Surface Enrichment and Depletion of Components in a Ternary Drug-Surfactant-Polymer Amorphous Solid Dispersion.

Amorphous solid dispersions (ASDs) can be used to enhance the solubility and bioavailability of poorly soluble drugs. An ASD is often a ternary system containing a drug, a surfactant, and a polymer. Recent work on binary ASDs has observed significant differences between surface and bulk compositions, with impacts on wettability and stability. Here we investigate a ternary ASD composed of the antifungal posaconazole, the surfactant Span 80, and a dispersion polymer (PVP or PVP/VA). The surfactant loading was fixed at the typical level of 5 wt %, and the drug/polymer ratio was varied. We observed strong surface enrichment of the surfactant and simultaneous depletion of the drug. This effect is already pronounced in the binary drug-surfactant system and is enhanced by the addition of the polymers. Between the two polymers, the more hydrophilic PVP causes a stronger enhancement of the surface enrichment effect. These results demonstrate the impact of component interactions on the surface composition of ASDs and the performance.

New insights into the role of VKORC1 polymorphisms for optimal warfarin dose selection in Caribbean Hispanic patients through an external validation of a population PK/PD model.

Warfarin, an oral anticoagulant, has been used for decades to prevent thromboembolic events. The complex interplay between CYP2C9 and VKORC1 genotypes on warfarin PK and PD properties is not fully understood in special sub-groups of patients. This study aimed to externally validate a population pharmacokinetic/pharmacodynamic (PK/PD) model for the effect of warfarin on international normalized ratio (INR) and to evaluate optimal dosing strategies based on the selected covariates in Caribbean Hispanic patients. INR, and CYP2C9 and VKORC1 genotypes from 138 patients were used to develop a population PK/PD model in NONMEM. The structural definition of a previously published PD model for INR was implemented. A numerical evaluation of the parameter-covariate relationship was performed. Simulations were conducted to determine optimal dosing strategies for each genotype combinations, focusing on achieving therapeutic INR levels. Findings revealed elevated IC50 for G/G, G/A, and A/A VKORC1 haplotypes (11.76, 10.49, and 9.22 mg/L, respectively), in this population compared to previous reports. The model-guided dosing analysis recommended daily warfarin doses of 3-5 mg for most genotypes to maintain desired INR levels, although subjects with combination of CYP2C9 and VKORC1 genotypes * 2/* 2-, * 2/* 3- and * 2/* 5-A/A would require only 1 mg daily. This research underscores the potential of population PK/PD modeling to inform personalized warfarin dosing in populations typically underrepresented in clinical studies, potentially leading to improved treatment outcomes and patient safety. By integrating genetic factors and clinical data, this approach could pave the way for more effective and tailored anticoagulation therapy in diverse patient groups.

Role of Heteronucleants in Melt Crystallization of Crystalline Solid Dispersions.

Few publications exist concerning polymorphic control during melt crystallization, particularly when employing heteronucleants. Here, the influence of a polymeric thin film (polyethylene terephthalate, PET) on the crystallization from melt of the polymorphic compound acetaminophen (ACM) in polyethylene glycol (PEG) was investigated. Molten ACM-PEG at different compositions was monitored using in situ Raman spectroscopy for nucleation induction time measurements and phase identification. Furthermore, X-ray diffraction (XRD) served to analyze the preferred orientation (PO) of the pastilles (solidified melt droplets) on PET-coated and uncoated substrates. The results indicate that PET-coated substrates qualitatively accelerate the nucleation of ACM form II (ACM II) in PEG compared to uncoated glass substrates. Additionally, the occurrence of ACM II in PEG was increased by an average of 10% when crystallized on PET-coated substrates compared to uncoated substrates. Overall, these results suggest that ACM can interact through hydrogen bonding with the PET-coated substrate, leading to faster nucleation. This investigation illustrates the effect of PET-coated substrates in the selective crystallization of ACM II in PEG as crystalline solid dispersions (CSDs). Ultimately, the results suggest the implementation of polymeric heteronucleants in melt crystallization processes, specifically, in advanced polymer-based formulation processes for the enhanced polymorphic form control of pharmaceutical compounds in CSDs.

Evaluation of a compact composite sensor array for concentration monitoring of solutions and suspensions via multivariate analysis.

Compact composite probes were identified as a priority to alleviate space constraints in miniaturized unit operations and pharmaceutical manufacturing platforms. Therefore, in this proof of principle study, a compact composite sensor array (CCSA) combining ultraviolet and near infrared features at four different wavelengths (280, 340, 600, 860 nm) in a 380 × 30 mm housing (length x diameter, 7 mm diameter at the probe head), was evaluated for its capabilities to monitor in situ concentration of solutions and suspensions via multivariate analysis using partial least squares (PLS) regression models. Four model active pharmaceutical ingredients (APIs): warfarin sodium isopropanol solvate (WS), lidocaine hydrochloride monohydrate (LID), 6-mercaptopurine monohydrate (6-MP), and acetaminophen (ACM) in their aqueous solution and suspension formulation were used for the assessment. The results demonstrate that PLS models can be applied for the CCSA prototype to measure the API concentrations with similar accuracy (validation samples within the United States Pharmacopeia (USP) limits), compared to univariate CCSA models and multivariate models for an established Raman spectrometer. Specifically, the multivariate CCSA models applied to the suspensions of 6-MP and ACM demonstrate improved accuracy of 63% and 31%, respectively, compared to the univariate CCSA models [1]. On the other hand, the PLS models for the solutions WS and LID showed a reduced accuracy compared to the univariate models [1].

Solvent-Mediated Polymorphic Transformations in Molten Polymers: The Account of Acetaminophen.

Solvent-mediated polymorphic transformations (SMPTs) employing nonconventional solvents (polymer melts) is an underexplored research topic that limits the application of polymer-based formulation processes. Acetaminophen (ACM), a widely studied active pharmaceutical ingredient (API), is known to present SMPTs spontaneously (<30 s) in conventional solvents such as ethanol. In situ Raman spectroscopy was employed to monitor the induction time for the SMPT of ACM II to I in polyethylene glycol (PEG) melts of different molecular weights (Mw, 4000, 10 000, 20 000, 35 000 g/mol). The results presented here demonstrate that the induction time for the SMPT of ACM II to I in PEG melts is driven by its diffusivity through the polymer melts. Compared to conventional solvents (i.e., ethanol) the mass transfer (diffusion coefficient, D) in melts is significantly hindered (Dethanol = 4.84 × 10-9 m2/s > DPEGs = 5.32 × 10-11-8.36 × 10-14 m2/s). Ultimately, the study proves that the induction time for the SMPT can be tuned by understanding the dispersant's physicochemical properties (i.e., η) and, thus, the D of the solute in the dispersant. This allows one to kinetically access and stabilize metastable forms or delay their transformations under given process conditions.

Polymorphic selectivity in crystal nucleation.

Crystal nucleation rates have been measured in the supercooled melts of two richly polymorphic glass-forming liquids: ROY and nifedipine (NIF). ROY or 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile is known for its crystals of red, orange, and yellow colors and many polymorphs of solved structures (12). Of the many polymorphs, ON (orange needles) nucleates the fastest with the runner up (Y04) trailing by a factor of 103 when compared under the same mobility-limited condition, while the other unobserved polymorphs are slower yet by at least 5 orders of magnitude. Similarly, of the six polymorphs of NIF, γ' nucleates the fastest, ß' is slower by a factor of 10, and the rest are slower yet by at least 5 decades. In both systems, the faster-nucleating polymorphs are not built from the lowest-energy conformers, while they tend to have higher energies and lower densities and thus greater similarity to the liquid phase by these measures. The temperature ranges of this study covered the glass transition temperature Tg of each system, and we find no evidence that the nucleation rate is sensitive to the passage of Tg. At the lowest temperatures investigated, the rates of nucleation and growth are proportional to each other, indicating that a similar kinetic barrier controls both processes. The classical nucleation theory provides an accurate description of the observed nucleation rates if the crystal growth rate is used to describe the kinetic barrier for nucleation. The quantitative rates of both nucleation and growth for the competing polymorphs enable prediction of the overall rate of crystallization and its polymorphic outcome.

Surfactants Accelerate Crystallization of Amorphous Nifedipine by Similar Enhancement of Nucleation and Growth Independent of Hydrophilic-Lipophilic Balance.

Amorphous formulations, increasingly employed to deliver poorly soluble drugs, generally contain surfactants to improve wetting and dissolution. These surfactants are often liquids and can potentially increase the mobility of the drug and reduce its stability, but little is known about this effect. Here we investigate the effect of four common nonionic surfactants (Tween 80, Span 80, Triton X-100, and Poloxamer 407) on the crystallization of amorphous nifedipine (NIF). We find that the surfactants significantly enhance the rates of crystal nucleation and growth even at low concentrations, by up to 2 orders of magnitude at 10 wt %. The surfactants tested show similar enhancement effects independent of their structural details and hydrophilic-lipophilic balance (HLB), suggesting that surfactant adsorption at solid/liquid interfaces does not play a major role in crystal nucleation and growth. Importantly, the surfactants accelerate crystal nucleation and growth by a similar factor. This result mirrors the previous finding that a polymer dopant in a molecular glass-former causes similar slowdown of nucleation and growth. These results indicate that nucleation and growth in a deeply supercooled liquid are both mobility-limited, and a dopant mainly functions as a mobility modifier (enhancer or suppressor depending on the dopant). The common surfactants tested are all mobility enhancers and destabilize the amorphous drug, and this negative effect must be managed using stabilizers such as polymers. The effect of surfactants on nucleation can be predicted from the effect on crystal growth and the crystallization kinetics of the pure system, using the same principle previously established for drug-polymer systems. We show how the independently measured nucleation and growth rates enable predictions of the overall crystallization rates.

Real-time concentration monitoring using a compact composite sensor array for in situ quality control of aqueous formulations.

Recent advancements have demonstrated the feasibility of refrigerator-sized pharmaceutical manufacturing platforms (PMPs) for integrated end-to-end manufacturing of active pharmaceutical ingredients (APIs) into formulated drug products. Unlike typical laboratory- or industrial-scale setups, PMPs present unique requirements for process analytical technology (PAT) with respect to versatility, flexibility, and physical size to fit into the PMP space constraints. In this proof of principle study, a novel compact composite sensor array (CCSA) combining ultraviolet (UV) and near infrared (NIR) features at four different wavelengths (280, 340, 600, 860 nm) with temperature measuring capability in a 380 × 30 mm housing (length x diameter, 7 mm diameter at the probe head), were evaluated. The results indicate that the CCSA prototype is capable of measuring the solution and suspension concentrations in aqueous formulations of four model APIs (warfarin sodium isopropanol solvate, lidocaine hydrochloride monohydrate, 6-mercaptopurine monohydrate, acetaminophen) in situ and in real-time with similar accuracy as an established Raman spectrometer commonly applied for method development.

Polymorphism in early development: The account of MBQ-167.

With McCrone's famous statement in mind, we set out to investigate the polymorphic behavior of a small-molecule dual inhibitor of Rac and Cdc42, currently undergoing preclinical trials. Herein, we report the existence of two polymorphs for 9-ethyl-3-(5-phenyl-1H-1,2,3-triazol-3-yl)-9H-carbazole (MBQ-167). These were characterized by differential scanning calorimetry, thermogravimetric analysis, Raman and Infrared spectroscopy, as well as powder and single crystal X-ray diffraction. The results obtained from the thermal analysis revealed that MBQ-167 form II undergoes an exothermic phase transition to form I, making this the thermodynamically stable form. An examination of the Burger-Ramberger rules for assigning thermodynamic relationships in polymorphic pairs indicate that this system is monotropic. The structure elucidation reveals that these forms crystallize in the orthorhombic (Pbca) and monoclinic (P21/n) space groups. A conformational analysis shows that the metastable form (form II) presents the most planar conformation along the significant torsion angles identified. Hirshfeld surface analysis confirms that van der Waals contacts are the primary interactions and only subtle differences in short contacts help differentiate each form. These findings support the notion that polymorphism is prevalent in organic molecules and that one should invest time and money probing possible polymorphs, particularly in early development as in the case of MBQ-167.

Solubility Measurements and Correlation of MBQ-167 in Neat and Binary Solvent Mixtures.

MBQ-167 is a novel, small-molecule dual inhibitor of Rac and Cdc42, small GTPases that are involved in cytoskeletal organization, cell cycle progression, and cell migration. In an in vivo mouse model, MBQ-167 has been shown to significantly reduce mammary tumor growth and metastasis and is currently undergoing preclinical studies for the treatment of metastatic cancer. To date, no solubility data have been reported for this compound. For this reason, the present study aims to determine the solubility of this compound in eight neat solvents (acetonitrile, 1-butanol, 2-butanol, ethanol, ethyl acetate, methanol, 1-propanol, and 2-propanol) and two binary solvent mixtures [ethyl acetate (2) + heptane (3) and ethanol (2) + water (3)] between the temperatures of 278.15 and 333.15 K. The results obtained employing the polythermal method show that the solubility of MBQ-167 increases with an increase in temperature in all neat solvents used within this study. Moreover, in the two binary solvent mixtures, the solubility of this compound increases with increasing temperature and decreases with an increasing mass fraction of the antisolvent (heptane or water). The experimental solubility data were correlated using the modified Apelblat and λh model equations. The predicted solubility data acquired from the Apelblat and λh model equations correlate well with the experimental solubility data as indicated by the low ARD % (≤1.8304 and ≤6.5366, respectively). No solvent-mediated polymorphic phase transitions were observed while performing the solubility studies, and no other solid forms were detected after the recrystallization in the solvents and solvent mixtures. The solubility data determined here can offer pathways to develop pharmaceutical crystallization processes that can further the translation of MBQ-167 into a clinical setting.

Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans.

Objectives The inter-individual variability of warfarin dosing has been linked to genetic polymorphisms. This study was aimed at performing genotype-driven pharmacokinetic (PK) simulations to predict warfarin levels in Puerto Ricans. Methods Analysis of each individual dataset was performed by one-compartmental modeling using WinNonlin®v6.4. The k e of warfarin given a cytochrome P450 2C9 (CYP2C9) genotype ranged from 0.0189 to 0.0075 h-1. K a and V d parameters were taken from literature. Data from 128 subjects were divided into two groups (i.e., wild-types and carriers) and statistical analyses of PK parameters were performed by unpaired t-tests. Results In the carrier group (n=64), 53 subjects were single-carriers and 11 double-carriers (i.e., *2/*2, *2/*3, *2/*5, *3/*5, and *3/*8). The mean peak concentration (Cmax) was higher for wild-type (0.36±0.12 vs. 0.32±0.14 mg/L). Likewise, the average clearance (CL) parameter was faster among non-carriers (0.22±0.03 vs. 0.17±0.05 L/h; p=0.0001), with also lower area under the curve (AUC) when compared to carriers (20.43±6.97 vs. 24.78±11.26 h mg/L; p=0.025). Statistical analysis revealed a significant difference between groups with regard to AUC and CL, but not for Cmax. This can be explained by the variation of k e across different genotypes. Conclusions The results provided useful information for warfarin dosing predictions that take into consideration important individual PK and genotyping data.

Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans.

OBJECTIVES: The inter-individual variability of warfarin dosing has been linked to genetic polymorphisms. This study was aimed at performing genotype-driven pharmacokinetic (PK) simulations to predict warfarin levels in Puerto Ricans. METHODS: Analysis of each individual dataset was performed by one-compartmental modeling using WinNonlin®v6.4. The ke of warfarin given a cytochrome P450 2C9 (CYP2C9) genotype ranged from 0.0189 to 0.0075 h-1. Ka and Vd parameters were taken from literature. Data from 128 subjects were divided into two groups (i.e., wild-types and carriers) and statistical analyses of PK parameters were performed by unpaired t-tests. RESULTS: In the carrier group (n=64), 53 subjects were single-carriers and 11 double-carriers (i.e., *2/*2, *2/*3, *2/*5, *3/*5, and *3/*8). The mean peak concentration (Cmax) was higher for wild-type (0.36±0.12 vs. 0.32±0.14 mg/L). Likewise, the average clearance (CL) parameter was faster among non-carriers (0.22±0.03 vs. 0.17±0.05 L/h; p=0.0001), with also lower area under the curve (AUC) when compared to carriers (20.43±6.97 vs. 24.78±11.26 h mg/L; p=0.025). Statistical analysis revealed a significant difference between groups with regard to AUC and CL, but not for Cmax. This can be explained by the variation of ke across different genotypes. CONCLUSIONS: The results provided useful information for warfarin dosing predictions that take into consideration important individual PK and genotyping data.

Polymorphism in Solid Dispersions.

Solid dispersions embed active pharmaceutical ingredients in polymeric carriers to improve their solubility. Three solid dispersion preparation techniques are typically employed: solvent evaporation, solvent-fusion, and fusion methods. Although these are also widely recommended as preparative methods for phase diagram determination, few examples exist concerning their effect on the resulting polymorph, once the solid dispersion is produced. In this study, the influence of these methods on the polymorphic form obtained in crystalline solid dispersions (CSDs) composed of flufenamic acid (FFA) and poly(ethylene glycol) was investigated. The physical mixtures and CSDs were characterized by powder X-ray diffraction, infrared spectroscopy, and differential scanning calorimetry. The results reveal that the fusion method leads to concomitant polymorphs (mainly FFA I and III) in the CSDs. In contrast, the solvent evaporation and solvent-fusion methods lead to FFA III. Collectively, these results demonstrate that preparative methods have a significant influence on the phase diagrams determined (average relative deviation ≤8%), which are often used to justify the design space of manufacturing processes, including those deemed "continuous." Consequently, choosing a preparation method that results in the desired polymorph is crucial to ensure accurate determination of phase diagrams and critical quality attributes of formulations.

In the Context of Polymorphism: Accurate Measurement, and Validation of Solubility Data.

Solubility measurements for polymorphic compounds are often accompanied by solvent-mediated phase transformations. In this study, solubility measurements from undersaturated solutions are employed to investigate the solubility of the two most stable polymorphs of flufenamic acid (FFA forms I and III), tolfenamic acid (TA forms I and II), and the only known form of niflumic acid (NA). The solubility was measured from 278.15 to 333.15 K in four alcohols of a homologous series (methanol, ethanol, 1-propanol, n-butanol) using the polythermal method. It was established that the solubility of these compounds increases with increasing temperature. The solubility curves of FFA forms I and III intersect at ~315.15 K (42 °C) in all four solvents, which represents the transition temperature of the enantiotropic pair. In the case of TA, the solubility of form II could not be reliably obtained in any of the solvents because of the fast solvent-mediated phase transformation. The solubility of the only known form of NA was also determined, and no other polymorphs of NA were observed. The experimental solubility data of FFA (forms I and III), TA (form I), and NA in these four solvents was correlated using the modified Apelblat and λh model equations. The correlated and experimentally determined solubility data obtained serves to (i) guide the accurate determination of the solubility for polymorphic compounds, (ii) assess the role of the solvent in mediating transformations, and (iii) provide a route to engineer advanced crystallization processes for these pharmaceutical compounds.

Solubility Determination and Correlation of Warfarin Sodium 2­Propanol Solvate in Pure, Binary, and Ternary Solvent Mixtures.

The solubility of warfarin sodium isopropanol solvate (WS·IPA), a widely used anticoagulant, was determined at temperatures ranging from 278.15 to 333.15 K in four pure solvents (acetone, ethanol, IPA, and water), five binary solvent mixtures (IPA + acetone, IPA + ethanol, IPA + water, IPA + heptane, and IPA + hexane), and five ternary solvent mixtures (IPA + acetone + heptane, IPA + acetone + hexane, IPA + ethanol + heptane, IPA + ethanol + hexane, and IPA + water + heptane) using the polythermal method. It was demonstrated that the solubility of WS·IPA increases with increasing temperature in the pure solvents and at constant solvent composition in the solvent mixtures. In addition, the solubility of WS·IPA in IPA increases with increasing content of acetone, ethanol, and water, which act as cosolvents, and decreases with increasing content of heptane and hexane, which act as antisolvents. The experimental solubility data of WS·IPA in pure solvents and binary and ternary solvent mixtures were correlated using the modified Apelblat and λh model equations. The correlated solubility data agree with the experimental data based on the relative deviation and the average relative deviation (ARD %) values. Thus, the correlated and experimentally derived solubility data of WS·IPA provide a pathway to engineer advanced pharmaceutical crystallization processes for WS·IPA.

Advanced Continuous Flow Platform for On-Demand Pharmaceutical Manufacturing.

As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including the large production footprint and lengthy time-scale, we previously reported a refrigerator-sized continuous flow system for the on-demand production of essential medicines. Building on this technology, herein we report a second-generation, reconfigurable and 25 % smaller (by volume) continuous flow pharmaceutical manufacturing platform featuring advances in reaction and purification equipment. Consisting of two compact [0.7 (L)×0.5 (D)×1.3 m (H)] stand-alone units for synthesis and purification/formulation processes, the capabilities of this automated system are demonstrated with the synthesis of nicardipine hydrochloride and the production of concentrated liquid doses of ciprofloxacin hydrochloride, neostigmine methylsulfate and rufinamide that meet US Pharmacopeia standards.

Revealing Polymorphic Phase Transformations in Polymer-Based Hot Melt Extrusion Processes.

The inadvertent occurrence of polymorphic phase transformations in active pharmaceutical ingredients (APIs) during hot melt extrusion (HME) processes has been claimed to limit the application of this technique. Hence, the control of polymorphism would need to be addressed if there is any prospect of HME to be successfully implemented as an alternative solid dosage formulation strategy in integrated, continuous end-to-end pharmaceutical manufacturing settings. This work demonstrates that flufenamic acid (FFA), one of the most polymorphic APIs known, thus far, can be processed using temperature-simulated HME with polyethylene glycol (PEG) as polymeric carrier. At temperatures above the transition point of FFA forms III and I (42 °C), the induction time of the polymorphic phase transformation is longer than the average reported residence time in conventional HME processes (5 min). Moreover, it was demonstrated that thorough understanding of the thermodynamic and kinetic design space for the PEG-FFA system leads to polymorphic control in the produced crystalline solid dispersions. Ultimately, this investigation helps to gain fundamental understanding of the processing needs of crystalline solid dispersions, which will lead to the broader application of HME as a continuous manufacturing strategy for drug products containing APIs prone to polymorphism, representing about 80% of all APIs.

Measurement and Correlation of the Solubility of 5-Fluorouracil in Pure and Binary Solvents.

The solubility of 5-ffuorouracil (5-FU), a widely used chemotherapeutic agent to treat solid tumors, which include colorectal, head and neck, breast, and lung cancer, was determined at temperatures ranging from 278.15 to 333.15 K in 11 pure solvents and binary water + ethanol solvent mixtures using the polythermal method. It was demonstrated that the solubility of 5-FU increases with increasing temperature in the pure solvents and at constant solvent composition in the solvent mixtures. Moreover, the solubility of 5-FU in the solvent mixtures exceeds its solubility in pure water and ethanol. The experimental solubility data of 5-FU in the pure solvents and solvent mixtures were correlated using the modified Apelblat and λh model equations. The predicted solubility data obtained agree with the experimental data based on the calculated relative deviation (RD) and the average relative deviation (ARD%) values. The selected solvents are categorized as either Class 2 or 3 (less toxic and lower risk to human health) solvents, and hence the correlated and experimentally derived solubility data of 5-FU presented provide a pathway to develop and engineer enhanced pharmaceutical processes and products based on this compound.

On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system.

Pharmaceutical manufacturing typically uses batch processing at multiple locations. Disadvantages of this approach include long production times and the potential for supply chain disruptions. As a preliminary demonstration of an alternative approach, we report here the continuous-flow synthesis and formulation of active pharmaceutical ingredients in a compact, reconfigurable manufacturing platform. Continuous end-to-end synthesis in the refrigerator-sized [1.0 meter (width) × 0.7 meter (length) × 1.8 meter (height)] system produces sufficient quantities per day to supply hundreds to thousands of oral or topical liquid doses of diphenhydramine hydrochloride, lidocaine hydrochloride, diazepam, and fluoxetine hydrochloride that meet U.S. Pharmacopeia standards. Underlying this flexible plug-and-play approach are substantial enabling advances in continuous-flow synthesis, complex multistep sequence telescoping, reaction engineering equipment, and real-time formulation.

Real-Time Analysis of Ambient Organic Aerosols Using Aerosol Flowing Atmospheric-Pressure Afterglow Mass Spectrometry (AeroFAPA-MS).

Organic compounds contribute to a major fraction of atmospheric aerosols and have significant impacts on climate and human health. However, because of their chemical complexity, their measurement remains a major challenge for analytical instrumentation. Here we present the development and characterization of a new soft ionization technique that allows mass spectrometric real-time detection of organic compounds in aerosols. The aerosol flowing atmospheric-pressure afterglow (AeroFAPA) ion source is based on a helium glow discharge plasma, which generates excited helium species and primary reagent ions. Ionization of the analytes occurs in the afterglow region after thermal desorption and produces mainly intact quasimolecular ions, facilitating the interpretation of the acquired mass spectra. We illustrate that changes in aerosol composition and concentration are detected on the time scale of seconds and in the ng m(-3) range. Additionally, the successful application of AeroFAPA-MS during a field study in a mixed forest region is presented. In general, the observed compounds are in agreement with previous offline studies; however, the acquisition of chemical information and compound identification is much faster. The results demonstrate that AeroFAPA-MS is a suitable tool for organic aerosol analysis and reveal the potential of this technique to enable new insights into aerosol formation, growth, and transformation in the atmosphere.