Effects of magnesium stearate on the efficient dispersion of salbutamol sulphate from carrier-based dry powder inhaler formulations

Dry powder inhaler (DPI) formulations is one of the most useful aerosol preparations in which drugs may be formulated as carrier-based interactive mixtures with micronised drug particles (<5 μm) adhered onto the surface of large inert carriers (lactose powders). The addition of magnesium stearate (MgSt) (1-3), was found to increase dispersion of various drugs from DPI formulations. Recently, some active compounds coated with 5% (wt/wt) MgSt using the mechanofusion method showed significant improvements in aerosolization behavior due to the reduction in intrinsic cohesion force (4). Application of MgSt in powder formulations is not new; however, no studies demonstrated the minimum threshold level for this excipient in efficient aerosolization of drug powders from the interactive mixtures. Therefore, this study investigated the role of MgSt concentration on the efficient dispersion of salbutamol sulphate (SS) from DPI formulations.

Mixed saturated-unsaturated alkyl-chain assemblies: Solid solutions of zinc stearate and zinc oleate

The linear saturated stearic acid and the bent mono-unsaturated oleic acid do not mix and form solid solutions. However, the zinc salts of these acids can. From X-ray diffraction and DSC measurements we show that the layered zinc stearate and zinc oleate salts form a homogeneous solid solution at all composition ratios. The solid solutions exhibit a single melting endotherm, with the melting temperature varying linearly with composition but with the enthalpy change showing a minimum. By monitoring features in the infrared spectra that are characteristic of the global conformation of the hydrocarbon chain, and hence can distinguish between stearate and oleate chains, it is shown that solid solution formation is realized by the introduction of gauche defects in a fraction of the stearate chains that are then no longer linear. This fraction increases with oleate concentration. It has also been possible from the spectroscopic measurements to establish a quantitative relation between molecular conformational order and the thermodynamic enthalpy of melting of the solid solutions.

Micellar size and shape in solutions of calcium stearate in cetane from optical depolarization data

Observations at a series of temperatures of the changes in viscosities and depolarization factors of 1% and 18% solutions of calcium stearate in cetane to which varying amounts of water have been added can be interpreted in terms of the existence of anisometric micelles. In general, changes in the size of the micelles inferred from values of ρh agree with those deduced from the viscosity data. The correlation between anisometry of micelles from rheological and optical observations is much poorer in the case of ρν, presumably because of the difficulty in differentiating the contribution of anisometry and anisotropy to ρν.

The subsidence rates of suspensions of lithium stearate in n-heptane with n-alcohols as additives

Suspensions of lithium stearate in n-heptane are highly unstable, undergoing gelation even at concentrations as low as 1 g./1. The rate of subsidence of these weakly gelled suspensions is decreased at first by the addition of n-alcohols, but passes through a minimum in some cases. The minimum subsidence rate occurs while the adsorption of the alcohol is still below its saturation value. One possible explanation of the effect is that the solvent layer between particles at the junction points in the gel becomes simultaneously more polar, tending toward an increased gel strength, and also thicker, tending toward a decreased gel strength.

Compatibility and decomposition kinetics studies of prednicarbate alone and associated with glyceryl stearate

In this work, TG/DTG and DSC techniques were used to the determination of thermal behavior of prednicarbate alone and associated with glyceryl stearate excipient ( 1: 1 physical mixture). TG/DTG curves obtained for the binary mixture showed a reduction of approximately 37 degrees C to the thermal stability of drug (T(dm/dt-0) (Max)(DTG)). The disappearance of stretching band at 1280 cm(-1) (nu(as) C-O, carbonate group) and the presence of streching band with less intensity at 1750 cm(-1) (nu(s) C-O, ester group) in IR spectrum obtained to the binary mixture submitted at 220 degrees C, when compared with IR spectrum of drug submitted to the same temperature, confirmed the chemical interaction between these substances due to heating. Kinetics parameters of decomposition reaction of prednicarbate were obtained using isothermal (Arrhenius equation) and non-isothermal (Ozawa) methods. The reduction of approximately 45% of activation energy value (E(a)) to the first step of thermal decomposition reaction of drug in the 1:1 (mass/mass) physical mixture was observed by both kinetics methods.

BaTiO3 obtained through metallic stearate precursors

Metallic stearates were used as precursors to obtain BaTiO3. Barium and titanium stearate mixtures were homogenized in ball mill containing some amount of ammonium stearate. The mixture of the precursors was evaluated by simultaneous TG/ DTA and TMA, and residues from thermal decomposition were characterized by XRD and SEM. It could be verified that the residues from the thermal decomposition in both oxidant and inert atmospheres were the BaTiO3 but with characteristic morphological and crystalline aspects depending on the experimental conditions in which the mixtures of precursors were obtained. (C) 2002 Elsevier B.V. B.V. All rights reserved.

Polycaprolactone microspheres as carriers for dry powder inhalers : effect of surface coating on aerosolization of salbutamol sulfate

This study reports the factors controlling aerosolization of salbutamol sulfate (SS) from mixtures with polycaprolactone (PCL) microspheres fabricated using an emulsion technique with polyvinyl alcohol (PVA) as stabilizer. The fine particle fraction (FPF) of SS from PCL measured by a twin-stage impinger was unexpectedly found to be zero, although scanning electron microscopy showed that the drug coated the entire microsphere. Precoating the microspheres with magnesium stearate (MgSt) excipient solutions (1%–2%) significantly increased (p < 0.05, n = 5) the FPF of SS (11.4%–15.4%), whereas precoating with leucine had a similar effect (FPF = 11.3 ± 1.1%), but was independent of the solution concentration. The force of adhesion (by atomic force microscopy) between the PCL microspheres and SS was reduced from 301.4 ± 21.7 nN to 110.9 ± 30.5 nN and 121.8 ± 24.6 nN, (p < 0.05, n = 5) for 1% and 2% MgSt solutions, respectively, and to 148.1 ± 21.0 nN when coated with leucine. The presence of PVA on the PCL microspheres (detected by X-ray photoelectron spectroscopy) affected the detachment of SS due to strong adhesion between the two, presumably due to capillary forces acting between them. Precoating the microspheres with excipients increased the FPF significantly by reducing the drug–carrier adhesion. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:733–745, 2012

Studies on the effect of the size of polycaprolactone microspheres for the dispersion of Salbutamol Sulfate from dry powder inhaler formulations

Purpose: To study the effect of the size of the surface-coated polycaprolactone (PCL) microparticle carriers on the aerosolization and dispersion of Salbutamol Sulfate (SS) from Dry Powder Inhaler (DPI) formulations. Methods: The microparticles were fabricated using an emulsion technique in four different sizes (25, 48, 104 and 150 μm) and later coated with Magnesium stearate (MgSt) and leucine. They were characterized by laser diffraction and SEM. The Fine Particle Fraction (FPF) of SS from powder mixtures was determined by a Twin Stage Impinger (TSI). Results: As the carrier size increased from 25 μm to 150 μm, the FPF of the SS delivered by the coated PCL particles increased approximately four fold. A linear relationship was found between the FPF and Volume mean Diameter (VMD) of the particles over this range. Conclusions: The dispersion behaviour of SS from PCL carriers was dependent on the inherent size of the carriers and the increased FPF of SS with increased carrier size probably reflects the higher mechanical forces produced due to the carrier-carrier collisions or collisions between the carrier particles and the internal walls of the inhaler during aerosolization.

Studies on the surface properties of biodegradable polymer carriers in respiratory delivery of drug from Dry Powder Inhaler formulations

Dry Powder Inhaler (DPI) technology has a significant impact in the treatment of various respiratory disorders. DPI formulations consist of a micronized drug (<5ìm) blended with an inert coarse carrier, for which lactose is widely used to date. DPIs are one of the inhalation devices which are used to target the delivery of drugs to the lungs. Drug delivery via DPI formulations is influenced by the physico-chemical characteristics of lactose particles such as size, shape, surface roughness and adhesional forces. Commercially available DPI formulations, which utilise lactose as the carrier, are not efficient in delivering drug to the lungs. The reasons for this are the surface morphology, adhesional properties and surface roughness of lactose. Despite several attempts to modify lactose, the maximum efficient drug delivery to the lungs remains limited; hence, exploring suitable alternative carriers for DPIs is of paramount importance. Therefore, the objective of the project was to study the performance of spherical polymer microparticles as drug carriers and the factors controlling their performance. This study aimed to use biodegradable polymer microspheres as alternative carriers to lactose in DPIs for achieving efficient drug delivery into the lungs. This project focused on fabricating biodegradable polymer microparticles with reproducible surface morphology and particle shape. The surface characteristics of polymeric carriers and the adhesional forces between the drug and carrier particles were investigated in order to gain a better understanding of their influence on drug dispersion. For this purpose, two biodegradable polymers- polycaprolactone (PCL) and poly (DL-lactide-co-glycolide) (PLGA) were used as the carriers to deliver the anti-asthmatic drug - Salbutamol Sulphate (SS). The first study conducted for this dissertation was the aerosolization of SS from mixtures of SS and PCL or PLGA microparticles. The microparticles were fabricated using an emulsion technique and were characterized by laser diffraction for particle size analysis, Scanning Electron Microscopy (SEM) for surface morphology and X-ray Photoelectron Spectroscopy (XPS) to obtain surface elemental composition. The dispersion of the drug from the DPI formulations was determined by using a Twin Stage Impinger (TSI). The Fine particle Fraction (FPF) of SS from powder mixtures was analyzed by High Performance Liquid Chromatography (HPLC). It was found that the drug did not detach from the surface of PCL microspheres. To overcome this, the microspheres were coated with anti-adherent agents such as magnesium stearate and leucine to improve the dispersion of the drug from the carrier surfaces. It was found that coating the PCL microspheres helped in significantly improving the FPF of SS from the PCL surface. These results were in contrast to the PLGA microspheres which readily allowed detachment of the SS from their surface. However, coating PLGA microspheres with antiadherent agents did not further improve the detachment of the drug from the surface. Thus, the first part of the study demonstrated that the surface-coated PCL microspheres and PLGA microspheres can be potential alternatives to lactose as carriers in DPI formulations; however, there was no significant improvement in the FPF of the drug. The second part of the research studied the influence of the size of the microspheres on the FPF of the drug. For this purpose, four different sizes (25 ìm, 48 ìm, 100 ìm and 150 ìm) of the PCL and PLGA microspheres were fabricated and characterized. The dispersion of the drug from microspheres of different sizes was determined. It was found that as the size of the carrier increased there was a significant increase in the FPF of SS. This study suggested that the size of the carrier plays an important role in the dispersion of the drug from the carrier surface. Subsequent experiments in the third part of the dissertation studied the surface properties of the polymeric carrier. The adhesion forces existing between the drug particle and the polymer surfaces, and the surface roughness of the carriers were quantified using Atomic Force Microscopy (AFM). A direct correlation between adhesion forces and dispersion of the drug from the carrier surface was observed suggesting that adhesion forces play an important role in determining the detachment potential of the drug from the carrier surface. However, no direct relationship between the surface roughness of the PCL or PLGA carrier and the FPF of the drug was observed. In conclusion, the body of work presented in this dissertation demonstrated the potential of coated PCL microspheres and PLGA microspheres to be used in DPI formulations as an alternative carrier to sugar based carriers. The study also emphasized the role of the size of the carrier particles and the forces of interaction prevailing between the drug and the carrier particle surface on the aerosolization performances of the drug.

Plasma metabolomics reveals biomarkers of the atherosclerosis

Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in industrialized societies. The lack of metabolite biomarkers has impeded the clinical diagnosis of atherosclerosis so far. In this study, stable atherosclerosis patients (n=16) and age- and sex-matched non-atherosclerosis healthy subjects (n=28) were recruited from the local community (Harbin, P. R. China). The plasma was collected from each study subject and was subjected to metabolomics analysis by GC/MS. Pattern recognition analyses (principal components analysis, orthogonal partial least-squares discriminate analysis, and hierarchical clustering analysis) commonly demonstrated plasma metabolome, which was significantly different from atherosclerotic and non-atherosclerotic subjects. The development of atherosclerosis-induced metabolic perturbations of fatty acids, such as palmitate, stearate, and 1-monolinoleoylglycerol, was confirmed consistent with previous publication, showing that palmitate significantly contributes to atherosclerosis development via targeting apoptosis and inflammation pathways. Altogether, this study demonstrated that the development of atherosclerosis directly perturbed fatty acid metabolism, especially that of palmitate, which was confirmed as a phenotypic biomarker for clinical diagnosis of atherosclerosis.

The effect of some catalysts on the curing of oxiranes with p-phenylenediamine

The effect of some alcohols, acetylacetonates of transition metals, and manganese stearate and naphthenate on the curing reaction of a diglycidyl ether of ether of bisphenol-A with p-phenylenediamine is studied. Maximum catalytic activity is shown by the manganese compounds and triethanolamine.

Algal biofuel from urban wastewater in India: Scope and challenges

Rapidly depleting stocks of fossil fuels and increasing greenhouse gas (GHG) emissions have necessitated the exploration of cost effective sustainable energy sources focussing on biofuels through algae. Abundant wastewaters generated in urban localities every day provide the nourishment to nurture algae for biofuel generation. The present communication focuses on the lipid prospects of algae grown in wastewater systems. Euglena sp., Spirogyra sp. and Phormidium sp. were collected from selected locations of sewage fed urban lakes and sewage treatment plants of Bangalore and Mysore. The total lipid content of Euglena sp. was higher (24.6%) compared to Spirogyra sp. (18.4%) followed by Phormidium sp. (8.8%) and their annual lipid yield potential was 6.52, 1.94 and 2.856 t/ha/year, respectively. These species showed higher content of fatty acids (palmitate, stearate followed by oleic and linoleic acids) with the desirable biofuel properties. (C) 2013 Elsevier Ltd. All rights reserved.

Effect of Layered MoS2 Nanoparticles on the Frictional Behavior and Microstructure of Lubricating Greases

Lithium stearate soap and layered MoS2 nanoparticles encapsulated in lithium stearate soap are prepared in the laboratory, and their lubricating properties are compared with respect to the particle and particle concentration. The tribotracks after friction test was investigated with Raman Spectroscopy, scanning electron microscopy (SEM) and 3D optical profilometry to understand the action mechanism. The status of the soap particles on a tribotrack changes with time, contact pressure and sliding speed. At low pressure and speed, individual solid undeformed soap particle stand proud of the surface and the topography shows marginal difference with sliding time. In these conditions, no frictional difference between the performance of grease with and without the nanoparticles is observed. Increasing the contact pressure and temperature (low speed and high speed) has a dramatic effect as the soap particles melt and the liquid soap flows over the track releasing the hitherto encapsulated nanoparticles. Consequently, the soap smears the track like a liquid, and the nanoparticles now come directly into the interface and are sheared to generate a low-friction tribofilm. At high particle concentration, the sliding time required for melting of the soap and release of MoS2 is reduced, and the tribofilm is more substantial and uniform consisting of smeared MoS2 and carboxylate soap as observed by SEM and 3D optical profilometry. A change in the Raman Spectra is observed with particle concentration, and this is related to morphology and microstructure of the tribofilm generated.

Organic passivation layer on flexible Surlyn substrate for encapsulating organic photovoltaics

Barrier materials are required for encapsulating organic devices. A simple methodology based on organic passivation layer on a flexible substrate has been developed in this work. Stearyl stearate ( SS) was directly coated over the flexible Surlyn film. The barrier films with SS passivation layer exhibited much lower water vapor transmission rates compared to the neat Surlyn films. Moreover, the effect of the process of deposition of organic passivation layer on the resultant water vapor properties of the barrier films was evaluated. The accelerated lifetime studies conducted on encapsulated organic photovoltaics showed that the passivation layer improved the device performance by several fold compared to the non-passivated barrier films. (C) 2014 AIP Publishing LLC.