Salmeterol Research Articles

Copper(II) isonicotinate metal-organic framework for reusable adsorption of salmeterol from wastewater

This study investigates the adsorption of salmeterol (SMT) from aqueous solutions using a novel nano-sized copper-based metal-organic framework (Cu-MOF). The Cu-MOF was synthesized under solvent-free conditions, enhancing its environmental sustainability. Key parameters such as adsorbent dosage, initial SMT concentration, temperature, and pH were systematically evaluated to optimize adsorption performance. The results demonstrate the exceptional adsorption capacity of the Cu-MOF, reaching a maximum of 400mg/g within 50minutes of contact time under optimal conditions of 4mg Cu-MOF, 50mg/L SMT, and pH 11. The kinetic and isotherm studies revealed that the pseudo-second-order and Langmuir models exhibited superior fitting to the experimental data, as evidenced by their exceptional R² values of 0.999 and 0.999, minimal RMSE values of 0.034 and 0.001, and significantly lower AIC values of -45.77 and -129.17 for the kinetic and isotherm models, respectively. Thermodynamic analysis confirmed the exothermic and spontaneous nature of the adsorption process. Moreover, the Cu-MOF exhibited excellent reusability, maintaining its adsorption efficiency over six consecutive cycles. Therefore, these findings highlight the potential of Cu-MOF as a promising and sustainable adsorbent for effectively removing salmeterol from wastewater.

Microstructural Characterization of Dry Powder Inhaler Formulations Using Orthogonal Analytical Techniques

PurposeFor locally-acting dry powder inhalers (DPIs), developing novel analytical tools that are able to evaluate the state of aggregation may provide a better understanding of the impact of material properties and processing parameters on the invivo performance. This study explored the utility of the Morphologically-Directed Raman Spectroscopy (MDRS) and dissolution as orthogonal techniques to assess microstructural equivalence of the aerosolized dose of DPIs collected with an aerosol collection device.MethodsCommercial DPIs containing different strengths of Fluticasone Propionate (FP) and Salmeterol Xinafoate (SX) as monotherapy and combination products were sourced from different regions. These inhalers were compared with aerodynamic particle size distribution (APSD), dissolution, and MDRS studies.ResultsAPSD testing alone might not be able to explain differences reported elsewhere in invivo studies of commercial FP/SX drug products with different Advair® strengths and/or batches. Dissolution studies demonstrated different dissolution rates between Seretide™ 100/50 and Advair® 100/50, whereas Flixotide™ 100 and Flovent® 100 had similar dissolution rates between each other. These differences in dissolution profiles were supported by MDRS results: the dissolution rate is increased if the fraction of FP associated with high soluble components is increased. Principle component analysis was used to identify the agglomerate classes that better discriminate different products.ConclusionsMDRS and dissolution studies of the aerosolized dose of DPIs were successfully used as orthogonal techniques. This study highlights the importance of further assessing invitro tools that are able to provide a bridge between material attributes or process parameters and invivo performance.

Investigation of controlled salmeterol xinafoate and fluticasone propionate release from double molecular imprinted nanoparticles

Salmeterol xinafoate (SAM) and fluticasone propionate (FLU) are one of the drug combinations used together in the treatment of lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). The aim of this study is to investigate the usability of novel dual molecular imprinted nanoparticles (poly(2-hydroxyethyl methacrylate-N-methacryloyl-(L)-alanine-N-methacryloyl-(L)-histidine) [p(HEMA-MAAL-MAH)], abbr. DMIPNPs) as a controlled drug release systems. In this study, SAM and FLU drugs were chosen as model drugs because they are used in the treatment of these diseases. DMIPNPs were prepared by surfactant-free emulsion polymerization method and characterized by scanning electron microscopy (SEM) and fourier transform infrared spectrometer (FTIR). In in vitro drug release experiments, drug release conditions were optimized. SAM and FLU release from DMIPNPs experiments were also performed in the simulated lung fluid (SLF). The amount of released SAM and FLU were found as 4.79 and 5.68 mg/g in the SLF medium at the end of 48 h, respectively. The release kinetics of SAM and FLU from DMIPNPs were calculated in the SLF medium. The release of SAM and FLU was determined to be compatible with the Higuchi release models. According to these results, these DMIPNPs, dual-template molecular imprinted nanoparticles with dual monomers, are promising materials that can be used in the controlled release of two different drugs.Graphical abstract

A New HPLC-Fluorescence Method for the Simultaneous Determination of Fluticasone Propionate and Salmeterol Xinafoate in Their Solutions Involving Schiff-Base Derivatization with Hydrazine

A partially validated high-performance liquid chromatographic method with UV and fluorescence detection was developed to determine fluticasone propionate (FP) and salmeterol xinafoate (SX) simultaneously in their solutions. RP-HPLC (Hypersil C18 column, 250 mm × 4.6 mm, 5 µm) was used for chromatographic separation employing an isocratic mobile phase consisting of methanol, acetonitrile and water (50/20/30, v/v/v) at a flow rate of 0.8 mL.min–1. With the aid of the Schiff-base reaction, the hydrazine derivative of FP was prepared to enhance the fluorescence signal of FP. The method was employed at an excitation maximum of λ = 246, 262 and 298 nm for FP, SX and FP derivatives, respectively. The method is accurate, precise and linear (R2 ≥ 0.999) in the range of 0.246–86.957 µg×mL–1 for FP in its derivatives mixture and 0.156–50.00 µg×mL–1 for SX. The calculated LOD values are 0.081 and 0.052 µg×mL–1, respectively. It was noted that the fluorescence detection sensitivity of FP and SX is better than that of UV (LOD = 0.396 and 0.254 µg×mL–1 for FP and SX, respectively). The advantage of the validated HPLC-Fluorescence method compared with expensive and sophisticated LC-MS methods is its simplicity. When compared with other HPLC-UV/Fluorescence methods, the proposed method includes simple chromatographic conditions (no column oven nor high flow rate) and uses non-buffered mobile phase solvents; it is the first HPLC-Fluorescence method for the simultaneous determination of SX and FP. Moreover, the Fluorescence signal of FP was enhanced by derivatization with hydrazine. This was confirmed by computational and Mass spectrometric analysis.

Preclinical evaluation of novel synthesised nanoparticles based on tyrosine poly(ester amide) for improved targeted pulmonary delivery

Fixed dose combinations (FDCs) incorporating two or three medicines in a single inhaler have been created to enhance patient compliance and hence clinical outcomes. However, the development of dry powder inhalers (DPIs), particularly for FDCs, faces challenges pertinent to formulation uniformity and reproducibility. Therefore, this project aimed to employ nanotechnology to develop a FDC of DPIs for market-leading medicines—fluticasone propionate (FP) and salmeterol xinafoate (SAL)—for asthma management. Nanoaggregates were prepared using a novel biocompatible and biodegradable poly(ester amide) based on the amino acid tyrosine, utilising a one-step interfacial polymerisation process. The produced tyrosine poly (ester amide) drug-loaded nanoparticles were evaluated for content uniformity, PSA, FTIR, TEM, DSC, XRD and aerodynamic performance (in vitro and in vivo). The optimised formulation demonstrated high entrapment efficiency– > 90%. The aerodynamic performance in terms of the emitted dose, fine particle fraction and respirable dose was superior to the carrier-based marketed product. In-vivo studies showed that FP (above the marketed formulation) and SAL reached the lungs of mice in a reproducible manner. These results highlight the superiority of novel FDC FP/SAL nanoparticles prepared via a one-step process, which can be used as a cost-effective and efficient method to alleviate the burden of asthma.

Pharmacokinetic Models for Inhaled Fluticasone Propionate and Salmeterol Xinafoate to Quantify Batch-to-Batch Variability.

Advair Diskus is an essential treatment for asthma and chronic obstructive pulmonary disease. It is a dry powder inhaler with a combination of fluticasone propionate (FP) and salmeterol xinafoate (SX). However, the pharmacokinetics (PK) batch-to-batch variability of the reference-listed drug (RLD) hindered its generic product development. This work developed the PK models for inhaled FP and SX that could represent potential batch variability. Two batches each of the reference and the test product (R1, R2, T1, T2) of Advair Diskus (100μg FP/50μg SX inhalation) were administered to 60 healthy subjects in a 4-period, 4-sequence crossover study. The failure of the bioequivalence (BE) between R1 and R2 confirmed the high between-batch variability of the RLD. Non-linear mixed effect modeling was used to estimate the population mean PK parameters for each batch. For FP, a 2-compartment model with a sequential dual zero-order absorption best described the PK profile. For SX, a 2-compartment model with a first-order absorption model best fit the data. Both models were able to capture the plasma concentration, the maximum concentration, and the total exposure (AUCinf) adequately for each batch, which could be used to simulate the BE study in the future. In vitro properties were also measured for each batch, and the batch with a higher fraction of the fine particle (diameter < 1µm, < 2µm) had a higher AUCinf. This positive correlation for both FP and SX could potentially assist the batch selection for the PK BE study.

Nanoscale colocalized thermal and chemical mapping of pharmaceutical powder aerosols

Inhalation of pharmaceutical aerosol formulations is widely used to treat respiratory diseases. Spatially resolved thermal characterization offers promise for better understanding drug release rates from particles; however, this has been an analytical challenge due to the small particle size (from a few micrometers down to nanometers) and the complex composition of the formulations. Here, we employ nano-thermal analysis (nanoTA) to probe the nanothermal domain of a pharmaceutical aerosol formulation containing a mixture of fluticasone propionate (FP), salmeterol xinafoate (SX), and excipient lactose, which is widely used to treat asthma and chronic obstructive pulmonary disease (COPD). Furthermore, atomic force microscopy-infrared spectroscopy (AFM-IR) and AFM force measurements are performed to provide nanochemical and nanomechanical information to complement the nanothermal data. The colocalized thermal and chemical mapping clearly reveals the surface heterogeneity of the drugs in the aerosol particles and demonstrates the contribution of the surface chemical composition to the variation in the thermal properties of the particles. We present a powerful analytical approach for in-depth characterization of thermal/chemical/morphological properties of dry powder inhaler particles at micro- and nanometer scales. This approach can be used to facilitate the comparison between generics and reference inhalation products and further the development of high-performance pharmaceutical formulations.

Abstract 3162: Antagonizing beta-2 adrenergic receptor’s function triggers death in glioma cells and down-regulates survivin

Abstract Introduction: Epidemiological studies showed that beta-adrenergic antagonists caused a low incidence of several cancer types. Glioblastoma highly expresses beta-2-adrenergic receptors. GBM accounts for 50% of central nervous system cancers. After standard-of-care therapeutic intervention, there is a survival time of 15 months. Our goal is to develop a translational therapy that will trigger the death of GBM cells while preserving healthy cells Methodology: Salmeterol xinafoate is a biased agonist that activates the G-protein pathway. Biased agonists activate signaling through the G-protein or the beta-arrestin pathway of G-protein coupled receptors. Dose-response experiments were performed using beta1 and beta2-adrenergic receptor antagonists and biased beta2-adrenergic receptor agonists to determine loss of glioma cell viability in GBM5, GBM12, and LN229 glioma cell lines. Western immunoblotting gauged survivin expression levels in all three lines. Epoxomicin was used to inhibit the proteasome complex. Annexin V and propidium iodide were employed to measure apoptotic or necrotic cell death. Results: Disrupting beta2-adrenergic receptor signaling by salmeterol xinafoate led to cell death of glioma cells but spared healthy neuron-glia cells using similar doses. Salmeterol xinafoate revealed greater efficacy for killing glioma cells than beta1 and beta2-adrenergic receptor antagonists. To determine the mechanism of glioma cell death, LN229 cells were treated with escalating doses of Salmeterol xinafoate, and at 24 hours, annexin V staining showed early apoptosis, and Annexin V/propidium iodide co-staining also showed late apoptosis. Propidium iodide revealed minor necrosis in LN229 glioma cells. Western immunoblotting showed salmeterol xinafoate downregulated survivin in a dose-dependent manner. However, the epoxomicin's inhibition of the proteasome complex prevented dose-escalated downregulation of survivin for all three glioma cell lines. Conclusion: The bitopic structure of salmeterol enables this drug to bind to the beta2-adrenergic receptors ligand binding site and an exosite site by its aryloxyalkyl tail that may contribute to the increased efficacy. Salmeterol xinafoate triggers glioma cell death by apoptosis at least in one glioma cell line. Salmeterol Xinafoate down-regulates survivin through protease degradation. Promising results show that the FDA-approved drug salmeterol xinafoate enables a favorable transition to the clinic. Repurposing this drug for GBMs may be combined with the current standard-of-care chemotherapies to enhance more significant loss of tumor volume and increase patient survival. Citation Format: Orli Algranatti, Ji Yae Lee, James M. Angelastro. Antagonizing beta-2 adrenergic receptor’s function triggers death in glioma cells and down-regulates survivin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3162.

Regional lung targeting with a fluticasone/salmeterol aerosol using a bolus breath hold method of the PreciseInhale® system: A first evaluation in humans

BackgroundIn development of inhaled drugs- and formulations the measured concentration in the systemic circulation is often used as a surrogate for local dosimetry in the lungs. To further elucidate regional differences in the fate of drugs in the lungs, different aerodynamic sizes of aerosols have been used to target major airway regions. An alternative approach to achieve regional targeting of aerosols, is to use a defined aerosol bolus together with a bolus breath hold strategy. A small volume of test aerosol is intercalated and stopped at different penetration depths, to achieve increased drug deposition at chosen lung locations. Drug permeation from the lung regions is then investigated by repeatedly sampling venous blood from the systemic circulation.The PreciseInhale® (PI) exposure platform was developed to allow generation of aerosols from different sources, including clinical inhalers, into a holding chamber, for subsequent use with alternative exposure modules in vitro and in vivo. In the current first-in-human study was investigated the feasibility of a new clinical exposure module added to the PI system. By extracting aerosol puffs from a medical inhaler for subsequent delivery to volunteers, it was possible to administer whole lung exposures, as well as regional targeting exposures. MethodsAerosols containing 250 µg/25 µg fluticasone propionate (FP)/salmeterol xinafoate (SMX) were automatically actuated and extracted from the pressurized Metered Dose Inhaler (pMDI) Evohaler Seretide forte into the PI system's holding chamber, then administered to the healthy volunteers using controlled flowrate and volume exposure cycles.Two main comparisons were made by measuring the systemic PK response: I. One label dose directly from the inhaler to the subject was compared to the same dose extracted from the pMDI into the PI system and then administered to the subject. II A small aerosol bolus at a penetration level in the central airways was compared to a small aerosol bolus at a penetration level in the peripheral lung. Results and ConclusionsWhen one inhaler dose was administered via the PI system, the absorbed dose, expressed as AUC24, was approximately twice as high and the CV was less than half, compared to direct inhalation from the same pMDI. Bolus breath hold targeting of drugs from the same aerosol mixture to the peripheral lung and the central airways showed a difference in their appearance in the systemic circulation. Normalized to the same deposited dose, SMX had a 57 % higher Cmax in the peripheral lung compared to the central airways. However, from 6 to 24 h after dosing the systemic concentrations of SMX from both regions were quite similar. FP had parallel concentrations curves with a 23 % higher AUC24 in the peripheral lung with no noticeable elevation around Cmax. The permeability of these two substances from similar sized aerosols was indeed higher in the thinner air/blood barriers of the peripheral lung compared to the central airways, but differences as measured on the venous side of the circulation were not dramatic. In conclusion, the PI system provided better control of actuation, aspiration, and dispensation of aerosols from the clinical inhaler and thereby delivered higher quality read outs of pharmacokinetic parameters such as tmax, Cmax, and AUC. Improved performance, using PI system, can likely also be employed for studying regional selectivity of other responses in the lungs, for use in drug development.

User Friendly Analytical Method Development and Validation of Salmeterol Xinafoate an Antiasthmatic Drug in Bulk and Formulated Product

A simple, precise, accurate, sensitive cheap and selective RP-HPLC method has been developed of salmeterol in bulk and pharmaceutical formulation. The method was carried out on an Inertsil ODS C18 (250 x 4.6mm, packed with 5µ). The maximum absorbance was found to be at 203nm. The Salmeterol xinafoate followed linearity in the concentration range 20 to 70ppm and correlation coefficient was found to be 0.999. Injection volume was selected to be 20µl and the flow rate was fixed at 1.0ml/min. Mobile phase selected with the ratio of methanol and water (60:40 v/v). Run time was selected to be 8min. Retention team was found to be 3.521. The LOD and LOQ were found to be 0.00471 and 0.01429.

Controller therapy attenuates asthma exacerbations associated with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children

Controller therapy attenuates asthma exacerbations associated with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children

Simultaneous Quantitative Analysis of Salmeterol and Fluticasone in Inhalation Spray Using HPLC and a Fast Spectrophotometric Technique Combined with a Time Series Neural Network and Multivariate Calibration Methods.

Chromatographic methods have been used for the simultaneous determination of salmeterol (SMT) and fluticasone (FLU). The methods take a lot of analysis time, need sample pre-treatment and large amounts of solvents, and are costly. The aim of this paper was to propose a simple, quick, and low-cost method for the determination of SMT and FLU using a time series neural network and multivariate calibration methods, including partial least-squares (PLS) and principal component regression (PCR). The simultaneous spectrophotometric determination of SMT and FLU in binary mixtures and anti-asthma spray was performed by applying multivariate calibration methods and an intelligent approach. The coefficient of determination (R2) of the time series neural network was obtained: 1 and 0.9997 for SMT and FLU, respectively. The mean recovery of PLS was found to be 99.29% and 99.84% for SMT and FLU, respectively. Also, the mean recovery related to the PCR method was 102.05% and 103.72% for SMT and FLU, respectively. The inhalation spray was assessed using HPLC and the results were compared with chemometrics methods via an analysis of variance (ANOVA) test. Intelligent and multivariate calibration methods were proposed. Simultaneous spectrophotometric determination of salmeterol and fluticasone was studied in an anti-asthma spray. HPLC as a reference method was performed and compared with chemometrics methods. Rapid, simple, low-cost, and accurate are the benefits of the proposed approaches.

The impact of unsupervised and unconsented switch of inhalers in patients with controlled asthma - A targeted literature review.

Inhaler combination formulations consisting of an inhaled corticosteroid (ICS) (fluticasone propionate) and a long-acting β2 agonist (salmeterol xinafoate) are indicated as maintenance treatments for patients with asthma and/or for selected patients with chronic obstructive pulmonary disease. The emergence of generic equivalents to branded inhalers is expected to offer economic edge/savings; however, some may argue that cost advantages offered by generic inhalers may be offset by worsening outcomes due to improper inhaler use, reduced adherence, and consequently worse disease control. To understand how unsupervised and unconsented switch of dry-powder inhalers and/or metered-dose inhalers affects clinical and humanistic outcomes in asthma, comprehensive searches of Embase and MEDLINE were conducted to identify research articles published in the English language since 2011. Patients with asthma of any age who underwent an unsupervised and unconsented switch from an ICS/long-acting β2 agonist to another (brand-to-generic or brand-to-brand) for non-medical reasons were the target of this research. Relevant outcomes included asthma control, medication adherence, and healthcare resource utilization. In total, 11 studies were identified for review (ten non-interventional and one post hoc); cohorts ranged from 19 to 42,553 patients. Six studies indicated that unsupervised and unconsented inhaler switch had a negative impact on asthma control; six studies indicated reduced medication adherence post-switching; and five studies reporting healthcare resource utilization showed it was unchanged or increased post-switching. Findings from this targeted review support concerns that unsupervised and unconsented inhaler switch has a largely negative impact on asthma-associated outcomes. Additional studies are warranted to further explore unsupervised and unconsented switch in asthma.

Optical photothermal infrared spectroscopy for nanochemical analysis of pharmaceutical dry powder aerosols

The aim of this research was to chemically analyse the distribution of drugs and excipients in pharmaceutical dry powder inhalation (DPI) aerosol particles of various sizes in solid state. The conventional wet assay of the chemical composition of particles after collection in a cascade impactor lacks the capability to differentiate spatially resolved morphology and chemical composition of particles in complex DPI formulations. In this proof-of-concept study, we aim to demonstrate the feasibility of using optical photothermal infrared spectroscopy (O-PTIR) to characterize micro- to nano-scale chemical composition of size-segregated particles of pharmaceutical DPI formulations. These formulations were prepared by spray drying a solution or a suspension comprising an inhaled corticosteroid fluticasone propionate, a long-acting β2-agonist salmeterol xinafoate, and excipient lactose. The active ingredients fluticasone propionate and salmeterol xinafoate are widely used for the treatment of asthma and chronic obstructive pulmonary disease. Spatially resolved O-PTIR spectra acquired from the particles collected from stages 1–7 of a Next Generation Impactor (NGI) for both formulations confirmed the presence of peaks related to fluticasone propionate (1746 cm−1, 1702 cm−1, 1661 cm−1 and 1612 cm−1), salmeterol xinafoate (1582 cm−1), and lactose (1080 cm−1). There was no significant difference in the drug to lactose peak ratio among various size fractions of particles spray dried from solution indicating a homogeneity in drug and lactose content in the aerosol formulation. In contrast, the suspension-spray dried formulation showed the drug content increased while the lactose content decreased in the particles collected down the NGI from stage 1 to stage 7, indicating heterogeneity in the ratio of drug-excipient distribution. The qualitative chemical compositions from O-PTIR were comparable to conventional wet chemical assays of various size fractions, indicating the suitability of O-PTIR to serve as a valuable analytical platform for screening the physicochemical properties of DPIs in solid state.

SYNTHESIS OF MOLECULAR IMPRINTED POLYMER SALBUTAMOL USING METHACRYLIC ACID MONOMER AND TRIMETHYL PROPANE TRIMETHACRYLATE (TRIM) AS A CROSS-LINKER THROUGH SUSPENSION POLYMERIZATION

Objective: This study aims to determine the analytical performances and characteristics of MIP salbutamol made with methacrylic acid (MAA) monomer and trimethylpropane trimethacrylate (TRIM) cross-linker through suspension polymerization.&#x0D; Methods: The MIP salbutamol was synthesized using suspension polymerization. The analytical performances of MIP, such as the adsorption ability, adsorption capacity and selectivity, were evaluated by Spectrophotometer UV-Vis. The physical characterization of MIP and NIP were evaluated using FTIR, TEM-EDS, Brunauer-Emmett-Teller (BET) method and Barret-Joyner-Halenda (BJH) method.&#x0D; Results: Molecular Imprinted Polymer (MIP) showed better analytical performance than Non-Imprinted Polymer (NIP), the adsorption ability of MIP and NIP reached about 90.43% and 53.92%, respectively. The MIP was selective for salbutamol when compared to terbutaline and salmeterol xinafoate with an imprinting factor (IF) of 1.2841. The MIP has spherical shape particles with diameters in the range of 10-100 µm with a surface area of 185.546 m2/g, pore volume of 0.257 cm3/g, and pore size of 16.599 Å.&#x0D; Conclusion: The Based on these results, MIP salbutamol, has the potential to be developed as a method for the preparation of salbutamol analysis from biological samples.

Predicting in vitro lung deposition behavior of combined dry powder inhaler via rheological properties

Dry powder inhaler (DPI) for pulmonary delivery is currently the primary treatment for asthma and COPD (chronic obstructive pulmonary disease), an increasing number of combined DPIs (containing two or more drugs in one inhaler) have been developed to complement the effect of single DPIs. Based on our previous studies, the rheological properties can be a potential tool used to predict the in vitro lung deposition behavior of DPI formulations. However, it is unknown whether such a prediction model is suitable for combination systems. Therefore, this study aimed to verify the applicability of using powder rheological properties to predict in vitro drug deposition behavior in combined DPI formulations. Two drugs (fluticasone propionate and salmeterol xinafoate) and their combination of DPI formulations were prepared using fine lactose content (in the range of 1%-20%) as a variable. The physicochemical properties of the powder mixtures such as particle size and content uniformity were characterized. The rheological properties of the powder mixtures were measured by FT4 rheometer, the aerodynamic behavior of the DPI formulations was evaluated by a new generation impactor (NGI), and the effect of flowability and adhesion on the deposition of the fine particle fraction (FPF) was investigated by principal component analysis (PCA). The results showed that the combined DPI formulations with larger particle interaction forces have certain differences from the aerodynamic behavior of the single DPI formulations. The regularity of rheological properties affecting FPF revealed in single DPI is still applicable to combined DPI, the parameters basic flowability energy (BFE), representing flowability, and flow factor (ff), Cohesion representing adhesion, can be well linearly related to the FPF. The results of the principal component analysis showed that better flowability and suitable adhesion contributed to higher in vitro deposition of the drug in the formulation, and the contribution of adhesion (75.42%) was greater than that of flowability (24.58%). In conclusion, rheological properties is an effective tool for predicting the deposition behavior of DPI not only in single but also in combined DPIs.

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.

Evaluation of Asthma Management Outcomes

Background: Asthma is a serious global health problem with an estimated 300 million affected individuals. Clinical manifestations of asthma can be controlled with appropriate treatment. When asthma is controlled, severe exacerbations should be rare. The goal of treatment in Asthma is to reduce inflammation and to achieve¸ total control. Treatment with anti-inflammatory drugs can, to a large extent, reverse some of these processes; however, the successful response to therapy often requires weeks to achieve and, in some situations, may be incomplete. Objectives of the study: This study was performed to evaluate the outcomes of Asthma treatment amongst asthmatic patients on follow-up at King Hussein Medical Centre (KHMC) at the Royal Medical Services (RMS) in Jordan/Amman. Methods: A retrospective, observational study was designed and performed on the basis of the asthma patient medical files. The patients’ medical profiles of were revised and the results were assessed according global initiative for asthma (GINA) guidelines. The collected data was analyzed by using statistical Package for the Social Sciences (SPSS) version 22. Results: A total of 210 asthmatic patient’s profiles were revised, and amongst the patient's majority (62.6%) were males and the average age of the participants was 35.1 years with standard deviation (SD) of 9.4. The most (53.3%) have been prescribed asthmatic drug combination was fluticasone propionate and salmeterol xinafoate (Seretide®) for long term asthmatic symptoms management. Amongst the asthmatic patients, 58 % had used antibacterial for their respiratory tract infections (RTIs) and urinary tract infections (UTIs). Conclusion: This study has shown that, despite the existence of an effective medication for asthma, disease control is insufficient and falls short of the accepted global guidelines.

Efficacy of salmeterol and magnesium isoglycyrrhizinate combination treatment in rats with chronic obstructive pulmonary disease

The most classic treatment recommended in the current chronic obstructive pulmonary disease (COPD) guidelines is glucocorticoid and β2 receptor agonist combination, such as salmeterol xinafoate and fluticasone propionate (Sal/Flu), causing many adverse reactions due to hormones. Magnesium isoglycyrrhizinate (MgIG) is an anti-inflammatory glycyrrhizic acid preparation for treating chronic inflammation, contributing to its structure is similar to steroidal anti-inflammatory drugs. In this study, we successfully established COPD rat model by endotracheal-atomized lipopolysaccharide exposure and cigarette smoke induction, as characterized by lung function decline. We discovered that salmeterol xinafoate/MgIG combination could alleviated lung inflammation infiltration, airway wall thickness (AWT) and the secretion of bronchial mucin MUC5AC of COPD rats more than salmeterol xinafoate, MgIG, or salmeterol xinafoate and fluticasone propionate treatment did, as well as reduced inflammatory cells (white blood cells, neutrophils and lymphocytes) accumulation in bronchoalveolar lavage fluid and decreased TNF-α, IL-6 and IL-1β production in the serum of COPD rats. Finally, we found that Moreover, the mechanism involved might be related to the suppression of JAK/STAT signaling pathway. Overall, our studies suggested that MgIG might be a potential alternative adjuvant drug for fluticasone propionate for the clinical treatment of patients with COPD.

Molecular Dynamic Study of Mechanism Underlying Nature of Molecular Recognition and the Role of Crosslinker in the Synthesis of Salmeterol-Targeting Molecularly Imprinted Polymer for Analysis of Salmeterol Xinafoate in Biological Fluid.

The rational preparation of molecularly imprinted polymers (MIPs) in order to have selective extraction of salmeterol xinafoate (SLX) from serum was studied. SLX is an acting β-adrenergic receptor agonist used in the treatment of asthma and has an athletic performance-enhancing effect. Molecular dynamics were used for the simulation of the SLX-imprinted pre-polymerization system, to determine the stability of the system. The computational simulation showed that SLX as a template, 4-hydroxyethyl methacrylate (HEMA) as a monomer, and trimethylolpropane trimethacrylate (TRIM) as a crosslinker in mol ratio of 1:6:20 had the strongest interaction in terms of the radial distribution functional. To validate the computational result, four polymers were synthesized using the precipitation polymerization method, and MIP with composition and ratio corresponding with the system with the strongest interaction as an MD simulation result showed the best performance, with a recovery of 96.59 ± 2.24% of SLX in spiked serum and 92.25 ± 1.12% when SLX was spiked with another analogue structure. Compared with the standard solid phase extraction sorbent C-18, which had a recovery of 79.11 ± 2.96%, the MIP showed better performance. The harmony between the simulation and experimental results illustrates that the molecular dynamic simulations had a significant role in the study and development of the MIPs for analysis of SLX in biological fluid.