RÉSUMÉ
Extracellular vesicles are nanosized lipid-bilayered spheres secreted from every living cell and they serve physiological and pathophysiological functions. Bacterial membrane vesicles are shed from both Gram-negative and Gram-positive bacteria and harbor many virulence factors, nuclear material, polysaccharides, proteins, and antigenic determinants, which are essential for immune recognition and evasion. Hence, bacterial membrane vesicles are very promising vaccine candidates. Spray drying is a well-established pharmaceutical technique to produce inhalable dry powders with enhanced stability for formulations of vaccines. In this chapter, we illustrate general guidelines for spray drying of bacterial extracellular vesicles to improve their stability without compromising their immunogenic protective effect. We discuss some of the most important experiments to characterize the generated spray-dried bacterial membrane vesicle powder vaccine.
Sujet(s)
Vésicules extracellulaires , Vésicules extracellulaires/composition chimique , Vésicules extracellulaires/métabolisme , Vésicules extracellulaires/immunologie , Vaccins antibactériens/immunologie , Vaccins antibactériens/composition chimique , Séchage par pulvérisation , Poudres/composition chimique , Humains , Membrane cellulaire/métabolisme , Membrane cellulaire/composition chimique , AnimauxRÉSUMÉ
There is currently a growing interest in health-promoting foods. The beneficial effects of food on human health are actively promoted by health professionals and nutritionists. This growing awareness is influencing the increasing range of functional foods and the pursuit of more innovative solutions. Recent research indicates that spherical nanoparticles have the potential to be used as functional biomaterials in the food industry, particularly for encapsulating hydrophobic natural phytochemicals. Techniques and systems based on micro- and nano-encapsulation are of great importance in the food and pharmaceutical industries. It is of paramount importance that encapsulation materials are safe for use in food. The aim of this study was to obtain micelles containing extracts from chokeberry fruit pomace using egg yolk powder (EYP) for emulsification (as a source of lecithin) and egg white powder (EWP) for stabilisation. The structural properties of the micelles in the resulting powders were characterised using Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) analysis confirmed the presence of spherical micellar structures between 500 and 1000 nm in size. The water activity and water content of the obtained powders were determined, and the thermal (DSC) and antioxidant properties were investigated. The results indicated that the powder with the micellar structures had a higher stability compared to the powder obtained by simple mixing without the use of encapsulation techniques.
Sujet(s)
Antioxydants , Blanc d'oeuf , Jaune d'Åuf , Fruit , Micelles , Extraits de plantes , Extraits de plantes/composition chimique , Jaune d'Åuf/composition chimique , Fruit/composition chimique , Blanc d'oeuf/composition chimique , Antioxydants/composition chimique , Antioxydants/pharmacologie , Spectroscopie infrarouge à transformée de Fourier , Nanoparticules/composition chimique , Phénomènes chimiques , Poudres/composition chimiqueRÉSUMÉ
The study investigated the effect of Compound Shougong Powder(CSGP) on the biological functions of triple-negative breast cancer(TNBC) cells and whether its mechanism of action was related to the epithelial-mesenchymal transition(EMT) signaling pathway. TNBC cells(MDA-MB-231 and BT-549) were treated with different concentrations of CSGP-containing serum. MTS assay was used to detect the effect of CSGP on the proliferation of TNBC cells. The EdU staining was used to detect the effect of CSGP on the proliferation of TNBC cells. Flow cytometry was used to examine the impact of CSGP on apoptosis of TNBC cells. Wound-healing and Transwell assays were used to evaluate the effects of different concentrations of CSGP on the migration and invasion capabilities of TNBC cells. RNA sequencing technology was utilized to elucidate its mechanism. Subsequently, qRT-PCR was performed to measure the mRNA expression levels of E-cadherin, N-cadherin, Slug, Snail, Vimentin, Twist, Zinc finger E-box-Binding homeobox 1(Zeb1), and Zinc finger E-box-Binding homeobox 2(Zeb2). Western blot was used to assess the protein expression levels of Slug, Vimentin, and E-cadherin. After intervention with CSGP, the proliferation of MDA-MB-231 and BT-549 cells significantly decreased, while the apoptosis rate markedly increased. The expression levels of the epithelial marker protein E-cadherin significantly increased, while the expression levels of the EMT-related transcription factors Slug and Vimentin showed a decrease. In conclusion, CSGP inhibits the EMT, thereby suppressing the malignant progression of TNBC.
Sujet(s)
Apoptose , Prolifération cellulaire , Médicaments issus de plantes chinoises , Transition épithélio-mésenchymateuse , Tumeurs du sein triple-négatives , Transition épithélio-mésenchymateuse/effets des médicaments et des substances chimiques , Humains , Tumeurs du sein triple-négatives/traitement médicamenteux , Tumeurs du sein triple-négatives/génétique , Tumeurs du sein triple-négatives/métabolisme , Tumeurs du sein triple-négatives/anatomopathologie , Médicaments issus de plantes chinoises/pharmacologie , Lignée cellulaire tumorale , Prolifération cellulaire/effets des médicaments et des substances chimiques , Femelle , Apoptose/effets des médicaments et des substances chimiques , Mouvement cellulaire/effets des médicaments et des substances chimiques , Poudres/composition chimique , Cadhérines/génétique , Cadhérines/métabolismeRÉSUMÉ
This work aimed to evaluate the impact of enrichment processing on the quality parameters, bioactivity and sensorial aspects of Myristica fragrans (mace)-flavored olive oil storage for one year. The mace powder was added to extra virgin olive oil through two different processes: immediately after crushing the olives by mixing mace (1% weight/weight (w/w)) with the olive paste (MAVOO-M) and by adding mace to extra virgin olive oil (C) (2% w/w) (MAVOO-I). A multi-analytical approach was applied to measure the main qualitative indexes, such as the free acidity, peroxide value and ultraviolet parameters. The total phenolic and carotenoid contents (TPC and TCC, respectively) and α-tocopherol were also evaluated, as well as the sensory attributes. The radical scavenging potential was estimated by using two different in vitro tests, namely, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH). A significant increase in the free acidity parameter was found in all the flavored oils, and particularly in the MAVOO-M (1.27% oleic acid); at the same time, this oil was the sample with the lowest peroxide value (i.e., 9.68 meqO2/kg) after 360 days of storage. At the end of the storage, an increase in L* values was found in both the MAVOO-M and -I vs. the C (43.88 and 43.02, respectively, vs. 42.62). The TCC was strongly influenced by the addition of mace, especially when the infusion process was used. In fact, after one year of storage, the TCC in the MAVOO-I resulted in ~34.7% more than the MAVOO-M. A promising DPPH radical scavenging activity was observed independently by the applied aromatization process, with IC50 values of 19.77 and 17.80 µg/mL for the MAVOO-M and MAVOO-I, respectively. However, this activity decreased during storage, and a similar trend was observed using the ABTS test. In conclusion the infusion as enrichment methodology led to more promising results in terms of functionality compared with the co-mixing one.
Sujet(s)
Myristica , Myristica/composition chimique , Antioxydants/composition chimique , Antioxydants/pharmacologie , Poudres/composition chimique , Phénols/composition chimique , Huile d'olive/composition chimique , Aromatisants/composition chimique , Stockage des aliments/méthodes , Caroténoïdes/composition chimiqueRÉSUMÉ
The study investigated the impact of Lonicera caerulea L. juice matrix modification and drying techniques on powder characteristics. The evaluation encompassed phenolics (514.7-4388.7 mg/100 g dry matter), iridoids (up to 337.5 mg/100 g dry matter), antioxidant and antiglycation capacity, as well as anti-ageing properties of powders produced using maltodextrin, inulin, trehalose, and palatinose with a pioneering role as a carrier. Spray drying proved to be competitive with freeze drying for powder quality. Carrier application influenced the fruit powder properties. Trehalose protected the phenolics in the juice extract products, whereas maltodextrin showed protective effect in the juice powders. The concentrations of iridoids were influenced by the matrix type and drying technique. Antiglycation capacity was more affected by the carrier type in juice powders than in extract products. However, with carrier addition, the latter showed approximately 12-fold higher selectivity for acetylcholinesterase than other samples. Understanding the interplay between matrix composition, drying techniques, and powder properties provides insights for the development of plant-based products with tailored attributes, including potential health-linked properties.
Sujet(s)
Lyophilisation , Lonicera , Extraits de plantes , Poudres , Séchage par pulvérisation , Lyophilisation/méthodes , Poudres/composition chimique , Lonicera/composition chimique , Extraits de plantes/composition chimique , Antioxydants/composition chimique , Antioxydants/analyse , Jus de fruits et de légumes/analyse , Polyosides/composition chimique , Polyosides/analyse , Phénols/analyse , Phénols/composition chimiqueRÉSUMÉ
Edible flowers are a potential source of bioactive ingredients and are also an area of scientific research. Particularly noteworthy are Cyani flos, which have a wide range of uses in herbal medicine. The below study aimed to investigate the influence of selected soluble fiber fractions on the selected properties of physical and biochemical powders obtained during spray drying a water extract of Cyani flos. The drying efficiency for the obtained powders was over 60%. The obtained powders were characterized by low moisture content (≤4.99%) and water activity (≤0.22). The increase in the addition of pectin by the amount of 2-8% in the wall material resulted in a decrease in hygroscopicity, water solubility, and protection of flavonoids and anthocyanins both before and after digestion in the tested powders in comparison to the sample with only inulin as a carrier. Additionally, it was noted that all samples were characterized by high bioaccessibility when determining antioxidant properties and xanthine oxidase inhibition.
Sujet(s)
Antioxydants , Fleurs , Extraits de plantes , Poudres , Séchage par pulvérisation , Extraits de plantes/composition chimique , Poudres/composition chimique , Fleurs/composition chimique , Antioxydants/composition chimique , Antioxydants/pharmacologie , Flavonoïdes/composition chimique , Solubilité , Anthocyanes/composition chimiqueRÉSUMÉ
Pulmonary delivery and formulation of biologics are among the more complex and growing scientific topics in drug delivery. We herein developed a dry powder formulation using disordered mesoporous silica particles (MSP) as the sole excipient and lysozyme, the most abundant antimicrobial proteins in the airways, as model protein. The MSP had the optimal size for lung deposition (2.43 ± 0.13 µm). A maximum lysozyme loading capacity (0.35 mg/mg) was achieved in 150 mM PBS, which was seven times greater than that in water. After washing and freeze-drying, we obtained a dry powder consisting of spherical, non-aggregated particles, free from residual buffer, or unabsorbed lysozyme. The presence of lysozyme was confirmed by TGA and FT-IR, while N2 adsorption/desorption and SAXS analysis indicate that the protein is confined within the internal mesoporous structure. The dry powder exhibited excellent aerodynamic performance (fine particle fraction <5 µm of 70.32%). Lysozyme was released in simulated lung fluid in a sustained kinetics and maintaining high enzymatic activity (71-91%), whereas LYS-MSP were shown to degrade into aggregated nanoparticulate microstructures, reaching almost complete dissolution (93%) within 24 h. MSPs were nontoxic to in vitro lung epithelium. The study demonstrates disordered MSP as viable carriers to successfully deliver protein to the lungs, with high deposition and retained activity.
Sujet(s)
Poumon , Lysozyme , Taille de particule , Poudres , Silice , Silice/composition chimique , Lysozyme/administration et posologie , Lysozyme/composition chimique , Poumon/métabolisme , Poumon/effets des médicaments et des substances chimiques , Porosité , Poudres/composition chimique , Vecteurs de médicaments/composition chimique , Administration par inhalation , Systèmes de délivrance de médicaments/méthodes , Nanoparticules/composition chimique , Humains , Excipients/composition chimique , Animaux , Chimie pharmaceutique/méthodes , Spectroscopie infrarouge à transformée de Fourier , LyophilisationRÉSUMÉ
PURPOSE: Twin-screw wet granulation (TSWG) is a manufacturing process that offers several advantages for the processing of water-insoluble active pharmaceutical ingredients (APIs) and has been used for increasing the solubility and dissolution rates. Here we introduce a novel TSWG approach with reduced downstream processing steps by using non-volatile solvents as granulating binders. METHODS: Herein, TSWG was carried out using Transcutol a non-volatile protic solvent as a granulating binder and dissolution enhancer of ibuprofen (IBU) blends with cellulose polymer grades (Pharmacoat® 603, Affinisol™, and AQOAT®). RESULTS: The physicochemical characterisation of the produced granules showed excellent powder flow and the complete transformation of IBU into the amorphous state. Dissolution studies presented immediate release rates for all IBU formulations due to the high drug-polymer miscibility and the Transcutol solubilising capacity. CONCLUSIONS: Overall, the study demonstrated an innovative approach for the development of extruded granules by processing water-insoluble APIs with non-volatile solvents for enhanced dissolution rates at high drug loadings.
Sujet(s)
Cellulose , Chimie pharmaceutique , Préparation de médicament , Excipients , Ibuprofène , Solubilité , Solvants , Technologie pharmaceutique , Solvants/composition chimique , Cellulose/composition chimique , Chimie pharmaceutique/méthodes , Excipients/composition chimique , Préparation de médicament/méthodes , Ibuprofène/composition chimique , Technologie pharmaceutique/méthodes , Poudres/composition chimique , Libération de médicament , Polymères/composition chimique , Taille de particule , Eau/composition chimique , Éthylène glycolsRÉSUMÉ
High shear wet granulation (HSWG) is widely used in tablet manufacturing mainly because of its advantages in improving flowability, powder handling, process run time, size distribution, and preventing segregation. In line process analytical technology measurements are essential in capturing detailed particle dynamics and presenting real-time data to uncover the complexity of the HSWG process and ultimately for process control. This study presents an opportunity to predict the properties of the granules and tablets through torque measurement of the granulation bowl and the force exerted on a novel force probe within the powder bed. Inline force measurements are found to be more sensitive than torque measurements to the granulation process. The characteristic force profiles present the overall fingerprint of the high shear wet granulation, in which the evolution of the granule formation can improve our understanding of the granulation process. This provides rich information relating to the properties of the granules, identification of the even distribution of the binder liquid, and potential granulation end point. Data were obtained from an experimental high shear mixer across a range of key process parameters using a face-centred surface response design of experiment (DoE). A closed-form analytical model was developed from the DOE matrix using the discovery of evolutionary equations. The model is able to provide a strong predictive indication of the expected tablet tensile strength based only on the data in-line. The use of a closed form mathematical equation carries notable advantages over other AI methodologies such as artificial neural networks, notably improved interpretability/interrogability, and minimal inference costs, thus allowing the model to be used for real-time decision making and process control. The capability of accurately predicting, in real time, the required compaction force required to achieve the desired tablet tensile strength from upstream data carries the potential to ensure compression machine settings rapidly reach and are maintained at optimal values, thus maximising efficiency and minimising waste.
Sujet(s)
Excipients , Poudres , Comprimés , Résistance à la traction , Comprimés/composition chimique , Poudres/composition chimique , Excipients/composition chimique , Préparation de médicament/méthodes , Technologie pharmaceutique/méthodes , Taille de particule , Chimie pharmaceutique/méthodesRÉSUMÉ
Powder flow is one of the crucial factors affecting several pharmaceutical manufacturing processes. Problems due to insufficient powder flow reduce production process efficiency and cause suboptimum product quality. The U.S. Pharmacopoeia has specified four methods to evaluate the flowability of pharmaceutical powders, including angle of repose (AoR), compressibility index (CI) and Hausner ratio (HR), Flow through an orifice, and shear cell. Comparison within and between those methods with 21 powders (covering a wide range of flowability) was performed in this study. Strong correlation was observed between fixed base cone AoR, and fixed height cone AoR (R2 = 0.939). CI and HR values calculated from a tapped density tester (meeting USP standards), manual tapping, and Geopyc® correlated strongly (R2 > 0.9). AoR, CI/HR, minimum diameter for flowing through an orifice (dmin), and shear cell results generally correlate strongly for materials with flowability worse than Avicel® PH102. Both shear cell and CI/HR methods can reliably distinguish powders exhibiting poor flow. For materials with good flow, the ability to distinguish powders follows the order of AoR ≈ CI/HR > shear cell > dmin. The systematic comparison of the four common methods provides useful information to guide the selection of methods for future powder flow characterization. Given the limitations observed in all four methods, we recommend that multiple techniques should be used, when possible, to more holistically characterize the flowability of a wide range of powders.
Sujet(s)
Poudres , Poudres/composition chimique , Taille de particule , Technologie pharmaceutique/méthodes , Préparation de médicament/méthodes , Pharmacopées comme sujet , Excipients/composition chimiqueRÉSUMÉ
The influence of different preparation methods on the physicochemical properties of amorphous solid forms have gained considerable attention, especially with recent publications on pharmaceutical polyamorphism. In the present study, we have investigated the possible occurrence of polyamorphism in the drug celecoxib (CEL) by investigating the thermal behavior, morphology, structure, molecular mobility and physical stability of amorphous CEL obtained by quench-cooling (QC), ball milling (BM) and spray drying (SD). Similar glass transition temperatures but different recrystallization behaviors were observed for CEL-QC, CEL-BM and CEL-SD using modulated differential scanning calorimetry analysis. A correlation between the different recrystallization behaviors of the three CEL amorphous forms and the respective distinct powder morphologies, was also found. Molecular dynamics simulations however, reveal that CEL presents similar molecular conformational distributions when subjected to QC and SD. Moreover, the obtained molecular conformational distributions of CEL are different from the ones found in its crystal structure and also from the ones found in the lowest-energy structure obtained by quantum mechanical calculations. The type and strength of CEL hydrogen bond interactions found in CEL-QC and CEL-SD systems are almost identical, though different from the ones presented in the crystal structure. Pair distribution function analyses and isothermal microcalorimetry show similar local structures and structural relaxation times, respectively, for CEL-QC, CEL-BM and CEL-SD. The present work shows that not only similar physicochemical properties (glass transition temperature, and structural relaxation time), but also similar molecular conformational distributions were observed for all prepared CEL amorphous systems. Hence, despite their different recrystallization behaviors, the three amorphous forms of CEL did not show any signs of polyamorphism.
Sujet(s)
Calorimétrie différentielle à balayage , Célécoxib , Cristallisation , Simulation de dynamique moléculaire , Température de transition , Célécoxib/composition chimique , Stabilité de médicament , Liaison hydrogène , Chimie pharmaceutique/méthodes , Préparation de médicament/méthodes , Poudres/composition chimiqueRÉSUMÉ
Berberine is used in the treatment of metabolic syndrome and its low solubility and very poor oral bioavailability of berberine was one of the primary hurdles for its market approval. This study aimed to improve the solubility and bioavailability of berberine by preparing pellet formulations containing drug-excipient complex (obtained by solid dispersion). Berberine-excipient solid dispersion complexes were obtained with different ratios by the solvent evaporation method. The maximum saturation solubility test was performed as a key factor for choosing the optimal complex for the drug-excipient. The properties of these complexes were investigated by FTIR, DSC, XRD and dissolution tests. The obtained pellets were evaluated and compared in terms of pelletization efficiency, particle size, mechanical strength, sphericity and drug release profile in simulated media of gastric and intestine. Solid-state analysis showed complex formation between the drug and excipients used in solid dispersion. The optimal berberine-phospholipid complex showed a 2-fold increase and the optimal berberine-gelucire and berberine-citric acid complexes showed more than a 3-fold increase in the solubility of berberine compared to pure berberine powder. The evaluation of pellets from each of the optimal complexes showed that the rate and amount of drug released from all pellet formulations in the simulated gastric medium were significantly lower than in the intestine medium. The results of this study showed that the use of berberine-citric acid or berberine-gelucire complex could be considered a promising technique to increase the saturation solubility and improve the release characteristics of berberine from the pellet formulation.
Sujet(s)
Berbérine , Chimie pharmaceutique , Préparation de médicament , Libération de médicament , Excipients , Taille de particule , Solubilité , Berbérine/composition chimique , Berbérine/administration et posologie , Berbérine/pharmacocinétique , Excipients/composition chimique , Préparation de médicament/méthodes , Chimie pharmaceutique/méthodes , Biodisponibilité , Spectroscopie infrarouge à transformée de Fourier/méthodes , Poudres/composition chimique , Diffraction des rayons X/méthodes , Calorimétrie différentielle à balayage/méthodesRÉSUMÉ
Carboxymethyl Salix psammophila wood powder-imprinted membranes (CMSM-MIPs) were prepared by using wet spinning technology and molecular-imprinting technology for the selective removal of tetracycline from wastewater. Scanning electron microscopy, X-ray diffraction, thermogravimetry, and X-ray photoelectron spectroscopy characterizations demonstrate that CMSM-MIPs retain the membranous structure of Carboxymethyl Salix psammophila wood powder membranes, successfully encapsulate thin layers of imprinted polymers on the membrane surface, and exhibit excellent thermal stability. The adsorption results showed that CMSM-MIPs had the highest selective adsorption capacity for tetracycline, which was 253.8 mg/g. In addition, the adsorption capacities for oxytetracycline and chlortetracycline were 208.8 and 188 mg/g, respectively. It can be observed that CMSM-MIPs not only exhibit a high adsorption capacity for tetracycline but also demonstrate good adsorption capacities for oxytetracycline and chlortetracycline. The experimental results showed that CMSM-MIPs were best fitted with pseudo-second-order kinetics and most consistent with Freundlich fitting. The regeneration experiment showed that CMSM-MIPs still had good regeneration performance after 5 regeneration cycles. In conclusion, the CMSM-MIPs can not only have the natural adsorption performance of Salix psammophila wood powder but also give it higher selectivity through molecular imprinting, so as to achieve efficient removal of target organic pollutants in water.
Sujet(s)
Salix , Tétracycline , Bois , Adsorption , Bois/composition chimique , Tétracycline/composition chimique , Tétracycline/isolement et purification , Salix/composition chimique , Poudres/composition chimique , Membrane artificielle , Polluants chimiques de l'eau/composition chimique , Polluants chimiques de l'eau/isolement et purification , Empreinte moléculaire/méthodes , Antibactériens/composition chimique , Antibactériens/isolement et purificationRÉSUMÉ
Principal component analysis (PCA) and partial least squares regression (PLS) were combined in this study to identify key material descriptors determining tabletability in direct compression and roller compaction. An extensive material library including 119 material descriptors and tablet tensile strengths of 44 powders and roller compacted materials with varying drug loads was generated to systematically elucidate the impact of different material descriptors, raw API and filler properties as well as process route on tabletability. A PCA model was created which highlighted correlations between different powder descriptors and respective characterization methods and, thus, can enable reduction of analyses to save resources to a certain extent. Subsequently, PLS models were established to identify key material attributes for tabletability such as density and particle size but also surface energy, work of cohesion and wall friction, which were for the first time demonstrated by PLS as highly relevant for tabletability in roller compaction and direct compression. Further, PLS based on extensive material characterization enabled the prediction of tabletability of materials unknown to the model. Thus, this study highlighted how PCA and PLS are useful tools to elucidate the correlations between powder and tabletability, which will enable more robust prediction of manufacturability in formulation development.
Sujet(s)
Poudres , Analyse en composantes principales , Comprimés , Résistance à la traction , Comprimés/composition chimique , Méthode des moindres carrés , Poudres/composition chimique , Excipients/composition chimique , Taille de particule , Préparation de médicament/méthodesRÉSUMÉ
This research investigates the modeling of the pharmaceutical roller compaction process, focusing on the application of the Johanson model and the impact of varying roll speeds from 1 to 15 RPM on predictive accuracy of ribbon solid fraction. The classical Johanson's model was integrated with a dwell time parameter leading to an expression of a floating correction factor as a function of roll speed. Through systematic analysis of the effect of different roll speeds on the solid fraction of ribbons composed of microcrystalline cellulose, lactose, and their blends, corrective adjustment to the Johanson model was found to depend on both roll speed and formulation composition. Interestingly, the correction factor demonstrated excellent correlation with the blend's mechanical properties, namely yield stress (Py) and elastic modulus (E0), representative of the deformability of the powder. Validated by a multicomponent drug formulation with ±0.4-1.3 % differences, the findings underscore the utility of this modified mechanistic approach for precise prediction of ribbon solid fraction when Py or E0 is known for a given blend. Hence, this work advances the field by offering early insights for more accurate and controllable roller compaction operations during late-stage pharmaceutical manufacturing.
Sujet(s)
Cellulose , Préparation de médicament , Excipients , Lactose , Poudres , Cellulose/composition chimique , Lactose/composition chimique , Préparation de médicament/méthodes , Excipients/composition chimique , Poudres/composition chimique , Chimie pharmaceutique/méthodes , Module d'élasticitéRÉSUMÉ
Continuous manufacturing is gaining increasing interest in the pharmaceutical industry, also requiring real-time and non-destructive quality monitoring. Multiple studies have already addressed the possibility of surrogate in vitro dissolution testing, but the utilization has rarely been demonstrated in real-time. Therefore, in this work, the in-line applicability of an artificial intelligence-based dissolution surrogate model is developed the first time. NIR spectroscopy-based partial least squares regression and artificial neural networks were developed and tested in-line and at-line to assess the blend uniformity and dissolution of encapsulated acetylsalicylic acid (ASA) - microcrystalline cellulose (MCC) powder blends in a continuous blending process. The studied blend is related to a previously published end-to-end manufacturing line, where the varying size of the ASA crystals obtained from a continuous crystallization significantly affected the dissolution of the final product. The in-line monitoring was suitable for detecting the variations in the ASA content and dissolution caused by the feeding of ASA with different particle sizes, and the at-line predictions agreed well with the measured validation dissolution curves (f2 = 80.5). The results were further validated using machine vision-based particle size analysis. Consequently, this work could contribute to the advancement of RTRT in continuous end-to-end processes.
Sujet(s)
Acide acétylsalicylique , Cellulose , Poudres , Solubilité , Spectroscopie proche infrarouge , Spectroscopie proche infrarouge/méthodes , Poudres/composition chimique , Cellulose/composition chimique , Acide acétylsalicylique/composition chimique , Taille de particule , , Libération de médicament , Préparation de médicament/méthodes , Chimie pharmaceutique/méthodes , Cristallisation , Méthode des moindres carrés , Excipients/composition chimiqueRÉSUMÉ
After RNAi was first discovered over 20 years ago, siRNA-based therapeutics are finally becoming reality. However, the delivery of siRNA has remained a challenge. In our previous research, we found that spermine-based poly(ß-amino ester)s are very promising for siRNA delivery. However, the role of hydrophobic modification in siRNA delivery of spermine-based poly(ß-amino ester)s is not fully understood yet. In the current work, we synthesized spermine-based poly(ß-amino ester)s with different percentages of oleylamine side chains, named P(SpOABAE). The chemical structures of the polymers were characterized by 1H NMR. The polymers showed efficient siRNA encapsulation determined by SYBR Gold assays. The hydrodynamic diameters of the P(SpOABAE) polyplexes from charge ratio N/P 1 to 20 were 30-100 nm except for aggregation phenomena observed at N/P 3. Morphology of the polyplexes was visualized by atomic force microscopy, and cellular uptake was determined by flow cytometry in H1299 cells, where all the polyplexes showed significantly higher cellular uptake than hyperbranched polyethylenimine (25 kDa). The most hydrophobic P(SpOABAE) polyplexes were able to achieve more than 90% GFP knockdown in H1299/eGFP cells. The fact that gene silencing efficacy increased with hydrophobicity but cellular uptake was affected by both charge and hydrophobic interactions highlights the importance of endosomal escape. For pulmonary administration and improved storage stability, the polyplexes were spray-dried. Results confirmed the maintained siRNA activity after storage for 3 months at room temperature, indicating potential for dry powder inhalation.
Sujet(s)
Interactions hydrophobes et hydrophiles , Petit ARN interférent , Spermine , Petit ARN interférent/composition chimique , Petit ARN interférent/administration et posologie , Petit ARN interférent/pharmacologie , Spermine/composition chimique , Humains , Administration par inhalation , Polymères/composition chimique , Poudres/composition chimique , Lignée cellulaire tumoraleRÉSUMÉ
Aflatoxin B1, a major global food safety concern, is produced by toxigenic fungi during crop growing, drying, and storage, and shows increasing annual prevalence. This study aimed to detect aflatoxin B1 in chili samples using ATR-FTIR coupled with machine learning algorithms. We found that 83.6% of the chili powder samples were contaminated with Aspergillus and Penicillium species, with aflatoxin B1 levels ranging from 7.63 to 44.32 µg/kg. ATR-FTIR spectroscopy in the fingerprint region (1800-400 cm-1) showed peak intensity variation in the bands at 1587, 1393, and 1038 cm-1, which are mostly related to aflatoxin B1 structure. The PCA plots from samples with different trace amounts of aflatoxin B1 could not be separated. Vibrational spectroscopy combined with machine learning was applied to address this issue. The logistic regression model had the best F1 score with the highest %accuracy (73%), %sensitivity (73%), and %specificity (71%), followed by random forest and support vector machine models. Although the logistic regression model contributed significant findings, this study represents a laboratory research project. Because of the peculiarities of the ATR-FTIR spectral measurements, the spectra measured for several batches may differ, necessitating running the model on multiple spectral ranges and using increased sample sizes in subsequent applications. This proposed method has the potential to provide rapid and accurate results and may be valuable in future applications regarding toxin detection in foods when simple onsite testing is required.
Sujet(s)
Aflatoxine B1 , Aspergillus , Capsicum , Contamination des aliments , Capsicum/composition chimique , Spectroscopie infrarouge à transformée de Fourier/méthodes , Aflatoxine B1/analyse , Contamination des aliments/analyse , Aspergillus/composition chimique , Poudres/composition chimique , Penicillium/composition chimiqueRÉSUMÉ
In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.
Sujet(s)
Comprimés , Comprimés/composition chimique , Taille de particule , Préparation de médicament , Poudres/composition chimique , Acides stéariques/composition chimique , Résistance à la traction , Excipients/composition chimique , SolubilitéRÉSUMÉ
Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply of drugs and the safety of customers. In Japan, in 2020, a mix-up containing a sleeping drug went undetected by liquid chromatography during the final quality test because the test focused only on the main active pharmaceutical ingredient (API) and known impurities. In this study, we assessed the ability of a powder rheometer to analyze powder characteristics in detail to determine whether it can detect the influence of foreign APIs on powder flow. Aspirin, which was used as the host API, was combined with the guest APIs (acetaminophen from two manufacturers and albumin tannate) and subsequently subjected to shear and stability tests. The influence of known lubricants (magnesium stearate and leucine) on powder flow was also evaluated for standardized comparison. Using microscopic morphological analysis, the surface of the powder was observed to confirm physical interactions between the host and guest APIs. In most cases, the guest APIs were statistically detected due to characteristics such as their powder diameter, pre-milling, and cohesion properties. Furthermore, we evaluated the flowability of a formulation incorporating guest APIs for direct compression method along with additives such as microcrystalline cellulose, potato starch, and lactose. Even in the presence of several additives, the influence of the added guest APIs was successfully detected. In conclusion, powder rheometry is a promising method for ensuring stable product quality and reducing the risk of unforeseen cross-contamination by foreign APIs.