Polyoxometalate Nanoclusters for High Proton Conduction.

Flexible electrolytes with solid self-supporting properties are highly desired in the fields of energy and electronics. However, traditional flexible electrolytes prepared by doping ionic liquids or salt solutions into a polymer matrix pose a risk of liquid component leakage during device operation. In this work, the development of supramolecular ionic network electrolytes using polyoxometalate nanoclusters as supramolecular crosslinkers to solidify bola-type zwitterionic liquids is reported. The resulting self-supporting electrolytes possess semi-solid features and show a high proton conductivity of 8.2 × 10-4 S cm-1 at low humidity (RH = 30%). Additionally, the electrolytes exhibit a typical plateau region in rheological tests, indicating that their dynamic network structures can contribute mechanical behavior similar to the entangled networks in covalent polymer materials. This work introduces a new paradigm for designing flexible solid electrolytes and expands the concept of reticular chemistry to noncrystalline systems.

Detection of Semi-Solid Materials Utilizing Triple-Rings CSRR Microwave Sensor.

This article proposes the design, fabrication and measurement of a triple-rings complementary split-ring resonator (CSRR) microwave sensor for semi-solid material detection. The triple-rings CSRR sensor was developed based on the CSRR configuration with curve-feed designed together, utilizing a high-frequency structure simulator (HFSS) microwave studio. The designed triple rings CSRR sensor resonates at 2.5 GHz, performs in transmission mode, and senses shift in frequency. Six cases of the sample under tests (SUTs) were simulated and measured. These SUTs are Air (without SUT), Java turmeric, Mango ginger, Black Turmeric, Turmeric, and Di-water, and detailed sensitivity analysis is conducted for the frequency resonant at 2.5 GHz. The semi-solid tested mechanism is undertaken using a polypropylene (PP) tube. The samples of dielectric material are filled into PP tube channels and loaded in the CSRR centre hole. The e-fields near the resonator will affect the interaction with the SUTs. The finalized CSRR triple-rings sensor was incorporated with defective ground structure (DGS) to deliver high-performance characteristics in microstrip circuits, leading to a high Q-factor magnitude. The suggested sensor has a Q-factor of 520 at 2.5 GHz with high sensitivity of about 4.806 and 4.773 for Di-water and Turmeric samples, respectively. The relationship between loss tangent, permittivity, and Q-factor at the resonant frequency has been compared and discussed. These given outcomes make the presented sensor ideal for detecting semi-solid materials.

Identification of the Solid Stem Suppressor Gene Su-TdDof in Synthetic Hexaploid Wheat Syn-SAU-117.

Lodging is one of the most important factors affecting the high and stable yield of wheat worldwide. Solid-stemmed wheat has higher stem strength and lodging resistance than hollow-stemmed wheat does. There are many solid-stemmed varieties, landraces, and old varieties of durum wheat. However, the transfer of solid stem genes from durum wheat is suppressed by a suppressor gene located on chromosome 3D in common wheat, and only hollow-stemmed lines have been created. However, synthetic hexaploid wheat can serve as a bridge for transferring solid stem genes from tetraploid wheat to common wheat. In this study, the F1, F2, and F2:3 generations of a cross between solid-stemmed Syn-SAU-119 and semisolid-stemmed Syn-SAU-117 were developed. A single dominant gene, which was tentatively designated Su-TdDof and suppresses stem solidity, was identified in synthetic hexaploid wheat Syn-SAU-117 by using genetic analysis. By using bulked segregant RNA-seq (BSR-seq) analysis, Su-TdDof was mapped to chromosome 7DS and flanked by markers KASP-669 and KASP-1055 within a 4.53 cM genetic interval corresponding to 3.86 Mb and 2.29 Mb physical regions in the Chinese Spring (IWGSC RefSeq v1.1) and Ae. tauschii (AL8/78 v4.0) genomes, respectively, in which three genes related to solid stem development were annotated. Su-TdDof differed from a previously reported solid stem suppressor gene based on its origin and position. Su-TdDof would provide a valuable example for research on the suppression phenomenon. The flanking markers developed in this study might be useful for screening Ae. tauschii accessions with no suppressor gene (Su-TdDof) to develop more synthetic hexaploid wheat lines for the breeding of lodging resistance in wheat and further cloning the suppressor gene Su-TdDof.

Development of New Dermato-Cosmetic Therapeutic Formulas with Extracts of Vinca minor L. Plants from the Dobrogea Region.

A new trend in the use of indole alkaloids from natural products is the preparation of topical pharmaceutical formulations with applications in the field of regenerative medicine. These formulations can be characterized through the ease of administration, the proven healing action of indole alkaloids, the protection of skin lesions, and the assurance of oxygen permeability. Based on the numerous benefits that indole compounds extracted from the Vinca minor plant show externally, the purpose of this study was to develop new semi-solid biocomposites for topical application obtained from hydroalcoholic macerates of 40%, 70%, and 96% concentrations from the stems and leaves of the Vinca minor L. plant from the Dobrogea area. A total of 12 pharmaceutical formulations (named P1-P12) were prepared for which the physicochemical properties, pH, thermal stability, spreading capacity, and rheological behavior were determined. The optimal formulas with antioxidant and antimicrobial capacity were evaluated and determined (P3, P4, P9, and P10). Antioxidant activity was elicited using the photochemiluminescence method. The microorganisms used for the evaluation of antimicrobial activity were Gram-positive Staphylococcus aureus (ATCC 25923), Gram-negative Escherichia coli (ATCC 25922), and a fungal species, Candida albicans (ATCC 900288). The study of the rheological profile for the obtained composites revealed Newtonian, pseudoplastic, and thixotropic fluid behaviors. Following determinations using the photochemiluminescence method, the best antioxidant activity was obtained in the P3 and P9 preparations. The results of the antimicrobial analysis confirmed that both the leaves and the stems of the Vinca minor plant represent a valuable source of antibacterial substances, and the biocomposites analyzed may represent an alternative in the realization of new pharmaceutical preparations with topical applications based on hydroalcoholic macerates obtained from the Vinca minor plant.

Continuous Manufacturing of Oil in Water (O/W) Emulgel by Extrusion Process.

Pharmaceutical industries and drug regulatory agencies are inclining towards continuous manufacturing due to better control over the processing conditions and in view to improve product quality. In the present work, continuous manufacturing of O/W emulgel by melt extrusion process was explored using lidocaine as an active pharmaceutical ingredient. Emulgel was characterized for pH, water activity, globule size distribution, and in vitro release rate. Additionally, effect of temperature (25°C and 60°C) and screw speed (100, 300, and 600 rpm) on the globule size and in vitro release rate was studied. Results indicated that at a given temperature, emulgel prepared under screw speed of 300 rpm resulted in products with smaller globules and faster drug release.

Preliminary Study on the Development of Caffeine Oral Solid Form 3D Printed by Semi-Solid Extrusion for Application in Neonates.

Apnea of prematurity can be treated with a body-weight-adjusted dosage of caffeine. Semi-solid extrusion (SSE) 3D printing represents an interesting approach to finely tailor personalized doses of active ingredients. To improve compliance and ensure the right dose in infants, drug delivery systems such as oral solid forms (orodispersible film, dispersive form, and mucoadhesive form) can be considered. The aim of this work was to obtain a flexible-dose system of caffeine by SSE 3D printing by testing different excipients and printing parameters. Gelling agents (sodium alginate (SA) and hydroxypropylmethyl cellulose (HPMC)) were used to obtain a drug-loaded hydrogel matrix. Disintegrants (sodium croscarmellose (SC) and crospovidone (CP)) were tested for get rapid release of caffeine. The 3D models were patterned by computer-aided design with variable thickness, diameter, infill densities, and infill patterns. The oral forms produced from the formulation containing 35% caffeine, 8.2% SA, 4.8% HPMC, and 52% SC (w/w) were found to have good printability, achieving doses approaching to those used in neonatology (between 3 and 10 mg of caffeine for infants weighing approximately between 1 and 4 kg). However, disintegrants, especially SC, acted more as binder/filler, showing interesting properties to maintain the shape after extrusion and enhance printability without a significant effect on caffeine release.

The influence of household structure and composition on the introduction of solid, semisolid and soft foods among children aged 6-8 months: An analysis based on Ethiopia Demographic and Health Surveys.

The early and late introduction of complementary food, both prevalent in Ethiopia, are associated with morbidities, growth faltering and developmental risks in children. The interhousehold network around the primary caregiver's intrahousehold network is critical in influencing the age of introducing complementary foods. This study examined the influence of household composition and structures on complementary food introduction. This is a secondary data analysis of four Ethiopian Demographic and Health Surveys conducted between 2000 and 2016. The household structure and composition variables were calculated from household members' kinship status and attribute, respectively. The introduction of solid, semisolid or soft foods was dichotomised as whether the children within 6 to 8 months have been given complementary foods. Multivariable logistic regression with adjustment for the primary caregiver and household characteristics was run to examine the associations between household structure and composition variables and the introduction of complementary foods. The marginal effects (ME) were calculated to facilitate the practical interpretation of the study findings. Large households (>3 nonredundant contacts) with extended family or unrelated people (high effective size, ME = 6.01%, 95% confidence interval [CI]: -8.53, -3.49) lowered the proportion of children starting food within the recommended 6-8 months. Households with close kins (high constraint) (ME = 7.22%, 95% CI: -13.65, 28.09) and greater age diversity (ME = 0.65%, 95% CI: 0.15, 1.15) increased the proportion of children receiving complementary food at an appropriate age. This study revealed that interhousehold structure and composition influence the age of introduction of complementary foods. These factors, therefore, need to be considered in designing interventions to improve age at the introduction of complementary foods.

A Semi-solid Zinc Powder-based Slurry Anode for Advanced Aqueous Zinc-ion Batteries.

The booming of aqueous zinc-ion batteries (AZIBs) draws the researchers' attention to issues of zinc metal anodes, such as uncontrollable dendrite growth, corrosion, and volume effects. Zinc powder anode is more suitable for the industrial application of AZIBs than the widely used zinc foil anode due to its low cost, tunability and processability. However, the related solutions are rarely studied because the above issues of zinc metal anode are more serious in zinc powder anode. Herein, for the first time, we design a semi-solid zinc slurry anode consisting of zinc powder and zincophilic tin additive dispersed in a conductive elastic rheological network. Zinc can be deposited homogeneously on the dispersed tin particles, which avoids agglomerative zinc deposition and alleviates volume change during repeated zinc stripping/plating. Moreover, the practical application of the full cell with slurry is very promising since its operating life can be easily extended by facile slurry renewal.

Robust Multiscale Electron/Ion Transport and Enhanced Structural Stability in SiOx Semi-Solid Anolytes Enabled by Trifunctional Artificial Interfaces for High-Performance Li-Ion Slurry Flow Batteries.

SiOx suspension is regarded as an attractive anolyte for high-energy-density Li-ion slurry flow batteries. However, the poor electronic conductivity and non-negligible volume variation of SiOx greatly hinder its practical applications. Herein, these issues are successfully addressed by rationally designing a trifunctional interface with mixed electron/ion and hard/soft modulated properties on SiOx surface via H-bonding interactions. The interface comprises a lithiated polymer layer (LiPN) interfused with functionalized single-walled carbon nanotubes. Carbon nanotubes work as electrical tentacles to enhance the multiscale electron conduction. The LiPN layer with transferable Li-ions facilitates ion transport. In addition, the LiPN layer employs lithiated rigid polyacrylic acid as a framework to provide mechanical support and soft nafion as a buffer to accommodate volume change, which maintains the structural integrity of SiOx . Hence, SiOx @LiPN/S anolytes exhibit significantly improved rate and cycle performances. Specially, the interface enables the anolytes to load more active particles (30 wt%) or less conductive additives (0.4 wt%). The semi-solid pouch cells based on high-active-content anolytes with stable cyclability are first demonstrated and the flow cell using low-conductive-content anolytes displays a high volumetric capacity of 207 Ah L-1 . This strategy paves a novel approach for optimizing semi-solid electrodes for high-performance Li-ion slurry flow batteries.

Mechanistic Modeling of In Vitro Skin Permeation and Extrapolation to In Vivo for Topically Applied Metronidazole Drug Products Using a Physiologically Based Pharmacokinetic Model.

Physiologically based pharmacokinetic (PBPK) modeling has increasingly been employed in dermal drug development and regulatory assessment, providing a framework to integrate relevant information including drug and drug product attributes, skin physiology parameters, and population variability. The current study aimed to develop a stepwise modeling workflow with knowledge gained from modeling in vitro skin permeation testing (IVPT) to describe in vivo exposure of metronidazole locally in the stratum corneum following topical application of complex semisolid drug products. The initial PBPK model of metronidazole in vitro skin permeation was developed using infinite and finite dose aqueous metronidazole solution. Parameters such as stratum corneum lipid-water partition coefficient (Ksclip/water) and stratum corneum lipid diffusion coefficient (Dsclip) of metronidazole were optimized using IVPT data from simple aqueous solutions (infinite) and MetroGel (10 mg/cm2 dose application), respectively. The optimized model, when parameterized with physical and structural characteristics of the drug products, was able to accurately predict the mean cumulative amount permeated (cm2/h) and flux (µg/cm2/h) profiles of metronidazole following application of different doses of MetroGel and MetroCream. Thus, the model was able to capture the impact of differences in drug product microstructure and metamorphosis of the dosage form on in vitro metronidazole permeation. The PBPK model informed by IVPT study data was able to predict the metronidazole amount in the stratum corneum as reported in clinical studies. In summary, the proposed model provides an enhanced understanding of the potential impact of drug product attributes in influencing in vitro skin permeation of metronidazole. Key kinetic parameters derived from modeling the metronidazole IVPT data improved the predictions of the developed PBPK model of in vivo local metronidazole concentrations in the stratum corneum. Overall, this work improves our confidence in the proposed workflow that accounts for drug product attributes and utilizes IVPT data toward improving predictions from advanced modeling and simulation tools.

The Effects of Solid Particle Containing Inks on the Printing Quality of Porous Pharmaceutical Structures Fabricated by 3D Semi-Solid Extrusion Printing.

PURPOSE: Semi-solid extrusion (SSE) 3D printing has potential pharmaceutical applications for producing personalised medicine. However, the effects of ink properties and drug incorporation on the quality of printed medication have not been thoroughly studied, particularly for porous geometries. This study aimed to investigate the effects of the presence of solid drug particles in SSE inks on the printing quality of porous structures. METHOD: The rheological behaviour of model inks of paracetamol (PCM)-hypromellose (HPMC) with different drug loadings were investigated and correlated to their printing qualities. RESULTS: For the inks with PCM loading above the drug solubility in which suspended solid drug particulates were present, the results confirmed that PCM loading and particle size significantly affected the ink viscosities at a low shear rate. At a low shear rate, the highest viscosity was identified when the highest drug loading and the smallest PCM particles were incorporated into the inks. However, the results indicated that the SSE printing parameters and printing quality of porous structures (with less porous structural deformation) have no clear correlation with the shear viscosity data, but a strong correlation with the dynamic oscillatory rheology of the inks. CONCLUSION: The key rheological parameters including storage modulus, loss modulus and complex viscosity of the ink increased with increasing drug loading for the inks containing solid drug particles. However, decreasing the particle size did not have a clear effect on the oscillatory rheology of the inks which can be potentially used for optimising the SSE 3D printing quality of porous geometries.

Liposomal Formulation for Oral Delivery of Cyclosporine A: Usefulness as a Semisolid-Dispersion System.

PURPOSE: This study aims to understand the process and mechanism of oral drug absorption from liposomes and to verify the usefulness of liposomal formulation for poorly soluble drugs. METHODS: Cyclosporine A (CsA) was used as a model drug and entrapped into Dipalmitoylphosphatidylcholine (DPPC) and distearoylphosphatidylcholine (DSPC) liposomes. Molecular state of CsA in the liposomes was analyzed using powder X-ray diffraction (PXRD) and polarized light microscopy (PLM). Release profiles of CsA from liposomes were observed in fasted state simulated intestinal fluid (FaSSIF). Oral absorption of CsA from liposomal formulations were investigated in rats. RESULTS: PXRD and PLM analyses suggested that CsA exists in the lipid layer of liposomes as a molecular dispersed state. Although both liposomes retained CsA stably in the simple buffer, DPPC liposomes quickly released CsA within 10 min in FaSSIF due to the interaction with bile acid. In contrast, effect of bile acid was negligible in DSPC, indicating a high resistivity to membrane perturbation. Oral bioavailability of CsA from liposomal formulations were almost comparable with that from a marketed product (Neoral). However, the absorption profiles were clearly different. CsA was absorbed quickly from DPPC liposomes and Neoral, while sustained absorption profile was observed from DSPC liposomes. Further study in which ritonavir was co-entrapped in the liposomes with CsA showed the higher efficacy of ritonavir to increase oral bioavailability of CsA. CONCLUSION: Liposomes allows the appropriate formulation design for oral delivery of poorly soluble drugs, not only to increase the extent but also to control the rate of absorption.