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1.
J Chem Phys ; 151(12): 124307, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31575165

RESUMO

Ce atom reactions with ethylene, 2-butene, and isobutene are carried out in a pulsed laser vaporization molecule beam source. Ce-containing species are observed with time-of-flight mass spectrometry, and Ce(C4H6) is characterized with mass-analyzed threshold ionization (MATI) spectroscopy and relativistic quantum chemical calculations. Two structural isomers are identified for Ce(C4H6): one is the tetrahedronlike Ce[C(CH2)3] in C3v symmetry and the other is the five-membered metallocyclic Ce(CH2CHCHCH2) in Cs. The MATI spectrum of the C3v isomer exhibits two vibronic band systems separated by 88 cm-1, while that of the Cs isomer displays three split by 60 and 101 cm-1. The multiple band systems are attributed to spin-orbit splitting and vibronic transitions involving metal-hydrocarbon and hydrocarbon-based vibrations. The splitting in the C3v isomer arises from interactions of two triplet and two singlet states at the lowest energies, while each splitting in the Cs isomer involves two triplets and a singlet. Although the Ce atom has ground electron configuration 4f15d16s2, Ce valence electron configurations in both isomers are 4f16s1 in the neutral ground state and 4f1 in the ion. The remaining Ce 5d electrons in the isolated atom are spin paired in molecular orbitals that are a bonding combination between Ce 5dπ and hydrocarbon π* orbitals.

2.
Nat Genet ; 51(7): 1106-1112, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31182810

RESUMO

Head or ear blight, mainly caused by Fusarium species, can devastate almost all staple cereal crops (particularly wheat), resulting in great economic loss and imposing health threats on both human beings and livestock1-3. However, achievement in breeding for highly resistant cultivars is still not satisfactory. Here, we isolated the major-effect wheat quantitative trait locus, Qfhs.njau-3B, which confers head blight resistance, and showed that it is the same as the previously designated Fhb1. Fhb1 results from a rare deletion involving the 3' exon of the histidine-rich calcium-binding-protein gene on chromosome 3BS. Both wheat and Arabidopsis transformed with the Fhb1 sequence showed enhanced resistance to Fusarium graminearum spread. The translation products of this gene's homologs among plants are well conserved and might be essential for plant growth and development. Fhb1 could be useful not only for curbing Fusarium head blight in grain crops but also for improving other plants vulnerable to Fusarium species.

3.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 36(5): 493-497, 2018 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-30465341

RESUMO

OBJECTIVE: This study aimed to evaluate the clinical effect of pulp-less molars with defects of different degrees repaired by cast ceramic onlays of three marginal types. METHODS: A total of 165 endodontically treated molars of 105 patients were included in this study and were divided into three kinds of defect (mild, moderate, severe) according to the number of remaining axial walls. Each defect was divided into three groups according to the shape of edge to edge, bevel edge, and concave shoulder. After tooth preparation, the casting of ceramic onlays was performed. Treatment follow-up was done for the evaluation of the success and survival rates of three groups under the same defect. RESULTS: The average follow-up was 925.44 days. Under the mild defect, the success and survival rates of the edge to edge onlays were respectively 100% and 100%; bevel edge onlays, 100% and 100%; and concave shoulder onlays, 94.4% and 100%. Under the moderate defect, the success and survival rates of the edge to edge onlays were respectively 96.0% and 100%; bevel edge onlays, 80.0% and 93.3%; and concave shoulder onlays, 95.2% and 95.2%. Under the severe defect, the success and survival rates of the edge to edge onlays were respectively 95.2% and 100%; bevel edge onlays, 73.7% and 89.5%; and concave shoulder onlays, 73.3% and 80.0%. Under different defects, the success or survival rates of the three kinds of onlays had no significant difference (P>0.05). CONCLUSIONS: The edge to edge type is the most preferable way of onlay tooth preparation and can achieve good clinical results in the mild, middle, and severe tooth defection with root canal treatment.

4.
J Chem Phys ; 148(19): 194302, 2018 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-30307187

RESUMO

La atom reaction with isoprene is carried out in a laser-vaporization molecular beam source. The reaction yields an adduct as the major product and C-C cleaved and dehydrogenated species as the minor ones. La(C5H8), La(C2H2), and La(C3H4) are characterized with mass-analyzed threshold ionization (MATI) spectroscopy and quantum chemical computations. The MATI spectra of all three species exhibit a strong origin band and several weak vibronic bands corresponding to La-ligand stretch and ligand-based bend excitations. La(C5H8) is a five-membered metallacycle, whereas La(C2H2) and La(C3H4) are three-membered rings. All three metallacycles prefer a doublet ground state with a La 6s1-based valence electron configuration and a singlet ion. The five-membered metallacycle is formed through La addition and isoprene isomerization, whereas the two three-membered rings are produced by La addition and insertion, hydrogen migration, and carbon-carbon bond cleavage.

5.
J Chem Phys ; 149(3): 034303, 2018 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-30037237

RESUMO

La atom reactions with 1-pentene and 2-pentene are carried out in a laser-vaporization molecular beam source. The two reactions yield the same metal-hydrocarbon products from the dehydrogenation and carbon-carbon bond cleavage of the pentene molecules. The dehydrogenated species La(C5H8) is the major product, whereas the carbon-carbon bond cleaved species La(C2H2) and La(C3H4) are the minor ones. La(C10H18) is also observed and is presumably formed by La(C5H8) addition to a second pentene molecule. La(C5H8) and La(C2H2) are characterized with mass-analyzed threshold ionization (MATI) spectroscopy and quantum chemical computations. The MATI spectra of each species from the two reactions exhibit the same transitions. Adiabatic ionization energies and metal-ligand stretching frequencies are determined for the two species, and additional methyl bending and torsional frequencies are measured for the larger one. Five possible isomers are considered for La(C5H8), and a C1 metallacyclopentene (Iso A) is identified as the most possible isomer. La(C2H2) is confirmed to be a C2v metallacyclopropene. The ground electronic state of each species is a doublet with a La 6s1-based electron configuration, and ionization yields a singlet state. The formation of the lanthanacyclopentene includes La addition to the C=C double bond, La insertion into two C(sp3)-H bonds, and concerted dehydrogenation. For the 2-pentene reaction, the formation of the five-membered ring may also involve 2-pentene to 1-pentene isomerization. In addition to the metal addition and insertion, the formation of the three-membered metallacycle from 1-pentene includes C(sp3)-C(sp3) bond breakage and hydrogen migration from La to C(sp3), whereas its formation from 2-pentene may involve the ligand isomerization.

6.
J Chem Phys ; 148(4): 044312, 2018 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-29390854

RESUMO

La atom reactions with 1-butene, 2-butene, and isobutene are carried out in a laser-vaporization molecular beam source. The three reactions yield the same La-hydrocarbon products from the dehydrogenation and carbon-carbon bond cleavage and coupling of the butenes. The dehydrogenated species La(C4H6) is the major product, which is characterized with mass-analyzed threshold ionization (MATI) spectroscopy and quantum chemical computations. The MATI spectrum of La(C4H6) produced from the La+1-butene reaction exhibits two band systems, whereas the MATI spectra produced from the La+2-butene and isobutene reactions display only a single band system. Each of these spectra shows a strong origin band and several vibrational progressions. The two band systems from the spectrum of the 1-butene reaction are assigned to the ionization of two isomers: La[C(CH2)3] (Iso A) and La(CH2CHCHCH2) (Iso B), and the single band system from the spectra of the 2-butene and isobutene reactions is attributed to Iso B and Iso A, respectively. The ground electronic states are 2A1 (C3v) for Iso A and 2A' (Cs) for Iso B. The ionization of the doublet state of each isomer removes a La 6s-based electron and leads to the 1A1 ion of Iso A and the 1A' ion of Iso B. The formation of both isomers consists of La addition to the C=C double bond, La insertion into two C(sp3)-H bonds, and H2 elimination. In addition to these steps, the formation of Iso A from the La+1-butene reaction may involve the isomerization of 1-butene to isobutene prior to the C-H bond activation, whereas the formation of Iso B from the La+trans-2-butene reaction may include the trans- to cis-butene isomerization after the C-H bond activation.

7.
J Phys Chem A ; 121(44): 8440-8447, 2017 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-29061045

RESUMO

Lan(benzene) (n = 1 and 2) are formed in a pulsed laser-ablation molecular beam source and characterized by low-energy photoelectron imaging spectroscopy. The photoelectron spectrum of La2(benzene) displays a strong origin band, a short metal-ligand stretching progression, and a weak ring deformation band. Four isomers are considered for La2(benzene), and the preferred structure is an inverse sandwich with two La atoms residing on the opposite sides of the benzene ring. The ground electronic state of the inverse sandwich is 1A1g (D3d) with (5dxy,x2-y2 + π*)46s2 electron configuration. Ionization removes a La-based 6s electron and yields a 2A1g ion. The spectrum of La(benzene) is similar to the zero-electron kinetic energy spectrum reported previously by our group, although the spectral line width is somewhat broader. The measurement of the photoelectron angular distribution of La(benzene) confirms that the ejected electron has largely a p wave character. The metal-ligand bonding of La2(benzene) is considerably stronger than that of La(benzene) due to the threefold binding of each La atom in the dilanthanum species and the twofold binding in the monolanthanum complex.

8.
J Chem Phys ; 147(6): 064303, 2017 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-28810759

RESUMO

La atom reactions with 1-butyne and 2-butyne are carried out in a laser-vaporization molecular beam source. Both reactions yield the same La-hydrocarbon products from the dehydrogenation and carbon-carbon bond cleavage and coupling of the butynes. The dehydrogenated species La(C4H4) is characterized with mass-analyzed threshold ionization (MATI) spectroscopy and quantum chemical computations. The MATI spectra of La(C4H4) produced from the two reactions exhibit two identical transitions, each consisting of a strong origin band and several vibrational intervals. The two transitions are assigned to the ionization of two isomers: La(η4-CH2CCCH2) (Iso A) and La(η4-CH2CHCCH) (Iso B). The ground electronic states are 2A1 (C2v) for Iso A and 2A (C1) for Iso B. The ionization of the doublet state of each isomer removes a La 6s-based electron and results in a 1A1 ion of Iso A and a 1A ion of Iso B. The formation of Iso A from 2-butyne and Iso B from 1-butyne involves the addition of La to the C≡C triple bond, the activation of two C(sp3)-H bonds, and concerted elimination of a H2 molecule. The formation of Iso A from 1-butyne and Iso B from 2-butyne involves the isomerization of the two butynes to 1,2-butadiene in addition to the concerted H2 elimination.

9.
J Chem Phys ; 146(7): 074305, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-28228024

RESUMO

La(C3H4) and La(C3H6) are observed from the reaction of laser-vaporized La atoms with propene by photoionization time-of-flight mass spectrometry and characterized by mass-analyzed threshold ionization spectroscopy. Two isomers of La(C3H4) are identified as methyl-lanthanacyclopropene [La(CHCCH3)] (Cs) and lanthanacyclobutene [La(CHCHCH2)] (C1); La(C3H6) is determined to be H-La(η3-allyl) (Cs), a C-H bond inserted species. All three metal-hydrocarbon radicals prefer a doublet ground state with a La 6s-based electron configuration. Ionization of the neutral doublet state of each of these radicals produces a singlet ion state by removing the La-based 6s electron. The threshold ionization allows accurate measurements of the adiabatic ionization energy of the neutral doublet state and metal-ligand and ligand-based vibrational frequencies of the neutral and ionic states. The formation of the three radicals is investigated by density functional theory computations. The inserted species is formed by La inserting into an allylic C-H bond and lanthanacyclopropene by concerted vinylic H2 elimination, whereas lanthanacyclobutene involves both allylic and vinylic dehydrogenations. The inserted species is identified as an intermediate for the formation of lanthanacyclobutene.

10.
J Phys Chem A ; 121(6): 1233-1239, 2017 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-28124565

RESUMO

The reaction between La atoms and 1,3-butadiene is carried out in a laser-vaporization molecular beam source. Metal-hydrocarbon species with formulas La(CnHn) (n = 2, 4, and 6) and La(CmHm+2) (m = 4 and 6) are observed with time-of-flight mass spectrometry and characterized with mass-analyzed threshold ionization spectroscopy. A lanthanum-benzene complex [La(C6H6)] is formed by 1,3-butadiene addition to lanthanacyclopropene [La(C2H2)] followed by molecular hydrogen elimination. Lanthanacyclopropene is an intermediate generated by the primary reaction between La and 1,3-butadiene. Two other intermediates produced by the La + 1,3-butadiene reaction are La[η4-(1-buten-3-yne)] [La(C4H4)] and 1-lanthanacyclopent-3-ene [La(C4H6)]. The La(benzene) complex exhibits distinctive metal-ligand bonding from that of the three intermediates as shown by the adiabatic ionization energies and ground electron configurations.

11.
J Phys Chem A ; 120(26): 4482-9, 2016 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-27322131

RESUMO

La(C2H2) and La(C4H6) are observed from the reaction of laser-vaporized La atoms with ethylene molecules by photoionization time-of-flight mass spectrometry and characterized by mass-analyzed threshold ionization spectroscopy. La(C2H2) is identified as a metallacyclopropene and La(C4H6) as a metallacyclopentene. The three-membered ring is formed by concerted H2 elimination and the five-membered cycle by dehydrogenation and C-C bond coupling. Both metallacycles prefer a doublet ground state with a La 6s-based unpaired electron. Ionization of the neutral doublet state of either complex produces a singlet ion state by removing the La-based electron. The ionization allows accurate measurements of the adiabatic ionization energy of the neutral doublet state and metal-ligand and ligand-based vibrational frequencies of the neutral and ionic states. Although the La atom is in a formal oxidation state of +2, the ionization energies of these metal-hydrocarbon cycles are lower than that of the neutral La atom. Deuteration has a small effect on the ionization energies of the two cyclic radicals but distinctive effects on their vibrational frequencies.

12.
J Am Chem Soc ; 138(8): 2468-71, 2016 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-26875834

RESUMO

We report the first example of metal-mediated acetylene bicyclopentamerization to form naphthalene in the gas phase. The bicyclic aromatic compound was observed in a complex with La. The La(naphthalene) complex was formed by the reaction of laser-ablated La atoms with acetylene molecules in a molecular beam source and was characterized by mass-analyzed threshold ionization spectroscopy. The bicyclo-oligomerization reaction occurs through sequential acetylene additions coupled with dehydrogenation. Three intermediates in the reaction have been identified: lanthanacyclopropene [La(C2H2)], La(cyclobut-1-en-3-yne) [La(C4H2)], and La(benzyne) [(La(C6H4)]. The metal-ligand bonding in the three intermediates is considerably different from that in the La(naphthalene) complex, as suggested by accurately measured adiabatic ionization energies.

13.
J Pharm Sci ; 104(2): 686-97, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25219372

RESUMO

Sorbitol crystallization-induced aggregation of mAbs in the frozen state was evaluated. The effect of protein aggregation resulting from sorbitol crystallization was measured as a function of formulation variables such as protein concentration and pH. Long-term studies were performed on both IgG1 and IgG2 mAbs over the protein concentration range of 0.1-120 mg/mL. Protein aggregation was measured by size-exclusion HPLC (SE-HPLC) and further characterized by capillary-electrophoresis SDS. Sorbitol crystallization was monitored and characterized by subambient differential scanning calorimetry and X-ray diffraction. Aggregation due to sorbitol crystallization is inversely proportional to both protein concentration and formulation pH. At high protein concentrations, sorbitol crystallization was suppressed, and minimal aggregation by SE-HPLC resulted, presumably because of self-stabilization of the mAbs. The glass transition temperature (Tg ') and fragility index measurements were made to assess the influence of molecular mobility on the crystallization of sorbitol. Tg ' increased with increasing protein concentration for both mAbs. The fragility index decreased with increasing protein concentration, suggesting that it is increasingly difficult for sorbitol to crystallize at high protein concentrations.


Assuntos
Anticorpos Monoclonais/química , Congelamento , Sorbitol/química , Animais , Anticorpos Monoclonais/metabolismo , Calorimetria/métodos , Química Farmacêutica , Cristalização , Imunoglobulina G/química , Imunoglobulina G/metabolismo , Agregados Proteicos/fisiologia , Sorbitol/metabolismo
14.
Int J Mol Sci ; 15(12): 21896-912, 2014 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-25464379

RESUMO

We have constructed three bacterial artificial chromosome (BAC) libraries of wheat cultivar Triticum aestivum Wangshuibai, germplasms T. monococcum TA2026 and TA2033. A total of 1,233,792,170,880 and 263,040 clones were picked and arrayed in 384-well plates. On the basis of genome sizes of 16.8 Gb for hexaploid wheat and 5.6 Gb for diploid wheat, the three libraries represented 9.05-, 2.60-, and 3.71-fold coverage of the haploid genomes, respectively. An improved descending pooling system for BAC libraries screening was established. This improved strategy can save 80% of the time and 68% of polymerase chain reaction (PCR) with the same successful rate as the universal 6D pooling strategy.


Assuntos
Cromossomos Artificiais Bacterianos/genética , Biblioteca Gênica , Triticum/genética , DNA de Plantas/genética , Genoma de Planta , Reação em Cadeia da Polimerase
15.
J Exp Bot ; 64(11): 3299-312, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23918966

RESUMO

Rht-B1c, allelic to the DELLA protein-encoding gene Rht-B1a, is a natural mutation documented in common wheat (Triticum aestivum). It confers variation to a number of traits related to cell and plant morphology, seed dormancy, and photosynthesis. The present study was conducted to examine the sequence variations of Rht-B1c and their functional impacts. The results showed that Rht-B1c was partially dominant or co-dominant for plant height, and exhibited an increased dwarfing effect. At the sequence level, Rht-B1c differed from Rht-B1a by one 2kb Veju retrotransposon insertion, three coding region single nucleotide polymorphisms (SNPs), one 197bp insertion, and four SNPs in the 1kb upstream sequence. Haplotype investigations, association analyses, transient expression assays, and expression profiling showed that the Veju insertion was primarily responsible for the extreme dwarfing effect. It was found that the Veju insertion changed processing of the Rht-B1c transcripts and resulted in DELLA motif primary structure disruption. Expression assays showed that Rht-B1c caused reduction of total Rht-1 transcript levels, and up-regulation of GATA-like transcription factors and genes positively regulated by these factors, suggesting that one way in which Rht-1 proteins affect plant growth and development is through GATA-like transcription factor regulation.


Assuntos
Fatores de Transcrição GATA/metabolismo , Proteínas de Plantas/metabolismo , Triticum/metabolismo , Fatores de Transcrição GATA/genética , Haplótipos , Proteínas de Plantas/genética , Polimorfismo de Nucleotídeo Único/genética , Triticum/genética
16.
Eur J Pharm Biopharm ; 85(2): 287-93, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23702275

RESUMO

An increasing number of protein therapies require chronic administration at high doses (>200 mg) by subcutaneous (sc) injection. Due to the injection volume limitation (<1.5 mL) associated with sc administration, high protein concentration formulations at or exceeding 100 mg/mL are required to achieve the dose. Development of a high concentration protein formulation can be challenging due to increased aggregation at higher concentration and/or chemical instability, which necessitates the development of lyophilized formulation for high protein concentration drug products. Unique challenges, such as long reconstitution time for a lyophilized high protein concentration drug product, can limit practical usage and commercial marketability of the product. In this paper, a systematic approach is presented to develop a lyophilized high concentration protein formulation. The focus is on achieving reasonable reconstitution times with multidisciplinary strategies. Many strategies have been shown to provide nominal improvement in reconstitution times, such as adding wetting agents in the diluents, incorporating high annealing steps in the lyophilization cycle and reconstituting under vacuum. The reconstitution strategy of reduced diluent volume, however, has enabled significant decrease in reconstitution time (4-7-fold) of lyophilized high protein concentration formulations.


Assuntos
Proteínas/química , Química Farmacêutica/métodos , Estabilidade de Medicamentos , Liofilização/métodos , Agentes Molhantes/química
17.
Pharm Res ; 30(1): 131-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22907420

RESUMO

PURPOSE: To study the impact of different process conditions and formulation compositions on metastable mannitol forms in protein formulations during lyophilization. METHODS: Mannitol was studied with and without other formulation components. A cryostage was used to mimic the different processing steps during lyophilization. The different mannitol forms were monitored and quantified with an in situ Raman spectroscopic method. In addition, a Raman imaging method was developed to characterize the spatial distribution of mannitol forms in final lyophilization samples from the freeze-drying stage. RESULTS: Amorphous mannitol was observed during fast cooling (10 °C/min) and with the addition of other formulation component. Amorphous mannitol crystallized into mainly δ and hemihydrate forms during annealing at -20 °C. Under vacuum without moisture, dried amorphous mannitol could transform to mainly α form at 45 °C and greater. The transformation mechanism of the hemihydrate mannitol was similar to that of amorphous form. CONCLUSION: Mannitol tends to crystallize into stable crystalline forms by itself, but the addition of lyoprotectant (e.g. sucrose) and protein helps stabilize the metastable forms (hemihydrate and amorphous). The metastable forms are capable of transforming into mixtures of different forms, with heat and moisture being the critical processing factors.


Assuntos
Liofilização , Manitol/química , Cristalização , Liofilização/métodos , Difração de Pó , Proteínas/química , Análise Espectral Raman , Sacarose/química , Difração de Raios X
18.
Pharm Res ; 25(10): 2292-301, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18523875

RESUMO

PURPOSE: To develop a novel multivariate curve resolution (MCR)-based Raman spectroscopic method to characterize and quantify five known mannitol solid-state forms in lyophilized protein formulations. MATERIALS AND METHODS: The multivariate quantitation method was developed based on second derivative Raman spectra of three anhydrous crystalline forms (alpha-, beta-, and delta-mannitol), a hemihydrate and an amorphous mannitol form. The method showed a 5% quantitation limit of mannitol forms in lyophilized model protein formulations. Binary mixtures of beta- and delta-mannitol combined with evaluation of the prediction residue were used for the method validation. X-ray powder diffractometry data was used to confirm the existence of mannitol forms in the sample. RESULTS: The various polymorphic forms of mannitol were characterized and quantified based on the Raman spectra of the existing pure forms, and the results are consistent with the X-ray powder diffraction data. This Raman method has been demonstrated for the application of monitoring and controlling of mannitol polymorphic forms in the lyophilized drug products during formulation and process development. It has implications in monitoring and improving the quality of the drug product. CONCLUSIONS: An MCR-Raman method has been developed for the quantitative determination of five different mannitol polymorphic forms in the presence of sucrose and protein.


Assuntos
Excipientes/química , Manitol/química , Proteínas/química , Análise Espectral Raman , Tecnologia Farmacêutica/métodos , Química Farmacêutica , Cristalografia por Raios X , Liofilização , Difração de Pó
19.
J Pharm Sci ; 95(9): 2077-86, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16850397

RESUMO

Mannitol hydrate is a metastable form produced during lyophilization. It is unstable, and therefore can undergo dehydration to release water to the surrounding environment at room temperature. The analysis of this form is challenging due to its thermodynamic instability. This study describes the development of a fast and non-invasive method to determine the mannitol hydrate and surface water content in a lyophilized product using near-infrared (NIR) spectroscopy. The mannitol hydrate was produced through lyophilization and characterized using XRPD, TGA, and NIR spectroscopy. Quantitative methods for hydrate and surface water were developed for NIR spectra with curve fitting and partial least square (PLS) regression models. The curve fitting method deconvoluted the NIR spectra into hydrate and surface water peaks and generated a calibration model by correlating pure spectra peak area to concentration. The standard error of prediction (SEP) for hydrate and surface water content were 0.65 and 0.40%, respectively. The PLS model developed for the same sample set was better than the curve fitting model; SEP = 0.50% for hydrate water and 0.22% for surface water, respectively. The methods can be used to monitor the formation and stability of mannitol hydrate in mannitol-containing formulations during the lyophilization process.


Assuntos
Manitol/química , Interpretação Estatística de Dados , Liofilização , Modelos Químicos , Soluções Farmacêuticas , Reprodutibilidade dos Testes , Espectroscopia de Luz Próxima ao Infravermelho , Propriedades de Superfície , Termogravimetria , Água/química , Difração de Raios X
20.
J Pharm Sci ; 94(11): 2568-80, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16200560

RESUMO

The effects of milling and compression on the solid-state Maillard reaction between metoclopramide hydrochloride and lactose were investigated. Anhydrous metoclopramide hydrochloride was milled for various times, and then mixed with amorphous lactose. The mixtures were stored at 105 degrees C and 0% RH. The reactivity of metoclopramide hydrochloride towards the Maillard reaction increased with milling time, as the result of increased surface area, formation of amorphous content, and creation of defects. Metoclopramide hydrochloride anhydrate and lactose were mixed and the mixtures were compressed into tablets under pressure varied from 70 to 350 MPa. Both tablets and mixtures were stored at 105 degrees C and 0% RH for 9 days. For all three types of lactose used, spray-dried anhydrous lactose, spray-dried lactose monohydrate, and amorphous lactose, tablets exhibited higher reaction rate toward the Maillard reaction than the powder mixtures. Tablets containing metoclopramide hydrochloride and amorphous lactose prepared at higher pressure showed higher reaction rates than those prepared at lower pressure. This is due to increased contact between reactants and an increased amount of water retained in the tablets.


Assuntos
Antagonistas de Dopamina/química , Excipientes/química , Lactose/química , Metoclopramida/química , Força Compressiva , Composição de Medicamentos , Estabilidade de Medicamentos , Reação de Maillard , Tamanho da Partícula , Pós , Propriedades de Superfície , Comprimidos , Tecnologia Farmacêutica , Fatores de Tempo , Água/química
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