RESUMO
Various upgrades have been completed at the XRD1 beamline at the Brazilian synchrotron light source (LNLS). The upgrades are comprehensive, with changes to both hardware and software, now allowing users of the beamline to conduct X-ray powder diffraction experiments with faster data acquisition times and improved quality. The main beamline parameters and the results obtained for different standards are presented, showing the beamline ability of performing high-quality experiments in transmission geometry. XRD1 operates in the 5.5-14â keV range and has a photon flux of 7.8 × 109â photonsâ s-1 (with 100â mA) at 12â keV, which is one of the typical working energies. At 8â keV (the other typical working energy) the photon flux at the sample position is 3.4 × 1010â photonsâ s-1 and the energy resolution ΔE/E = 3 × 10-4.
RESUMO
Deflazacort (DFZ), a derivate of prednisolone, is a poorly soluble drug which has been proposed to have major advantages over other corticosteroids. Poorly soluble drugs present limited bioavailability due to their low solubility and dissolution rate and several strategies have been developed in order to find ways to improve them. In general, pharmaceutical laboratories use a micronized process to reduce the particle size in order to increase the dissolution of the drugs. However, this process causes changes such as polymorphic transitions, particle agglomeration and a reduction in fluidity and wettability. These solid-state properties affect the dissolution behavior and stability performance of drugs. Crystallization techniques are widely used in the pharmaceutical industry and antisolvent crystallization has been used to obtain ultrafine particles. In this study, DFZ was investigated in terms of its antisolvent crystallization in different solvents and under various preparation conditions (methanol/water ratio, stirring and evaporation rate, etc.), in order to compare the physicochemical properties between crystallized samples and raw materials available on the Brazilian market with and without micronization. Crystalline structure, morphology, and particle size, and their correlation with the Intrinsic Dissolution Rate (IDR) and dissolution profile as relevant biopharmaceutical properties were studied. Crystallization conditions were achieved which provided crystalline samples of hollow-shaped crystals with internal channels, which increased the dissolution rate of DFZ. The antisolvent crystallization process allowed the formation of hollow crystals, which demonstrated a better dissolution profile than the raw material (crystalline and micronized), making this a promising technique as a crystallization strategy for improving the dissolution and thus the bioavailability of poorly soluble drugs.
Assuntos
Anti-Inflamatórios/química , Pregnenodionas/química , Química Farmacêutica/métodos , Cristalização , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Solubilidade , Difração de Raios XRESUMO
A new polymorphic form of ciprofloxacin saccharinate (CIP-SAC II) is presented, and compared with CIP-SAC I, a different polymorph which we had previously reported. The characterization techniques used were single crystal and powder X-ray diffraction, differential scanning calorimetry, thermogravimetry analysis and infrared and (13)C solid-state nuclear magnetic resonance spectroscopy. The results obtained from these techniques are consistent. Differential scanning calorimetry and thermogravimetric analysis showed that the reaction between the precursors is completed and the crystalline forms of both salts obtained (I and II) are highly pure. Infrared spectroscopy gave clear evidence of a salt formation. Solid-state nuclear magnetic resonance spectroscopy would indicate some degree of qualitative similarity in the intermolecular interaction scheme in both polymorphs, while thermal analysis data might indicate a difference in quantitative terms. A thorough single crystal structure determination of the new form CIP-SAC II allowed disclosing the most important inter- and intramolecular interactions.
Assuntos
Ciprofloxacina/química , Cristalização/métodos , Sacarina/química , Ciprofloxacina/síntese química , Cristalografia/métodos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Termogravimetria/métodosRESUMO
Latex, a polyisoprene (PI) hydrophobic elastomer, was evaluated in vitro and in vivo as a matrix for intravaginal steroid hormone delivery. Matrices containing hormone were prepared by swelling latex in chloroform that contained soluble progesterone (P4). In vitro studies demonstrate that P4 release from PI follows a zero order model during at least 100 h and depends on initial load up to 10 mg cm(-2). The release of P4 from a PI matrix was found to be two times faster than from a polydimethylsiloxane (PDMS) matrix. FT-IR and X-ray powder diffraction analysis of P4 polymorphs show that when nucleated in PDMS, the hormone crystallizes only in alpha-form while in latex, crystallizes as a mixture of alpha- and beta-form. In vivo studies show that devices with a PI matrix containing 0.5 g of P4 are effective to reach plasma levels above 1 ng ml(-1) that are needed to synchronize estrous in cattle. Altogether, the results show that PI, a vulcanized polymer with a carbon-carbon backbone, can be used as a new matrix for the intravaginal administration of progesterone with improved release profile than silicone and that the matrix can influence the crystalline state of the hormone.
Assuntos
Portadores de Fármacos , Fármacos para a Fertilidade Feminina/administração & dosagem , Látex/química , Progesterona/administração & dosagem , Administração Intravaginal , Animais , Bovinos , Química Farmacêutica , Cristalização , Cristalografia por Raios X , Dimetilpolisiloxanos/química , Composição de Medicamentos , Sincronização do Estro/efeitos dos fármacos , Feminino , Fármacos para a Fertilidade Feminina/sangue , Fármacos para a Fertilidade Feminina/química , Fármacos para a Fertilidade Feminina/farmacocinética , Ovariectomia , Difração de Pó , Progesterona/sangue , Progesterona/química , Progesterona/farmacocinética , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Tecnologia Farmacêutica/métodosRESUMO
Solid-state physical characterization of a pharmaceutical substance is necessary for successful development and approval of the final product. Different physical analytical techniques are available to do so: X-ray diffraction (XRD), IR, Raman, DSC, TG and NMR. Moreover, all of them detect the presence of excipients perturbing the analysis of the pure substance in low doses. In order to study polymorphism and pseudo polymorphism of drug, this paper introduces possible applications of pure nuclear quadrupole resonance, as a non-destructive technique in qualitative and quantitative approaches. Chlorpropamide and diclofenac sodium were used as examples. Unlike the mentioned techniques, the nuclear quadrupole resonance (NQR) signal of pharmaceutical compounds is not perturbed by the presence of solid excipient or other substances unless they possess resonance frequencies in the same frequency range of the compound studied.