PVP solid dispersions containing Poloxamer 407 or TPGS for the improvement of ursolic acid release

Solid dispersions (SDs) of ursolic acid (UA) were developed using polyvinylpyrrolidone K30 (PVP K30) in combination with non-ionic surfactants, such as D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) or poloxamer 407 (P407) with the aim of enhancing solubility and in vitro release of the UA. SDs were investigated using a 24 full factorial design, subsequently the selected formulations were characterized for water solubility, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), particle diameter, scanning electron microscopy, drug content, physical-chemical stability and in vitro release profile. SDs showed higher UA water-solubility than physical mixtures (PMs), which was attributed by transition of the drug from crystalline to amorphous or molecular state in the SDs, as indicated by XRD and DSC analyses. SD1 (with P407) and SD2 (with TPGS) were chosen for further investigation because they had higher drug load. SD1 proved to be more stable than SD2, revealing that P407 contributed to ensure the stability of the UA. Furthermore, SD1 and SD2 increased UA release by diffusion and swelling-controlled transport, following the Weibull model. Thus, solid dispersions obtained with PVP k-30 and P407 proved to be advantageous to enhance aqueous solubility and stability of UA

Aplicação do Método de Rietveld em caracterização estrutural e nanoestrutural do espinélio 'Ni IND. 1'- 'delta' Co'delta''Fe IND.2''O IND.4' preparado por reação de combustão

Os espinélios têm como sua fórmula unitária geral (A1-iBi)[AiB2-i]O4 (0 =i =1), em que os parênteses são os sítios tetraédricos, os colchetes representam os sítios octaédricos e i é o grau de inversão que representa a distribuição dos cátions na rede cristalográfica. Para i igual a 1 o espinélio é chamado de inverso e tem os cátions distribuídos nos sítios tetraédrico e octaédrico de acordo com a fórmula (B)[AB]O4 e igual a 0 o espinélio é chamado de normal com a fórmula (A)[B2]O4, e para 0 < i < 1 os cátions A e B estão distribuídos entre os dois sítios randomicamente e são chamados de parcialmente invertidos ou mistos. As propriedades desses materiais dependem dos tipos de cátions e do grau de inversão. Neste trabalho utilizamos o processo de combustão, o qual tem sido apresentado como um método eficiente para a produção de partículas nanométricas, para a obtenção do sistema Ni1-d Co d Fe2O4 (d = 0; o; u; ; 1). Os materiais resultantes foram caracterizados usando o método de Rietveld para determinar a distribuição dos cátions nos sítios tetraédrico e octaédrico. Análises de espectroscopia Mössbauer foram utilizadas para corroborar os resultados obtidos pelo Método de Rietveld. A principal variável para promover a síntese de óxidos por reação de combustão e otimizá-la é a razão combustível/oxidante, que foram variadas de 1X (estequiométrica), 1,5X e 2X (dobro) e estabelecida o dobro para o desenvolvimento do trabalho. Observamos também, indicações que a razão combustível/oxidante deve variar para cada estequiometria (d ), e que o Co e Ni ocupam apenas os sítios octaédricos. O método de Rietveld e a luz síncrotron permitiram a determinação da estequiometria em cada composição, e os cálculos de microdeformação mostram a existência de flutuação composicional.The spinels have the general unity formulae (A1-iBi)[AiB2-i]O4 (0 =i =1), where () represents the tetrahedral sites, [ ] represents the octahedral sites and i is the degree of inversion that represents the distribution of cations in the crystal lattice. For i equal to 1 it is the inverted spinel (B)[AB]O4 and i = 0 it is the normal spinel (A)[B2]O4, and for 0 < i < 1 the cations A and B are randomly distributed between the two sites. The properties of these materials depend on the types of cations and the degree of inversion. In this work we use the combustion process, which has been presented as an efficient method for the production of nanometrics particles, for the attainment of the system Ni1-d Co d Fe2O4 (d = 0; o; u; ; 1). The resulting materials were characterized using the Rietveld Method (RM) to determine the cations distribution in the tetrahedral and octahedral sites. Analyses of Mössbauer spectroscopy carried through by E. Miola and H. Rechenberg had been also used to corroborate the results obtained using Rietveld Method. The main variable to promote the oxide synthesis through combustion reaction is the fuel/oxidant ratio that, in this work, varied from stoichiometric (ratio = 1) up to two times (ratio = 2). We observe that the ratio varies from one stoichiometry to another(d ), and that Co and Ni occupy only the octahedral sites. We observe, also, that the procedure is not yet adjusted to get itself homogeneous material, since the materials present particles with very varied sizes and degree of agglomeration. The Rietveld method and the synchrotron light allowed the determination of the stoichiometry for each composition.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Crystal structure of propylthiouracil determined using high-resolution synchrotron X-ray powder diffraction

The crystal structure of propylthiouracil, a drug used in the treatment of hyperthyroidism, was determined by means of high-resolution synchrotron X-ray powder diffraction data. The Rietveld method was employed to refine the structure. This drug crystallizes in an orthorhombic (Pcab) space group, with unit cell parameters a = 28.67338(23) angstrom, b = 11.15287(6) angstrom, c = 10.66821(5) angstrom, V = 3411.59 (4) angstrom(3), Z = 16, Z' = 2, M = 170.23 g mol(-1), rho(calc) = 1.3258(1) g cm(-3). The goodness-of-fit and R-factors were, respectively: chi(2) = 1.599, R-Bragg = 1.57%, R-wp = 8.85% and R-exp = 5.53%. Four hydrogen bonds involving the atoms N(6)-H(12)center dot center dot center dot S(39), N(19)-H(21)center dot center dot center dot O(41), N(27)-H(33)center dot center dot center dot S(18) and N(40)-H (42)center dot center dot center dot O(20) form a network of molecular aggregates in propylthiouracil.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Crystal structure of isotibolone: a major degradation product of tibolone

Isotibolone is frequently found as an impurity in tibolone, a drug used for hormone reposition of post-menopause women, due to some inadequate tibolone synthesis or as a result of degradation during drug storage. The presence of isotibolone impurities should be detected and quantified in active pharmaceutical ingredient products of tibolone before its use in the manufacturing of medicaments. The X-ray powder diffraction technique offers the possibility of quantifying isotibolone amounts at different stages of drug production and storage, from the chemical synthesis to the final formulation. In the course of a study involving the quantitative analysis of isotibolone by X-ray powder diffraction, the authors determined the structure of the title compound using a recently developed approach (A. Gomez and S. Kycia, J. Appl. Crystallogr. 2011, 44, 708-713). The structure is monoclinic, space group P2(1) (4), with unit cell parameters a = 6.80704(7) angstrom, b = 20.73858(18) angstrom, c = 6.44900(6) angstrom, beta = 76.4302(5)degrees, V = 884.980(15) angstrom(3) and two molecules per unit cell (Z = 2). The molecules are hydrogen bonded in the ab plane forming layers that are held together in the crystal by van der Waals interactions along the c-axis.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Synchrotron X-ray powder diffraction data of atorvastatin

X-ray powder diffraction data collected in transmission and high-throughput geometries were used to analyze form I of atorvastatin. The X-ray wavelength of the synchrotron radiation used in this study was determined to be lambda = 1.3771 angstrom. Form I of atorvastatin was found to be triclinic with space 0 group P1 and unit cell parameters a=5.4568(2) angstrom, b=9.8887(4) angstrom, c=30.3091(9) angstrom, alpha=76.801(3)degrees, beta=99.177(5)degrees, gamma=105.318(5)degrees, V=1527.1(1) angstrom(3), Z= 1, and M= 1209.41 g mol(-1) Alternatively, another unit cell dimension can be used to describe the same P1 crystal with a =5.4564(2) angstrom, b=9.8883(4) angstrom, c=29.6555(8) angstrom, alpha=95.745(3)degrees, beta=94.297(5)degrees, gamma= 105.327(5)degrees and V= 1526.8(1) angstrom(3). (C) 2008 International Centre for Diffraction Data. [DOI: 10.1154/1.2996511]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Quantifying Isotibolone in Raw Materials of Tibolone

Tibolone, a synthetic steroid, is used in the treatment of natural or surgical menopause disturbs resultant of estrogenic deficiency. Isotibolone (Δ4-tibolone) is one of the three active metabolic degradation products of tibolone that displays progestagenic effects on carcinoma cell growth and gene regulation. Isotibolone can be present in raw material of tibolone due to some inadequate synthesis or storage. Its presence is necessary to be identified and quantified in active pharmaceutical ingredients (API), before its use in the manufacturing of medicines. After a recent study on the crystal structure determination of isotibolone, quantitative phase analyses of both tibolone and isotibolone in raw materials and tablets became possible to be conducted. X-ray powder diffraction is one recommended tool for this purpose, but it can be highly frustrating due to the extreme peak overlap when conventional laboratory equipments are used. In this work we show that the use of Brazilian Synchrotron Light Source X-ray powder diffraction data and the Rietveld method can be successfully applied to identify and quantify the isotibolone in two samples of tibolone raw materials.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Polimorfismo na produção de medicamentos

Polymorphism can cause quality deviations during the production of medicines and can influence their effectiveness. Therefore, an understanding of this phenomenon and its implications opens a wide field of possibilities to be explored in the pharmaceutical field, including the emergence of new paradigms and tools for the quality assurance of medicines. This paper presents an introduction to basic aspects of the polymorphism phenomenon and its implications for the production and control of medicines, with emphasis on drug polymorphs.O polimorfismo pode ocasionar desvios de qualidade durante o processo produtivo e influenciar o desempenho dos medicamentos. Por isso, o entendimento do fenômeno e suas implicações abre um campo amplo de possibilidades a serem exploradas na área farmacêutica, incluindo o surgimento de novos paradigmas e ferramentas na garantia da qualidade de medicamentos. Este trabalho apresenta uma introdução aos aspectos básicos do fenômeno do polimorfismo e suas implicações na produção e controle de medicamentos, com ênfase no polimorfismo dos fármacos. Palavras-chave: Polimorfismo de fármacos. Caracterização no estado sólido. Cristalografia de policristais. ABSTRACT Polymorphism can cause quality deviations during the production of medicines and can influence their effectiveness. Therefore, an understanding of this phenomenon and its implications opens a wide field of possibilities to be explored in the pharmaceutical field, including the emergence of new paradigms and tools for the quality assurance of medicines. This paper presents an introduction to basic aspects of the polymorphism phenomenon and its implications for the production and control of medicines, with emphasis on drug polymorphs. Keywords: Polymorphism of drugs. Solid State Characterization. Crystallography of Polycrystals

Quantitative Phase Analyses Through The Rietveld Method with X-Ray Powder Diffraction Data of Heat-Treated Carbamazepine Form III

The present work shows that the heated carbamazepine (CBZ) powder form III can be described as purely triclinic form I or a mixture of triclinic form I and monoclinic form III, depending on the resolution of the X-ray diffraction equipment used. Visual identification of the minor phase is possible when high-resolution synchrotron light is used. Quantitative phase analyses of CBZ forms I and III, after thermal treatment, were performed by using both synchrotron and conventional copper rotating anode X-ray powder diffraction data and the Rietveld method. Also, the Rietveld method could be adequately applied to determine the phase percentage in the heated material, even when usual resolution data are acquired. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 2658-2664, 2011Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Effects of artificial aging conditions on yttria-stabilized zirconia implant abutments

© 2016 Editorial Council for the Journal of Prosthetic Dentistry Statement of problem Most ceramic abutments are fabricated from yttria-stabilized tetragonal zirconia (Y-TZP). However, Y-TZP undergoes hydrothermal degradation, a process that is not well understood. Purpose The purpose of this in vitro study was to assess the effects of artificial aging conditions on the fracture load, phase stability, and surface microstructure of a Y-TZP abutment. Material and methods Thirty-two prefabricated Y-TZP abutments were screwed and tightened down to external hexagon implants and divided into 4 groups (n = 8): C, control; MC, mechanical cycling (1×106 cycles; 10 Hz); AUT, autoclaving (134°C; 5 hours; 0.2 MPa); and TC, thermal cycling (104 cycles; 5°/55°C). A single-load-to-fracture test was performed at a crosshead speed of 0.5 mm/min to assess the assembly\u27s resistance to fracture (ISO Norm 14801). X-ray diffraction (XRD) analysis was applied to observe and quantify the tetragonal-monoclinic (t-m) phase transformation. Representative abutments were examined with high-resolution scanning electron microscopy (SEM) to observe the surface characteristics of the abutments. Load-to-fracture test results (N) were compared by ANOVA and Tukey test (α=.05). Results XRD measurements revealed the monoclinic phase in some abutments after each aging condition. All the aging conditions reduced the fracture load significantly (P\u3c.001). Mechanical cycling reduced the fracture load more than autoclaving (P=.034). No differences were found in the process of surface degradation among the groups; however, the SEM detected grinding-induced surface flaws and microcracks. Conclusions The resistance to fracture and the phase stability of Y-TZP implant abutments were susceptible to hydrothermal and mechanical conditions. The surface microstructure of Y-TZP abutments did not change after aging conditions