Edaravone for the Treatment of Motor Neurone Disease: A Critical Review of Approved and Alternative Formulations against a Proposed Quality Target Product Profile.

Edaravone is one of two main drugs for treating motor neurone disease (MND). This review proposes a specific quality target product profile (QTPP) for edaravone following an appraisal of the issues accounting for the poor clinical uptake of the approved IV and oral liquid edaravone formulations. This is followed by a review of the alternative oral formulations of edaravone described in the published patent and journal literature against the QTPP. A total of 14 texts published by six research groups on 18 novel oral formulations of edaravone for the treatment of MND have been reviewed. The alternative oral formulations included liquid and solid formulations developed with cyclodextrins, lipids, surfactants, co-surfactants, alkalising agents, tablet excipients, and co-solvents. Most were intended to deliver edaravone for drug absorption in the lower gastrointestinal tract (GIT); however, there were also four formulations targeting the oral mucosal absorption of edaravone to avoid first-pass metabolism. All the novel formulations improved the aqueous solubility, stability, and oral bioavailability (BA) of edaravone compared to an aqueous suspension of edaravone. A common limitation of the published formulations is the lack of MND-patient-centred data. Except for TW001, no other formulations have been trialled in MND patients. To meet the QTPP of an oral edaravone formulation for MND patients, it is recommended that a tablet of appropriate size and with acceptable taste and stability be designed for the effective sublingual or buccal absorption of edaravone. This tablet should be designed with input from the MND community.

The Development of a Chocolate-Based Chewable Tablet of Prednisolone-Enhancing the Palatability of Steroids for Pediatric Use.

Oral liquid prednisolone medications have poor acceptance among paediatric patients due to ineffective masking of the bitterness taste of prednisolone. This study aimed to develop a child-friendly prednisolone tablet using a patented chewable chocolate-based delivery system (CDS) previously applied successfully to mask the bitterness tastes of midazolam and tramadol. Prednisolone sodium phosphate (PSP) and prednisolone base (PB) CDS tablets were prepared, and the manufacturing process was optimised using a design of experiments (DoE) approach. Stability was assessed by quantifying residual drug content via a validated HPLC assay. A pilot randomised crossover taste study involving 25 young adult volunteers evaluated taste-masking effectiveness against Redipred™, a commercial oral PSP liquid medicine. The results showed that the PSP CDS tablet was chemically stable following storage for three months at ambient temperature, while the PB CDS tablet was unstable. The optimised PSP CDS tablet, manufactured at 50 °C with a stirring time of 26 h, was found to release over 80% of its drug load within 20 min in 0.1 M HCl and had a significantly better mean taste score compared to Redipred™ (7.08 ± 2.40 vs. 5.60 ± 2.33, p = 0.03). Fifty six percent of the participants preferred the PSP CDS tablet. In conclusion, compared to Redipred™, the CDS technology provided a more effective taste masking of PSP, potentially offering a child-friendly prednisolone formulation with improved compliance, dosing accuracy, and storage stability.

Correction: Benington et al. In Vitro Assessment of Wound-Healing Efficacy of Stabilized Basic Fibroblast Growth Factor (FGF-2) Solutions. Pharmaceuticals 2024, 17, 247.

In the original publication [...].

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.

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.

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.

Application of a Customised Franz-Type Cell Coupled with HPTLC to Monitor the Timed Release of Bioactive Components in Complex Honey Matrices.

The aim of this study was to assess the release profile of components in five different honeys (a New Zealand Manuka and two Western Australian honeys, a Jarrah honey and a Coastal Peppermint honey) and their corresponding honey-loaded gel formulations using a custom-designed Franz-type diffusion cell in combination with High-Performance Thin-Layer Chromatography (HPTLC). To validate the suitability of the customised setup, release data using this new approach were compared with data obtained using a commercial Franz cell apparatus, which is an established analytical tool to monitor the release of active ingredients from topical semisolid products. The release profiles of active compounds from pure honey and honey-loaded formulations were found to be comparable in both types of Franz cells. For example, when released either from pure honey or its corresponding pre-gel formulation, the percentage release of two Jarrah honey constituents, represented by distinct bands at RF 0.21 and 0.53 and as analysed by HPTLC, was not significantly different (p = 0.9986) at 12 h with over 99% of these honey constituents being released in both apparatus. Compared to the commercial Franz diffusion cell, the customised Franz cell offers several advantages, including easy and convenient sample application, the requirement of only small sample quantities, a large diffusion surface area, an ability to analyse 20 samples in a single experiment, and lower cost compared to purchasing a commercial Franz cell. Thus, the newly developed approach coupled with HPTLC is conducive to monitor the release profile of minor honey constituents from pure honeys and honey-loaded semisolid formulations and might also be applicable to other complex natural-product-based products.

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.

Taste-Masked Flucloxacillin Powder Part 2: Formulation Optimisation Using the Mixture Design Approach and Storage Stability.

Flucloxacillin is prescribed to treat skin infections but its highly bitter taste is poorly tolerated in children. This work describes the application of the D-optimal mixture experimental design to identify the optimal component ratio of flucloxacillin, Eudragit EPO and palmitic acid to prepare flucloxacillin taste-masked microparticles that would be stable to storage and would inhibit flucloxacillin release in the oral cavity while facilitating the total release of the flucloxacillin load in the lower gastrointestinal tract (GIT). The model predicted ratio was found to be very close to the stoichiometric equimolar component ratio, which supported our hypothesis that the ionic interactions among flucloxacillin, Eudragit EPO and palmitic acid underscore the polyelectrolyte complex formation in the flucloxacillin taste-masked microparticles. The excipient-drug interactions showed protective effects on the microparticle storage stability and minimised flucloxacillin release at 2 min in dissolution medium. These interactions had less influence on flucloxacillin release in the dissolution medium at 60 min. Storage temperature and relative humidity significantly affected the chemical stability of the microparticles. At the preferred storage conditions of ambient temperature under reduced RH of 23%, over 90% of the baseline drug load was retained in the microparticles at 12 months of storage.

Paediatric Medicinal Formulation Development: Utilising Human Taste Panels and Incorporating Their Data into Machine Learning Training.

This review paper explores the role of human taste panels and artificial neural networks (ANNs) in taste-masking paediatric drug formulations. Given the ethical, practical, and regulatory challenges of employing children, young adults (18-40) can serve as suitable substitutes due to the similarity in their taste sensitivity. Taste panellists need not be experts in sensory evaluation so long as a reference product is used during evaluation; however, they should be screened for bitterness taste detection thresholds. For a more robust evaluation during the developmental phase, considerations of a scoring system and the calculation of an acceptance value may be beneficial in determining the likelihood of recommending a formulation for further development. On the technological front, artificial neural networks (ANNs) can be exploited in taste-masking optimisation of medicinal formulations as they can model complex relationships between variables and enable predictions not possible previously to optimise product profiles. Machine learning classifiers may therefore tackle the challenge of predicting the bitterness intensity of paediatric formulations. While advancements have been made, further work is needed to identify effective taste-masking techniques for specific drug molecules. Continuous refinement of machine learning algorithms, using human panellist acceptability scores, can aid in enhancing paediatric formulation development and overcoming taste-masking challenges.

Design, Preparation, and Physicochemical Characterisation of Alginate-Based Honey-Loaded Topical Formulations.

Honey has widespread use as a nutritional supplement and flavouring agent. Its diverse bioactivities, including antioxidant, antimicrobial, antidiabetic, anti-inflammatory, and anticancer properties, have also made it an aspirant natural product for therapeutic applications. Honey is highly viscous and very sticky, and its acceptance as a medicinal product will require formulation into products that are not only effective but also convenient for consumers to use. This study presents the design, preparation, and physicochemical characterisation of three types of alginate-based topical formulations incorporating a honey. The honeys applied were from Western Australia, comprising a Jarrah honey, two types of Manuka honeys, and a Coastal Peppermint honey. A New Zealand Manuka honey served as comparator honey. The three formulations were a pre-gel solution consisting of 2-3% (w/v) sodium alginate solution with 70% (w/v) honey, as well as a wet sheet and a dry sheet. The latter two formulations were obtained by further processing the respective pre-gel solutions. Physical properties of the different honey-loaded pre-gel solutions (i.e., pH, colour profile, moisture content, spreadability, and viscosity), wet sheets (i.e., dimension, morphology, and tensile strength) and dry sheets (i.e., dimension, morphology, tensile strength, and swelling index) were determined. High-Performance Thin-Layer Chromatography was applied to analyse selected non-sugar honey constituents to assess the impacts of formulation on the honey chemical composition. This study demonstrates that, irrespective of the honey type utilised, the developed manufacturing techniques yielded topical formulations with high honey content while preserving the integrity of the honey constituents. A storage stability study was conducted on formulations containing the WA Jarrah or Manuka 2 honey. The samples, appropriately packaged and stored over 6 months at 5, 30, and 40 °C, were shown to retain all physical characteristics with no loss of integrity of the monitored honey constituents.

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.

Antioxidant Activity and Phenolic Compound Identification and Quantification in Western Australian Honeys.

This study reports on the total phenolic content and antioxidant activity as well as the phenolic compounds that are present in Calothamnus spp. (Red Bell), Agonis flexuosa (Coastal Peppermint), Corymbia calophylla (Marri) and Eucalyptus marginata (Jarrah) honeys from Western Australia. The honey's total phenolic content (TPC) was determined using a modified Folin-Ciocalteu assay, while their total antioxidant activity was determined using FRAP and DPPH assays. Phenolic constituents were identified using a High Performance Thin-Layer Chromatography (HTPLC)-derived phenolic database, and the identified phenolic compounds were quantified using HPTLC. Finally, constituents that contribute to the honeys' antioxidant activity were identified using a DPPH-HPTLC bioautography assay. Based on the results, Calothamnus spp. honey (n = 8) was found to contain the highest (59.4 ± 7.91 mg GAE/100 g) TPC, followed by Eucalyptus marginata honey (50.58 ± 3.76 mg GAE/100 g), Agonis flexuosa honey (36.08 ± 4.2 mg GAE/100 g) and Corymbia calophylla honey (29.15 ± 5.46 mg GAE/100 g). In the FRAP assay, Calothamnus spp. honey also had the highest activity (9.24 ± 1.68 mmol Fe2+/kg), followed by Eucalyptus marginata honey (mmol Fe2+/kg), whereas Agonis flexuosa (5.45 ± 1.64 mmol Fe2+/kg) and Corymbia calophylla honeys (4.48 ± 0.82 mmol Fe2+/kg) had comparable FRAP activity. In the DPPH assay, when the mean values were compared, it was found that Calothamnus spp. honey again had the highest activity (3.88 ± 0.96 mmol TE/kg) while the mean DPPH antioxidant activity of Eucalyptus marginata, Agonis flexuosa, and Corymbia calophylla honeys were comparable. Kojic acid and epigallocatechin gallate were found in all honeys, whilst other constituents (e.g., m-coumaric acid, lumichrome, gallic acid, taxifolin, luteolin, epicatechin, hesperitin, eudesmic acid, syringic acid, protocatechuic acid, t-cinnamic acid, o-anisic acid) were only identified in some of the honeys. DPPH-HPTLC bioautography demonstrated that most of the identified compounds possess antioxidant activity, except for t-cinnamic acid, eudesmic acid, o-anisic acid, and lumichrome.

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.

Optimisation of an agar overlay assay for the assessment of the antimicrobial activity of topically applied semi-solid antiseptic products including honey-based formulations.

The aim of this study was to optimise the so-called agar overlay assay to investigate the antimicrobial activity of some currently available topical antimicrobial products against a range of Gram positive and Gram negative bacteria. During the optimisation process, various assay parameters including base agar volume, overlay agar volume, overlay agar concentration, placement of products into wells or onto coverslip and inoculum concentration were taken into consideration. The optimised assay was found to be a convenient, suitable and effective platform for the assessment of the antimicrobial activity of commercial semi-solid over-the-counter (OTC) products (i.e. non-prescription medicines for topical application used commonly without supervision by a healthcare professional) containing a range of active pharmaceutical ingredients and to be potentially also applicable to complex natural product-based formulations (e.g. honey-based formulation, melaleuca oil-based formulation). The most auspicious aspect of the optimised method was its capability of determining the antimicrobial activity of intact products without further manipulation, unlike other tests that require products to be dissolved or dilute, thus compromising their integrity.

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.

Upconversion Nanoparticle-Based Cell Membrane-Coated cRGD Peptide Bioorthogonally Labeled Nanoplatform for Glioblastoma Treatment.

Glioblastoma is hard to be eradicated partly because of the obstructive blood-brain barrier (BBB) and the dynamic autophagy activities of glioblastoma. Here, hydroxychloroquine (HDX)-loaded yolk-shell upconversion nanoparticle (UCNP)@Zn0.5Cd0.5S nanoparticle coating with the cyclic Arg-Gly-Asp (cRGD)-grafted glioblastoma cell membrane for near-infrared (NIR)-triggered treatment of glioblastoma is prepared for the first time. UCNPs@Zn0.5Cd0.5S (abbreviated as YSN, yolk-shell nanoparticle) under NIR radiation will generate reactive oxygen species for imposing cytotoxicity. HDX, the only available autophagy inhibitor in clinical studies, can enhance cytotoxicity by preventing damaged organelles from being recycled. The cRGD-decorated cell membrane allowed the HDX-loaded nanoparticles to efficiently bypass the BBB and specifically target glioblastoma cells. Exceptional treatment efficacy of the NIR-triggered chemotherapy and photodynamic therapy was achieved in U87 cells and in the mouse glioblastoma model as well. Our results provided proof-of-concept evidence that HDX@YSN@CCM@cRGD could overcome the delivery barriers and achieve targeted treatment of glioblastoma.

Development of an Add-On Device Using 3D Printing for the Enhancement of Drug Administration Efficiency of Dry Powder Inhalers (Accuhaler).

The goal of this study was to develop an add-on device for dry powder inhalers (Accuhaler) via 3D printing to improve drug administration efficiency in patients with limited inspiratory capacity, including young children, the elderly, and those with chronic obstructive pulmonary disease. With salmeterol xinafoate and fluticasone propionate as model active pharmaceutical ingredients (API), the emitted API doses were used to assess the effectiveness of the add-on device. The APIs were quantified by an HPLC assay validated for specificity, range, linearity, accuracy, and precision. The motor power of the add-on device could be regulated to moderate fan speed and the air flow in the assembled device. When 50-100% of the fan motor power of the add-on device was used, the emitted dose from the attached dry powder inhaler (DPI) was increased. A computational fluid dynamics application was used to simulate the air and particle flow in the DPI with the add-on device in order to elucidate the operating mechanism. The use of the add-on device combined with a sufficient inhalation flow rate resulted in a larger pressure drop and airflow velocity at the blister pocket. As these characteristics are associated with powder fluidization, entrainment, and particle re-suspension, this innovative add-on device might be utilized to enhance the DPI emitted drug dose for patients with low inspiratory rates and to facilitate the provision of adequate drug doses to achieve the treatment outcomes.