RESUMO
The aim of our study was to develop a solventless drug pelletization and polymer coating technique for pharmaceutical manufacturing. This review describes a dry coating technique using a mechanical powder processor and a V-shaped blender to produce coated pellets or tablets by mechanically mixing polymer particles and core materials (such as drug pellets and uncoated tablets) without the need for a solvent. First, aqueous latexes comprising colloidal polymethacrylates and ethylcellulose were solidified by freeze drying to produce polymer particles for the dry coating process. These particles and the cores were then subjected to mechanical powder processing or V-shaped blending to provide coated formulations with controlled-release characteristics. Polymer coating was achieved by using agglomerates comprising assembled colloidal polymer. The agglomerated polymer was easily pulverized during the mixing treatments due to its loose structure (the lack of close contacts between the colloidal particles), and the resulting fine polymer with high adhesiveness was deposited on the cores. Colloidal polymer dispersed in aqueous latex tends to coagulate in the freeze-drying process due to condensation of the dispersion, yielding dense agglomerates with poor coating characteristics. The presence of surfactants (such as sodium lauryl sulfate) in the latex can prevent adhesion between colloidal particles in the freeze-drying process, providing loosely structured agglomerates suitable for dry coating. Dry coating with a V-shaped blender could thus be achieved with these polymer particles instead of having to use a mechanical powder processor.
Assuntos
Celulose , Liofilização , Polímeros , Celulose/química , Celulose/análogos & derivados , Polímeros/química , Tecnologia Farmacêutica/métodos , Pós , Solventes , Composição de Medicamentos/métodos , Comprimidos , Coloides , Preparações de Ação Retardada , Tensoativos/química , Ácidos Polimetacrílicos/química , Química Farmacêutica/métodos , Látex/químicaRESUMO
BACKGROUND: Facilitating the healing process of injured anterior cruciate ligament (ACL) tissue is crucial for patients to safely return to sports. Stem cell derived exosomes have shown positive effects on enhancing the regeneration of injured tendons/ligaments. However, clinical application of exosomes in terms of storage and pre-assembly is challenging. We hypothesized that lyophilized exosomes derived from human umbilical cord stem cells (hUSC-EX) could enhance the cell activity of chronically injured ACL cells. MATERIALS AND METHODS: We harvested the 8 weeks injured ACL cells from rabbit under IACUC (No. 110232) approval. The studied exosomes were purified from the culture medium of human umbilical cord stem cells (IRB approval No. A202205014), lyophilized to store, and hydrated for use. We compared exosome treated cells with non-exosome treated cells (control group) from the same rabbits. We examined the cell viability, proliferation, migration capability and gene expression of type I and III collagen, TGFß, VEGF, and tenogenesis in the 8 weeks injured ACL cells after hUSC-EX treatment. RESULTS: After hydration, the average size of hUSC-EX was 84.5 ± 70.6 nm, and the cells tested positive for the Alix, TSG101, CD9, CD63, and CD81 proteins but negative for the α-Tubulin protein. After 24 h of treatment, hUSC-EX significantly improved the cell viability, proliferation and migration capability of 8 weeks injured ACL cells compared to that of no exosome treatment group. In addition, the expression of collagen synthesis, TGFß, VEGF, and tenogenesis gene were all significantly increased in the 8 weeks injured ACL cells after 24 h hUSC-EX delivery. DISCUSSION: Lyophilized exosomes are easily stored and readily usable after hydration, thereby preserving their characteristic properties. Treatment with lyophilized hUSC-EX improved the activity and gene expression of 8 weeks injured ACL cells. CONCLUSION: Lyophilized hUSC-EX preserve the characteristics of exosomes and can improve chronically injured (8 weeks) ACL cells. Lyophilized hUSC-EX could serve as effective and safe biomaterials that are ready to use at room temperature to enhance cell activity in patients with partial ACL tears and after remnant preservation ACL reconstruction.
Assuntos
Lesões do Ligamento Cruzado Anterior , Exossomos , Animais , Coelhos , Exossomos/metabolismo , Lesões do Ligamento Cruzado Anterior/terapia , Humanos , Liofilização , Proliferação de Células , Cordão Umbilical/citologia , Células Cultivadas , Sobrevivência Celular/fisiologia , Movimento Celular/fisiologia , Doença CrônicaRESUMO
BACKGROUND: Chitosan oligosaccharides (COS) have great potential for applications in several fields, including agriculture, food industry or medicine. Nevertheless, the large-scale use of COS requires the development of cost-effective technologies for their production. The main objective of our investigation was to develop an effective method of enzymatic degradation of chitosan in a column reactor using Mucor circinelloides IBT-83 cells, immobilized in a polyurethane foam (PUF). These cells serve as a source of chitosanolytic enzymes. RESULTS: The study revealed that the process of freeze-drying of immobilized mycelium increases the stability of the associated enzymes during chitosan hydrolysis. The use of stabilized preparations as an active reactor bed enables the production of COS at a constant level for 16 reactor cycles (384 h in total), i.e. 216 h longer compared to non-stabilized mycelium. In the hydrolysate, oligomers ranging in structure from dimer to hexamer as well as D-glucosamine were detected. The potential application of the obtained product in agriculture has been verified. The results of phytotests have demonstrated that the introduction of COS into the soil at a concentration of 0.01 or 0.05% w/w resulted in an increase in the growth of Lepidium sativum stem and root, respectively (extensions by 38 and 44% compared to the control sample). CONCLUSIONS: The research has verified that the PUF-immobilized M. circinelloides IBT-83 mycelium, which has been stabilized through freeze-drying, is a promising biocatalyst for the environmentally friendly and efficient generation of COS. This biocatalyst has the potential to be used in fertilizers.
Assuntos
Reatores Biológicos , Quitosana , Mucor , Oligossacarídeos , Mucor/enzimologia , Mucor/metabolismo , Quitosana/metabolismo , Quitosana/química , Oligossacarídeos/metabolismo , Oligossacarídeos/biossíntese , Poliuretanos/química , Hidrólise , Células Imobilizadas/metabolismo , Enzimas Imobilizadas/metabolismo , Enzimas Imobilizadas/química , Micélio/metabolismo , LiofilizaçãoRESUMO
The aim of this research was to synthesize and characterize alginate-calcium composites using a freeze-drying method, with a focus on their potential applications in biomedicine. This study specifically explored the biochemical properties of these composites, emphasizing their role in blood coagulation and their capacity to interact with DNA. Additionally, the research aimed to assess how the cross-linking process influences the structural and chemical characteristics of the composites. Detailed analyses, including microscopic examination, surface area assessment, and atomic absorption spectrometry, yielded significant results. The objective of this study was to examine the impact of calcium chloride concentration on the calcium content in alginate composites. Specifically, the study assessed how varying concentrations of the cross-linking solution (ranging from 0.5% to 2%) influence the calcium ion saturation within the composites. This investigation is essential for understanding the physicochemical properties of the materials, including calcium content, porosity, and specific surface area. The results are intended to identify the optimal cross-linking conditions that maximize calcium enrichment efficiency while preserving the material's structural integrity. The study found that higher calcium chloride concentrations in alginate cross-linking improve the formation of a porous structure, enhanced by two-stage freeze-drying. Increased calcium levels led to a larger surface area and pore volume, and significantly higher calcium content. Furthermore, assays of activated partial thromboplastin time (aPTT) showed a reduction in clotting time for alginate composites containing calcium ions, indicating their potential as hemostatic agents. The aPTT test showed shorter clotting times with higher calcium ion concentrations, without enhanced activation of the extrinsic clotting pathway. The developed alginate material with calcium effectively supports hemostasis and reduces the risk of infection. The study also explored the capacity of these composites to interact with and modify the structure of plasmid DNA, underscoring their potential for future biomedical applications.
Assuntos
Alginatos , Coagulação Sanguínea , Cálcio , DNA , Liofilização , Alginatos/química , Coagulação Sanguínea/efeitos dos fármacos , DNA/química , Cálcio/química , Cloreto de Cálcio/química , Tempo de Tromboplastina Parcial , Animais , Porosidade , Humanos , Reagentes de Ligações Cruzadas/químicaRESUMO
The gardenia flower not only has extremely high ornamental value but also is an important source of natural food and spices, with a wide range of uses. To support the development of gardenia flower products, this study used headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) technology to compare and analyze the volatile organic compounds (VOCs) of fresh gardenia flower and those after using four different drying methods (vacuum freeze-drying (VFD), microwave drying (MD), hot-air drying (HAD), and vacuum drying (VD)). The results show that, in terms of shape, the VFD sample is almost identical to fresh gardenia flower, while the HAD, MD, and VD samples show significant changes in appearance with clear wrinkling; a total of 59 volatile organic compounds were detected in the gardenia flower, including 13 terpenes, 18 aldehydes, 4 esters, 8 ketones, 15 alcohols, and 1 sulfide. Principal component analysis (PCA), cluster analysis (CA), and partial least-squares regression analysis (PLS-DA) were performed on the obtained data, and the research found that different drying methods impact the VOCs of the gardenia flower. VFD or MD may be the most effective alternative to traditional sun-drying methods. Considering its drying efficiency and production cost, MD has the widest market prospects.
Assuntos
Dessecação , Flores , Gardenia , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química , Gardenia/química , Flores/química , Dessecação/métodos , Cromatografia Gasosa-Espectrometria de Massas , Liofilização/métodos , Análise de Componente Principal , Análise dos Mínimos QuadradosRESUMO
This study scrutinized the phytochemical composition, curative, hepato and nephro protective effect of different doses of lyophilized juice of Citrus reticulata fruit against paracetamol induced toxicity. Phytochemical screening and RP-HPLC analysis were conducted to quantify total polyphenols and flavonoids respectively. For evaluation of in vivo curative and protective effects, thirty six rats were randomly divided into six groups. In first four groups 1, II, III and IV paracetamol 75mg/kg, i.p, 150mg/kg, 250mg/kg and 500mg/kg p.o doses of lyophilized juice were administered to rats respectively. Blood samples were withdrawn at 0, 24, 48 and 72 hours in paracetamol treated rats. For screening of hepato and nephro protective effect Group V and VI were fed on lyophilized juice (250mg/kg and 500mg/kg p.o) for seven days and on 8th day blood samples were collected at 0,24,48 and 72 hours. Hepatic and renal biomarkers were monitored. Phytochemical analysis revealed the presence of total polyphenols (20.7±0.3GAEmg/g) and flavonoid contents (21.2±0.4QE mg/g). RP-HPLC also confirmed the presence of Myricetin, Quercetin and Kaempferol in fruit juice. The lyophilized juice at 500mg/kg dose have shown profound decrease in paracetamol induced elevated serum levels of liver and kidney functions, which suggests a possible therapeutic role of its constituents in hepatic and kidney malfunctions.
Assuntos
Acetaminofen , Citrus , Liofilização , Sucos de Frutas e Vegetais , Animais , Acetaminofen/toxicidade , Citrus/química , Sucos de Frutas e Vegetais/análise , Ratos , Masculino , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Frutas/química , Polifenóis/farmacologia , Polifenóis/análise , Flavonoides/farmacologia , Flavonoides/análise , Ratos Wistar , Extratos Vegetais/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controleRESUMO
The effect of different methods of drying celery root enriched with beet juice by vacuum impregnation (VI) was studied. The process of convection drying, vacuum drying and freeze drying was carried out. Compared to dried indigenous celery, dry impregnated tissue was characterized by lower values of dry matter, L* and b* color parameters, as well as higher values of water activity, density and a* color parameter. In addition, VI reduced the drying time. Forty Volatile Organic Compounds (VOCs) were found in celery, while fifty-one VOCs were found in the profile of celery with beetroot juice. The innovative method of vacuum impregnation made it possible to produce a new type of product with changed properties and a variable VOCs profile. The best fit of the drying process kinetics was achieved by using the logistic model. Increasing the temperature during convection drying resulted in shorter drying time, increased values of dry matter, reduced the water activity value and altered VOCs.
Assuntos
Apium , Beta vulgaris , Dessecação , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/análise , Beta vulgaris/química , Cinética , Dessecação/métodos , Apium/química , Sucos de Frutas e Vegetais/análise , Raízes de Plantas/química , Liofilização/métodos , Água/químicaRESUMO
Currently, phage biocontrol is increasingly used as a green and natural technology for treating Salmonella and other infections, but phages exhibit instability and activity loss during storage. Therefore, in this study, the effects of lyophilization on the activity and stability of phage cocktails for the control of multidrug-resistant Salmonella in broiler chickens were determined. Eight serotypes of Salmonella were isolated and identified from broiler chicken farms, and bacteriophages against multidrug-resistant Salmonella enterica subsp. enterica serovar Kentucky, Salmonella enterica subsp. enterica serovar Typhimrium and Salmonella enterica subsp. enterica serovar Enteritidis were isolated. The bacteriophage cocktail was prepared and lyophilized, and it was subjected to in vitro and in vivo examinations. A reconstituted lyophilized bacteriophage cocktail was used for the oral treatment of chicks before and after challenge with multidrug-resistant S. Kentucky. The colonization of cecum by S. Kentucky was detected by using real-time PCR, and the serum levels of IgM, IgA and IL-4 and pathological changes in the different groups were detected. Three Caudovirales phages families were identified including Autographiviridae, Straboviridae and Drexlerviridae against multidrug-resistant S. Kentucky, S. Typhimrium and S. Enteritidis. The groups treated with the bacteriophage cocktail showed no clinical signs, no postmortem lesions, and a mortality rate of 0%, which improved the growth performance parameters. Additionally, the estimated serum levels of IgM, IgA and IL-4 were significantly greater in the bacteriophage cocktail-treated groups. Lyophilization effectively preserves the long-term storage stability of phages. Therefore, lyophilized bacteriophage cocktail therapy is a valuable approach for controlling multidrug-resistant Salmonella infections in broiler chickens.
Assuntos
Galinhas , Farmacorresistência Bacteriana Múltipla , Liofilização , Doenças das Aves Domésticas , Salmonelose Animal , Fagos de Salmonella , Salmonella , Animais , Galinhas/microbiologia , Liofilização/métodos , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/terapia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/prevenção & controle , Salmonelose Animal/microbiologia , Salmonelose Animal/terapia , Salmonella/virologia , Fagos de Salmonella/fisiologia , Ceco/microbiologia , Ceco/virologia , Terapia por Fagos/métodos , Bacteriófagos/genética , Bacteriófagos/fisiologia , Bacteriófagos/isolamento & purificaçãoRESUMO
This study aimed to assess the role of the combination of design techniques of the engineered substrates, and the effect of encapsulating Marjoram (Origanum Majorana L.) into the matrix network was studied. To this end, PVA-PEG matrices were designed through 3 techniques of freeze-thaw (FT), the combination of both methods of freeze-drying and freeze-thawing(FT-FD), and ternary technique(freeze-drying,freeze-thawing,cross-linking(FT-FD/CL)), by combining equal volume ratios of both polymers. The results indicated the ternary technique can provide better physicochemical properties(porosity: 96%, lower degradation rate, higher modulus) compared to FT and FT-FD methods. Afterward, encapsulation of Marjoram-extracted bio-actives in the matrix network designed with the ternary technique demonstrated that the increase in the extract concentration up to 3% can increase encapsulation efficiency. The encapsulation also caused a more cohesive network by better bonding between functional groups in herbal biomolecules and polymer chains of the matrix. Mass transport mechanisms and release kinetics of matrix-encapsulated bio-actives indicated a deviation from Fickian diffusion and the release by diffusion and swelling process. Biologically, matrix-loaded herbal carbohydrate(Epi-alpha-Cadinol) improved fibroblast adhesion and distribution on the substrate surface, and led to the better synthesis of collagen fibers, especially in 3% herbal extract, and antibacterial activities owing to the controlled release of sesquiterpenoids and N-Acetyl-L-proline.
Assuntos
Colágeno , Extratos Vegetais , Colágeno/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Humanos , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Liofilização , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacosRESUMO
This study aimed to optimize the ultrasound-assisted extraction (UAE) of anthocyanins from oven-dried and freeze-dried Vitis labrusca grape pomace, using acidified water as the solvent. The effects of power density (8.3-16.7 W/mL), pulse interval (0-2 s), and extraction time (1-5 min) on both total and specific anthocyanins were investigated. The findings suggested that acidified water can be a viable alternative to conventional solvents and that oven drying was an effective method for drying the pomace. Using response surface methodology, the study identified power density and extraction time as key factors influencing total anthocyanin content, with extracts reaching contents up to 2.56 mg/g. The analysis using LC-MS identified 14 anthocyanins, while NMR quantified 3 and malvidin diglucoside was generally the most abundant. However, higher power and longer extraction times were found to reduce its content while increasing malvidin monoglucoside content, suggesting ultrasound-induced anthocyanin hydrolysis. In conclusion, this study presents a sustainable method for extracting anthocyanins using acidified water, contributing to the valorization of Vitis labrusca grape pomace for industrial use.
Assuntos
Antocianinas , Vitis , Água , Antocianinas/análise , Antocianinas/isolamento & purificação , Vitis/química , Água/química , Extratos Vegetais/química , Extratos Vegetais/análise , Ultrassom/métodos , Frutas/química , Solventes/química , LiofilizaçãoRESUMO
The flavonoid compounds in C. caudatus K., known for their various benefits, are prone to quick degradation, leading to reduced biological activity. This research aimed to evaluate the types of coatings: gum Arabic (GA), maltodextrin (MD), and a combination of both (MDGA) in C. caudatus K. extract microcapsules. The extract of C. caudatus K. was encapsulated by different coating materials, GA, MD, and MDGA, and then dried using a freeze-drying technique. The evaluation was carried out by comparing the encapsulation efficiency values, biological activity, and release tests of each type of microcapsule coating. The research results indicate that coating agents have impacts significantly at p < 0.05 on efficiency encapsulation. Flavonoids were retained up to 79.67% by the MDGA coating, compared with 72.8% and 47.66%a retained by single GA and MD coatings, respectively. The results of the encapsulation efficiency are supported by the results of characterization using a scanning electron microscope (SEM), where MDGA has rounder shapes with smoother surfaces compared with a single coating alone, like GA or MD. In addition, by particle size analysis using a particle size analyzer (PSA), the average sizes of MDGA, GA, and MD microcapsules were shown at 154.13 µm, 152 µm, and 166.81 µm, respectively. The three microcapsules showed an order of activities as MDGA > GA > MD coatings in alpha-amylase inhibition assay. Similar results were also shown in the antioxidant assay, which demonstrated that the three microcapsules had moderate antioxidant activities, again in the order of MDGA > GA > MD. The three different coating types showed greater release at pH 7.4 compared to those at pH 2.2 in the controlled release test, which ran from 30 to 120 min. In summary, freeze-drying microencapsulation using biodegradable polymers was identified as a viable method for harnessing the health benefits of C. caudatus K. extracts. This process produced a convenient powder form that could be used in drug delivery systems. The use of MDGA mixed coating resulted in better impact based on %EE value and biological activity, as well as improved characteristics of microcapsules compared with single coating.
Assuntos
Cápsulas , Composição de Medicamentos , Liofilização , Goma Arábica , Composição de Medicamentos/métodos , Goma Arábica/química , Antioxidantes/química , Antioxidantes/farmacologia , Flavonoides/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Polímeros/químicaRESUMO
Molecular diagnostics by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based detection have high diagnostic accuracy and attributes that are suitable for use at point-of-care settings such as fast turnaround times for results, convenient simple readouts, and no requirement of complicated instruments. However, the reactions can be cumbersome to perform at the point of care due to their many components and manual handling steps. Herein, we provide a step-by-step, optimized protocol for the robust detection of disease pathogens and genetic markers with recombinase-based isothermal amplification and CRISPR-based reagents, which are premixed and then freeze-dried in easily stored and ready-to-use formats. Premixed, freeze-dried reagents can be rehydrated for immediate use and retain high amplification and detection efficiencies. We also provide a troubleshooting guide for commonly found problems upon preparing and using premixed, freeze-dried reagents for CRISPR-based diagnostics, to make the detection platform more accessible to the wider diagnostic/genetic testing communities.
Assuntos
Liofilização , Técnicas de Amplificação de Ácido Nucleico , Sistemas Automatizados de Assistência Junto ao Leito , Liofilização/métodos , Humanos , Técnicas de Amplificação de Ácido Nucleico/métodos , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Sistemas CRISPR-Cas/genética , Indicadores e Reagentes/química , Técnicas de Diagnóstico Molecular/métodosRESUMO
Based on the previous research results that the addition of sucrose in the medium improved the biofilm formation of Tetragenococcus halophilus, the influence of sucrose on biofilm formation was explored. Moreover, the influence of exogenous expression of related genes sacA and galE from T. halophilus on the biofilm formation of L. lactis NZ9000 was investigated. The results showed that the addition of sucrose in the medium improved the biofilm formation, the resistance of biofilm cells to freeze-drying stress, and the contents of exopolysaccharides (EPS) and eDNA in the T. halophilus biofilms. Meanwhile, the addition of sucrose in the medium changed the monosaccharide composition of EPS and increased the proportion of glucose and galactose in the monosaccharide composition. Under 2.5% (m/v) salt stress condition, the expression of gene sacA promoted the biofilm formation and the EPS production of L. lactis NZ9000 with the sucrose addition in the medium and changed the EPS monosaccharide composition. The expression of gene galE up-regulated the proportion of rhamnose, galactose, and arabinose in the monosaccharide composition of EPS, and down-regulated the proportion of glucose and mannose. This study will provide a theoretical basis for regulating the biofilm formation of T. halophilus, and provide a reference for the subsequent research on lactic acid bacteria biofilms.
Assuntos
Biofilmes , Sacarose , Biofilmes/crescimento & desenvolvimento , Sacarose/metabolismo , Polissacarídeos Bacterianos/metabolismo , Enterococcaceae/genética , Enterococcaceae/metabolismo , Enterococcaceae/fisiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Monossacarídeos/metabolismo , Regulação Bacteriana da Expressão Gênica , LiofilizaçãoRESUMO
Extracellular matrix sponge plays a positive role in the wound healing process, but requires proper structural strength and biological properties. In order to solve the problem of lyophilized dissolution of placenta-derived sponge, glutaraldehyde was selected for use in the lyophilized crosslinking process to improve the necessary mechanical properties of the placental decellularization matrix sponge. In this work, the effects of three cross-linking methods of glutaraldehyde (Fumigation/Slurry/Soak) on the physical and biological characteristics of lyophilised sponges derived from placental acellular matrix was investigated. The results revealed that the sponges prepared by all three cross-linking methods exhibited excellent blood coagulation ability and stability. The fumigation cross-linked sponges had good mechanical properties of soft and elastic, and safe cytotoxicity, which were more compatible with the requirements of wound dressing. The slurry cross-linking process was uneven due to the stacked matrix materials, resulting in obvious cracks and easy to break when stretching. The soak crosslinking can obtain a higher degree of crosslinking, which leads to the poor antibacterial performance and the harder sponge scaffold with larger elastic modulus and smaller tensile ratio. In general, fumigation cross-linking is more suitable for the preparation of acellular sponge derived from placenta materials which can maintain basic mechanical properties and biological validity.
Assuntos
Reagentes de Ligações Cruzadas , Glutaral , Placenta , Glutaral/química , Placenta/citologia , Feminino , Reagentes de Ligações Cruzadas/química , Gravidez , Animais , Matriz Extracelular Descelularizada/química , Matriz Extracelular Descelularizada/farmacologia , Humanos , Alicerces Teciduais/química , Liofilização/métodos , Coagulação Sanguínea/efeitos dos fármacos , Resistência à Tração , Matriz Extracelular/química , Teste de MateriaisRESUMO
To ensure product stability, it is critical to maintain the monohydrate state of cyclophosphamide following lyophilization, as this is the most stable solid form of the Cyclophosphamide. On the other hand, because of their limited aqueous solubility and stability, non-aqueous solvents are preferred for determining the composition and stability of bulk solutions. Hence, the purpose of this study was to use non-aqueous solvents for determining the composition and stability of bulk solutions, and to shorten the lyophilization process by retaining the cyclophosphamide monohydrate. Furthermore, prior to selecting the solvent for the bulk solution consisting of 90:10 tertiary butyl alcohol (TBA) and acetonitrile (ACN), various factors were taken into account, including the freezing point, vapor pressure of solvents, solubility, and stability of cyclophosphamide monohydrate. The concentration of the bulk solution was adjusted to 200 mg/mL in order to optimize the fill volume, enhance sublimation rates at lower temperatures during primary drying, and eliminate the need for secondary drying. The differential scanning calorimetry (DSC) measurements of bulk solution were used to improve the lyophilization cycle. The lyophilization cycle opted was freezing at a temperature of -55 °C with annealing step at -22 °C by which the reconstitution time was significantly reduced. The drying was performed at below - 25 °C while maintaining a chamber pressure of 300 mTorr. The complete removal of non-aqueous solvents was achieved by retaining water within the system. The presence of cyclophosphamide monohydrate was confirmed using X-ray diffraction (XRD). The reduction of lyophilization process time was established by conducting mass transfer tests and evaluating the physicochemical properties of the pharmaceutical product. Using non-aqueous solvents for freeze-drying cyclophosphamide is a viable option, and this study provides significant knowledge for the advancement of future generic pharmaceuticals.
Assuntos
Acetonitrilas , Ciclofosfamida , Estabilidade de Medicamentos , Liofilização , Solubilidade , Solventes , Liofilização/métodos , Ciclofosfamida/química , Solventes/química , Acetonitrilas/química , Química Farmacêutica/métodos , Varredura Diferencial de Calorimetria/métodos , Composição de Medicamentos/métodos , terc-Butil Álcool/química , Congelamento , TemperaturaRESUMO
Fenbendazole is an antiparasitic drug widely used in veterinary medicine to treat parasitic infections caused in animals like cattle, horses, sheep, and dogs. Recently, it has been repositioned as a potential alternative for cancer treatment. However, it is a highly hydrophobic molecule (0.9 ug/mL), which can compromise its dissolution rate and absorption. Thus, this work aimed to apply a nanotechnological approach to improve drug solubility and dissolution performance. Fenbendazole nanoparticles stabilized by different poloxamers were obtained by lyophilization without cryoprotectants. The behavior of the drug in the solid state was analyzed by X-ray diffractometry, differential scanning calorimetry, and infrared spectroscopy. The nanosystems were also evaluated for solubility and dissolution rate. A long-term stability evaluation was performed for three years at room temperature. The yields of the lyophilization ranged between 75 and 81% for each lot. The nanoparticles showed a submicron size (< 340 nm) and a low polydispersity depending on the stabilizer. The physicochemical properties of the prepared systems indicated a remarkable amorphization of the drug, which influenced its solubility and dissolution performance. The drug dissolution from both the fresh and aged nanosystems was significantly higher than that of the raw drug. In particular, nanoparticles prepared with poloxamer 407 showed no significant modifications in their particle size in three years of storage. Physical stability studies indicated that the obtained systems prepared with P188, P237, and P407 suffered certain recrystallization during long storage at 25 °C. These findings confirm that selected poloxamers exhibited an important effect in formulating fenbendazole nanosystems with improved dissolution.
Assuntos
Estabilidade de Medicamentos , Fenbendazol , Liofilização , Nanopartículas , Solubilidade , Nanopartículas/química , Fenbendazol/química , Liofilização/métodos , Varredura Diferencial de Calorimetria/métodos , Armazenamento de Medicamentos , Tamanho da Partícula , Difração de Raios X/métodos , Liberação Controlada de Fármacos , Química Farmacêutica/métodos , Poloxâmero/química , Crioprotetores/químicaRESUMO
The objective of this study was to investigate the nutrient composition of low-grade New Zealand commercial fish (Gemfish and Hoki) roe and to investigate the effects of delipidation and freeze-drying processes on roe hydrolysis and antioxidant activities of their protein hydrolysates. Enzymatic hydrolysis of the Hoki and Gemfish roe homogenates was carried out using three commercial proteases: Alcalase, bacterial protease HT, and fungal protease FP-II. The protein and lipid contents of Gemfish and Hoki roes were 23.8% and 7.6%; and 17.9% and 10.1%, respectively. The lipid fraction consisted mainly of monounsaturated fatty acid (MUFA) in both Gemfish roe (41.5%) and Hoki roe (40.2%), and docosahexaenoic (DHA) was the dominant polyunsaturated fatty acid (PUFA) in Gemfish roe (21.4%) and Hoki roe (18.6%). Phosphatidylcholine was the main phospholipid in Gemfish roe (34.6%) and Hoki roe (28.7%). Alcalase achieved the most extensive hydrolysis, and its hydrolysate displayed the highest 2,2-dipheny1-1-picrylhydrazyl (DPPH)Ë and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities and ferric reducing antioxidant power (FRAP). The combination of defatting and freeze-drying treatments reduced DPPHË scavenging activity (by 38%), ABTSË scavenging activity (by 40%) and ferric (Fe3+) reducing power by18% (p < 0.05). These findings indicate that pre-processing treatments of delipidation and freeze-drying could negatively impact the effectiveness of enzymatic hydrolysis in extracting valuable compounds from low grade roe.
Assuntos
Antioxidantes , Hidrolisados de Proteína , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacologia , Nova Zelândia , Liofilização , Hidrólise , Peixes/metabolismo , Peptídeo Hidrolases/metabolismo , Peptídeo Hidrolases/química , Produtos Pesqueiros/análise , SubtilisinasRESUMO
This study explores the potential of Cucumaria frondosa (C. frondosa) viscera as a natural source of omega-3 FAs using supercritical carbon dioxide (scCO2) extraction. The extraction conditions were optimized using a response surface design, and the optimal parameters were identified as 75 °C and 45 MPa, with a 20 min static and a 30 min dynamic extraction, and a 2:1 ethanol to feedstock mass ratio. Under these conditions, the scCO2 extraction yielded higher FAs than the solvent-based Bligh and Dyer method. The comparative analysis demonstrated that scCO2 extraction (16.30 g of FAs/100 g of dried samples) yielded more fatty acids than the conventional Bligh and Dyer method (9.02 g, or 13.59 g of FAs/100 g of dried samples with ultrasonic assistance), indicating that scCO2 extraction is a viable, green alternative to traditional solvent-based techniques for recovering fatty acids. The pre-treatment effects, including drying methods and ethanol-soaking, were investigated. Freeze-drying significantly enhanced FA yields to almost 100% recovery, while ethanol-soaked viscera tripled the FA yields compared to fresh samples, achieving similar EPA and DHA levels to hot-air-dried samples. These findings highlight the potential of sea cucumber viscera as an efficient source of omega-3 FA extraction and offer an alternative to traditional extraction procedures.
Assuntos
Dióxido de Carbono , Ácidos Graxos Ômega-3 , Vísceras , Animais , Dióxido de Carbono/química , Ácidos Graxos Ômega-3/isolamento & purificação , Ácidos Graxos Ômega-3/química , Vísceras/química , Cromatografia com Fluido Supercrítico/métodos , Cucumaria/química , Pepinos-do-Mar/química , LiofilizaçãoRESUMO
Lanthanide-containing luminescent hydrogels have shown potential for sensing and imaging applications. Nonetheless, integrating lanthanide ions or complexes into the polymer matrix often results in the poor stability and mechanical strength of the hydrogels. This work presents an innovative approach to fabricating luminescent hydrogels with three dynamic cross-links: imine bond, boronate ester bond, and metal-ligand coordination. Europium(III) (Eu3+) ions are incorporated into a dual-cross-linked matrix composed of phenylboronic acid-polyethylenimine-modified gelatin (PPG) and alginate dialdehyde (ADA) through a combined treatment involving freeze-drying-swelling (FDS) and freeze-thawing (FT) processes. The FDS process facilitates the formation of additional europium-carboxylate cross-links within the polymeric network to enhance its luminescence and stability, while the FT process strengthens the network physically. The impact of the FDS-FT cycle number on the microstructures and properties of PPG/ADA-Eu3+ hydrogels is thoroughly investigated, and their potential for monitoring bacterial growth and detecting copper(II) ions is also demonstrated.
Assuntos
Alginatos , Gelatina , Hidrogéis , Alginatos/química , Hidrogéis/química , Gelatina/química , Európio/química , Reagentes de Ligações Cruzadas/química , Liofilização/métodos , Luminescência , Congelamento , Ácido Glucurônico/química , Ácidos Hexurônicos/químicaRESUMO
Active pharmaceutical ingredient (API) embedded dry powder for inhalation (AeDPI) shows higher drug loading and delivery dose for directly treating various lung infections. Inspired by the dandelion, we propose a novel kind of AeDPI microparticle structure fabricated by spray freeze drying technology, which would potentially enhance the alveoli deposition efficiency. When inhaling, such microparticles are expected to be easily broken-up into fragments containing API that acts as 'seed' and could be delivered to alveoli aided by the low density 'pappus' composed of excipient. Herein, itraconazole (ITZ), a first-line drug for treating pulmonary aspergillosis, was selected as model API. TPGS, an amphiphilic surfactant, was used to achieve stable primary ITZ nanocrystal (INc) suspensions for spray freeze drying. A series of microparticles were prepared, and the dandelion-like structure was successfully achieved. The effects of feed liquid compositions and freezing parameters on the microparticle size, morphology, surface energy, crystal properties and in vitro aerosol performance were systematically investigated. The optimal sample (SF(-50)D-INc7Leu3-2) in one-way experiment showed the highest fine particle fraction of â¼ 68.96â¯% and extra fine particle fraction of â¼ 36.87â¯%, equivalently â¼ 4.60â¯mg and â¼ 2.46â¯mg could reach the lung and alveoli, respectively, when inhaling 10â¯mg dry powders. The response surface methodology (RSM) analysis provided the optimized design space for fabricating microparticles with higher deep lung deposition performance. This study demonstrates the advantages of AeDPI microparticle with dandelion-like structure on promoting the delivery efficiency of high-dose drug to the deep lung.