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A fatal hereditary condition, cystic fibrosis (CF) causes severe lung problems. Ibuprofen (IBU), a non-steroidal anti-inflammatory drug, slows the progression of disease without causing significant side effects. Considering the poor water-solubility of the drug, IBU nanoparticles are beneficial for local pulmonary administration. We aimed to formulate a carrier-free dry powder inhaler containing nanosized IBU. We combined high-performance ultra-sonication and nano spray-drying. IBU was dissolved in ethyl acetate; after that, it was sonicated into a polyvinyl alcohol solution, where it precipitated as nanoparticles. Mannitol and leucine were added when producing dry particles using nano-spray drying. The following investigations were implemented: dynamic light scattering, laser diffraction, surface tension measurement, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, in vitro dissolution test, and in vitro aerodynamic assessment (Andersen Cascade Impactor). The particle diameter of the IBU was in the nano range. The spray-dried particles showed a spherical morphology. The drug release was rapid in artificial lung media. The products represented large fine particle fractions and proper aerodynamic diameters. We successfully created an inhalable powder, containing nano-sized IBU. Along with the exceptional aerodynamic performance, the ideal particle size, shape, and drug-release profile might offer a ground-breaking local therapy for CF. [ABSTRACT FROM AUTHOR]

A high energy input during pharmaceutical formulation is capable of decreasing the crystallinity of compounds in the product. The presence of the amorphous form can cause serious problems at any stage of the formulation. Crystallinity changes of a model powder mixture containing clopidogrel bisulfate (CLP) and a colloidal silicon dioxide as additive were investigated during a long-time co-grinding process. The crystallinity of CLP was reduced sigmoidally by co-grinding with longer co-grinding time. X-ray powder diffraction and differential scanning calorimetry examinations confirmed that the product had become totally amorphous after four hours of grinding. Thermogravimetric results proved that no major mass reduction happened and FT-IR changes referred to formulation of a secondary bond between the components. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine quantitatively the crystallinity in crystalline/amorphous powder mixtures of lactose, to asses the capability of Near Infrared Spectroscopy (NIRS) for quantitative determination of crystallinity and to compare the accuracy of the NIRS method with that of conventional X-ray powder diffraction (XRPD). Amorphous lactose was prepared by spray drying. Samples with different crystallinity were prepared by physical mixing of 100% amorphous and 100% crystalline materials. The samples were characterized by XRPD and NIRS. Analysis was performed on the data sets by multiple linear regression (MLR). There is a close correlation between the predicted and the actual crystallinity of physical mixtures of crystalline and amorphous lactose, determined by NIRS (R2=0.9994). NIRS results were compared to the XRPD using the same sample sets. The correlation coefficients was 0.9981. The results showed that NIRS is an useful method for accurately determining low quantities of the crystalline lactose in a physical mixture. Therefore, NIRS can be used for the quantitative determination of crystallinity of materials during pharmaceutical procedures. [Copyright &y& Elsevier]

Abstract Dry Powder Inhaler (DPI) could offer a propellant-free, easy-to-use powder form ensuring better stability than liquid dosage forms. Therefore the development of traditional carrier-based and carrier-free new generation systems is a determinative factor in the field of DPI formulation. The purpose of our research work was to combine these two systems, utilizing their beneficial properties to produce a novel pulmonary drug delivery system containing ciprofloxacin hydrochloride (CIP). Co-spray drying, surface smoothing and the preparation of an interactive physical mixture were applied as the technological procedures of sample preparation. The carrier-based and carrier-free formulations, as well as the developed novel product were compared to each other. Structural investigations were made by X-ray powder diffraction and micrometric properties (habit, bulk density) were determined. Particle interactions were also evaluated to investigate surface free energy, cohesive-adhesive forces, and spreading coefficient. In vitro aerodynamic properties (mass median aerodynamic diameter), fine particle fraction (FPF) and emitted dose of DPIs were measured using Andersen Cascade Impactor. A novel in silico Stochastic Lung Model was also used to quantify the amount of particles deposited at the target area. The novel-formulated composition presented amorphous spherical particles with an average size of about 2 μm. The in vitro aerodynamic investigations showed a variance in FPF as a function of formulation method (carrier-based: 24%, carrier-free: 54% and applying the novel combination method: 63%). The in silico deposition results were in line with the in vitro measurements and yielded increased lung doses for the sample prepared by the combined technology. This novel DPI formulation provides an opportunity for a more effective therapy with deeper deposition of CIP. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

The aim of this work was an investigation of the physical changes of the amorphous model material spray-dried trehalose through the use of various analytical techniques and to identify a suitable, rapid method able to quantify the changes. The crystallinity changes and recrystallization process of amorphous samples were investigated by hot-humidity stage X-ray powder diffractometry (HH-XRPD) with fresh samples, conventional X-ray powder diffractometry (XRPD) used stored samples and by differential scanning calorimetry (DSC). The data from the three methods were compared and the various forms of trehalose were analysed. HH-XRPD demonstrated that the recrystallization began at 40 and 60 °C up to 45% RH and at 70 °C up to 30% RH into dihydrate form. At 70 °C up to 60% RH the anhydrous form of trehalose appeared too. Conventional XRPD results showed, that in the 28 days stored samples the dihydrate form was detected at 40 °C, 50% RH. Storage at 60 °C, 40% RH resulted in the appearance of the anhydrous form and at 60 °C, 50% RH both polymorphic forms were detected. By carrying out the DSC measurements at different temperatures the fraction of recrystallized trehalose dihydrate was detected. The recrystallization investigated by HH-XRPD and DSC followed Avrami kinetics, the calculated rate constants of isothermal crystallization ( K ) were same. Both HH-XRPD and conventional XRPD was suitable for the detection of the physical changes of the amorphous model material. DSC measurements showed similar results as HH-XRPD. Primarily HH-XRPD could be suggested for prediction, because the method is fast and every changes could be studied on one sample. [ABSTRACT FROM AUTHOR]

The use of dry powder formulations presents an alternative through which to achieve better deposition and residence time in the nasal cavity, increased stability and possible absorption enhancement. The most important factors involved in the preformulation are particle size and physical stability. Propranolol hydrochloride a model drug was subjected to spray-drying technology to form an intranasal dry powder. Particle size reduction of the drug was carried out by integration (spray-drying) methods, using different excipients. The micrometric properties were characterized by size and morphology. The structure was determined through the use of differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy investigations. It was concluded that the intranasal dry powder formulation of propranolol hydrochloride can be achieved with a suitable particle size without polymorph modification or chemical decomposition. [ABSTRACT FROM AUTHOR]

Abstract: Sucrose esters (SEs) have a wide range of hydrophilic–lipophilic balance (HLB) values (1–16), and hence can be applied as surfactants, or as solubility or penetration enhancers. In general, SEs are used in hot-melt technology, because of their low melting points, but literature data are not available on the effects of active agents on the structures of SEs and the possible solid-state interactions. In this study, drug–SE products were prepared by melt technology and investigated by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), rheological measurements and dissolution tests. The model drugs meloxicam and diclofenac sodium and three SEs with different polarities (P1670, S970 and B370) were chosen for the preparation of the products. The DSC and XRPD results revealed that the structures of the SEs were rearranged, with a decrease in the degree of crystallinity. The dissolved drug molecules broke down the structures of the SEs, but were not built into the crystalline phase of the carrier. The dissolution of the drugs was influenced by the different HLB values and gel-forming behaviour of the SEs, and also by the polarity of the drug and the interactions between the drug and the SEs. [Copyright &y& Elsevier]

Abstract: Sugar esters (SEs) are widely used in the pharmaceutical and food industries. They have a wide range of HLB values (1–16), and hence they can be applied as surfactants, or as solubility or penetration enhancers. SEs can be employed in hot-melt technology, because their melting points are low and they decompose only above 220°C. The aims of this work were to study the thermal properties of SEs and to demonstrate differences between SEs with various HLB values. The results revealed that SEs with high or medium HLB values were vitrified by melting. Their glass transitions (T g) were determined by modulated differential scanning calorimetry. To visualize the changes in the samples during heating, hot-stage microscopy was used. Hydrophilic SEs were only softened, while lipophilic SEs were melted by heating. After melting and solidification, SEs have partially amorphous layered structures which slowly crystallize in time. Time-dependent solid-state changes (crystalline and amorphous phases) were observed, and analysed by means of differential scanning calorimetry and X-ray powder diffraction. [Copyright &y& Elsevier]

Abstract: In this study, the influence of microwave irradiation on some physico-chemical properties and several pharmaceutical technological parameters of potato and maize starches was investigated. Changes in their habits were observed and decrease in moisture contents caused by the electromagnetic irradiation was determined. The crystalline structures and the micromorphological parameters of the starches were affected by microwave irradiation in different ways depending on the botanical origin of the samples. The tensile strengths of the compacts containing starches were decreased, their wetting properties were enhanced by the thermal process applied. Furthermore, microwave irradiation reduced the surface free energy and the polarity of the compacts significantly. Samples treated by conventional heating were used to compare the effects of microwave irradiation on the examined properties and parameters of these starches. [Copyright &y& Elsevier]