Exploring Intestinal Surface Receptors in Oral Nanoinsulin Delivery.

Subcutaneous and inhaled insulins are associated with needle phobia, lipohypertrophy, lipodystrophy, and cough in diabetes treatment. Oral nanoinsulin has been developed, reaping the physiologic benefits of peroral administration. This review profiles intestinal receptors exploitable in targeted delivery of oral nanoinsulin. Intestinal receptor targeting improves oral insulin bioavailability and sustains blood glucose-lowering response. Nonetheless, these studies are conducted in small animal models with no optimization of insulin dose, targeting ligand type and content, and physicochemical and molecular biologic characteristics of nanoparticles against the in vivo/clinical diabetes responses as a function of the intestinal receptor population characteristics with diabetes progression. The interactive effects between nanoinsulin and antidiabetic drugs on intestinal receptors, including their up-/downregulation, are uncertain. Sweet taste receptors upregulate SGLT-1, and both have an undefined role as new intestinal targets of nanoinsulin. Receptor targeting of oral nanoinsulin represents a viable approach that is relatively green, requiring an in-depth development of the relationship between receptors and their pathophysiological profiles with physicochemical attributes of the oral nanoinsulin. SIGNIFICANCE STATEMENT: Intestinal receptor targeting of oral nanoinsulin improves its bioavailability with sustained blood glucose-lowering response. Exploring new intestinal receptor and tailoring the design of oral nanoinsulin to the pathophysiological state of diabetic patients is imperative to raise the insulin performance to a comparable level as the injection products.

Determination of Physicochemical Characteristics, Phytochemical Profile and Antioxidant Activity of Various Clover Honeys.

This paper reports on some physicochemical and phytochemical characteristics (i. e. pH, electrical conductivity, colour, moisture content, total phenolic content, sugar profile) and in vitro antioxidant activity of honeys harvested from five legume species, red clover (Trifolium pratense), balansa clover (T. michelianum), Persian clover (T. resupinatum), purple clover (T. purpureum) and sanfoin, also known as holy clover (Onobrychis viciifolia), that were grown in enclosed shade houses to ensure that the honeys' characteristics are reflective of a truly monofloral honey. Glucose and fructose, determined via High-Performance Thin-Layer Chromatography (HPTLC) analysis, were found as the main sugars in all investigated honeys with the ratio of fructose to glucose ranging from 1 : 1.2 to 1 : 1.6. The honeys' pH values ranged from 3.9 to 4.6 which met Codes Alimentarius (CA) requirements. The moisture content was found to be between 17.6 and 22.2 % which in some cases was slightly higher than CA requirements (≤20 %). The honeys' colour values, prior and after filtration, were between 825.5-1149.5 mAU and 532.4-824.8 mAU respectively, illustrating golden yellow to deep yellow hues. The total phenolic content (TPC) of the honeys was determined using a modified Folin-Ciocalteu assay. Their antioxidant activity was captured by the Ferric Reducing-Antioxidant Power (FRAP) assay as well as HPTLC analysis coupled with 2,2-diphenyl-1-picrylhydrazyl (DPPH) derivatisation. The highest total phenolic content was found in red clover honey (45.4 mg GAE/100 g) whereas purple clover honey showed the highest level of activity in the FRAP assay (7.3 mmol Fe2+/kg). HPTLC-DPPH analysis of the honeys' organic extracts demonstrated the presence of various bioactive compounds that contribute to their overall antioxidant activity. This study developed a methodology for producing monofloral clover honeys in a space limited, enclosed production system, which allowed to collate important baseline data for these honeys that can serve as the foundation for their potential future development into commercial honeys, including honeys that can be used for medicinal purposes.

Clinical efficacy of crushed prednisolone and hydrocolloid powder in the primary treatment of peristomal pyoderma gangrenosum and correlation to in vitro drug release data.

We evaluated the primary application of crushed prednisolone combined with hydrocolloid powder for clinically diagnosed peristomal pyoderma gangrenosum (PPG). We present our data on this cohort and follow-up of our previous patients. Of the 23 patients who were commenced on this regime, 18 healed (78%). Twenty-two patients commenced on this regime as the primary treatment for their PPG, and for one, it was a rescue remedy after failed conventional therapy. Four patients with significant medical comorbidities failed to heal and one had their stomal reversal surgery before being fully healed. The proposed treatment regime for PPG is demonstrated to be effective, inexpensive and able to be managed in the patient's usual home environment. In vitro drug release analysis was undertaken, and data are presented to provide further insights into the efficacy of this regime.

Monitoring the Release of Methylglyoxal (MGO) from Honey and Honey-Based Formulations.

Methylglyoxal (MGO) is considered to be one of the vital components responsible for the anti-bacterial activity of Leptospermum spp. (Manuka) honey. While many studies have demonstrated a dose-dependent antibacterial activity for MGO in vitro, from a therapeutic viewpoint, it is also important to confirm its release from Manuka honey and also from Manuka honey-based formulations. This study is the first to report on the release profile of MGO from five commercial products containing Manuka honey using a Franz diffusion cell and High-Performance Liquid Chromatography (HPLC) analysis. The release of MGO expressed as percentage release of MGO content at baseline was monitored over a 12 h period and found to be 99.49 and 98.05% from an artificial honey matrix and NZ Manuka honey, respectively. For the investigated formulations, a time-dependent % MGO release between 85% and 97.18% was noted over the 12 h study period.

Effects of Formulation on the Palatability and Efficacy of In-Feed Praziquantel Medications for Marine Finfish Aquaculture.

Praziquantel (PZQ) provides an effective treatment against monogenean parasitic infestations in finfish. However, its use as an in-feed treatment is challenging due to palatability issues. In this study, five formulations of PZQ beads (1−4 mm) were developed using marine-based polymers, with allicin added as a flavouring agent. All formulations attained PZQ loading rates ≥74% w/w, and the beads were successfully incorporated into fish feed pellets at an active dietary inclusion level of 10 g/kg. When tested for palatability and digestibility in small yellowtail kingfish, the PZQ-loaded beads produced with alginate-chitosan, alginate-Cremophor® RH40, and agar as carriers resulted in high consumption rates of 99−100% with no digesta or evidence of beads in the gastrointestinal tract (GIT) of fish fed with diets containing either formulation. Two formulations produced using chitosan-based carriers resulted in lower consumption rates of 68−75%, with undigested and partly digested beads found in the fish GIT 3 h post feeding. The PZQ-loaded alginate-chitosan and agar beads also showed good palatability in large (≥2 kg) yellowtail kingfish infected with gill parasites and were efficacious in removing the parasites from the fish, achieving >90% reduction in mean abundance relative to control fish (p < 0.001). The two effective formulations were stable upon storage at ambient temperature for up to 18 months, showing residual drug content >90% compared with baseline levels. Overall, the palatability, efficacy and stability data collected from this study suggest that these two PZQ particulate formulations have potential applications as in-feed anti-parasitic medications for the yellowtail kingfish farming industry.

The Development and Application of a HPTLC-Derived Database for the Identification of Phenolics in Honey.

This study reports on the development and validation of a HPTLC-derived database to identify phenolic compounds in honey. Two database sets are developed to contain the profiles of 107 standard compounds. Rich data in the form of Rf values, colour hues (H°) at 254 nm and 366 nm, at 366 nm after derivatising with natural product PEG reagent, and at 366 nm and white light after derivatising with vanillin-sulfuric acid reagent, λ max and λ min values in their fluorescence and λ max values in their UV-Vis spectra as well as λ max values in their fluorescence and UV-Vis spectra after derivatisation are used as filtering parameters to identify potential matches in a honey sample. A spectral overlay system is also developed to confirm these matches. The adopted filtering approach is used to validate the database application using positive and negative controls and also by comparing matches with those identified via HPLC-DAD. Manuka honey is used as the test honey and leptosperine, mandelic acid, kojic acid, lepteridine, gallic acid, epigallocatechin gallate, 2,3,4-trihydroxybenzoic acid, o-anisic acid and methyl syringate are identified in the honey using the HPTLC-derived database.

A Comprehensive HPTLC-Based Analysis of the Impacts of Temperature on the Chemical Properties and Antioxidant Activity of Honey.

Honeys are commonly subjected to a series of post-harvest processing steps, such as filtration and/or radiation treatment and heating to various temperatures, which might affect their physicochemical properties and bioactivity levels. Therefore, there is a need for robust quality control assessments after honey processing and storage to ensure that the exposure to higher temperatures, for example, does not compromise the honey's chemical composition and/or antioxidant activity. This paper describes a comprehensive short-term (48 h) and long-term (5 months) study of the effects of temperature (40 °C, 60 °C and 80 °C) on three commercial honeys (Manuka, Marri and Coastal Peppermint) and an artificial honey, using high-performance thin-layer chromatography (HPTLC) analysis. Samples were collected at baseline, at 6 h, 12 h, 24 h and 48 h, and then monthly for five months. Then, they were analysed for potential changes in their organic extract HPTLC fingerprints, in their HPTLC-DPPH total band activities, in their major sugar composition and in their hydroxymethylfurfural (HMF) content. It was found that, while all the assessed parameters changed over the monitoring period, changes were moderate at 40 °C but increased significantly with increasing temperature, especially the honeys' HPTLC-DPPH total band activity and HMF content.

Australian Honeypot Ant (Camponotus inflatus) Honey-A Comprehensive Analysis of the Physiochemical Characteristics, Bioactivity, and HPTLC Profile of a Traditional Indigenous Australian Food.

Despite its cultural and nutritional importance for local Aboriginal people, the unusual insect honey produced by Western Australian honeypot ant (Camponotus inflatus) has to date been rarely investigated. This study reports on the honey's physicochemical properties, its total phenolic, major sugars and 5-hydroxymethylfurfural contents, and its antioxidant activities. The honey's color value is 467.63 mAU/63.39 mm Pfund, it has a pH of 3.85, and its electric conductivity is 449.71 µSiemens/cm. Its Brix value is 67.00, corresponding to a 33% moisture content. The total phenolics content is 19.62 mg gallic acid equivalent/100 g honey. Its antioxidant activity measured using the DPPH* (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing-antioxidant power) assays is 1367.67 µmol Trolox/kg and 3.52 mmol Fe+2/kg honey, respectively. Major sugars in the honey are glucose and fructose, with a fructose-to-glucose ratio of 0.85. Additionally, unidentified sugar was found in minor quantities.

Prior administration of chocolate improves the palatability of bitter drugs: The Choc-with-Med study.

AIM: The paediatric population has a low adherence and acceptance rate of unpalatable medicines. This study aimed to determine whether eating chocolate immediately prior to drug administration would help to mask the bitter taste of a drug. The difference in taste masking efficacy between white, milk and dark chocolate was a secondary measure outcome. METHODS: A controlled repeated measures crossover taste trial was conducted using a taste panel of 29 young healthy adults who met the criteria to differentiate intensity in bitterness taste. Participants separately tasted solutions of quinine, flucloxacillin and clindamycin using the swill and spit method, singularly and following blinded prior administration of white, milk or dark chocolate. Drug solutions administered without prior chocolate served as controls. Bitterness score for each tasting was recorded using a 5-point scale. RESULTS: Regardless of chocolate type, mean taste scores with prior chocolate for quinine (range 2.00-2.34), clindamycin (3.72-3.83) and flucloxacillin (3.38-3.45) were all lower than mean scores for respective drugs without chocolate (3.24, 4.75 and 4.28, respectively; P < 0.0001 for all comparisons). Dark chocolate was most efficacious for masking the bitter taste of quinine, but the differences in taste masking efficacy between dark, milk and white chocolates were not statistically significant for flucloxacillin and clindamycin. CONCLUSIONS: Prior administration of chocolate results in lower perceived bitterness compared to control tastings of quinine, flucloxacillin and clindamycin solutions; however, there is no clear difference in this effect between the dark, milk and white chocolates used in this study.

Metal ion-responsive nanocarrier derived from phosphonated calix[4]arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage.

Primary intracerebral hemorrhage (ICH) is a leading cause of long-term disability and death worldwide. Drug delivery vehicles to treat ICH are less than satisfactory because of their short circulation lives, lack of specific targeting to the hemorrhagic site, and poor control of drug release. To exploit the fact that metal ions such as Fe2+ are more abundant in peri-hematomal tissue than in healthy tissue because of red blood cell lysis, we developed a metal ion-responsive nanocarrier based on a phosphonated calix[4]arene derivative in order to deliver the neuroprotective agent dauricine (DRC) specifically to sites of primary and secondary brain injury. The potential of the dauricine-loaded nanocarriers for ICH therapy was systematically evaluated in vitro and in mouse models of autologous whole blood double infusion. The nanocarriers significantly reduced brain water content, restored blood-brain barrier integrity and attenuated neurological deficits by inhibiting the activation of glial cells, infiltration by neutrophils as well as production of pro-inflammatory factors (IL-1ß, IL-6, TNF-α) and matrix-metalloprotease-9. These results suggest that our dauricine-loaded nanocarriers can improve neurological outcomes in an animal model of ICH by reducing inflammatory injury and inhibiting apoptosis and ferroptosis.

Sugar Profiling of Honeys for Authentication and Detection of Adulterants Using High-Performance Thin Layer Chromatography.

Honey adulteration, where a range of sugar syrups is used to increase bulk volume, is a common problem that has significant negative impacts on the honey industry, both economically and from a consumer confidence perspective. This paper investigates High-Performance Thin Layer Chromatography (HPTLC) for the authentication and detection of sugar adulterants in honey. The sugar composition of various Australian honeys (Manuka, Jarrah, Marri, Karri, Peppermint and White Gum) was first determined to illustrate the variance depending on the floral origin. Two of the honeys (Manuka and Jarrah) were then artificially adulterated with six different sugar syrups (rice, corn, golden, treacle, glucose and maple syrup). The findings demonstrate that HPTLC sugar profiles, in combination with organic extract profiles, can easily detect the sugar adulterants. As major sugars found in honey, the quantification of fructose and glucose, and their concentration ratio can be used to authenticate the honeys. Quantifications of sucrose and maltose can be used to identify the type of syrup adulterant, in particular when used in combination with HPTLC fingerprinting of the organic honey extracts.

Targeting strategies for drug delivery to the kidney: From renal glomeruli to tubules.

Kidney diseases have become a global public health problem. The application of kidney-targeted drug-delivery systems in the management of kidney diseases has profound transformative potential. Kidney-targeted drug delivery can reduce the undesired side effects of often potent drugs and enhance drug efficacy in alleviating the kidney disease. Here, we review the literature on the potential strategies for targeting drugs to the kidneys. Specifically, we provide a broad overview of the targeting vectors and targeting pathways for renal tubules and glomeruli, as well as how the unique structural features of the glomerulus and the receptor-mediated internalization pathways of the tubules allows for drug targeting. Finally, we summarized the literature examples of drug delivery to the kidneys and elaborated strategies suitable for renal targeting to provide new therapeutic approaches for kidney diseases.

Alginate-C18 Conjugate Nanoparticles Loaded in Tripolyphosphate-Cross-Linked Chitosan-Oleic Acid Conjugate-Coated Calcium Alginate Beads as Oral Insulin Carrier.

Simple alginate, alginate-stearic acid, and alginate-C18 conjugate nanoparticles and tripolyphosphate-cross-linked chitosan-oleic acid conjugate-coated calcium alginate beads as the vehicle of nanoparticles were designed. Their size, ζ potential, morphology, drug load, drug release, matrix molecular characteristics, mucus penetration, HT-29 cell line cytotoxicity and intracellular trafficking, in vivo blood glucose lowering, and insulin delivery profiles were characterized. Alginate-C18 conjugate nanoparticles were nontoxic. Among all nanoparticle variants, they had reduced size and ζ potential thus enhancing particulate mucus penetration and intracellular trafficking. Their insulin reabsorption tendency was minimized as alginate active COOH/COO- sites were preoccupied with C18. Their loading into coated beads was translated to reduced drug release in simulated gastric phase with nanoparticles being released in the intestinal phase. The combination dosage form increased the blood glucose lowering extent of insulin and blood insulin level compared with nanoparticles or beads alone. Nanoparticles in beads represented a viable approach for oral insulin delivery.

Curcumin, Piperine, and Capsaicin: A Comparative Study of Spice-Mediated Inhibition of Human Cytochrome P450 Isozyme Activities.

Inhibition of cytochrome P450 (P450) enzymes (CYP) has been shown to lower the metabolism of drugs that are P450 substrates and to consequently alter their pharmacokinetic profiles. Curcumin (CUR), piperine (PIP), and capsaicin (CAP) are spice components (SC) that inhibit the activities of a range of P450 enzymes, but the selection of which SC to be prioritized for further development as an adjuvant will depend on the ranking order of the inhibitory potential of the SCs on specific P450 isozymes. We used common human recombinant enzyme platforms to provide a comparative evaluation of the inhibitory activities of CUR, PIP, and CAP on the principal drug-metabolizing P450 enzymes. SC-mediated inhibition of CYP3A4 was found to rank in the order of CAP (IC50 1.84 ± 0.71 µM) ∼ PIP (2.12 ± 0.45 µM) > CUR (11.93 ± 3.49 µM), while CYP2C9 inhibition was in the order of CAP (11.95 ± 4.24 µM) ∼ CUR (14.58 ± 4.57 µM) > PIP (89.62 ± 9.17 µM). CAP and PIP were significantly more potent inhibitors of CYP1A2 (IC50 2.14 ± 0.22 µM and 14.19 ± 4.15 µM, respectively) than CUR (IC50 > 100 µM), while all three SCs exhibited weak activity toward CYP2D6 (IC50 95.42 ± 12.09 µM for CUR, 99.99 ± 5.88 µM for CAP, and 110.40 ± 3.23 µM for PIP). Of the three SCs, CAP thus has the strongest potential for further development into an inhibitor of multiple CYPs for use in the clinic. Data from this study are also useful for managing potential drug-SC interactions.

Dose-Dependent Therapeutic Distinction between Active and Passive Targeting Revealed Using Transferrin-Coated PGMA Nanoparticles.

The paradigm of using nanoparticle-based formulations for drug delivery relies on their enhanced passive accumulation in the tumor interstitium. Nanoparticles with active targeting capabilities attempt to further enhance specific delivery of drugs to the tumors via interaction with overexpressed cellular receptors. Consequently, it is widely accepted that drug delivery using actively targeted nanoparticles maximizes the therapeutic benefit and minimizes the off-target effects. However, the process of nanoparticle mediated active targeting initially relies on their passive accumulation in tumors. In this article, it is demonstrated that these two tumor-targeted drug delivery mechanisms are interrelated and dosage dependent. It is reported that at lower doses, actively targeted nanoparticles have distinctly higher efficacy in tumor inhibition than their passively targeted counterparts. However, the enhanced permeability and retention effect of the tumor tissue becomes the dominant factor influencing the efficacy of both passively and actively targeted nanoparticles when they are administered at higher doses. Importantly, it is demonstrated that dosage is a pivotal parameter that needs to be taken into account in the assessment of nanoparticle mediated targeted drug delivery.

Development and validation of a LC/TOF MS method for the determination of carboplatin and paclitaxel in nanovesicles.

Carboplatin and paclitaxel co-loaded nanovesicles (CPT-PTX-CLV), a novel intravenous formulation void of cremophor EL, may have significant advantages over conventional carboplatin and paclitaxel formulations with respect to tumor targeting, sustained drug release, reduced toxicity, and synergistic efficacy profiles. The aim of this study was to develop and validate a rapid, specific, sensitive, and reliable liquid chromatography-time of flight-mass spectrometry (LC/TOF MS)-based bioanalytical method for the simultaneous quantification of CPT and PTX in a fetal bovine serum (FBS) vehicle containing the dispersed nanovesicles. The analytes were extracted from FBS by simple protein precipitation, with subsequent separation of CPT and PTX on a Waters HPLC SunFire C18 column at a flow rate of 0.25 ml/min using gradient elution mode. The total analytical time was only 12 min. Detection and quantitation was performed by electrospray ionization (ESI) in the positive ionization mode with selective ion monitoring (SIM) at m/z 310.0152 for CPT and 876.3224 for PTX. The calibration curves were linear over the concentration range of 10-4,000 ng/ml for CPT and 5-2,000 ng/ml for PTX (r (2) > 0.99), with the respective lower limit of quantification (LLOQ) at 10 and 5 ng/ml. The intra- and inter-day precision and accuracy of analysis of the quality control samples at low, medium, and high concentration levels were ≤13.6 % relative standard deviation (RSD) and ≤14.6 % relative errors (RE). The rapid, sensitive, and reproducible LC/TOF MS method may be used to support preclinical and clinical pharmacological studies of the CPT-PTX-CLV administered by injection in animal and human cancer models.

Antioxidant Activity, Physicochemical and Sensory Properties of Stingless Bee Honey from Australia.

This study reports on the physicochemical and sensory attributes, total phenolic content, and antioxidant activity of 36 honey samples produced by two different stingless bee species (Tetragonula carbonaria and Tetragonula hockingsi) from Australia. The findings reveal moisture content across all samples ranges from 24.9% to 30.8% (w/w), electrical conductivity from 1.02 to 2.15 mS/cm, pH levels between 3.57 and 6.54, soluble solids from 69.2 to 75.1 °Brix, trehalulose concentrations from 6.20 to 38.2 g/100 g, fructose levels from 7.79 to 33.4 g/100 g, and glucose content from 3.36 to 26.8 g/100 g. Sucrose was undetectable in all investigated samples. In a sensory analysis involving 30 participants, Australian stingless bee honey was perceived as having a more pronounced sourness compared with New Zealand Manuka honey. The study reveals considerable variability in the composition of Australian stingless bee honey, influenced by factors such as floral availability, geographical origin, and time of harvest. It also demonstrates the presence of phenolic compounds and antioxidant activity in stingless bee honey, underlining their potential as a natural source of antioxidants. All investigated samples contain trehalulose, which supports the findings of other recent studies that propose this unusual disaccharide as a marker compound of stingless bee honey.

Estrogenic Isoflavones in Clover Plants, Flower Nectar, Unripe Honeys and Mature Honeys: A Natural Biochemical Transformation of Isoflavones by Honeybees.

This study is the first to report on the presence of oestrogenic compounds in different clover flower nectar samples, in bee-deposited nectars collected from hive combs (unripe honey) and in mature honeys harvested from the same hives. The clover species investigated were two red clover (Trifolium pratense) cultivars, bred specifically for high isoflavone content, alongside a sainfoin (Onobrychis viciifolia) and a purple clover (T. purpureum) cultivar. A total of eight isoflavones, four of them non-glycosidic (biochanin A, formononetin, genistein and daidzein) the others glycosidic (sissotrin, ononin, genistin and daidzin), were targeted for identification and quantification in this study using high-performance thin-layer chromatography (HPTLC). Leaves and flower bracts of the clover samples were also investigated. Different isoflavone profiles were found across the four clover species and also in the different samples collected from each species indicating that, most likely due to the activity of honeybee (Apis mellifera) salivary enzymes, biochemical conversions take place when these bioactive compounds transition from flower nectar into ripe honey. Among the four investigated clover species, the two red clover cultivars, including their honeys, were found to contain higher levels of estrogenic compounds compared to other two cultivars.

In Vitro Assessment of Wound-Healing Efficacy of Stabilized Basic Fibroblast Growth Factor (FGF-2) Solutions.

Chronic tympanic membrane perforations (TMP) pose a significant clinical challenge, but basic fibroblast growth factor (FGF-2) shows promise for their treatment, despite its instability in aqueous solutions which hampers the sustained delivery crucial for the healing process. Addressing this, our research focused on the development of stabilized FGF-2 formulations, F5 and F6, incorporating dual, generally regarded as safe (GRAS) excipients to enhance stability and therapeutic efficacy. F5 combined FGF-2 (1600 ng/mL) with 0.05% w/v methylcellulose (MC) and 20 mM alanine, while F6 used FGF-2 with 0.05% w/v MC and 1 mg/mL human serum albumin (HSA). Our findings demonstrate that these novel formulations not only significantly improve the cytoproliferation of human dermal fibroblasts but also exhibit the most potent chemoattractant effects, leading to the highest fibroblast monolayer closure rates (92.5% for F5 and 94.1% for F6 within 24 h) compared to other FGF-2 solutions tested. The comparable performance of F5 and F6 underscores their potential as innovative, less invasive, and cost-effective options for developing otic medicinal products aimed at the effective treatment of chronic TMP.

Taste-Masked Flucloxacillin Powder Part 1: Optimisation of Fabrication Process Using a Mixture Design Approach.

It is extremely challenging to formulate age-appropriate flucloxacillin medicines for young children, because flucloxacillin sodium (FS) has a lingering, highly bitter taste, dissolves quickly in saliva, and requires multiple daily dosing at relatively large doses for treating skin infections. In this paper, we describe a promising taste-masked flucloxacillin ternary microparticle (FTM) formulation comprising FS, Eudragit EPO (EE), and palmitic acid (PA). To preserve the stability of the thermolabile and readily hydrolysed flucloxacillin, the fabrication process employed a non-aqueous solvent evaporation method at ambient temperature. Optimisation of the fabrication method using a mixture design approach resulted in a robust technique that generated stable and reproducible FTM products. The optimised method utilised only a single solvent evaporation step and minimal amounts of ICH class III solvents. It involved mixing two solution phases-FS dissolved in ethanol:acetone (1:4 v/v), and a combination of EE and PA dissolved in 100% ethanol-to give a ternary FS:EE:PA system in ethanol: acetone (3:1 v/v). Solvent evaporation yielded the FTMs containing an equimolar ratio of FS:EE:PA (1:0.8:0.6 w/w). The fabrication process, after optimisation, demonstrated robustness, reproducibility, and potential scalability.