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1.
Electron. j. biotechnol ; 44: 1-5, Mar. 2020. graf, tab
Artigo em Inglês | LILACS | ID: biblio-1087706

RESUMO

Background: Freeze-drying is known as one of the best methods to preserve bacterial strains. Protectant is the key factor affecting the survival rate of freeze-dried strains. In addition, salinity, bacterial suspension concentration, drying time, and other factors can also affect the survival rate of strains to varying degrees. At present, there are relatively few studies on freeze-drying preservation of marine bacteria. In the present study, we performed the freeze-drying protectant screening and optimized the preservation conditions for Pseudoalteromonas nigrifaciens, which is widely distributed in marine environment. The protective effects of the screened protectants were verified by 18 other marine bacterial strains. Results: The results indicated that the combination of 5.0% (w/v) lactose, 5.0% (w/v) mannitol, 5.0% (w/v) trehalose, 10.0% (w/v) skim milk powder, 0.5% (w/v) ascorbic acid and 0.5% (w/v) gelatin was the best choice for the preservation of P. nigrifaciens. The suggested salinity and concentration of initial cell suspension were 10 g/L NaCl and 1.0 × 109 CFU/mL, respectively. Furthermore, stationary-phase cells were the best choice for the freeze-drying process. The highest survival rate of P. nigrifaciens reached 52.8% when using 5­10% (w/v) skim milk as rehydration medium. Moreover, the other 18 marine strains belonging to Pseudoalteromonas, Vibrio, Photobacterium, Planomicrobium, Edwardsiella, Enterococcus, Bacillus, and Saccharomyces were freezedried under the abovementioned conditions. Their survival rates were 2.3­95.1%. Conclusion: Collectively, our results supported that the protectant mixture and parameters were beneficial for lyophilization of marine bacteria


Assuntos
Preservação Biológica/métodos , Pseudoalteromonas/fisiologia , Liofilização/métodos , Trealose/química , Sobrevivência Celular , Fenômenos Fisiológicos Bacterianos , Dissacarídeos/química , Viabilidade Microbiana , Salinidade , Lactose/química , Manitol/química
2.
Chem Pharm Bull (Tokyo) ; 68(3): 251-257, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115532

RESUMO

A concise spherical granulation method is required to prepare extemporaneously granules remanufactured from oral dosage forms for administration to individuals who cannot swallow tablets or capsules. In this study, we determined the feasibility of spherical granulation using a planetary centrifugal mixer. A model formulation, 20% ibuprofen (IBP) granules, was prepared using a lactose/cornstarch (7 : 3, w/w) mixture or D-mannitol as diluents, and changes in granule characteristics (mean diameter (d50), distribution range of granule size (span), and yield) were evaluated according to the amount of water added and the granulation time. The amount of water was assessed using the plastic limit value as measured using a digital force gauge. We successfully produced granules, and larger amounts of water and longer granulation times resulted in larger d50 values and smaller span values. The optimal granulation time was 45 s and the optimal water contents were 70 and 67.5% of the plastic limit value for the lactose/cornstarch mixture and D-mannitol, respectively. When compared to commercial 20% IBP granules, powder X-ray diffraction and differential scanning calorimetry analyses showed that the granulation process did not alter the crystallinity of the drug. Thus, this novel granulation method using a planetary centrifugal mixer may be a promising technique for compounding in pharmacies and in pharmaceutical manufacturing.


Assuntos
Centrifugação , Ibuprofeno/química , Lactose/química , Manitol/química , Amido/química , Varredura Diferencial de Calorimetria , Ibuprofeno/isolamento & purificação , Tamanho da Partícula , Difração de Pó , Propriedades de Superfície
3.
J Agric Food Chem ; 68(9): 2773-2782, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32013417

RESUMO

The influence of covalent protein modifications resulting from the Maillard reaction (glycation) of casein and lactose on the noncovalent association behavior of the protein was studied. Nonenzymatic cross-linking with methylglyoxal (MGO) and glutaraldehyde (GTA) as well as enzymatic cross-linking with microbial transglutaminase (mTG) was investigated in comparison. Molar mass, particle size, and conformational characteristics of nonmicellar casein associates as well as the extent of intraparticle protein cross-linking were examined utilizing size-exclusion chromatography (SEC) combined with UV detection and static and dynamic light scattering. Cross-linking resulted in the stabilization of a certain fraction of casein associates, with particle sizes of approximately 30 nm in radius of gyration (Rg), and promoted an incorporation of further casein molecules into those particles, yielding molar masses (Mw) of 1.0-1.2 × 106 g/mol. When caseins were additionally conjugated with lactose during the early Maillard reaction, a further growth of the associates up to approximately 50 nm in Rg with a Mw of 2.1 × 106 g/mol was observed. Furthermore, glycation reactions induced a transition from slightly elongated, random-coil structures toward more anisotropic conformations. Associates consisting of caseins cross-linked with GTA appeared to preserve the original particle conformation.


Assuntos
Caseínas/química , Cromatografia em Gel , Reagentes para Ligações Cruzadas/química , Difusão Dinâmica da Luz , Glutaral/química , Lactose/química , Reação de Maillard , Tamanho da Partícula , Aldeído Pirúvico/química
4.
Food Chem ; 304: 125418, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31479994

RESUMO

Low and high protein dairy powders are prone to caking and sticking and can also be highly insoluble; with powder storage conditions an important factor responsible for such issues. The aim of this study focused on the bulk and surface properties of anhydrous and humidified spray-dried milk protein concentrate (MPC) powders (protein content ~40, 50, 60, 70 or 80%, w/w). Water sorption isotherms, polarized light and scanning electron micrographs showed crystallized lactose in low protein powders at high water activities. High protein systems demonstrated increased bulk diffusion coefficients compared to low protein systems. Glass transition temperatures, α-relaxation temperatures and structural strength significantly decreased with water uptake. CLSM measurements showed that humidified systems have slower real time water diffusion compared to anhydrous systems. Overall, the rate of water diffusion was higher for low protein powders but high protein powders absorbed higher levels of water under high humidity conditions.


Assuntos
Lactose/química , Proteínas do Leite/química , Pós/química , Água/química , Laticínios/análise , Difusão , Umidade , Propriedades de Superfície , Temperatura
5.
Biochim Biophys Acta Proteins Proteom ; 1868(1): 140271, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31494342

RESUMO

ß-Galactosidase is one of the most important industrial enzymes, that has been used for many decades in the dairy industry. The main application of ß-galactosidase is related to the production of low-lactose and lactose-free milk and dairy products, which are now common consumer goods in supermarket shelves. This is a well-established market that is expected to keep on growing as these products become more accessible to mid-income people worldwide. However, a fresh air has come into the ß-galactosidase business as non-conventional applications arose in recent decades based on its transgalactosylation activity. This capacity is certainly a major asset for a commodity enzyme that can be used now as a catalyst for the upgrading of readily available and cheap lactose into high added-value glycosides in processes of organic synthesis in tune with green chemistry principles within the framework of sustainability. This is a reflection of a paradigm shift, where enzymes are now being considered as apt catalysts for the synthesis of valuable organic compounds. This article reviews the main applications of ß-galactosidase, going from its conventional use related to its hydrolytic activity to the ongoing non-conventional applications in the synthesis of high added-value oligosaccharides based on its transgalactosylation activity.


Assuntos
beta-Galactosidase/química , Catálise , Lactose/química
6.
J Dairy Res ; 86(4): 477-482, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31823833

RESUMO

The work described in this Research Communication concerns the production of Dulce de leche (DL), that is a traditional product from South America obtained by concentration. Maillard reaction (MR) products are mainly responsible for the formation of color and flavor in this product. Lactose-hydrolyzed products have been developed to supply consumer demand, but this hydrolysis may affect the flavor, color, taste, texture and even some nutritional aspects of the product. We studied the influence of different levels of lactose-hydrolysis, sucrose addition and initial pH on the development of MR, appraised by the determination of 5-hydroxymethylfurfural (HMF). A process simulator with multi-monitoring system was used to produce 15 DL. Box-Behnken 33 experimental design was applied for the three factors: pH, lactose-hydrolysis level and sucrose concentration. Lipids, protein, ashes, carbohydrates, water activity, dissolved solids, colorimetric analysis and HMF (free and total) are among the physicochemical attributes and MR indicators analyzed in this work. The products showed significant differences in composition but all the values were in agreement with the literature. Moreover, higher levels of lactose hydrolysis and higher pH presented a direct relation with the development of MR, observed by an increase in coloration (lower luminosity) and more formation of HMF, both free and total. The present study expands the knowledge about DL spread made of lactose-hydrolyzed milk, allowing the food industries to produce a lactose free DL with nutritional and sensory characteristics closer to the traditional product.


Assuntos
Furaldeído/análogos & derivados , Lactose/química , Leite/química , Animais , Fenômenos Químicos , Cor , Manipulação de Alimentos/métodos , Furaldeído/química , Concentração de Íons de Hidrogênio , Hidrólise , Reação de Maillard , América do Sul , Sacarose/análise , Sacarose/química , Paladar
7.
J Agric Food Chem ; 67(46): 12863-12874, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31670949

RESUMO

A comprehensive quantitative characterization of Maillard reaction products was carried out for conventional (CON) and lactose-hydrolyzed (LH) ultrahigh temperature (UHT) milk during storage at 20, 30, and 40 °C for 1 year. The accumulation of 3-deoxyglucosone (3-DG) and 3-deoxygalactosone (3-DGal) in LH-UHT milk ranged from 20-fold (at 20 °C) to 44-fold (at 40 °C) higher than that in CON-UHT milk. High temperature storage (40 °C) significantly accelerated the accumulation of 3-DG, 3-DGal, and 5-hydroxymethyl furfural but not the majority of the analyzed advanced glycation endproducts (AGEs). The concentrations of major AGEs including N-ε-carboxymethyllysine (CML), N-ε-carboxyethyllysine (CEL), methylglyoxal-hydroimidazolone isomers (MG-H1/H3), glyoxal-hydroimidazolone isomers (G-H1/H3), and G-H2 detected in CON milk during storage were in the range 12-700, 1-14, 8-45, 4-13, and 1-30 µM, respectively, while they were 30-570, 2-88, 17-150, 9-20, and 5-34 µM, respectively, in LH milk. Pyrraline, S-(carboxymethyl)cysteine (CMC), and glyoxal-lysine dimer were detected in lower levels, while MG-H2, methylglyoxal-lysine dimer, argpyrimidine, glyoxal-lysine-amide, glycolic acid-lysine-amide, and pentosidine were not detected in any of the milk samples. This work demonstrates for the first time that five of the analyzed AGEs (CML, CEL, MG-H1/H3, G-H1/H3, and G-H2) could be selected as markers for evaluation of the extent of the Maillard reaction in UHT milk. These results contribute to a better understanding of how Maillard reactions progress during storage of UHT milk and can be used to develop strategies to inhibit Maillard reactions in LH milk.


Assuntos
Produtos Finais de Glicação Avançada/análise , Lactose/química , Leite/química , Animais , Bovinos , Desoxiglucose/análogos & derivados , Desoxiglucose/análise , Armazenamento de Alimentos , Galactose/análogos & derivados , Galactose/análise , Isomerismo , Lisina/análogos & derivados , Lisina/análise , Reação de Maillard , Aldeído Pirúvico/análise , Temperatura
8.
Molecules ; 24(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31510031

RESUMO

Enzymatic hydrolysis of lactose is a crucial step to improve the efficiency and selectivity of membrane-based separations toward the recovery of milk oligosaccharides free from simple sugars. Response surface methodology was used to investigate the effects temperature (25.9 to 54.1 °C) and amount of enzyme (0.17 to 0.32% w/w) at 1, 2, and 4 h of reaction on the efficiency of lactose hydrolysis by Aspergillus oryzae ß-galactosidase, preservation of major goat whey oligosaccharides, and on the de-novo formation of oligosaccharides. Lactose hydrolysis above 99% was achieved at 1, 2, and 4 h, not being significantly affected by temperature and amount of enzyme within the tested conditions. Formation of 4 Hexose (Hex) and 4 Hex 1 Hex and an increased de-novo formation of 2 Hex 1 N-Acetyl-Neuraminic Acid (NeuAc) and 2 Hex 1 N-Glycolylneuraminic acid (NeuGc) was observed in all treatments. Overall, processing conditions using temperatures ≤40 °C and enzyme concentration ≤0.25% resulted in higher preservation/formation of goat whey oligosaccharides.


Assuntos
Lactose/química , Oligossacarídeos/química , Proteínas do Soro do Leite/química , beta-Galactosidase/química , Animais , Aspergillus oryzae/enzimologia , Cabras , Hexoses/química , Concentração de Íons de Hidrogênio , Hidrólise , Leite/química , Modelos Químicos , Ácidos Neuramínicos/química , Temperatura , Soro do Leite/química
9.
Carbohydr Polym ; 224: 115158, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472856

RESUMO

In this study, water-soluble chitosan (Ch) derivatives were synthesized by the Maillard reaction between Ch and lactose. The Ch derivatives were characterized by FT-IR, 1H-NMR and SLS to determine their structure, degree of deacetylation (DD), and molecular weight (Mw). The solubility at physiological pH, the in vitro antioxidant activity against hydroxyl radical, anion superoxide radical and ABTS cation radical, and the cytotoxicity against epithelial cells of the rat ileum (IEC-18) were also evaluated. The Maillard reaction, derivatives with lower Mw and DD and greater solubility than Ch were obtained. The biological properties of the derivatives were dependent on the concentration, Mw and DD, with antioxidant activity greater than or equal to that of Ch and non-cytotoxic in a wide range of concentrations. The results indicate that Ch derivatization with lactose produces new water-soluble polysaccharides, with antioxidant activity and non-cytotoxic, which can be used as biomaterials for food and pharmaceutical applications.


Assuntos
Fenômenos Químicos , Quitosana/química , Citotoxinas/química , Depuradores de Radicais Livres/química , Lactose/química , Água/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/toxicidade , Depuradores de Radicais Livres/toxicidade , Ratos , Solubilidade
10.
J Agric Food Chem ; 67(40): 11158-11166, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31537069

RESUMO

There are ongoing interests in improving the galactooligosaccharide (GOS) synthesis efficiency of ß-galactosidase by protein engineering. In this study, an intelligent double-hydrophobic amino acid scanning strategy was proposed and employed to target nine residues forming the glycon-binding site (-1 subsite) of ß-galactosidase Bgal1-3. Two mutants C510V and H512I with significantly improved GOS synthesis efficiency were obtained. When 40% (w/v) lactose was used as a substrate, Bgal1-3 reached a maximum GOS yield of 45.3% at 16 h, while the mutants reached higher yields in a much shorter time (59.1% at 10 h for C510V, 51.5% at 2 h for H512I). When skim milk was treated with these enzymes, more GOS was produced (19.9 g/L for C510V, 12.7 g/L for H512I) than that for Bgal1-3 (10.3 g/L) at a lactose conversion of 90%. These results validated hydrophobicity scanning as an efficient method to engineer ß-galactosidases into promising catalysts for the preparation of GOS and GOS-enriched milk.


Assuntos
Bactérias/enzimologia , Proteínas de Bactérias/química , Galactose/química , Oligossacarídeos/química , beta-Galactosidase/química , Sequência de Aminoácidos , Bactérias/química , Bactérias/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biocatálise , Domínio Catalítico , Galactose/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Lactose/química , Oligossacarídeos/metabolismo , Engenharia de Proteínas , Alinhamento de Sequência , beta-Galactosidase/genética , beta-Galactosidase/metabolismo
11.
Int J Pharm ; 570: 118607, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31421200

RESUMO

The aim of this study was to evaluate the influence of tableting process parameters, i.e. turret rotation speed, pre-compaction and main compaction pressures, and their interactions on layer adhesion of bilayer tablets. The elastic recovery after compaction was used as estimation for the elasticity of the material. Three potential pharmaceutical formulations were evaluated as combinations of immediate (microcrystalline cellulose, lactose, calcium phosphate, pregelatinized starch) and controlled drug release excipients (ethyl cellulose, hydroxypropyl methylcellulose, polyvinyl acetate/polyvinylpyrrolidone). A 3-levels 3-factors central composite Design of Experiment was performed on each formulation, with layer adhesion selected as response. A custom-made shear test was used to determine the tablet tendency to delaminate. Main compaction and turret rotation speed were the most important parameters to be optimized during tablet manufacturing. Main compaction was the principal parameter leading to delamination in case of formulations with plastic materials, particularly at high pressures where the difference in elasticity of excipients had a major impact and was followed by turret rotation speed. The rotation speed did not have an effect on layer adhesion in the case of formulations with brittle excipients.


Assuntos
Comprimidos/química , Fosfatos de Cálcio/química , Celulose/análogos & derivados , Celulose/química , Química Farmacêutica/métodos , Elasticidade , Excipientes/química , Derivados da Hipromelose/química , Lactose/química , Povidona/química , Pressão , Amido/química , Estresse Mecânico , Tecnologia Farmacêutica/métodos
12.
Carbohydr Res ; 484: 107773, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31404813

RESUMO

An HPLC method suitable for rapid monitoring of lactulose production by isomerization from lactose was developed. The separation of lactose and lactulose under hydrophilic interaction liquid chromatography (HILIC) mode was achieved with resolution 1.5 within 5 min. Since isocratic elution was used, there is no extra time necessary for the column equilibration. Application of the method was illustrated on monitoring lactulose isomerization with catalysis of sodium hydroxide in the presence of sodium tetraborate at 70 °C (pH = 11). The conversion yield obtained for lactulose was 86%, and corresponding purity 76%. For the first time, a polyhydroxy stationary phase for separation of lactose and lactulose is reported.


Assuntos
Fracionamento Químico/métodos , Lactose/química , Lactulose/análise , Boratos/química , Catálise , Cromatografia Líquida de Alta Pressão , Temperatura Alta , Interações Hidrofóbicas e Hidrofílicas , Isomerismo , Lactose/análise , Lactulose/química , Hidróxido de Sódio/química
13.
Eur J Pharm Biopharm ; 142: 543-552, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31398437

RESUMO

Recently we showed that nebulized ciprofloxacin and phage PEV20 in combination had a synergistic bactericidal effect against antibiotic-resistant Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Compared to nebulization, dry powders for inhalation may improve patient handling characteristics and compliance. In the present study, we co-spray dried ciprofloxacin and phage PEV20 using L-leucine with or without lactose as excipients. Two formulations were identified for testing in this study. The mass ratios were set at 1:1:1 for ciprofloxacin, lactose and L-leucine (Formulation A) or 2:1 for ciprofloxacin and L-leucine without lactose (Formulation B). Concentrations of PEV20 were set at 108 and 109 PFU/mL for two clinical P. aeruginosa strains FADD1-PA001 and JIP865, respectively. Formulations A and B were characterized as partially crystalline and the powders recrystallized at >40% relative humidity (RH). Both formulations exhibited strong synergistic antimicrobial killing effect on the two strains. Formulations A and B maintained bactericidal synergy after dispersion using both low and high resistance Osmohaler™. Powder aerosol performance was examined by next generation impactor (NGI) in low resistance inhaler at 100 L/min and by multi-stage liquid impinger (MSLI) in high resistance inhaler at 60 L/min. Fine particle fractions (FPF) obtained by NGI were 59.7 ±â€¯2.1% and 64.3 ±â€¯2.9% for A and B, respectively. FPF obtained by MSLI were 71.0 ±â€¯3.4% and 73.3 ±â€¯5.0%, respectively. In conclusion, it is feasible to prepare stable and inhalable combination powder formulations of phage PEV20 and ciprofloxacin for potential treatment of respiratory infections caused by multi-drug resistant (MDR) P. aeruginosa.


Assuntos
Bacteriófagos/classificação , Ciprofloxacino/administração & dosagem , Ciprofloxacino/química , Pós/química , Infecções Respiratórias/tratamento farmacológico , Administração por Inalação , Aerossóis/química , Antibacterianos/administração & dosagem , Antibacterianos/química , Química Farmacêutica/métodos , Fibrose Cística/microbiologia , Inaladores de Pó Seco/métodos , Excipientes/química , Humanos , Lactose/química , Nebulizadores e Vaporizadores , Tamanho da Partícula , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos
14.
Drug Dev Ind Pharm ; 45(10): 1674-1681, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31378098

RESUMO

Objective: The main objective of this research is to develop an immediate release Rupatadine fumarate 10 mg tablets formulation by direct compression, through a Quality by Design approach in Costa Rica. Methods: According to a Quality by Design approach; Target Product Profile, Quality Target Product Profile, and the Critical Quality Attributes were defined. In the preformulation study, compatibility tests were carried out between the raw materials. The Critical Material Attributes were established using Quality Risk Management. Three formulation prototypes were prepared by direct compression and its Critical Process Parameters were defined. The analysis of the prototypes was realized in terms of organoleptic properties, identification, potency, content uniformity, dissolution, disintegration, friability and loss by drying. Results: All the prototypes showed a white or slightly pink surface, potency between 90.0 -110.0 % of the labeling, an acceptance value for the content uniformity lower than the specification (AV < 15), the dissolved amount of active pharmaceutical ingredient was greater than 85.0 % at 30 minutes, friability less than 1.0 %, a disintegration time less than 15 minutes and moisture content less than 2.0 %. Conclusions: The approaching of a Quality by Design model to the current development allowed to obtain satisfactory results in the three formulation prototypes. The excipients to be used can be lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, pregelatinized starch, magnesium stearate, stearic acid, and PVP K-30.


Assuntos
Ciproeptadina/análogos & derivados , Fumaratos/química , Comprimidos/química , Carboximetilcelulose Sódica/química , Celulose/química , Química Farmacêutica/métodos , Ciproeptadina/química , Composição de Medicamentos/métodos , Excipientes/química , Lactose/química , Solubilidade/efeitos dos fármacos , Amido/química , Ácidos Esteáricos/química , Tecnologia Farmacêutica/métodos
15.
Food Chem ; 299: 125166, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31323443

RESUMO

Dynamic high-pressure microfluidization (DHPM) pretreatment and glycation with lactose were employed to modify α-Lactalbumin (α-LA) with respect to the IgE/IgG binding capacities. No significant difference on incorporation ratio value of glycated α-LA was observed with and without DHPM pretreatment. However, IgE/IgG binding capacities of α-LA were decreased after glycation and DHPM pretreatment promoted the reduction. The lowest IgE/IgG binding capacities of glycated α-LA were obtained by DHPM pretreatment at 110 MPa. Native α-LA was mainly glycated at K62, K94, K98, whereas glycation sites and degree of substitution per peptide (DSP) were added after DHPM treatment. Therefore, the reduced IgE/IgG binding capacities of α-LA was attributed to the characteristics of glycated sites, including the amount, location, and DSP values. Interestingly, K98 played the most important role in decreasing IgE/IgG binding capacities of α-LA. The study revealed that glycation combined with DHPM was a promising way to decrease the allergenicity of proteins.


Assuntos
Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Lactalbumina/metabolismo , Alérgenos/química , Animais , Bovinos , Ensaio de Imunoadsorção Enzimática , Indústria de Processamento de Alimentos/métodos , Humanos , Lactalbumina/química , Lactalbumina/imunologia , Lactose/química , Lisina/metabolismo , Espectrometria de Massas/métodos , Pressão , Coelhos
16.
Carbohydr Res ; 482: 107744, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306898

RESUMO

Iminosugars are known glycosidase inhibitors which are the subject of drug development efforts against several diseases. The access to structurally-related families of iminosugars is of primary importance for running structure-activity relationship studies. In this work, the double reductive amination (aminocyclization) reaction of a dicarbonyl derivative of the l-arabino series, in turn obtained from lactose, is reported. Different ratios of 1,6-di-deoxy-d-galacto and 1,6-di-deoxy-l-altro nojirimycin derivatives were obtained depending on the amine employed in this transformation which provided an insight into the effects of their structure on the outcome of the reaction. Of particular interest were the results obtained when two enantiomeric amino acids (d-Phe-OMe and l-Phe-OMe) were used, which resulted in the inversion of the reaction stereoselectivity.


Assuntos
1-Desoxinojirimicina/análogos & derivados , Lactose/química , 1-Desoxinojirimicina/química , Ciclização , Descoberta de Drogas , Estereoisomerismo , Relação Estrutura-Atividade
17.
Eur J Pharm Sci ; 137: 104987, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31295547

RESUMO

According to the European Pharmacopoeia monograph 1038 (Praeparationes homoeopathicae), homeopathic preparations are produced by successive dilution and succussion steps. Dilution levels beyond Avogadro's limit, however, render specific effects implausible according to standard scientific knowledge. Accordingly, we were interested in a critical empirical investigation of preparations produced according to this monograph. Within a precursor study we developed a bioassay based on a fingerprint metabolomic analysis of Lepidium sativum seeds germinated in vitro in either homeopathic preparations or controls in a blinded and randomized assignment. Results of the precursor study were not consistent with the hypothesis that the effects of a Stannum metallicum 30x preparation are identical to placebo. In the present study we investigated the reproducibility of these effects after scrutinizing and optimizing experimental procedures. Ten independent experiments were performed in a blinded and randomized assignment in two independent laboratories. Additionally, 10 systematic negative water control experiments were performed in both laboratories to critically assess the stability of the experimental set-up. The effects of the Stannum metallicum 30x treatment were reproduced. The systematic negative control experiments did not yield false-positive results, indicating a stable experimental set-up. We thus repeatedly observed biological effects conflicting with the assumption that Stannum metallicum 30x is identical to placebo. We therefore wish to discuss whether these findings are to be considered a scientific anomaly or whether they might stimulate further investigations to clarify whether application of the European Pharmacopoeia monograph 1038 may result in pharmaceutical preparations with specific effects.


Assuntos
Germinação/efeitos dos fármacos , Lepidium , Sementes/efeitos dos fármacos , Estanho/toxicidade , Bioensaio , Cristalização , Europa (Continente) , Lactose/química , Lactose/toxicidade , Metabolômica , Preparações Farmacêuticas , Farmacopeias Homeopáticas como Assunto , Reprodutibilidade dos Testes , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Estanho/química , Água/química
18.
Pharm Res ; 36(10): 139, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31359156

RESUMO

PURPOSE: To identify the minimum interfacial bonding strength (IBS) required for bilayer tablets to sustain the stresses experienced during manufacturing, transportation, and handling. METHODS: Bilayer tablets of a number of formulations with systematically varied IBS were prepared on a materials testing macine. Five bilayer tablets with the same IBS were repeatedly dropped at a fixed height in a friabilator and integrity of the interface was periodically examined. The number of tablets free from observable defects at the interface was plotted as a function of the number of drops. The IBS for all five tablets to remain intact after 1000 drops was taken as the minimum IBS for a given formulation. RESULTS: The minimum IBS depends on both layer composition and tablet size. For bilayer tablets made with more brittle materials or a larger size, a higher minimum IBS is required to pass the survival test. The incorporation of HPMC leads to a lower minimum IBS. An IBS of 0.26 MPa is sufficient for all bilayer tablet formulations and sizes to pass the survival test in this work. CONCLUSIONS: A minimum IBS of 0.26 MPa is recommended as a tentative criterion for bilayer tablets of most materials to avoid quality issues arising from inadequate IBS.


Assuntos
Excipientes/química , Comprimidos/química , Celulose/química , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Lactose/química , Tamanho da Partícula , Estresse Mecânico , Propriedades de Superfície , Resistência à Tração
19.
Int J Pharm ; 568: 118542, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31330171

RESUMO

This study presents a modelling framework to predict the flowability of various commonly used pharmaceutical powders and their blends. The flowability models were trained and validated on 86 samples including single components and binary mixtures. Two modelling paradigms based on artificial intelligence (AI) namely, a radial basis function (RBF) and an integrated network were employed to model the flowability represented by the flow function coefficient (FFC) and the bulk density (RHOB). Both approaches were utilized to map the input parameters (i.e. particle size, shape descriptors and material type) to the flow properties. The input parameters of the blends were determined from the particle size, shape and material type properties of the single components. The results clearly indicated that the integrated network outperformed the single RBF network in terms of the predictive performance and the generalization capabilities. For the integrated network, the coefficient of determination of the testing data set (not used for training the model) for FFC was R2=0.93, reflecting an acceptable predictive power of this model. Since the flowability of the blends can be predicted from single component size and shape descriptors, the integrated network can assist formulators in selecting excipients and their blend concentrations to improve flowability with minimal experimental effort and material resulting in the (i) minimization of the time required, (ii) exploration and examination of the design space, and (iii) minimization of material waste.


Assuntos
Modelos Teóricos , Pós/química , Reologia , Inteligência Artificial , Fosfatos de Cálcio/química , Celulose/química , Excipientes/química , Lactose/química , Tamanho da Partícula
20.
Int J Pharm ; 568: 118541, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31330172

RESUMO

In the present study the application of near-infrared chemical imaging (NIR-CI) for assessing particle segregation in granules from continuous twin screw granulation (TSG) granules, were the complex attributes of the machinery configuration in relation to particle segregation is not well understood was investigated. Experiments were performed along the compartmental length of the TSG barrel channel by varying the screw element type and liquid binder viscosity. Examination of the data showed a direct correlation between dispersion due to shear force and de-mixing of particles, which allowed for identification of fundamental granule segregation mechanisms affecting content uniformity in TSG. Particle segregation behavior was linked to dispersion due to shear force through a proposed regime mapping approach which links de-mixing potential to controlling granule formation mechanisms with a new dimensionless mixing number. This was carried out in order to provide a general guideline of how particles segregate along the length of the TSG barrel channel.


Assuntos
Tecnologia Farmacêutica/métodos , Lactose/química , Tamanho da Partícula , Pós , Ácidos Esteáricos/química
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