Nanosuspension-Loaded Dissolving Microneedle Patches for Enhanced Transdermal Delivery of a Highly Lipophilic Cannabidiol.

Purpose: Transdermal Drug Delivery System (TDDS) offers a promising alternative for delivering poorly soluble drugs, challenged by the stratum corneum's barrier effect, which restricts the pool of drug candidates suitable for TDDS. This study aims to establish a delivery platform specifically for highly lipophilic drugs requiring high doses (log P > 5, dose > 10 mg/kg/d), to improve their intradermal delivery and enhance solubility. Methods: Cannabidiol (CBD, log P = 5.91) served as the model drug. A CBD nanosuspension (CBD-NS) was prepared using a bottom-up method. The particle size, polydispersity index (PDI), zeta potential, and concentration of the CBD-NS were characterized. Subsequently, CBD-NS was incorporated into dissolving microneedles (DMNs) through a one-step manufacturing process. The intradermal dissolution abilities, physicochemical properties, mechanical strength, insertion depth, and release behavior of the DMNs were evaluated. Sprague-Dawley (SD) rats were utilized to assess the efficacy of the DMN patch in treating knee synovitis and to analyze its skin permeation kinetics and pharmacokinetic performance. Results: The CBD-NS, stabilized with Tween 80, exhibited a particle size of 166.83 ± 3.33 nm, a PDI of 0.21 ± 0.07, and a concentration of 46.11 ± 0.52 mg/mL. The DMN loaded with CBD-NS demonstrated favorable intradermal dissolution and mechanical properties. It effectively increased the delivery of CBD into the skin, extended the action's duration in vivo, and enhanced bioavailability. CBD-NS DMN exhibited superior therapeutic efficacy and safety in a rat model of knee synovitis, significantly inhibiting TNF-α and IL-1ß compared with the methotrexate subcutaneous injection method. Conclusion: NS technology effectively enhances the solubility of the poorly soluble drug CBD, while DMN facilitates penetration, extends the duration of action in vivo, and improves bioavailability. Furthermore, CBD has shown promising therapeutic outcomes in treating knee synovitis. This innovative drug delivery system is expected to offer a more efficient solution for the administration of highly lipophilic drugs akin to CBD, thereby facilitating high-dose administration.

Enhancing Corneal Drug Penetration Using Penetratin for Ophthalmic Suspensions.

Eye drops, including solutions and suspensions, are essential dosage forms to treat ophthalmic diseases, with poorly water-soluble drugs typically formulated as ophthalmic suspensions. In addition to low bioavailability, suspensions exhibit limited efficacy, safety, and usability due to the presence of drug particles. Improving bioavailability can reduce the drug concentrations and the risk of problems associated with suspended drug particles. However, practical penetration enhancers capable of improving bioavailability remain elusive. Herein, we focused on penetratin (PNT), a cell-penetrating peptide (CPP) that promotes active cellular transport related to macromolecule uptake, such as micropinocytosis. According to the in vitro corneal uptake study using a reconstructed human corneal epithelial tissue model, LabCyte CORNEA-MODEL24, PNT enhanced the uptake of Fluoresbrite® YG carboxylate polystyrene microspheres without covalent binding. In an ex vivo porcine eye model, the addition of 10 µM PNT to rebamipide ophthalmic suspension markedly improved the corneal uptake of rebamipide; however, the addition of 100 µM PNT was ineffective due to potentially increased particle size by aggregation. This article provides basic information on the application of PNT as a penetration enhancer in ophthalmic suspensions, including the in vitro and ex vivo studies mentioned above, as well as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay and storage stability at different pH values.

In vivo antimalarial efficacy of Artemisia afra powder suspensions.

BACKGROUND: A global death toll of 608,000 in 2022 and emerging parasite resistance to artemisinin, the mainstay of antimalarial chemotherapy derived from the Chinese herb Artemisia annua, urge the development of novel antimalarials. A clinical trial has found high antimalarial potency for aqueous extracts of A. annua as well as its African counterpart Artemisia afra, which contains only trace amounts of artemisinin. The artemisinin-independent antimalarial activity of A. afra points to the existence of other antimalarials present in the plant. However, the publication was retracted due to ethical and methodological concerns in the trial, so the only evidence for antimalarial activity of A. afra is built on in vitro studies reporting efficacy only in the microgram per milliliter range. HYPOTHESIS: Our study aims to shed more light on the controversy around the antimalarial activity of A. afra by assessing its efficacy in mice. In particular, we are testing the hypothesis that A. afra contains a pro-drug that is inactive in vitro but active in vivo after metabolization by the mammalian host. METHODS: Plasmodium berghei-infected mice were treated once or thrice (on three consecutive days) with various doses of A. afra, A. annua, or pure artemisinin. RESULTS: Aqueous powder suspensions of A. annua but not A. afra showed antimalarial activity in mice. CONCLUSION: Our experiments conducted in mice do not support the pro-drug hypothesis.

Edaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone. MECHANISM OF ACTION: The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals. PHARMACOKINETICS: Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5-9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates. CLINICAL TRIALS: The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure. THERAPEUTIC ADVANCE: Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.

Effect of cyclodextrin-complexed lyophilized nanosuspension of Nigella sativa seeds oleoresin on chronic unpredictable mild stress (CUMS)-induced depression in mice.

Depression is a prevalent global health concern necessitating alternative approaches to conventional antidepressant medications due to its associated adverse effects. Nigella sativa (NS) is recognized for its potential as an antidepressant, offering a promising solution with fewer side effects. This study investigated the antidepressant efficacy of cyclodextrin-complexed lyophilized nanosuspension of NS oleoresin (NSOR) in a murine model of chronic unpredictable mild stress (CUMS)-induced depression. This study sought to evaluate and contrast the antidepressant potential of the nano-NSOR with that of the NS ethanolic extract (NSEE). The prepared nano-NSOR was characterized physicochemically and evaluated for in vitro drug release and in vivo antidepressant activity. The particle size of nano-NSOR was determined to be 164.6 nm. In vitro drug release studies suggested the higher drug release from nano-NSOR (90.15 % after 72 h) compared to the native NSOR (59.55 % after 72 h). Furthermore, nano-NSOR exhibited a more pronounced antidepressant effect than NSEE in the context of CUMS-induced depression. This study highlights a potential alternative for managing depression, addressing the need for improved antidepressant treatments with reduced side effects. These results suggest that nano-NSOR ameliorates CUMS-induced depression by modulating neurotransmitter levels, reducing inflammation, and enhancing neuroprotection.

Differentiating Microplastics from Natural Particles in Aqueous Suspensions Using Flow Cytometry with Machine Learning.

Microplastics (MPs) in natural waters are heterogeneously mixed with other natural particles including algal cells and suspended sediments. An easy-to-use and rapid method for directly measuring and distinguishing MPs from other naturally present colloids in the environment would expedite analytical workflows. Here, we established a database of MP scattering and fluorescence properties, either alone or in mixtures with natural particles, by stain-free flow cytometry. The resulting high-dimensional data were analyzed using machine learning approaches, either unsupervised (e.g., viSNE) or supervised (e.g., random forest algorithms). We assessed our approach in identifying and quantifying model MPs of diverse sizes, morphologies, and polymer compositions in various suspensions including phototrophic microorganisms, suspended biofilms, mineral particles, and sediment. We could precisely quantify MPs in microbial phototrophs and natural sediments with high organic carbon by both machine learning models (identification accuracies over 93%), although it was not possible to distinguish between different MP sizes or polymer compositions. By testing the resulting method in environmental samples through spiking MPs into freshwater samples, we further highlight the applicability of the method to be used as a rapid screening tool for MPs. Collectively, this workflow can be easily applied to a diverse set of samples to assess the presence of MPs in a time-efficient manner.

Calcipotriol Nanosuspension-Loaded Trilayer Dissolving Microneedle Patches for the Treatment of Psoriasis: In Vitro Delivery and In Vivo Antipsoriatic Activity Studies.

Psoriasis, affecting 2-3% of the global population, is a chronic inflammatory skin condition without a definitive cure. Current treatments focus on managing symptoms. Recognizing the need for innovative drug delivery methods to enhance patient adherence, this study explores a new approach using calcipotriol monohydrate (CPM), a primary topical treatment for psoriasis. Despite its effectiveness, CPM's therapeutic potential is often limited by factors like the greasiness of topical applications, poor skin permeability, low skin retention, and lack of controlled delivery. To overcome these challenges, the study introduces CPM in the form of nanosuspensions (NSs), characterized by an average particle size of 211 ± 2 nm. These CPM NSs are then incorporated into a trilayer dissolving microneedle patch (MAP) made from poly(vinylpyrrolidone) and w poly(vinyl alcohol) as needle arrays and prefrom 3D printed polylactic acid backing layer. This MAP features rapidly dissolving tips and exhibits good mechanical properties and insertion capability with delivery efficiency compared to the conventional Daivonex ointment. The effectiveness of this novel MAP was tested on Sprague-Dawley rats with imiquimod-induced psoriasis, demonstrating efficacy comparable to the marketed ointment. This innovative trilayer dissolving MAP represents a promising new local delivery system for calcipotriol, potentially revolutionizing psoriasis treatment by enhancing drug delivery and patient compliance.

Wet SPF: A wet powder suspension for the detection of latent fingermarks on the sticky side of adhesive tape for use in Seychelles.

WET UCIO is an inexpensive carbon-based powder suspension, reportedly as effective as commercially available formulations for latent fingermark detection on the sticky side of adhesive tapes. However, the surfactant solution used in WET UCIO is not readily accessible outside Europe, limiting its use in Seychelles or other non-European jurisdictions. In this study, the UCIO formulation was modified based on a 'frugal forensic' approach, by replacing the surfactant solution with an in-house sodium dodecyl sulfate solution prepared in 5 % aqueous ethanol. A comparative assessment against Wetwop™ using eight different pressure-sensitive adhesive tapes found that the modified formulation was at least as effective as commercial powder suspension. Modifying this technique under the frugal forensic framework has enhanced its accessibility to other jurisdictions and is recommended for validation in Seychelles.

Preparation and in vitro/in vivo evaluation of a pantoprazole sodium drug-resin liquid delayed release suspension.

A drug-resin liquid delayed-release suspension of pantoprazole sodium (PAZ-Na) was prepared to improve the effectiveness, convenience and safety of peptic ulcer treatment in children, the elderly and patients with dysphagia. Pantoprazole sodium drug-resin complexes (PAZ-Na-DRC) were prepared using the bath method. The fluidized bed coating method is used to coat it and then add excipients to make a dry suspension prepared before use. The parameters of the in vitro release experimental conditions were optimized and the drug release curve showed delayed release. Rats were given commercial PAZ-Na enteric-coated pellet capsules and the PAZ-Na delayed release suspension via intragastric administration. The results showed that the Tmax of the PAZ-Na delayed release suspension was increased from 2h to 4h compared with the PAZ-Na enteric-coated pellet capsules. Similarly, the Cmax was reduced from 6.162µg/mL to 3.244µg/mL with the concentration-time curve is very gentle compared with the commercial drug capsules. After oral administration, the relative bioavailability of PAZ-Na delayed release suspension (AUC0-24 of 19.578 µg•h•mL-1) compared with the commercial drug (AUC0-24 of 17.388 µg•h•mL-1) was 112.67%. The findings showed that the PAZ-Na delayed release suspension for oral administration was successfully formulated with highly improved pharmacokinetic indices.

Development and in vitro/in vivo evaluation of famotidine hydrochloride bioadhesive sustained release suspension.

To develop a new kind of famotidine-resin microcapsule for gastric adhesion sustained release by screening out suitable excipients and designing reasonable prescriptions to improve patient drug activities to achieve the expected therapeutic effect. The famotidine drug resin was prepared using the water bath method with carbomer 934 used as coating material. Microcapsules were prepared using the emulsified solvent coating method and appropriate excipients were used to prepare famotidine sustained release suspension. Pharmacokinetics of the developed microcapsules were studied in the gastrointestinal tract of rats. The self-made sustained-release suspension of famotidine hydrochloride effectively reduced the blood concentration and prolonged the action time. The relative bioavailability of the self-made suspension of the famotidine hydrochloride to the commercially available famotidine hydrochloride was 146.44%, with an average retention time of about 5h longer, which indicated that the new suspension had acceptable adhesion properties. The findings showed that the newly developed famotidine-resin microcapsule increased the bioavailability of the drug with a significant sustained-release property.

Nanosuspensions in ophthalmology: Overcoming challenges and enhancing drug delivery for eye diseases.

This review article provides a comprehensive overview of the advancements in using nanosuspensions for controlled drug delivery in ophthalmology. It highlights the significance of ophthalmic drug delivery due to the prevalence of eye diseases and delves into various aspects of this field. The article explores molecular mechanisms, drugs used, and physiological factors affecting drug absorption. It also addresses challenges in treating both anterior and posterior eye segments and investigates the role of mucus in obstructing micro- and nanosuspensions. Nanosuspensions are presented as a promising approach to enhance drug solubility and absorption, covering formulation, stability, properties, and functionalization. The review discusses the pros and cons of using nanosuspensions for ocular drug delivery and covers their structure, preparation, characterization, and applications. Several graphical representations illustrate their role in treating various eye conditions. Specific drug categories like anti-inflammatory drugs, antihistamines, glucocorticoids, and more are discussed in detail, with relevant studies. The article also addresses current challenges and future directions, emphasizing the need for improved nanosuspension stability and exploring potential technologies. Nanosuspensions have shown substantial potential in advancing ophthalmic drug delivery by enhancing solubility and absorption. This article is a valuable resource for researchers, clinicians, and pharmaceutical professionals in this field, offering insights into recent developments, challenges, and future prospects in nanosuspension use for ocular drug delivery.

Physical-chemical Stability of the Extemporaneous Paracetamol Oral Suspension in Puccini Base.

This study describes a new method for the preparation of extemporaneous paracetamol-based suspensions for pediatric and adult patients. This method allows the preparation of extemporaneous suspensions up to concentrations of 50 mg/mL by using a liquid base, named "Puccini". A high-pressure liquid chromatographic method was developed and validated for the determination of chemical stability of paracetamol when the formulations were stored at 4°C and 25°C. The chemical stability of the active pharmaceutical ingredient in the base was demonstrated for more than 90 days. Visual analyses of the formulations showed a phenomenon of precipitation at both storage temperatures, but the simple agitation of the formulations before its use re-established the formation of homogeneous suspensions.

Preparation of Healthy Single Neuron or Astrocyte Suspension from Adult Mouse Brain for RNA-seq.

Single-cell RNA sequencing (scRNA-seq) has been widely applied in neuroscience research, enabling the investigation of cellular heterogeneity at the transcriptional level, the characterization of rare cell types, and the detailed analysis of the stochastic nature of gene expression. Isolation of single nerve cells in good health, especially from the adult rodent brain, is the most difficult and critical process for scRNA-seq. Here, we describe methods to optimize protease digestion of brain slices, which enable yield of millions of cells in good health from the adult brain.

Non-destructive Raman Method Development for Quantifying Active Pharmaceutical Ingredient in an Oral Suspension Through Plastic Dosing Syringes.

For liquid drug products, e.g., solutions or suspensions for oral or parenteral dosing, stability needs to be demonstrated in primary packaging during storage and in dosing devices during in-use periods per quality guidelines from the International Conference on Harmonisation (ICH) and the European Agency for the Evaluation of Medicinal Products (EMEA). One aspect of stability testing for liquid drug products is in-use stability, which typically includes transferring the liquid samples into another container for further sample preparation with extraction diluent and necessary agitation. Samples are then analyzed with traditional chromatography methods, which are laborious, prone to human errors, and time-consuming, especially when this process needs to be repeated multiple times during storage and in-use periods. Being able to analyze the liquid samples non-destructively would significantly improve testing efficiency. We investigated different Raman techniques, including transmission Raman (TRS) and back scatter Raman with a non-contact optic (NCO) probe, as alternative non-destructive tools to the UHPLC method for API quantitation in in-use liquid samples pulled into plastic dosing syringes. The linearity of the chemometric methods for these two techniques was demonstrated by cross-validation sample sets at three levels over an API concentration range of 60 to 80 mg/mL. The accuracy of the chemometric models was demonstrated by the accurate prediction of the API concentrations in independent samples from four different pilot plant batches manufactured at different sites. Both techniques were successful in measuring a signal through a plastic oral dosing syringe, and predicting the suspension API concentration to within 4% of the UHPLC-measured value. For future work, there are opportunities to improve the methodology by exploring additional probes or to expand the range of applications by using different sample presentations (such as prefilled syringes) or formulation matrices for solutions and suspensions.

Colorimetric and fluorometric determination of uric acid by a suspension-based assay using enzyme-immobilized micro-sized particles.

Daily monitoring of serum uric acid levels is very important to provide appropriate treatment according to the constitution and lifestyle of individual hyperuricemic patients. We have developed a suspension-based assay to measure uric acid by adding a sample solution to the suspension containing micro-sized particles immobilized on uricase and horseradish peroxidase (HRP). In the proposed method, the mediator reaction of uricase, HRP, and uric acid produces resorufin from Amplex red. This resorufin is adsorbed onto enzyme-immobilized micro-sized particles simultaneously with its production, resulting in the red color of the micro-sized particles. The concentration of resorufin on the small surface area of the microscopic particles achieves a colorimetric analysis of uric acid with superior visibility. In addition, ethanol-induced desorption of resorufin allowed quantitative measurement of uric acid using a 96-well fluorescent microplate reader. The limit of detection (3σ) and RSD (n = 3) were estimated to be 2.2 × 10-2 µg/mL and ≤ 12.1%, respectively. This approach could also be applied to a portable fluorometer.

An investigation into the effect of surfactants on iron oxide powder suspension formulations for fingermark development.

Iron oxide powder suspension (FePS) is a fingermark development technique that can be used on adhesive and non-porous surfaces, the efficacy of which is known to be influenced by the surfactant used in the formulation. Despite previous work optimising surfactants for use in FePS, there is limited understanding of the interactions between surfactants, powders and fingermark residue which aid the successful development of fingermarks. To better understand the effect of surfactant on development quality produced by FePS, this research assessed a wide range of surfactants of different ionic natures and evaluated their ability to develop fingermarks based on the quality of ridge detail, contrast and background development produced. It was found that surfactants play a critical role in the selective deposition of powder on fingermark residue, as formulations made with only water (no surfactant) produced heavy background deposition. The efficacy of each surfactant depended on the quality parameter considered, and the addition of some surfactants hindered fingermark development. Effective surfactants such as T20, KP and TX100 prevented background development and produced well contrasted developed marks. Poor contrast was produced by LN, SP80/T80 and T80 due to indiscriminate powder deposition either across the entire sample or preventing any powder to deposit on the surface, demonstrating the role surfactants play in allowing powder deposition in this technique. The effectiveness of a surfactant in PS was not directly dependent on its ionic nature, and most surfactants were more effective when diluted from stock concentrations. This research has provided a robust base for future work improving fundamental understanding of FePS, which will greatly aid the efficacy of future optimisation efforts.

Tannic acid coated nanosuspension for oral delivery of chrysin intended for anti-schizophrenic effect in mice.

Chrysin is a flavonoid drug with numerous therapeutic activities. It suffers from low intestinal absorption owing to its hydrophobicity. Therefore, the aim of this study is to exploit the efficient technique of nanosuspension (NSP) to formulate chrysin-NSP coated with tannic acid (TA) to improve the solubility and anti-schizophrenic activity of chrysin. A 23 full factorial design was constructed where the independent factors were type of polymer, surfactant concentration (0.5 or 1 %) and the aqueous phase volume (5 or 15 mL), while the dependent responses were the particle size (PS) of the obtained formulation as well as the % chrysin dissolved after 2 h (Q2h). The optimum formulation (NSP-4) composed of 1 % PEG 400 and 1 % Cremophor RH40 in 15 mL aqueous phase. It achieved a PS and Q2h values of 108.00 nm and 38.77 %, respectively. NSP-4 was then coated with TA (TA-coated NSP-4) for further enhancement of chrysin solubility. TA-coated NSP-4 revealed PS and zeta potential values of 150 ± 14 nm and -32.54 ± 2.45 mV, respectively. After 6 h, chrysin dissolved % were 53.97 and 80.22 for uncoated NSP-4 and TA-coated NSP-4, respectively, compared with only 9.47 for free chrysin. The developed formulations and free chrysin were assessed regarding their effect on schizophrenia induced in mice by cuprizone (CPZ). Treatment with the developed formulations and free chrysin ameliorated demyelination and behavioral deficit induced by CPZ via elevating MBP and PI3K/PKC activities as well as reducing GFAP expression levels. The developed formulations and free chrysin inhibited Galactin-3 and TGF-ß expressions and stimulated GST antioxidant enzyme. Furthermore, they maintained the balances in glutamatergic and dopaminergic neurotransmission via modulation on neuregulin-1 and alleviated nuclear pyknosis and degeneration in the neurons. The order of activity was: TA-coated NSP-4 > NSP-4 > free chrysin.

A novel approach to generate enzyme-free single cell suspensions from archived tissues for miRNA sequencing.

Obtaining high-quality omics data at the single-cell level from archived human tissue samples is crucial for gaining insights into cellular heterogeneity and pushing the field of personalized medicine forward. In this technical brief we present a comprehensive methodological framework for the efficient enzyme-free preparation of tissue-derived single cell suspensions and their conversion into single-cell miRNA sequencing libraries. The resulting data from this study have the potential to deepen our understanding of miRNA expression at the single-cell level and its relevance in the context of the examined tissues. The workflow encompasses tissue collection, RNALater immersion, storage, thawing, TissueGrinder-mediated dissociation, miRNA lysis, library preparation, sequencing, and data analysis. Quality control measures ensure reliable miRNA data, with specific attention to sample quality. The UMAP analysis reveals tissue-specific cell clustering, while miRNA diversity reflects tissue variations. The presented workflow effectively processes preserved tissues, extending opportunities for retrospective analysis and biobank utilization.

Embedded Printing of Hydrogels and Watery Suspensions of Cells in Patterned Granular Baths.

Bioprinting within support media has emerged as the superior alternative to conventional extrusion printing. Not only because it allows for more freedom over the shapes that can be printed but also because it allows for the printing of inks that would not retain shape fidelity in freeform deposition such as watery liquids. Apart from functioning as mechanical support during embedded printing, hydrogel microparticle support media can provide the unique advantage of offering distinct chemotactic cues to cells printed in the baths by varying the composition of the hydrogel microparticles. There is great potential in compartmentalized granular baths consisting of different hydrogel particle materials in the field of tissue engineering, as these allow for the local inclusion of properties or cues to guide tissue development. In this work, we present a method to create compartmentalized embedding baths by printing multiple granular hydrogel materials that are widely used in tissue engineering. After adapting the volume fraction (φp) of the particles in the bath, we print within them using both inks composed of hydrogel or of cells and other particles suspended in watery liquid. Our process consists of the following three steps: First, the hydrogel microparticles are packed at a φp that allows them to be extruded while being reversibly jammed, facilitating the localized deposition of the granular media to form a compartmentalized bath. Second, each granular media is deposited in succession to create a packed suspension compartment, and by adding liquid post deposition, φp is reduced to allow for embedded printing. Finally, we demonstrate the printing of multiple inks within the compartmentalized embedding bath and highlight the distinct differences between using inks composed of hydrogels or inks composed of particles suspended in watery liquid. This approach combines the advantages of embedded printing through the use of granular media with the added ability to pattern multiple bioactive granular materials to locally affect the behavior of cells printed within the bath. We expect that this workflow will allow researchers to create spatially compartmentalized, customized bioactive embedding baths that allow for the embedded printing of inks composed of hydrogels, cells, and other particles adapted to their need.

Exploring paediatric oral suspension development: Challenges, requirements, and formulation advancements.

Oral suspension is the most preferred dosage form for the paediatric population because of the difficulties related to solid medications, such as the swallowing limitations, bitter taste, and poor oral bioavailability, which can cause serious impairment to attain a successful treatment. Given the importance of successful therapies, there is a need for safe and effective commercially-available paediatric oral suspension and their characterization. For the latter, it is important to identify safe excipients and preservatives. The paediatric group is a diverse category which includes infants and teenagers, with major pharmacokinetics and pharmacodynamics differences, mainly because of physiological and behavioral variations. Therefore, finding a single formulation for paediatric population remains a challenge, as well asthe formulation of stable-in-time suspension. In addition, drug's dissolving characteristic and permeation, are the main determinants for oral absorption, which are closely related to drug release kinetics from the pharmaceutical form. In this context, drug release profile is an important and limiting step in oral bioavailability, particularly for BCS class II drugs; thus, it is possible to increase bioavailability and minimize adverse effects by changing the release rate of such drugs. This review covers all the aspects for paediatric oral suspension development, and analyses the considerations for excipients selection as a crucial task for effectively choosing a safe and effective pharmaceutical form and correctly dosing paediatric patients.