Biodegradable microparticulate drug delivery system of diltiazem HCl

The efficacy of a drug in a specific application requires the maintenance of appropriate drug blood level concentration during a prolonged period of time. Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development. The objective of this work is to prepare and evaluate diltiazem HCl loaded albumin microparticles using a factorial design. Albumin (natural polymer) microparticles were prepared by emulsion heat-stabilization method. Selected formulations were characterized for their entrapment efficiency, particle size, surface morphology, and release behavior. Analysis of variance for entrapment efficiency indicates that entrapment efficiency is best fitted to a response surface linear model. Surface morphology was studied by scanning electron microscopy. Scanning electron microscopy of the microparticles revealed a spherical, nonporous and uniform appearance, with a smooth surface. The geometric mean diameter of the microparticles was found to be 2-9 µm, which more than 75% were below 3.5 µm and drug incorporation efficiency of 59.74 to 72.48% (w/w). In vitro release profile for formulations containing diltiazem HCl loaded BSA microparticles with heat stabilization technique shows slow controlled the release of the drug up to 24 hours. The release pattern was biphasic, characterized by an initial burst effect followed by a slow release. All selected microparticles exhibited a prolonged release for almost 24 hours. On comparing regression-coefficient (r²) values for Hixson Crowel, Higuchi and Peppas kinetic models, different batches of microparticles showed Fickian, non-Fickian, and diffusion kinetics. The release mechanism was regulated by D:P ratio. From the statistical analysis it was observed that as the drug:polymer (D:P) ratio increased, there was a significant increase in the encapsulation efficiency. Based on the particle size, entrapment efficiency and physical appearance, DTM-3 formulations were selected for in vivo release study and stability study. The in vivo result of drug loaded microparticles showed preferential drug targeting to liver followed by lungs, kidneys and spleen. Stability studies showed that maximum drug content and closest in vitro release to initial data were found in the formulation stored at 4 ºC. In present study, diltiazem HCl loaded BSA microparticles were prepared and targeted to various organs to satisfactory level and were found to be stable at 4 ºC.A eficácia terapêutica de um fármaco depende da manutenção de seu nível plasmático adequado em determinado intervalo de tempo. Nesse sentido, a liberação modificada de fármacos está disponível em muitas vias de administração e oferece muitas vantagens (como micropartículas e nanopartículas) quando comparada às formulações de liberação imediata. Essas vantagens incluem reduzida frequência da dosagem, melhor controle terapêutico e menos efeitos colaterais. Assim sendo, esses produtos apresentam maior aceitação pelos pacientes. Os avanços na ciência dos materiais, na engenharia das partículas, em manufatura e em nanotecnologia permitiram a introdução no mercado de vários produtos de liberação modificada e vários outros se encontram em desenvolvimento pré-clínico e clínico. O objetivo do presente trabalho foi preparar e avaliar o fármaco cloridrato de diltiazem associado a micropartículas de albumina utilizando planejamento fatorial. As micropartículas de albumina, um polímero natural, foram preparadas por método de emulsão empregando estabilização por calor. As formulações selecionadas foram caracterizadas no que se refere à sua eficiência de encapsulamento, tamanho médio de partículas, morfologia de superfície e perfil de liberação do fármaco. A análise de variância relativa à eficiência de encapsulamento indicou superfície de resposta linear. Com referência à morfologia superficial, essa foi avaliada empregando microscopia eletrônica de varredura. Essa análise revelou micropartículas esféricas, não porosas e de aparência uniforme, com superfície lisa. O diâmetro médio das micropartículas foi entre 2 e 9 µm, sendo que mais de 75% das micropartículas se apresentaram abaixo de 3,5 µm. Além disso, a eficiência de encapsulamento foi entre 59,74 e 72,48%. Quanto ao ensaio para avaliação do perfil de liberação in vitro do fármaco associado às micropartículas, as formulações apresentaram liberação lenta até 24 horas. O comportamento foi caracterizado por liberação inicial (efeito burst) seguida por liberação lenta. Todas as fórmulas selecionadas apresentaram liberação prolongada por aproximadamente 24 horas. Na comparação entre os valores de coeficientes de regressão (R²), os modelos propostos por Hixson Crowel, Higuchi e Peppas, para diferentes formulações de micropartículas, demonstraram cinética de liberação de acordo com modelo Fickiano e não-Fickiano. O mecanismo de liberação do fármaco foi regulado pela razão entre o fármaco e o polímero. A análise estatística revelou significativo aumento da eficiência de encapsulamento quando essa razão aumentou. As avaliações relativas à análise dimensional das micropartículas, à eficiência de encapsulamento do fármaco e à morfologia permitiram a seleção da formulação DTM-3 para os ensaios de liberação in vivo e para o estudo da estabilidade. O ensaio de liberação in vivo do fármaco associado às micropartículas demonstrou sítio-alvo preferencial no fígado, seguido pelos pulmões rins e baço. No presente estudo, as micropartículas de albumina contendo cloridrato de diltiazem foram adequadamente preparadas e orientadas satisfatoriamente para vários órgãos. Além disso, a formulação selecionada apresentou estabilidade físico-química a 4 ºC

CRYSTAL FIELD AND MAGNETIC PROPERTIES OF Dy(OH)

The electric quadrupole and magnetic hyperfine interactions rneasured from the 161Dy Mössbauer resonance in crystalline Dy(OH)3 and from the 166Er resonance in crystalline Ho(OH)3 and Er(OH)3 are interpreted using the crystal field and molecular exchange field model . The crystal field parameters established from previous optical spectroscopy results account weIl for these hyperfine parameters. The crystal-field and magnetic properties of these ferromagnetic insulators are described weIl within the model

SPIN RELAXATION AND BREIT-RABI SPECTRA OF CUBIC Yb SALT

Le spectre Mössbauer de 170Yb dans le composé cubique Cs2NaYbCl6 a été mesuré en fonction de la température et d'un champ magnétique externe. Le spectre hyperfin du niveau fondamental Ɖ6 est fortement influencé par de faibles champs magnétiques. Les détails sont décrits par un diagramme de Breit-Rabi. La fréquence de relaxation de spin de Yb3+ dépend du champ externe mais est indépendante de la température jusqu'à 20 K.The Mössbauer spectrum of 170Yb in cubic Cs2NaYbCl6 has been measured as a function of temperature and external field. The hyperfine spectrum due to Ɖ6 CEF level, which is the ground state in this compound, is strongly influenced by small magnetic fields. The details are described using a Breit-Rabi diagram. The spin relaxation time of Yb3+ is strongly dependent on the external field but is independent of temperature up to 20 K

MÖSSBAUER RESONANCE IN 240Pu

L ' effet Mössbauer a été observé pour la transition de 42.9keV du 240Pu. Avec une source de 244 CmO2 et un absorbant de PuO2 à 4,2K ou à 77K on a trouvé une raie de résonance unique et légèrement élargie. Le composé de plutonyl (VI) puO2C2O4 présente une intéraction quadrupolaire |e2qQ| = 95m/s. Aucun déplacement isométrique n'a été detecté.The Mössbauer resonance of the 42.9keV transition in 240Pu has been observed. For a 244CmO2 source and a PuO2 absorber at 4.2K and 77K a slightly broadened single resonance was found. The plutony (VI) compound PuO2C2O4 showed a quadrupole splitting of |e2qQ | = 95mm/s. No isomer shifts could be detected

ELECTRONIC PROPERTIES OF Er3+ IN ErRh4B4

La configuration électronique de Er3+ le supraconducteur ternaire ErRh4B4 a été étudiée par spectroscopie Mössbauer de 166Ere. Le niveau fondamental de champ cristallin est un doublet comportant une contribution d'environ 90 % de la configuration |Jz = ± 15/2>. Le moment de l'ion Er est 8,1 ± 0,3 µB. Les effets de relaxation paramagnétique observés aux basses températures suggèrent la présence d'autres niveaux de champ cristallin à des énergies faibles.The electronic state of Er3+ in the ternary superconductor ErRh4B4 has been investigated using the Mossbauer effect in 166Er. The crystal field ground state is found to be a doublet, about 90 % of which is the state |Jz = ± 15/2>. The moment on the Er ion is 8.1 ± 0.3 µB. Effects of the paramagnetic relaxation at low temperatures indicate the presence of other low lying crystal-field levels

MÖSSBAUER STUDIES OF DILUTE ERBIUM IMPURITIES IN ZIRCONIUM HYDRIDES

On présente les spectres hyperfins d'impuretés d'erbium diluées dans le composé δ-ZrH1,5 de structure fluorine et ε-ZrH1,85 de structure fluorine avec une distorsion tetragonale. Les spectres hyperfins sont identiques dans les deux cas et révèlent un environnement cubique de l'ion Er, indépendemment de la structure cristallographique de la matrice ; ce fait révèle la formation d'un agrégat cubique Er-hydrogène. Les fréquences de relaxation paramagnétique sont également identiques dans les deux cas, malgré les modifications importantes des densités d'état électronique. Les mécanismes de formation de tels agrégats Er-hydrogène sont discutés.Hyperfine spectra are reported for Er present as a dilute impurity in the fluorite structure compound δ-ZrH1.5 and the tetragonally distorted fluorite ε-ZrH1.85. In both cases, the hyperfine spectra are identical and show cubic symmetry around the Er ion regardless of the host crystal structure, showing the formation of a locally cubic Er-hydrogen cluster. Paramagnetic relaxation frequencies are also identical in the two phases, in spite of large changes in the electronic density of states. Mechanisms for the formation of such Er-hydrogen clusters are discussed

VALENCE CHANGE OF EUROPIUM ATOMS DUE TO COLD-WORKING OF MgEu ALLOYS

On a réalisé une étude d'alliages de Mg contenant 50 à 6 300 ppm d'Eu. Les données de spectroscopie Mössbauer de 151Eu, de susceptibilité magnétique et de microscopie électronique à balayage montrent que ce système ne consiste pas en une solution solide mais que Eu précipite dans deux phases eutectiques. Tandis qu'en l'absence de contrainte les ions Eu sont dans l'état divalent à toute température, un laminage à froid induit une conversion à l'état trivalent d'une fraction élevée des ions. Des mesures de recuit isochrone montrent que l'état divalent est rétabli pour des températures de recuit supérieures à environ 450 °C . Les résultats sont discutés en invoquant la formation et le piégeage de défauts en ligne ainsi que leur recuit ultérieur.An investigation has been made of alloys of 50 to 6 300 ppm Eu in Mg. Data obtained by the use of the Mössbauer spectroscopy of 151Eu, magnetic susceptibility and scanning electron microscopy show that solid solutions do not form in this system, but that the Eu precipitates into two eutectic intermetallics. While the Eu ions are in a divalent state at all temperatures for strain-free samples, introduction of cold-work causes a large fraction of the ions to convert to the trivalent state. Isochronal annealing measurements show that the divalent state is recovered at annealing temperatures above ~ 450 C. Those results are discussed in terms of the formation and trapping of line defects and their subsequent annealing