Micropartículas lipídicas sólidas obtidas por spray drying para liberação intraocular de ibuprofeno

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influence of Edible Coating on the Drying and Quality of Papaya (Carica papaya)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Microparticulated Hydrochlorothiazide Solid Dispersion: Enhancing Dissolution Properties via Spray Drying

The aim of the present study was to obtain microparticles of hydrochlorothiazide, a diuretic drug that practically insoluble in water, by spray drying and to investigate the influence of process parameters using a three-level, three-factor Box-Behnken design. Process yields, moisture content, particle size, flowability, and solubility were used to evaluate the spray-dried microparticles. The data were analyzed by response surface methodology using analysis of variance. The independent variables studied were outlet temperature, atomization pressure, and drug content. The formulations were prepared using polyvinylpyrrolidone and colloidal silicon dioxide as the hydrophilic carrier and drying aid, respectively. The microparticle yield ranged from 18.15 to 59.02% and resulted in adequate flow (17 to 32 degrees), moisture content between 2.52 to 6.18%, and mean particle size from 45 to 59 mu m. The analysis of variance showed that the factors studied influenced the yields, moisture content, angle of repose, and solubility. Thermal analysis and X-ray diffractometry evidenced no drug interactions or chemical modifications. Photomicrographs obtained by scanning electron microscopy showed spherical particles. The solubility and dissolution rates of hydrochlorothiazide were remarkably improved when compared with pure drug. Therefore, the results confirmed the high potential of the spray-drying technique to obtain microparticulate hydrochlorothiazide with enhanced pharmaceutical and dissolution properties.

Engineering Active Pharmaceutical Ingredients by Spray Drying: Effects on Physical Properties and In Vitro Dissolution

Active pharmaceutical ingredients have very strict quality requirements; minor changes in the physical and chemical properties of pharmaceuticals can adversely affect the dissolution rate and therefore the bioavailability of a given drug. Accordingly, the aim of the present study was to investigate the effect of spray drying on the physical and in vitro dissolution properties of four different active pharmaceutical ingredients, namely carbamazepine, indomethacin, piroxicam, and nifedipine. Each drug was dispersed in a solution of ethanol and water (70:30) and subjected to single-step spray drying using similar operational conditions. A complete characterization of the spray-dried drugs was performed via differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), particle size distribution analysis, solubility analysis, and an in vitro dissolution study. The results from the thermal analysis and X-ray diffraction showed that, except for carbamazepine, no chemical modifications occurred as a result of spray drying. Moreover, the particle size distribution of all the spray-dried drugs significantly decreased. In addition, SEM images showed that most of the particles had an irregular shape. There was no significant improvement in the solubility of the spray-dried drugs compared with the unprocessed compounds; however, in general, the dissolution rates of the spray-dried drugs showed a remarkable improvement over their non-spray-dried counterparts. Therefore, the results from this study demonstrate that a single spray-drying step may lead to changes in the physical properties and dissolution characteristics of drugs and thus improve their therapeutic action.

In vitro evaluation of demineralized freeze-dried bone allograft in combination with enamel matrix derivative

BACKGROUND Preclinical and clinical studies suggest that a combination of enamel matrix derivative (EMD) with demineralized freeze-dried bone allograft (DFDBA) may improve periodontal wound healing and regeneration. To date, no single study has characterized the effects of this combination on in vitro cell behavior. The aim of this study is to test the ability of EMD to adsorb to the surface of DFDBA particles and determine the effect of EMD coating on downstream cellular pathways such as adhesion, proliferation, and differentiation of primary human osteoblasts and periodontal ligament (PDL) cells. METHODS DFDBA particles were precoated with EMD or human blood and analyzed for protein adsorption patterns via scanning electron microscopy. Cell attachment and proliferation were quantified using a commercial assay. Cell differentiation was analyzed using real-time polymerase chain reaction for genes encoding Runx2, alkaline phosphatase, osteocalcin, and collagen 1α1, and mineralization was assessed using alizarinred staining. RESULTS Analysis of cell attachment revealed no significant differences among control, blood-coated, and EMD-coated DFDBA particles. EMD significantly increased cell proliferation at 3 and 5 days after seeding for both osteoblasts and PDL cells compared to control and blood-coated samples. Moreover, there were significantly higher messenger ribonucleic acid levels of osteogenic differentiation markers, including collagen 1α1, alkaline phosphatase, and osteocalcin, in osteoblasts and PDL cells cultured on EMD-coated DFDBA particles at 3, 7, and 14 days. CONCLUSION The results suggest that the addition of EMD to DFDBA particles may influence periodontal regeneration by stimulating PDL cell and osteoblast proliferation and differentiation.

Transmission electron microscopy of the bacterial nucleoid.

Water-containing biological material cannot withstand the vacuum of the transmission electron microscope. The classical solution to this problem has been to dehydrate chemically fixed biological samples and then embed them in resin. During such treatment, the bacterial nucleoid is especially prone to aggregation, which affects its global shape and fine structure. Initial attempts to deal with aggregation by optimizing chemical fixation yielded contradictory results. Two decades ago, the situation improved with the introduction of freeze-substitution. This method is based on dehydration of unfixed cryo-immobilized samples at low temperature, which substantially reduces aggregation. As a result, the global shape of the nucleoid can be fairly well defined. Overall, in actively growing bacteria, the nucleoids are dispersed and "coralline" but become more confined when growth ceases. However, it is usually impossible to determine the molecular arrangement of DNA in the nucleoids of freeze-substituted bacteria because crystallization and the subsequent removal of water during substitution result in unavoidable distortions at the ultrastructural level. Recently, cryo-electron microscopy of vitreous sections has enabled the fully hydrated bacterial nucleoid to be studied close to the native state. Such studies have revealed aspects of bacterial nucleoid organization that are not preserved by freeze-substitution, including locally parallel or twisted bundles of DNA filaments, which are more frequently observed once bacterial growth has stopped, whereas in actively growing bacteria, the DNA is seen to be in a mostly disordered pattern.

Microscopy imaging of liposomes:from coverslips to environmental SEM

A plethora of techniques for the imaging of liposomes and other bilayer vesicles are available. However, sample preparation and the technique chosen should be carefully considered in conjunction with the information required. For example, larger vesicles such as multilamellar and giant unilamellar vesicles can be viewed using light microscopy and whilst vesicle confirmation and size prior to additional physical characterisations or more detailed microscopy can be undertaken, the technique is limited in terms of resolution. To consider the options available for visualising liposome-based systems, a wide range of microscopy techniques are described and discussed here: these include light, fluorescence and confocal microscopy and various electron microscopy techniques such as transmission, cryo, freeze fracture and environmental scanning electron microscopy. Their application, advantages and disadvantages are reviewed with regard to their use in analysis of lipid vesicles.

Environmental scanning electron microscope imaging of vesicle systems

The structural characteristics of liposomes have been widely investigated and there is certainly a strong understanding of their morphological characteristics. Imaging of these systems, using techniques such as freeze-fracturing methods, transmission electron microscopy, and cryo-electron imaging, has allowed us to appreciate their bilayer structures and factors that influence this. However, there are a few methods that study these systems in their natural hydrated state; commonly, the liposomes are visualized after drying, staining and/or fixation of the vesicles. Environmental scanning electron microscopy (ESEM) offers the ability to image a liposome in its hydrated state without the need for prior sample preparation. We were the first to use ESEM to study the liposomes and niosomes, and have been able to dynamically follow the hydration of lipid films and changes in liposome suspensions as water condenses onto, or evaporates from, the sample in real-time. This provides an insight into the resistance of liposomes to coalescence during dehydration, thereby providing an alternative assay for liposome formulation and stability.

Environmental scanning electron microscopy offers real-time morphological analysis of liposomes and niosomes

Liposomes have been imaged using a plethora of techniques. However, few of these methods offer the ability to study these systems in their natural hydrated state without the requirement of drying, staining, and fixation of the vesicles. However, the ability to image a liposome in its hydrated state is the ideal scenario for visualization of these dynamic lipid structures and environmental scanning electron microscopy (ESEM), with its ability to image wet systems without prior sample preparation, offers potential advantages to the above methods. In our studies, we have used ESEM to not only investigate the morphology of liposomes and niosomes but also to dynamically follow the changes in structure of lipid films and liposome suspensions as water condenses on to or evaporates from the sample. In particular, changes in liposome morphology were studied using ESEM in real time to investigate the resistance of liposomes to coalescence during dehydration thereby providing an alternative assay of liposome formulation and stability. Based on this protocol, we have also studied niosome-based systems and cationic liposome/DNA complexes. Copyright © Informa Healthcare.

Mechanisms of drying of skin forming materials

The literature relating to evaporation from single droplets of pure liquids, and to the drying of droplets containing solids and of droplet sprays has been reviewed. The heat and mass transfer rates for a single droplet suspended from a nozzle were studied within a 42mm I.D. horizontal wind tunnel designed to supply hot dry air, to simulate conditions encountered in a practical spray dryer. A novel rotating glass nozzle was developed to facilitate direct measurements of droplet weight and core temperature. This design minimised heat conduction through the nozzle. Revised correlations were obtained for heat and mass transfer coefficients, for evaporation from pure water droplets suspended from a rotating nozzle. Nu = 2.0 + 0.27 (l/B)°-18Re°-5Pr°-83 Sh = 2.0 + 0.575 ((T0-T.)/Tomfc) -o.o4Reo.5 ^0.33 Experimental drying studies were carried out on single droplets of different types of skin-forming materials, namely, custard, gelatin, skim milk and fructose at air temperatures ranging from 19°C to 198°C. Dried crusts were recovered and examined by Scanning Electron Microscopy. Skin-forming materials were classified into three types according to the mechanisms of skin formation. In the first type (typified by droplets of custard and starch) skin formed due to gelatinisation at high temperatures. Increasing the drying temperature resulted in increased crust resistance to mass transfer due to increased granule swelling and the crust resistance was completely transferred to a skin resistance at drying temperatures > 150°C. In the second type e.g. gelatin droplets the skin formed immediately drying had taken place at any drying temperature. At drying temperature > 60° C a more resistant skin was formed. In the third type (typified by droplets of skim milk and fructose) the skin appeared on the droplet surface at a certain stage of the drying process under any drying conditions. As the drying temperature was increased the resistance of the skin to mass transfer increased. The drying rate history of any material depended upon the nature of the skin formed which, in turn, depended upon the drying conditions. A mathematical model was proposed for the drying of the first type of skin-forming material. This was based on the assumption that, once all the granules gelatinised at the gelatinisation temperature, a skin appeared instantaneously on the droplet surface. The experimentally-observed times at which the skin appeared on the droplets surfaces were in excellent agreement with those predicted from the model. The work should assist in understanding the fundamentals of paniculate drying processes, particularly when skin-formation occurs and may be a crucial factor in volatiles retention.

A study of the drying of single droplets in free-flight

The literature relating to evaporation from single droplets of pure liquids and the drying of solution and slurry droplets, and of droplet sprays has been reviewed. The heat and mass transfer rates for individual droplets suspended in free-flight, were investigated using a specially-designed vertical wind tunnel, to simulate conditions in a spray drier. The technique represented a unique alternative method for investigating evaporation from unrestrained single droplets with variable residence times. The experiments covered droplets of pure liquid allowbreak (water, isopropanol) allowbreak and of significantly different solutions (sucrose, potassium sulphate) over a range of temperatures of 37oC to 97oC, initial concentrations of 5 to 40wt/wt% , and initial drop sizes of 2.8 to 4.6mm. Drop behaviour was recorded photographically and dried particles were examined by Scanning Electron Microscopy. Correlations were developed for mass transfer coefficients for pure water droplets in free-flight; (i) experiencing oscillations, rotation and deformation, Sh = -105 + 3.9 [Ta - Td/Tamb]0.18Re0.5Sc033 for Re approx. > 1380 (ii) when these movements had ceased or diminished, Sh = 2.0 + 0.71 [Ta - Td/Tamb]0.18Re0.5Sc033 for Re approx. < 1060. Data for isopropanol drops were correlated resonably well by these equations. The heat transfer data showed a similar transition range. The drying rate curves for drops of sucrose and potassium sulphate solution exhibited three distinct stages; an initial increase in the drying rate as drop temperature reduced to the wet-bulb temperature, a short constant-rate period and a falling-rate period characterised by formation of a crust which controlled the mass transfer rate. Due to drop perturbation the rates in the high Re number region were up to 5 times greater than predicted from theory for spherical droplets. In the case of sucrose solution a `skin' formed over the drop surface prior to crust formation. This provided an additional resistance to mass transfer and resulted in extended drying times and a smooth crust of low porosity. The relevance of the results to practical spray drying operations is discussed.

Mechanisms of drying of particulate slurries

The literature on the evaporation of pure liquid drops and the drying of drops of solutions and slurries has been reviewed with particular reference to spray drying. A 0.1-0.2 mm glass filament-thermocouple was constructed and used to study simultaneously, heat and mass transfer from a single suspended drop placed in a humidity and temperature controlled, 28 mm OD vertical wind tunnel. Heat conduction through the filament was minimised eg at 100¦C it accounted for only 9.3% of the total heat transferred to a drop. Evaporation of single water drops was also studied in a 101 mm OD vertical wind tunnel. The Nusselt number was found to be a function of the Reynolds, Prandtl and Transfer number over an air temperature range of 17¦C to 107¦C. The proposed correlation is: Nu = 2+(-12.96B+0.76)Re¦-5Pr0-33 Experimental drying studies were carried out on single suspended 1 to 2.5 mm diameter drops of aqueous sodium sulphate decahydrate, sodium chloride, potassium sulphate, copper sulphate and sodium acetate solutions and slurries at temperatures of 20¦C to 124¦C. Dried crusts were examined by Scanning Electron Microscopy. The drying history of any material depended upon the nature of the crust formed. Sodium acetate formed a non-rigid skin prior to the formation of a rigid crust. A modified receding evaporation interface model was proposed for the drying of solutions and slurries. This covered both the constant rate period prior to crust formation and the subsequent falling rate period. The model was solved numerically for the variation in core temperature, drop weight and crust thickness. Good agreement was obtained between model predictions and experimental results for materials forming rigid crusts i.e. sodium sulphate decahydrate, sodium chloride, potassium sulphate and copper sulphate. However, the drying histories of drops of 10-20% weight initial concentration sodium acetate were unpredictable since formation of a non-rigid skin deviated from the model assumption of a rigid outer surface. At higher initial concentrations (40% weight) where a rigid crust was formed for sodium acetate, good agreement was obtained between experimental results and model predictions. Single suspended drop studies are concluded to provide a valuable insight into the drying mechanisms of specific solutions and slurries.

Caking behaviour of spray-dried milk powders:using scanning probe microscopy to study nanoscale surface properties and material composition

Spray drying is widely used to manufacture many powdered products, with the drying process parameters having significant influence over the final powder's surface properties and propensity for unwanted caking. In most cases caking experiments are performed on bulk powders, but especially in multi-component powders, it is often difficult to interpret these results, where interaction effects between particles can be complex. Here the technique of scanning probe microscopy is used to characterize the nanoscale properties of spray dried model milk powders in order to investigate the surface properties of the powders.

Amphibian yolk platelet ultrastructure visualized by freeze-etching

Amphibian yolk platelets are composed of lipoprotein subunits arranged in an ordered crystalline structure. Freeze-etch electron microscopy of isolated Xenopus platelets provides a direct view of the structure of the crystal and aids the interpretation of fracture phenomena in lipoprotein systems. A study has been made both of fracture faces and of faces produced by fracturing and etching following partial dissolution of platelets in electrolyte solutions. In freeze-etch replicas, main body crystals appear to be composed of dimers. Rectangular and semihexagonal patterns are seen in fracture faces. Rectangular patterns are seen also in faces produced by partial dissolution and revealed by fracturing and etching. Dissolution faces with possible semihexagonal patterns are distinct but infrequent. Based on this evidence, a new closest-packing model of platelet structure is proposed using lipovitellin dimers as building blocks, with one molecule of the second major protein component, phosvitin, associated with each monomer of the lipovitellin dimer. © 1972 Academic Press, Inc.

Environmental scanning electron microscope imaging of vesicle systems

The structural characteristics of liposomes have been widely investigated and there is certainly a strong understanding of their morphological characteristics. Imaging of these systems, using techniques such as freeze-fracturing methods, transmission electron microscopy, and cryo-electron imaging, has allowed us to appreciate their bilayer structures and factors which can influence this. However, there are few methods which all us to study these systems in their natural hydrated state; commonly the liposomes are visualized after drying, staining, and/or fixation of the vesicles. Environmental Scanning Electron Microscopy (ESEM) offers the ability to image a liposome in its hydrated state without the need for prior sample preparation. Within our studies we were the first to use ESEM to study liposomes and niosomes and we have been able to dynamically follow the hydration of lipid films and changes in liposome suspensions as water condenses on to, or evaporates from, the sample in real time. This provides insight into the resistance of liposomes to coalescence during dehydration, thereby providing an alternative assay of liposome formulation and stability.