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Levothyroxine is a drug with a narrow therapeutic index. Changing the drug formulation composition or switching between pharmaceutical brands can alter the bioavailability, which can result in major health problems. However, the increased adverse drug reactions have not been fully explained scientifically yet and a thorough investigation of the formulations is needed.In this study, we used a non-targeted analytical approach to examine the various levothyroxine formulations in detail and to reveal possible chemical changes. Ultra-high-performance liquid chromatography coupled with a data-independent acquisition high-resolution mass spectrometry (UHPLC-DIA-HRMS) was employed.UHPLC-DIA-HRMS allowed not only the detection of levothyroxine degradation products, but also the presence of non-expected components in the formulations. Among these, we identified compounds resulting from reactions between mannitol and other excipients, such as citric acid, stearate, and palmitate, or from reactions between an excipient and an active pharmaceutical ingredient, such as levothyroxine-lactose adduct. In addition to these compounds, undeclared phospholipids were also found in three formulations. This non-targeted approach is not common in pharmaceutical quality control analysis. Revealing the presence of unexpected compounds in drug formulations proved that the current control mechanisms do not have to cover the full complexity of pharmaceutical formulations necessarily.

In this study, an in-depth comparison was made between batch and continuous direct compression using similar compression set-ups. The overall material processability and final tablet quality were compared and evaluated. Correlations between material properties, process parameters and final tablet properties were made via multivariate data analyses. In total, 10 low-dosed (1% w/w) and 10 high-dosed (40% w/w) formulations were processed, using a total of 10 different fillers/filler combinations. The trials indicated that the impact of filler type, drug load or process settings was similar for batch and continuous direct compression. The main differentiator between batch and continuous was the flow dynamics in the operating system, where properties related to flow, compressibility and permeability played a crucial role. The less consistent flow throughout a batch process resulted in a significantly higher variability within the tablet press (σCF) and for the tablet quality responses (σMass, σTS). However, the better controlled blending procedure prior to batch processing was reflected in a more consistent API concentration variability. Overall, the comparison showed the benefits of selecting appropriate excipients and process settings to achieve a specific outcome, keeping in mind some key differentiators between both processes.

Halal is a crucial concept for Muslim consumers regarding consumed products, including pharmaceutical ingredients, which are essential in modern medicine. To address the issue of using porcine-sourced ingredients in pharmaceuticals, it is essential to search for halal alternatives derived from poultry, animal by-products from meat processing, marine sources, and plants. However, the complexity of this problem is further compounded by the rapid advances in innovation and technology, which can lead to adulteration of ingredients derived from pigs. Other challenges include the sustainability of alternative materials, management of waste or by-products practice, halal awareness, certification, government policies, religious adherence of consumers, food suppliers, marketers, and purchasing of products. The importance of halal and non-halal problems, specifically in the context of pharmaceutical materials, is still rarely discussed, including alternatives derived from poultry, animal by-products, marine sources, and plants. Due to the increasing global population, there is a growing need to increase awareness and concern among Muslim consumers for halal products, including pharmaceuticals. Therefore, this research aimed to investigate the importance of halal and non-halal issues in pharmaceutical ingredients, the potential impact on the Muslim community, as well as opportunities and challenges in the search for alternative ingredients.

Some exudate gums such as acacia and tragacanth gums have been certified to be used in pharmacy as excipients. In this study exudate gums, obtained from two local trees in Ghana: Cussonia arborea and Cordia mellinii, were assessed for their safety for use as pharmaceutical excipients. The crude gums were purified using water and 96% ethanol and digested by di-acid procedure using 65% HNO3 and 37% HCl (2:3) at 95 °C for elemental analysis. Quantification of Ca, Fe, Mg, Cu, Zn, Mn, Ni, Hg, Cd, Pb and As ions was done using AAS 400; Na and K using the single channel flame photometer; and P using Spectronic 20 spectrophotometer. Microbial quality of the purified gums was also determined by the British Pharmacopoeia method. Toxicity of the purified gums was evaluated using acute and sub chronic murine toxicity models. Quantities of elemental ions detected in both purified gums were not significantly high to affect the utilization of these gums as pharmaceutical excipients even in large dose and high dosing frequency drugs. Total aerobic viable counts of the gums were within the acceptable Pharmacopoeial specification and no harmful microorganisms were detected. Acute and sub-chronic toxicity tests of the gums showed that they are safe for use even in long term dosage regimen medications. Thus, when these gums are included in even long term use medicines as excipients, may not cause any harm to the patient. The gums are therefore safe and qualified for use as pharmaceutical excipients when purified.

The vibrational spectroscopy (FT-IR/Raman) and X-ray diffraction techniques are combined alongside the principal component analysis (PCA) as novel integrated analytical techniques to comparatively investigate latent chemical information and quality discrepancies regarding twelve (12) commercialized paracetamol (APAP) brands. This research aim is to present an advanced computational screening approach using spectroscopic and X-ray diffraction techniques with PCA as a tool to investigate the structural properties of pharmaceutical solid drugs by vibrational mode and diffraction pattern analyzes. Herein, the acquired vibrational, absorption, and diffraction datasets of APAP functionalities were collected at spectra and diffraction regions of intense peaks to develop predictive PCA models. Interestingly, the PCA models invalidate drug falsification in all the brands and predicted dissimilarities arising from observed differences in the vibrational/absorption modes of APAP form (I) in some brands due to excessive use of cheap (fillers and hydrocolloid alternatives) excipients. The PCA-PXRD model unveils discrepancies regarding the contrasting diffraction patterns (structure-property relationships) observed for APAP form (I) in the brands, which suggests differences in their pharmacokinetic properties cause an unapparent structural modification. Nevertheless, the comparative drug release studies present a%CDR between 93 and 98% in 30 min for all the brands, thus, structural modifications of APAP form (I) as observed in some brands show no serious effects on the%CDR and/ or solubility. Finally, it is expected that this work will contribute to the advances in screening techniques toward addressing the global drug challenges, especially in developing countries.

The material properties of excipients and active pharmaceutical ingredients (API's) are important parameters that affect blend uniformity of pharmaceutical powder formulations. With the current shift from batch to continuous manufacturing in the pharmaceutical industry, blending of excipients and API is converted to a continuous process. The relation between material properties and blend homogeneity, however, is generally based on batch-wise blending trials. Limited information is available on how material properties affect blending performance in a continuous process. Here, blending of API and excipients is studied in both a batch and a continuous process. Homogeneity of the resulting mixtures is analyzed, which reveals that the impact of material properties is very different in a continuous process. Where parameters such as particle size, density and flowability have significant impact on blending performance in a traditional batch process, continuous blending is more robust resulting in uniform blends for a large variety of blend compositions.

Convolutional Neural Networks (CNNs) are image analysis techniques that have been applied to image classification in various fields. In this study, we applied a CNN to classify scanning electron microscopy (SEM) images of pharmaceutical raw material powders to determine if a CNN can evaluate particle morphology. We tested 10 pharmaceutical excipients with widely different particle morphologies. SEM images for each excipient were acquired and divided into training, validation, and test sets. Classification models were constructed by applying transfer learning to pretrained CNN models such as VGG16 and ResNet50. The results of a 5-fold cross-validation showed that the classification accuracy of the CNN model was sufficiently high using either pretrained model and that the type of excipient could be classified with high accuracy. The results suggest that the CNN model can detect differences in particle morphology, such as particle size, shape, and surface condition. By applying Grad-CAM to the constructed CNN model, we succeeded in finding particularly important regions in the particle image of the excipients. CNNs have been found to have the potential to be applied to the identification and characterization of raw material powders for pharmaceutical development.

Probiotics and live therapeutic bacteria (LTB), their strictly regulated therapeutic counterpart, are increasingly important in treating and preventing biofilm-related diseases. This necessitates new approaches to (i) preserve bacterial viability during manufacturing and storage and (ii) incorporate LTB into delivery systems for enhanced therapeutic efficacy. This review explores advances in probiotic and LTB product development, focusing on preservation, protection, and improved delivery. Preservation of bacteria can be achieved by drying methods that decelerate metabolism. These methods introduce stresses affecting viability which can be mitigated with suitable excipients like polymeric or low molecular weight stabilizers. The review emphasizes the incorporation of LTB into polymer-based nanofibers via electrospinning, enabling simultaneous drying, encapsulation, and delivery system production. Optimization of bacterial survival during electrospinning and storage is discussed, as well as controlled LTB release achievable through formulation design using gel-forming, gastroprotective, mucoadhesive, and pH-responsive polymers. Evaluation of the presence of the actual therapeutic strains, bacterial viability and activity by CFU enumeration or alternative analytical techniques is presented as a key aspect of developing effective and safe formulations with LTB. This review offers insights into designing delivery systems, especially polymeric nanofibers, for preservation and delivery of LTB, guiding readers in developing innovative biotherapeutic delivery systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Nanomedicine drug products have reached an unprecedented high in terms of global commercial acceptance and media exposure with the approvals of the mRNA COVID-19 vaccines in 2021. In this paper, we examine the current state of the art for nanomedicine technologies as applied for pharmaceutical products and compare those trends with results from a recent IQ Consortium industry survey on nanomedicine drug products. We find that 1) industry companies continue to push the envelope in terms of new technologies for characterizing their specific drug products, 2) new analytical technologies continue to be utilized by industry to characterize the increasingly complex nanomedicine drug products and 3) alignment and communication are key between industry and regulatory authorities to better understand the regulatory filings that are being submitted. There are many CMC challenges that a company must overcome to successfully file a nanomedicine drug product. In 2022, the FDA Guidance on Drug Products containing Nanomaterials was published, and it provides a roadmap for submission of a nanomedicine drug product. We propose that our paper serves as a complimentary guide providing knowledge on specific CMC issues such as quality attributes, physicochemical characterization methods, excipients, and stability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

The purpose of this study was to investigate the mechanical stresses and strains acting on pharmaceutical glass tubing vials during freezing and thawing of model pharmaceutical formulations. Strain measurements were conducted inside of a laboratory-scale freeze-dryer using a custom wireless sensor. In both sucrose and trehalose formulations at concentrations between 5 % and 20 % w/v, the strain measurements initially increased before peaking in magnitude at temperatures close to the respective glass transition temperatures of the maximally freeze concentrated solutes, Tg'. We attribute this behavior to a shift in the mechanical properties of the frozen system from a purely elastic glass below Tg' to a viscoelastic rubber-like material above Tg'. That is, when the interstitial region becomes mechanically compliant at temperature above Tg'. The outputs were less predictable below 5 % w/v and tended to exhibit two separate peaks in strain output, one near the equilibrium melting temperature of pure ice and the other near Tg'. The peaks merged at concentrations between 4 and 5 % w/v where the largest strain magnitude was observed. The strain on primary packaging has traditionally been applied to evaluate the risk of damage or breakage due to, for example, crystallization of excipients. However, data collected during this study suggest there may be utility in formulation design or as a process analytical technology to minimize potentially destabilizing stresses and strains in the frozen formulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Plant-based (natural) excipients can reduce the over reliance on synthetic ones. They have advantages such as low toxicity, biodegradability and low-cost relative to the synthetic ones. Telfairia occidentalis is a creeping plant that is cultivated for food in some African countries. The leaves, stem and root of the plant have been investigated as potential sources of medicine. This study aimed at evaluating the fruit pulp as a potential suspending agent. The ripe fruits of the plant were harvested and authenticated at the Department of Herbal Medicine, KNUST. The fruit pulp was extracted, freeze-dried and evaluated for its anti-microbial, phytochemical, physicochemical and anti-oxidant properties. Different concentrations of the dried pulp were used as a suspending agent in calamine lotion formulations, using bentonite as reference. The extract contained alkaloids, tannins, saponins, coumarins, glycosides, terpenoids magnesium and potassium. No antimicrobial and antioxidant activities were detected. The extract at all tested concentrations produced some level of suspendability. The test suspensions have good flow rates, high sedimentation volumes, high degree of flocculation, and relative ease of re-dispersion. However, these parameters were significantly (P < 0.05) lower (except flow rate) compared to those of bentonite as a suspending agent.

The European Commission (EC) has tasked the European Medicines Agency (EMA) to provide a recommendation towards the acceptability of titanium dioxide (TiO 2 ) in pharmaceutical products by early 2024 to inform on final decision in early 2025[1]. Unlike the already implemented ban of TiO 2 in foods, removing this excipient from pharmaceutical products will likely have significant impact on the pharmaceutical industry, regulatory agencies, and patients. This commentary explores the challenges facing the pharmaceutical industry tasked with supporting the development and registration of TiO 2 free (TF) drug products. Specifically, justification of formulation changes and potential impact to in vitro and in vivo performance, as well as differences in global regulatory comparative dissolution requirements to justify changing to TF drug product are discussed. Particularly, the uncertainties around how a formulation change such as removal of TiO 2 from immediate release solid oral dosage forms will be viewed in Europe compared to other regions is discussed. To respond to these challenges and avoid disruption to the medicines supply chain in case in vitro data such as dissolution is either too challenging or insufficient to justify changing to TF product, pharmaceutical companies may have to decide if the level of risk is worth the effort needed to reformulate, develop, and register a new TF product., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

The addition of antioxidants to pharmaceutical products is a potential approach to inhibit nitrosamine formation, particularly in solid oral dosage forms like tablets and capsules. The objective was to assess the effect of ten antioxidants on the permeability of four Biopharmaceutics Classification System (BCS) Class III drugs. Bi-directional drug permeability studies in the absence and presence of antioxidants were performed in vitro across MDCK-II monolayers. No antioxidant increased drug permeability, while the positive control sodium lauryl sulfate always increased drug permeability. Results support that any of the ten antioxidants, up to at least 10 mg, can be added to a solid oral dosage form without modulating passive drug intestinal permeability. Additional considerations are also discussed., Competing Interests: Declaration of Competing Interest There are no conflicts of interest for these authors to declare. The information in the paper reflects views from authors and should not be construed to represent FDA's views or policies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The majority of commercially available monoclonal antibody (mAb) formulations are stabilized with one of three non-ionic surfactants: polysorbate 20 (PS20), polysorbate 80 (PS80), or poloxamer 188 (P188). All three surfactants are susceptible to degradation, which can result in functionality loss and subsequent protein aggregation or free fatty acid particle formation. Consequently, quantitative, and qualitative analysis of surfactants is an integral part of formulation development, stability, and batch release testing. Due to the heterogeneous nature of both polysorbates and poloxamer, online isolation of all the compounds from the protein and other excipients that may disturb the subsequent liquid chromatography with charged aerosol detection (LC-CAD) analysis poses a challenge. Herein, we present an analytical method employing LC-CAD, utilizing a combination of anion and cation exchange columns to completely remove proteins online before infusing the isolated surfactant onto a reversed-phase column. The method allows high throughput analysis of polysorbates within 8 minutes and poloxamer 188 within 12 minutes, providing a separation of the surfactant species of polysorbates (unesterified species, lower esters, and higher esters) and poloxamer 188 (early eluters and main species). Accuracy and precision assessed according to the International Council for harmonisation (ICH) guideline were 96 - 109 % and ≤1 % relative standard deviation respectively for all three surfactants in samples containing up to 110 mg/mL mAb. Subsequently, the method was effectively applied to quantify polysorbate 20 and polysorbate 80 in nine commercial drug products with mAb concentration of up to 180 mg/mL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In this work, soybean lecithin (LC) was used to modify β-cyclodextrin (β-CD) with hydrophobic fat chains to become amphiphilic (LC-CD), and vitamin E (VE) was encapsulated in former modified β-CD complexes (LC-CD-VE), the new Pickering emulsions stabilized by LC-CD-VE and LC-CD complexes for the delivery of β-carotene (BC) were created. The surface tension, contact angle, zeta potential, and particle size were used to assess the changes in complexes nanoparticles at various pH values. Furthermore, LC-CD-VE has more promise as Pickering emulsion stabilizer than LC-CD because of the smaller particle size (271.11 nm), proper contact angle (58.02°), and lower surface tension (42.49 mN/m). The interactions between β-cyclodextrin, soybean lecithin, and vitamin E were confirmed using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and thermogravimetric analysis (TGA). The durability of Pickering emulsions was examined at various volume fractions of the oil phase and concentrations of nanoparticles. Compared to the emulsion stabilized by LC-CD, the one stabilized by LC-CD-VE showed superior storage stability. Moreover, for the delivery of BC, Pickering emulsions stabilized by LC-CD and LC-CD-VE can outperform bulk oil and Tween 80 stabilized emulsions in terms of UV light stability, storage stability, and bioaccessibility. This work could offer fresh perspectives on stabilizer alternatives for Pickering emulsion delivery systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pectin is widely used in several products in the industry. Conventionally, strong and harmful acids are used for its extraction. This study optimized the extraction of orange peel's pectin using citric acid, considering yield and degree of esterification (DE) as response variables. Proximal analyses were performed, and the samples were subjected to a Box-Behnken design on three central points, considering as variables the temperature, time, and pH. The results of proximate analyses of the orange peels revealed 11.76 % moisture content, 87.26 % volatiles, 0.09 % ash, 50.45 % soluble carbohydrates, 70.60 % total carbohydrates, 0.89 % fixed carbon, 5.35 % lipids, and 36.75 mg GAE/g of phenolic compounds. The resulting second-order polynomial model described the relation of the input and output variables related to each other. The best performance to obtain a higher yield (18.18 %) of high methoxyl pectin (DE 50 %) was set at 100 °C/30 min/pH 2.48. Pectin showed antioxidant properties by ABTS and DPPH assays and similar thermal properties to the commercial polymer. Its equivalent weight was 1219.51 mol/g, and the methoxyl and anhydrouronic acid were 2.23 and 67.10 %, respectively. Hence, pectin extraction with citric acid results in a high-quality polymer and could be used as a gelling agent, stabilizer, or texturizer in food products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Currently, people eat Undaria pinnatifida (UP) in a single way, and processing homogeneity is serious. However, UP has not gained any traction in the 3D printing industry to date. This study explored the incorporation of soy protein isolate (SPI), pea protein (PP), xanthan gum (XG), guar gum (GG), corn starch (CS), and potato starch (PS) into UP slurry liquid, the primary component of the study, to formulate a UP gel ink. The UP gel 3D printing ink system based on UP paste was established and characterized. The results show that hydrogen bonds are formed, and three-dimensional gel network structure is formed in all UP gel inks. UP gel inks containing high concentrations of SPI and GG exhibited good texture and rheological qualities and good 3D printing effect, with storage modulus (G') values of 8440.405 ± 3.893 and 8111.730 ± 3.585 Pa. The loss of modulus (G″) values were 1409.107 ± 3.524 and 1071.673 ± 3.669 Pa. Unfortunately, the properties of other UP gel inks are not suitable, resulting in poor 3D printing results. The food 3D printing method developed in this study provides valuable insights for expanding food 3D printing material choices and achieving high-value applications of UP., Competing Interests: Declaration of competing interest The authors declared that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cellulose nanocrystal (CNC) is an abundant biopolymer possessing high strength and biodegradability. In the present work, the extraction of CNCs from Napier grass stems was carried out. The CNCs were subsequently modified by maleic anhydride, called M-CNC, before being incorporated into the epoxidized natural rubber (ENR). The compounds were later cured by ultraviolet (UV) irradiation under various conditions. The obtained optimum condition was then used to fabricate the biocomposites filled with various CNC and M-CNC loadings for triboelectric nanogenerator (TENG) performance measurements. Output voltage and current increased continuously with increasing filler loading. Regardless of the filler type, an increase in filler loading enhanced TENG output. ENR/M-CNC exhibited a superior TENG output to ENR/CNC due to the greater electron transfer capability of the biocomposites, as proven by the reduction in the ionization potential (IP) value obtained from the quantum calculation. In this study, ENR/M-CNC5 exhibited the maximum output voltage (80.3 V), current (7.4 μA), and power density (1.32 W/m 2 ) at a load resistance of 9 MΩ., Competing Interests: Declaration of competing interest There is no conflict of interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The oral bioavailability of poorly soluble drugs has always been the focus of pharmaceutical researchers. We innovatively combined nanocrystal technology and solid dispersion technology to prepare novel nanocrystalline solid dispersions (NCSDs), which enable both the solidification and redispersion of nanocrystals, offering a promising new pathway for oral delivery of insoluble Chinese medicine ingredients. The rubusoside (Rub) was first used as the multifunctional stabilizer of novel apigenin nanocrystal-based solid dispersions (AP-NSD), improving the in vitro solubilization rate of the insoluble drug apigenin(AP). AP-NSD has been produced using a combination of homogenisation and spray-drying technology. The effects of stabilizer type and concentration on AP nanosuspensions (AP-NS) particles, span, and zeta potential were studied. And the effects of different types of protective agents on the yield and redispersibility of AP-NSD were also studied. Furthermore, AP-NSD was characterized by infrared spectroscopy (IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). Solubility was used to assess the in vitro dissolution of AP-NSD relative to APIs and amorphous solid dispersions (AP-ASD), and AP-ASD was prepared by the solvent method. The results showed that 20% Rub stabilized AP-NSD exhibited high drug-loading and good redispersibility and stability, and higher in vitro dissolution rate, which may be related to the presence of Rub on surface of drug. Therefore provides a natural and safe option for the development of formulations for insoluble drugs., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interests., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Assessing the robustness of a drug product formulation and manufacturing process to variations in raw material (RM) properties is an essential aspect of pharmaceutical product development. Motivated by the need to demonstrate understanding of attribute-performance relationships at the time of new product registration and for subsequent process maintenance, we review practices to explore RM variations. We describe limitations that can arise when active ingredients and excipients invariably undergo changes during a drug product lifecycle. Historical approaches, such as Quality-by-Design (QbD) experiments, are useful for initial evaluations but can be inefficient and cumbersome to maintain once commercial manufacturing commences. The relatively miniscule data sets accessible in product development - used to predict response to a hypothetical risk of variation - become less relevant as real-world experience of actual variability in the commercial landscape grows. Based on our observations of development and manufacturing, we instead propose a holistic framework exploiting a hierarchy of RM variability, and challenge this with common failure modes. By explicitly incorporating higher ranking RM variations as perturbations, material-conserving experiments are shown to provide powerful and enduring robustness data. Case studies illustrate how correctly contextualizing such data in formulation and process development can avoid the traps of historical QbD approaches and become valuable for evaluating changes occurring later in the drug product lifecycle., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Caffeine increases the analgesic properties of acetaminophen and therefore it is reasonable to use both substances together in one drug form in stronger pain. Currently, there are no commercially available pharmaceutical combination products containing acetaminophen and caffeine, which is present as granules. The aim of the study was to obtain twelve different granules with these therapeutic substances and determine the effect of various excipients on the quality of the drug form. All the granules were made by wet granulation. Two types of binders were used: polyethylene glycol 6000 (PEG) and polyvinylpyrrolidone K30 (PVP) as well as different types of fillers. The physical properties of granules were assessed in accordance to the requirements of the European Pharmacopoeia 8th ed. The highest apparent density was found in preparations containing calcium hydrophosphate (0.609 g/mL) and the lowest – containing mannitol (0.353 g/mL) as a filler. The Hausner ratio of most prepared granules ranged from 1.05 to 1.11, while the compressibility index ranged from 4.59 to 10.48%. The evaluation of properties of individual granules helped to indicate formulation with good features, which perhaps will be a good alternative to currently available painkillers with caffeine and acetaminophen.

In this study, the application of sodium bentonite (SB) in formulation of tablets prepared by direct compression for oral administration was tested. Three different model drugs with different solubilities: paracetamol, diclofenac sodium and metformin HCl were tested. Each drug was mixed with SB at ratio of 50% and the mixtures were subsequently compressed. Compatibility studies were conducted using both Deferential Scanning Calorimeter (DSC) and Fourier Transform Infrared Spectroscopy (FTIR). The dissolution profile for each drug was determined in USP-buffers at different time intervals. Diclofenac sodium in pH 6.8 buffer and paracetamol in both pH 6.8 and pH 4.5 buffers showed extended release. However, metformin HCl showed immediate release at the different pH values. The study showed that using SB was possible to prepare tablets with different release profiles. However, these profiles differ depending on dissolution media and drug type.

Cilazapril, a moisture-sensitive compound, is known to undergo rapid degradation which could be additionally facilitated by the presence of excipients that contain or absorb moisture. Hence we investigated the stability of cilazapril in two commercially-available dosage forms and in binary mixtures with the selected excipients used in the studied commercial formulations i.e.: hypromellose, lactose monohydrate, maize starch and talc in order to detect any possible, stability-affecting incompatibilities. Also the impact of the blister made of oriented polyamide/aluminum/polyvinyl chloride//aluminum on cilazapril-containing tablets was researched. A validated HPLC and HPLC-MS methods were used for analysis and the isothermal stress testing conditions were applied (temperature range 318–343 K, relative humidity 76.4% for tablets and temperature 333 K, relative humidity range 50.9–76.4% for binary mixtures). It was shown that the degradation of cilazapril in both, model mixtures and tablets follows the autocatalytic model kinetics and it is more rapid than that observed for pure substance, evidenced by higher degradation rate constants. The immediate packaging protects cilazapril in tablets from degradation only in case of the original drug while in its blistered generic counterpart a slight but statistically insignificant increase of cilazapril decay occurs when compared to bare tablets (p

Due to significant dietary supplement use in the US, product manufacturers must understand the importance of implementing a robust approach to establishing safety for all ingredients, including dietary ingredients, components, and finished dietary supplement products. Different regulatory pathways exist by which the safety of dietary ingredients can be established, and thus allowed to be marketed in a dietary supplement. For individual dietary ingredients, safety information may come from a variety of sources including history of safe use, presence of the ingredient in foods, and/or non-clinical and clinical data. On occasion safety data gaps are identified for a specific ingredient, particularly those of botanical origin. Modern toxicological methods and models can prove helpful in satisfying data gaps and are presented in this review. For finished dietary supplement products, issues potentially impacting safety to consider include claims, product labeling, overages, contaminants, residual solvents, heavy metals, packaging, and product stability. In addition, a safety assessment does not end once a product is marketed. It is important that manufacturers actively monitor and record the occurrence of adverse events reported in association with the use of their products, in accordance with the law. Herein, we provide a comprehensive overview of considerations for assessing dietary supplement safety., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jay E Sirois reports a relationship with Consumer Healthcare Products Association that includes: employment. Corresponding author is employed by a trade association (Consumer Healthcare Products Association) that represents manufacturers and marketers of dietary supplement products. Other co-authors are employed by companies that manufacture and or market dietary supplements., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Nowadays, various high-performance electromagnetic interference (EMI) shielding materials have enormous application potential in electronic field. However, traditional EMI shielding materials often have high conductivity, resulting in the serious mismatch between the impedance of the material surface and the free space, which will cause a large amount of reflection of electromagnetic (EM) waves, leading to secondary reflection pollution. In this paper, we report a novel flexible EMI shielding composite film with extremely low reflection loss and efficient EM wave absorption, which was prepared by assisted self-assembly based on simple vacuum filtration using carboxymethyl cellulose as the matrix and MWCNT@Fe 3 O 4 synthesized by chemical coprecipitation as the composite functional filler. By adjusting the Fe 3 O 4 coating degree of MWCNTs in the filler, the composite film achieved the construction of a conductive network with high Fe 3 O 4 content. Benefit by the good adaptability of conductivity and magnetic permeability, the composite film has good impedance matching ability and microwave absorption performance. The reflection loss of the composite film with the thickness of 28 μm in the X-band was only 0.23 dB, accounting for 1.7 % of the total loss. This work provides new insights for the development of EMI materials and effective mitigation secondary EM wave reflection pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bletilla striata has been used for thousands of years and shows the functions of stopping bleeding, reducing swelling, and promoting healing in traditional applications. For Bletilla striata, Bletilla striata polysaccharides (BSP) is the main active ingredient, exhibiting biological functions of anti-inflammatory, anti-oxidant, anti-fibrotic, immune modulation, anti-glycation, and so on. In addition, BSP has exhibited the characteristics of excipient such as bio-adhesion, bio-degradability, and bio-safety and has been prepared into a series of preparations such as nanoparticles, microspheres, microneedles, hydrogels, etc. BSP, as both a drug and an excipient, has already aroused more and more attention. In this review, publications in recent years related to the extraction and identification, biological activities, and excipient application of BSP are reviewed. Specifically, we focused on the advances in the application of BSP as a formulation excipient. We hold opinion that BSP not only needed more researches in the mechanisms, but also the development into hydrogels, nano-formulations, tissue engineering, and so on. And we believe that this paper provides a beneficial reference for further BSP innovation and in-depth research and promotes the use of these natural products in pharmaceutical applications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

This study investigated the impact of cellulose nanofibers (CNFs) on montmorillonites (MMTs) exfoliation within thermoplastic starch (TPS) nanocomposites during the melt blending process. TPS nanocomposite films were manufactured using an internal mixer with a controlled ratio of CNFs and MMTs to evaluate the effect of individual and hybrid fillers on the material interactions and characteristics of the TPS composites. The incorporation of hybrid fillers resulted in notable enhancements in torque values and rheological properties, suggesting interactions between the starch, CNFs, and MMTs. The degree of MMT intercalation, obtained via X-ray diffraction analysis, decreased with the addition of CNFs, indicating that CNFs positively impacted MMT exfoliation. Scanning electron microscopy (SEM) images of cryo- and tensile-fractured samples highlighted the effectiveness of CNFs in facilitating MMT exfoliation and reinforcing interactions between the MMTs and TPS matrix. These interactions enhanced the tensile strength and Young's modulus by up to 95.8 % and 278.2 %, respectively, with a 1:1 weight ratio of CNFs to MMTs. Additionally, well-dispersed MMTs within the TPS matrix caused passivation and created tortuous paths, improving the water contact angle and decreasing the water vapor sorption. These synergistic effects of the hybrid filler, achieved through a melt blending process, indicate the potential use of TPS nanocomposites as an eco-friendly packaging material., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In recent years, biopolymer aerogels as thermal insulation materials have received widespread attention due to natural abundance, cost-efficiency, and environment-friendly. However, the flammability and low strength hinder its practical application. Hollow glass microspheres (HGMs) as an inorganic thermal insulation filler have been filled in biopolymer aerogels to improve flame retardancy. However, the structure formed by HGMs embedded porous network of biopolymer aerogel has rarely been investigated, which not only reduce thermal conductivity through high porosity, but also adjust the filling volume of HGMs and achieve uniform distribution through chemical cross-linking. Herein, a biopolymer aerogel composite was assembled by chitosan aerogel (CSA) and different volume of HGMs by chemical cross-linking, freeze-drying, and silylation modification processes. When the filling volume fraction of HGMs reached 40 %, a skeleton structure was initially formed. The composites with HGMs volume of 40 %-60 % exhibited low density, high porosity, low thermal conductivity, good mechanical property, and excellent flame retardancy. According to GB 8624-2012 standard for classification, the composite with 60 % HGMs achieved class A1 non-combustible., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

To improve the paper strength, a number of resins and polymeric materials are being used, which is not environmental friendly and sustainable. Therefore, bio-based paper additives for the papermaking industry are essential. In this investigation, a water soluble biopolymer like carboxymethyl chitosan (CMCh) was prepared. The degree of substitution of the prepared CMCh was 2.49. The solubility of the prepared CMCh was 2.0 (w/v) % at 50 °C, and the conductivity increased with the increase of CMCh concentration in water. The prepared CMCh was applied as dry and wet strength agent of unrefined and refined softwood pulps. Both pulp increased dry and wet strength with increasing CMCh dose. An addition of 2.0 % CMCh increased dry strength by 125 % and wet strength by 293 % of unrefined pulp. On the other hand, the dry and wet tensile index of refined pulp increased from 59.48 N·m/g to 66.11 N·m/g and 2.48 N·m/g to 3.47 N·m/g, respectively, with the addition of 1.0 % CMCh. The CMCh was also used in filler modification. The precipitated calcium carbonate (PCC) modified with CMCh increased the ash content in paper with improved strength properties. The CMCh can be used in papermaking both for improving paper strength and filler retention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Understanding the interplay between gluten and wheat starch is crucial for elucidating the digestibility mechanism of gluten in wheat-based products. However, this mechanism remains under-investigated. This study sought to elucidate the influence of starch-induced protein structural modifications on gluten digestion. Our findings revealed that starch considerably enhanced gluten digestion. In the presence of starch, gluten protein digestibility increased from 10.91 % (in the control group with a gluten-to-starch ratio of 1:0) to 14.40 % (in the complex with a gluten-to-corn starch ratio of 1:1). The diminished gluten protein digestibility due to starch may be ascribed to modifications in protein configuration and aggregation behavior. Morphological studies suggested that starch not only functioned as filler particles but also diluted the gluten matrix. A protein network assessment further affirmed that both the junction density and branching rate of gluten proteins decreased notably by 29.9 % and 25.1 %, respectively. Conversely, lacunarity increased by 1.92-fold, compromising the cohesiveness and connectivity of the gluten matrix. Elevated starch concentrations suppressed the formation of disulfide bonds, impeding gluten protein aggregation. Concurrently, gluten-starch interactions were governed by hydrogen bonds and hydrophobic associations. In summary, starch augmented gluten protein digestibility by curtailing their polymerization. This revelation might offer novel perspectives on optimizing gluten protein digestion and utilization., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

For the drug delivery system, drug carriers' selection is critical to the drug's success in reaching the desired target. Drug carriers from natural biopolymers are preferred over synthetic materials due to their biocompatibility. The use of polysaccharide gums in the drug delivery system has received considerable attention in recent years. Polysaccharide gums are renewable resources and abundantly found in nature. They could be isolated from marine algae, microorganisms, and higher plants. In terms of carbohydrates, the gums are water-soluble, non-starch polysaccharides with high commercial value. Polysaccharide gums are widely used for controlled-release products, capsules, medicinal binders, wound healing agents, capsules, and tablet excipients. One of the essential applications of polysaccharide gum is drug delivery systems. The various kinds of polysaccharide gums obtained from different plants, marine algae, and microorganisms for the drug delivery system application are discussed comprehensively in this review paper., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Starch is a natural, renewable, affordable, and easily available polymer used as gelling agents, thickeners, binders, and potential raw materials in various food products. Due to these techno-functional properties of starch, food and non-food industries are showing interest in developing starch-based food products such as films, hydrogels, starch nanoparticles, and many more. However, the application of native starch is limited due to its shortcomings. To overcome these problems, modification of starch is necessary. Various single and dual modification processes are used to improve techno-functional, morphological, and microstructural properties, film-forming capacity, and resistant starch. This review paper provides a comprehensive and critical understanding of physical, chemical, enzymatic, and dual modifications (combination of any two single modifications), the effects of parameters on modification, and their applications. The sequence of modification plays a key role in the dual modification process. All single modification methods modify the physicochemical properties, crystallinity, and emulsion properties, but some shortcomings such as lower thermal, acidic, and shear stability limit their application in industries. Dual modification has been introduced to overcome these limitations and maximize the effectiveness of single modification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study aims to quantify ciprofloxacin in commercial tablets with varying excipient compositions using Fourier Transform Near-Infrared Spectroscopy (FT-NIR) and chemometric models: Partial Least Squares (PLS) and Multivariate Curve Resolution - Alternating Least Squares (MCR-ALS). Matrix variation, arising from differences in excipient compositions among the tablets, can impact quantification accuracy. We discuss this phenomenon, emphasizing potential issues introduced by varying certain excipients and its importance in reliable ciprofloxacin quantification. We evaluated the performance of PLS and MCR-ALS models independently on two sets of tablets, each containing the same drug substance but different excipients. The statistical results revealed promising results with PLS prediction error of 0.38% w/w of the first set and 0.47% w/w of the second set, while MCR-ALS achieved prediction errors of 0.67% w/w of the first set and 1.76% w/w of the second set. To address the challenge of matrix variation, we developed single models for PLS and MCR-ALS using a dataset combining both first and second sets. The PLS single model demonstrated a prediction error of 4.3% w/w and a relative error of 6.41% w/w, while the MCR-ALS single model showed a prediction error of 1.88% w/w and a relative error of 1.29% w/w. We then assessed the performance of the single PLS and MCR-ALS models developed based on the combination of the first and the second set in quantifying ciprofloxacin in various commercial tablet brands containing new excipients. The PLS model achieved a prediction error ranging between 6.2% w/w and 8.39% w/w, with relative errors varied between 8.53% w/w and 12.82% w/w. On the other hand, the MCR-ALS model had a prediction error between 1.11% w/w and 2.66% w/w, and the relative errors ranging from 0.8% to 1.74% w/w., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The solubility and permeability enhancement of curcumin (Cur) is crucial for its manufacture and application in medical field. Herein, Cur amorphous solid dispersions (ASDs) with enhanced drug solubility and permeability was formulated by Eudragit EPO (EuD) and biological macromolecules of hydroxypropyl methylcellulose E50 (HPMC), and significant functions of HPMC for Cur ASDs were mainly studied. The results showed that the mean particle size of Cur decreased from more than 300 nm to less than 200 nm with the addition of HPMC in excipient aqueous solution evidenced by dynamic light scattering result, confirming that HPMC had the ability to inhibit crystallization by lowering drug-rich droplets in the initial mixing process. Innovatively for molecular dynamic modeling study, crystalline Cur molecules in EuD medium trended to aggregate while not for EuD/HPMC 1:1 and EuD/HPMC 3:1 medium. HPMC functioned as surfactant converted the arrangement of phospholipid bilayers to un-ordered, and un-ordered state of phospholipids lead to the enhancement of Cur transmembrane using HPMC as auxiliary excipient. Cur-EuD/HPMC 3:1 contributed greatly to the Cur permeability, leading to obtain superior relative oral bioavailability and anti-inflammatory effect. Cur ASDs with proper amount of HPMC can be rendered as outstanding therapeutic strategy for medical application., Competing Interests: Declaration of competing interest There is no conflict of interest in the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Light-emitting perovskite quantum dots (PeQDs) are extensively investigated owing to their evident merits. However, it is still a challenge to adjust their intrinsic emissions and enhance their thermal stability to achieve full-color highly emissive QD-based light-emitting diodes (QLEDs), especially blue QLEDs. Herein, we demonstrate an effective strategy to fundamentally stabilize the crystal structure of CsPbBr 3 QDs by codoping Na + and Cu 2+ ions, which are designed to substitute Cs + (A sites) and Pb 2+ (B sites), respectively. It is found out that the codoping metal ions have significantly improved the thermal stability and the optical properties of the QDs. 40% of the emission intensity can be remained after 8 thermal cycles (20-120 °C) for CsPbBr 3 : Na + /Cu 2+ QDs, whilst less than 10% is maintained for undoped CsPbBr 3 QDs. Accordingly, stable blue QLEDs are packed by CsPbBr 3 : Na + /Cu 2+ QDs. Strong electroluminescence with the maximum luminance of 7161 cd m -2 and low turn-on voltage of 2.4 V are realized. The CIE coordinates are tuned from green (0.10, 0.74) to blue (0.17, 0.25) via Na + and Cu 2+ codoping. The maximum external quantum efficiency (EQE max ) is obtained as 4.52% for PeLEDs based on codoped QDs. The proposed metal ions A and B sites dual substitution strategy guarantees PeQDs as an extremely promising prospect in potential applications as high-resolution displays and high-quality lightings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The design and development of nanomaterials capable of penetrate cancer cells is fundamental when anticancer therapy is involved. The use of collagenase (Col) is useful since this enzyme can degrade collagen, mainly present in the tumor extracellular matrix. However, its use is often limited since collagenase suffers from inactivation and short half-life. Use of recombinant ultrapure collagenase or carrier systems for their delivery are among the strategies adopted to increase the enzyme stability. Herein, based on the more stability showed by recombinant enzymes and the possibility to use them in anticancer therapy, we propose a novel strategy to further increase their stability by using halloysite nanotubes (HNTs) as carrier. ColG and ColH were supramolecularly loaded onto HNTs and used as fillers for Veegum gels. The systems could be used for potential local administration of collagenases for solid tumor treatment. All techniques adopted for characterization showed that halloysite interacts with collagenases in different ways depending with the Col considered. Furthermore, the hydrogels showed a very slow release of the collagenases within 24 h. Finally, biological assays were performed by studying the digestion of a type-I collagen matrix highlighting that once released the Col still possessed some activity. Thus we developed carrier systems that could further increase the high recombinant collagenases stability, preventing their inactivation in future in vivo applications for potential local tumor treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Dry powder inhalers, comprising an active pharmaceutical ingredient (API) and carrier excipients, are often used in the delivery of pulmonary drugs. The stability of the API particle size within a formulation blend is a critical attribute for aerodynamic performance but can be challenging to measure. The presence of excipients, typically at concentrations much higher than API, makes measurement by laser diffraction very difficult. This work introduces a novel laser diffraction approach that takes advantage of solubility differences between the API and excipients. The method allows insight into the understanding of drug loading effects on API particle stability of the drug product. Lower drug load formulations show better particle size stability compared with high drug load formulations, likely due to reduced cohesive interactions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Metal-organic frameworks (MOFs) demonstrate strong potential in biosample separation. However, the obtained MOFs powders are unsuitable for recovery techniques in an aqueous solution, especially the challenges of withdrawing MOFs particles and expanding their functions for specific applications. Herein, a general strategy is designed utilizing metal oxide-nanochannel arrays as precursors and templates for in-situ selective growth of MOFs structures. The exemplary MOFs (Ni-bipy) with tailored composition are selectively grown in NiO/TiO 2 nanochannel membrane (NM) using NiO as the sacrificial precursor, which enables one to achieve a ∼262 times concentration of histidine-tagged proteins within 100 min. The significantly improved adsorption efficiency in a wide pH range and the effective enrichment from a complex matrix as a nanofilter illustrate the great potential of MOFs in nanochannels membranes for the high-efficiency recovery of essential proteins in complex biological samples. The porous self-aligned Ni-MOFs/TiO 2 NM exhibits biocompatibility and flexible functionalities, which is desirable for the generation of multifunctional nanofilter devices and developing biomacromolecule delivery vehicles., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Diabetic wound is considered as a kind of chronic wound prone to infection and difficult to repair due to high glucose level in the blood of patients. In this research, a biodegradable self-healing hydrogel with mussel inspired bioadhesion and anti-oxidation properties is fabricated based on Schiff-base cross-linking. The hydrogel was designed from dopamine coupled pectin hydrazide (Pec-DH) and oxidized carboxymethyl cellulose (DCMC) for mEGF loading as a diabetic wound repair dressing. The Pectin and CMC as natural feedstock endowed the hydrogel with biodegradability to avoid possible side effects, while the coupled catechol structure could enhance the tissue adhesion of the hydrogel for hemostasis. The results showed the Pec-DH/DCMC hydrogel formed fast and can cover irregular wounds with good sealing effect. The catechol structure also improved the reactive oxygen species (ROS) scavenging ability of the hydrogel, which can eliminate the negative effect of ROS during wound healing. The in vivo diabetic wound healing experiment revealed the hydrogel as mEGF loading vehicle greatly enhanced the diabetic wound repairing rate in mice model. As a result, the Pec-DH/DCMC hydrogel could show advantages as EGF carrier in wound healing applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To investigate and evaluate the chromatic dispersion of various hydrogel and silicon hydrogel contact lens materials., Methods: Eighteen different soft contact lens materials with high and low water content in lens power of -1.00 DS were measured by one operator at temperature of 20 °C ± 0.5° soaked in ISO standard phosphate-buffered saline (PBS) and in their respective packaging solutions (PS). An analogue Abbe refractometer (Model Zuzi 320, AUXILAB, S.L., Navarra, Spain) was used for refractive index (RI) measurements at 5 different wavelengths. All contact lenses were presented in a random and masked order to the operator. The Bland-Altman method with 95 % limits of agreement (LoA) and coefficient of repeatability (CoR) was used to characterise the repeatability of refractive index measurements. The Abbe numbers for each material were calculated by entering the measured and interpolated refractive indices into the Abbe number equation. One-way ANOVA analysis was used to test if there were significant differences between the 5 different wavelengths (470 nm-680 nm) within each material. An unpaired t-test was used to determine if there were differences in refractive index or dispersion between packaging solution and PBS results., Results: Nelfilcon A (Dailies Aqua Comfort Plus) soaked in PS showed the best repeatability of all 18 examined soft contact lenses across all wavelengths with an average refractive index of 1.3848 for all 6 contact lenses with a standard deviation of 0.00064. The 95 % limits of agreement were between 1.3835 and 1.3860. The mean coefficient of repeatability for nelfilcon A was 0.00125. For contact lenses soaked in ISO Standard PBS comfilcon A (Biofinity) had the best repeatability. The average refractive index of all 6 contact lenses was 1.4041 with a standard deviation of 0.00031 and a coefficient of repeatability of 0.00060. The 95 % limits of agreement were between 1.4035 and 1.4047. The analysis with One-way ANOVA with multiple comparisons involving Holm-Sidak post-hoc, showed that there are significant differences (p < 0.001, F ratio  = 376.2 between wavelengths and F ratio  = 1559 between different refractive indices) in the refractive index of most common lens materials across the visible wavelength range. Based on unpaired t-test, there is no significant difference (p > 0.05) in the Abbe numbers of the tested lens materials whether they have been placed in the packaging solution or in standard PBS (p > 0.05, 95 % CI = -4.8070 to 5.8680, t = 0.2054). The Abbe numbers for the calculated contact lenses soaked in PS ranged between 43.7 and 89.9. For contact lenses stored in PBS the range was between 46.3 and 81.6., Conclusion: There is a good repeatability between repeated RI measurements taken from the same lens and from the same material. The significant differences between the refractive indices across the 5 different wavelengths showed the presence of chromatic dispersion in the 18 evaluated soft contact lens materials. Furthermore, it could be shown that there is no significant difference in dispersion whether the contact lenses are soaked in standard PBS or in their respective packaging solutions. With no other published data available as a reference, absolute accuracy of the calculated Abbe numbers remains to be confirmed, however, this study did confirm that significant chromatic dispersion exists in soft contact lens materials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

The specifications of excipients are important to pharmaceutical manufacturers to ensure that the final product can be manufactured robustly over the entire lifecycle of a drug product. Particle size specifications are key for dry powder inhalation excipients and they should be agreed between users and suppliers. The current paper evaluates two development strategies to set particle size specifications. It is shown that the application of quality-by-design principles to specification setting could result in broader specifications, while it guarantees that efficacy, safety and manufacturing of the medication is not affected. A multitude of reasons exist to keep specifications broader than the production capability range, including improved risk-mitigation and potentially reduced regulatory challenges during and after registration., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Pickering emulsions are attracting increased attention owing to their therapeutic applications. However, the slow-release property of Pickering emulsions and the in vivo solid particle accumulation caused by the solid particle stabilizer film limit their applications in therapeutic delivery. In this study, drug-loaded, acid-sensitive Pickering emulsions were prepared using acetal-modified starch-based nanoparticles as stabilizers. The acetalized starch-based nanoparticles (Ace-SNPs) not only act as a solid-particle emulsifier to stabilize Pickering emulsions but also exhibit acid sensitivity and degradability, conducive to the destabilization of Pickering emulsions to release the drug and reduce the effect of particle accumulation in an acidic therapeutic environment. In vitro drug release profiles show that 50 % of curcumin was released in 12 h in an acidic medium (pH 5.4), whereas only 14 % of curcumin was released in 12 h at higher pH (7.4), indicating that the Ace-SNP stabilized Pickering emulsion possess good acid-responsive release characteristics in acidic environments. Moreover, acetalized starch-based nanoparticles and their degradation products showed good biocompatibility, and the resulting curcumin-loaded Pickering emulsions exhibited significant anticancer activity. These features suggest that the acetalized starch-based nanoparticle-stabilized Pickering emulsion has the potential for application as an antitumor drug carrier to enhance therapeutic effects., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)