Cyclodextrin encapsulation to prevent the loss of l-menthol and its retention during drying

The taste and flavor of spray-dried powdered products are the most important quality factors. In the present study, molecular encapsulation in cyclodextrin was applied to prevent the loss of a hydrophobic flavor compound (l-menthol) during the drying of a droplet. beta-Cyclodextrin appeared to be a better encapsulant for menthol than alpha- and gamma-cyclodextrin. The retention of menthol increased with increasing concentration of both cyclodextrin and maltodextrin. A simple mathematical model is proposed for estimating the flavor retention. The theoretical results by this model estimated well the final retention of menthol encapsulated in a blend of beta-cyclodextrin and maltodextrin.     

Inhibitory activity of shiitake flavor against platelet aggregation

Sulfuric-flavored compounds were extracted from shiitake (Lentinus edodes) and their inhibitory activity against platelet aggregation was investigated. Platelet aggregation induced by arachidonic acid and U-46619, the analog of thromboxane A(2), was inhibited by the essential oil from shiitake that contained lenthionine as a major sulfuric compound. This result indicates that the inhibitory site of the shiitake flavor compounds would be different from that of garlic-flavor compounds because the latter inhibits the passage between arachidonic acid and thromboxane A(2). The effect of the synthesized lenthionine was almost equivalent to that of the essential oil, which indicates that the inhibitory activity of the essential oil from shiitake would be mainly attributed to lenthionine.     

Formation of spray-dried powder of S-adenosyl-L-methionine

S-Adenosyl-L -methionine (SAM) is an essential metabolite in all living organisms. In clinical research, SAM has also been suggested as a chemotherapeutic agent in various diseases. The main problem of SAM is its instability at high temperatures, at neutral and alkaline pH, and in the presence of humidity. SAM retention in spray-dried powder was determined under various conditions of spray-drying. The highest SAM retention was obtained when maltodextrin (dextrose equivalent, DE, of 25) was used as the carrier solid with the SAM feed liquid at pH 4.0. The water content in the powder had a significant effect on the stability of SAM. SAM powder with lower water content exhibited higher stability.     

Spray-dried Bacillus thuringiensis Serovar israelensis formulations for control of Aedes aegypti larvae

Suspensions containing 0.25 and 1.25 g/liter of Bacillus thuringiensis subsp. israelensis (Bti) spore-toxin complex were spray-dried by using maltodextrin DE-6, corn starch, and nixtamalized corn flour (25 g/liter) as materials to entrap active delta-endotoxin. The inlet air temperature of the drier was kept constant at 141 degrees C and the outlet temperature was maintained at 60 or 70 degrees C. The Probit analysis of the concentration-mortality response of third instars of Aedes aegypti (L.) larvae of the spray-dried products at 60 degrees C showed that LC50 values for maltodextrin DE-6 with 1 and 5% spore-toxin complex were 4 and 10% higher in toxicity, respectively, than that for the unformulated spore-toxin complex without drying. The LC50 value for corn starch with 1 and 5% of spore-toxin complex were also higher in toxicity (7 and 8% respectively). However, LC50 values for nixtamalized corn flour with one and 5% spore-toxin complex were 81 and 55% higher in toxicity, respectively. Dried products contain an a(w) < or = 0.7, suggesting that they are able to keep the products without microorganism growth for longer periods. The scanning electron microscope of Bti spray-dried formulations with nixtamalized corn flour showed smooth spherical particles entrapping the active ingredient. These results suggested that Bti spore-toxin complex formulated with maltodextrin DE-6, corn flour, and nixtamalized corn flour, and then spray-dried may increase larval feeding and thus increase activity against Ae. aegypti larvae.     

Effect of Drying Process and Wall Material on the Properties of Encapsulated Cardamom Oil

The retention and shelf stability of cardamom oil entrapped in freeze- and spray-dried microcapsules coated with skim milk powder and modified starch was investigated. It was found that the retention of flavor in freeze-dried matrices was low and independent from the composition of wall material, whereas for the spray-dried microcapsules, it was much higher and markedly dependent on the type and percentage of coating material. It was also shown that the particle size of spray-dried powder greatly contributed to the flavor retention and surface oil content of microcapsules. Additionally, microscopic observation of powder particles revealed that the type of wall material and drying method distinctly influenced the morphological characteristics of powders which presumably caused a difference in their capability of cardamom oil retention.     

Physicochemical Characterization and Water Vapor Sorption of Organic Solution Advanced Spray-Dried Inhalable Trehalose Microparticles and Nanoparticles for Targeted Dry Powder Pulmonary Inhalation Delivery

Novel advanced spray-dried inhalable trehalose microparticulate/nanoparticulate powders with low water content were successfully produced by organic solution advanced spray drying from dilute solution under various spray-drying conditions. Laser diffraction was used to determine the volumetric particle size and size distribution. Particle morphology and surface morphology was imaged and examined by scanning electron microscopy. Hot-stage microscopy was used to visualize the presence/absence of birefringency before and following particle engineering design pharmaceutical processing, as well as phase transition behavior upon heating. Water content in the solid state was quantified by Karl Fisher (KF) coulometric titration. Solid-state phase transitions and degree of molecular order were examined by differential scanning calorimetry (DSC) and powder X-ray diffraction, respectively. Scanning electron microscopy showed a correlation between particle morphology, surface morphology, and spray drying pump rate. All advanced spray-dried microparticulate/nanoparticulate trehalose powders were in the respirable size range and exhibited a unimodal distribution. All spray-dried powders had very low water content, as quantified by KF. The absence of crystallinity in spray-dried particles was reflected in the powder X-ray diffractograms and confirmed by thermal analysis. DSC thermal analysis indicated that the novel advanced spray-dried inhalable trehalose microparticles and nanoparticles exhibited a clear glass transition (T _g). This is consistent with the formation of the amorphous glassy state. Spray-dried amorphous glassy trehalose inhalable microparticles and nanoparticles exhibited vapor-induced (lyotropic) phase transitions with varying levels of relative humidity as measured by gravimetric vapor sorption at 25°C and 37°C.     

A Statistical Approach to Optimize the Spray Drying of Starch Particles: Application to Dry Powder Coating

This article describes the preparation of starch particles, by spray drying, for possible application to a dry powder coating process. Dry powder coating consists of spraying a fine powder and a plasticizer on particles. The efficiency of the coating is linked to the powder morphological and dimensional characteristics. Different experimental parameters of the spray-drying process were analyzed, including type of solvent, starch concentration, rate of polymer feeding, pressure of the atomizing air, drying air flow, and temperature of drying air. An optimization and screening of the experimental parameters by a design of the experiment (DOE) approach have been done. Finally, the produced spray-dried starch particles were conveniently tested in a dry coating process, in comparison to the commercial initial starch. The obtained results, in terms of coating efficiency, demonstrated that the spray-dried particles led to a sharp increase of coating efficiency value.     

Synthesis of 1-Deoxy-L-rhamnojirimycin and Its Inhibitory Action against α-L-Rhamnosidase

To enhance the storage stability of essential oils such as d-limonene, a mixed powder of β-cyclodextrin and maltodextrin was used to encapsulate the liquid flavor in a powder state. In this study, powdery encapsulation of d-limonene was done by direct kneading of d-limonene with the mixed powder at low water content, using a twin screw kneader. The retention of d-limonene in the periodically sampled powder reached a maximum when the mass ratio of β-cyclodextrin to maltodextrin in the mixed powder equaled unity and the initial molar ratio of d-limonene to β-cyclodextrin was larger than unity. From X-ray diffraction of the powder, it could be guessed that the maximum retention of d-limonene might come from the adsorption of d-limonene upon maltodextrin. The equilibrium retention of d-limonene in the dry powder depended not only upon the mass ratio of β-cyclodextrin to maltodextrin in the mixed powder, but upon the initial moisture content in the powder. The equilibrium retention could be estimated well by a simple calculation.     

Effect of different dextrose equivalents of maltodextrin on oxidation stability in encapsulated fish oil by spray drying

Encapsulating fish oil by spray drying with an adequate wall material was investigated to determine if stable powders containing emulsified fish-oil-droplets can be formed. In particular, the dextrose equivalent (DE) of maltodextrin (MD) affects the powder structure, surface-oil ratio, and oxidative stability of fish oil. The carrier solution was prepared using MD with different DEs (DE = 11, 19, and 25) and sodium caseinate as the wall material and the emulsifier, respectively. The percentage of microcapsules having a vacuole was 73, 39, and 38% for MD with DE = 11, 19, and 25, respectively. Peroxide values (PVs) were measured for the microcapsules incubated at 60 °C. The microcapsules prepared with MD of DE = 25 and 19 had lower PVs than those prepared with MD of DE = 11. The difference in PV can be ascribed to the difference in the surface-oil ratio of the spray-dried microcapsules.     

Effect of drying methods on retention of moist sucralfate gel properties

The aim of this work was to find a drying procedure for moist sucralfate gel capable of producing dried sucralfate gel that retains the original gel properties of bioadhesion, rheology, and micromeritics. Spray-drying and microwave-drying procedures were employed. Mannitol was used as a gel-protective substance during the drying processes. The spray drying of moist sucralfate gel gave rise to a powder whose water suspensions showed significantly reduced viscosity. The bioadhesion of spray-dried sucralfate gel was strongly reduced by drying. When mannitol was used as a gel protector, the spray-dried sucralfate in part maintained the original bioadhesion of moist sucralfate gel. The preparation of a dried sucralfate gel retaining the bioadhesion characteristics, avoiding the use of mannitol, was made possible using the microwavedrying procedure. The microwave-dried product possesses a granular morphology suitable for direct compression because it is a free flowing and strongly coherent granular powder.     

Water Content�CWater Activity�CGlass Transition Temperature Relationships of Spray-Dried Boroj�� as Related to Changes in Color and Mechanical Properties

The water content–water activity–glass transition temperature relationships of commercial spray-dried borojó powder, with and without maltodextrin, have been studied as related to changes in color and mechanical properties. The GAB and Gordon and Taylor models were well fitted to the sorption and glass transition data, respectively. The Boltzman equation adequately described the evolution of the mechanical parameter characterized in the samples with the difference between the experimental temperature and the glass transition temperature (T _g) of the sample. The color of the samples showed a sigmoid change with water activity. The changes in the mechanical properties of borojó powder related to collapse development started when the sample moved to the rubbery state and began to be significant at about 10 °C above T _g. The increase in the molecular mobility from this point on also favors browning reactions. Maltodextrin presence slows the caking kinetics but induces color changes to spray-dried borojó powder.     

Theophylline Cocrystals Prepared by Spray Drying: Physicochemical Properties and Aerosolization Performance

The purpose of this work was to characterize theophylline (THF) cocrystals prepared by spray drying in terms of the physicochemical properties and inhalation performance when aerosolized from a dry powder inhaler. Cocrystals of theophylline with urea (THF-URE), saccharin (THF-SAC) and nicotinamide (THF-NIC) were prepared by spray drying. Milled THF and THF-SAC cocrystals were also used for comparison. The physical purity, particle size, particle morphology and surface energy of the materials were determined. The in vitro aerosol performance of the spray-dried cocrystals, drug-alone and a drug-carrier aerosol, was assessed. The spray-dried particles had different size distributions, morphologies and surface energies. The milled samples had higher surface energy than those prepared by spray drying. Good agreement was observed between multi-stage liquid impinger and next-generation impactor in terms of assessing spray-dried THF particles. The fine particle fractions of both formulations were similar for THF, but drug-alone formulations outperformed drug-carrier formulations for the THF cocrystals. The aerosolization performance of different THF cocrystals was within the following rank order as obtained from both drug-alone and drug-carrier formulations: THF-NIC > THF-URE > THF-SAC. It was proposed that micromeritic properties dominate over particle surface energy in terms of determining the aerosol performance of THF cocrystals. Spray drying could be a potential technique for preparing cocrystals with modified physical properties.

Electronic supplementary material

The online version of this article (doi:10.1208/s12249-012-9883-3) contains supplementary material, which is available to authorized users.Key words: aerodynamic diameter, cocrystal, spray drying, surface energy, theophylline     

Properties of agents that effectively entrap liquid lipids.

A droplet of an oil-in-water emulsion of methyl linoleate in a saccharide or protein solution that contained with a surfactant, a stabilizer, or both was dehydrated by drying equipment for a single droplet that resembled a spray drier. The lipid exposed on the surface of dehydated samples was extracted and measured by gas chromatography. Gum arabic or gelatin without additives resulted in little lipid being exposed; they were good entrapping agents. Little lipid was exposed with a pullulan solution containing lecithin, sugar ester, carboxymethylcellulose, or sodium caseinate but much was exposed with a maltodextrin solution containing any of the surfactants tested. When both the surfactant lecithin and the stabilizer xanthan gum were added to the emulsion prepared in a maltodextrin solution, lipid was not detected. The results suggested that effective entrapping agents of liquid lipids cause much emulsification, stabilize the emulsion (that is, they cause the continuous phase to be very viscous), and create a dehydrated matrix of fine, dense network layers.     

Effect of Cholesterol on the Properties of Spray-Dried Lysozyme-Loaded Liposomal Powders

The influence of cholesterol (Chol) in the liposomal bilayer on the properties of inhalable protein-loaded liposomal powders prepared by spray-drying technique was investigated. Lysozyme (LSZ) was used as a model protein. Feed solution for spray drying was prepared by direct mixing of aqueous solution of LSZ with mannitol solution and empty liposome dispersions composed of hydrogenated phosphatidylcholine and Chol at various molar ratios. The spray-dried powders were characterized with respect to morphology, thermal property, and crystallinity using scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction, respectively. Most formulations gave slightly aggregated, spherical particles, and percentage yields of the spray-dried powders decreased with increasing Chol content. Degree of particle aggregation depended on the powder composition. The powders spontaneously formed liposomes which efficiently entrapped LSZ after reconstitution with HEPES buffered saline (HBS) at 37°C. Lysozyme entrapment efficiency and size distribution of the reconstituted liposomes were evaluated after the powders were reconstituted with HBS. Increasing Chol content resulted in a decrease in size of the reconstituted liposomes and an increase in entrapment efficiency of LSZ. These results correlated with thermal behaviors of the reconstituted liposomes. Biological activity of LSZ was not affected by the spray-drying process. It was also demonstrated that LSZ-loaded liposomal powders could be produced without the need to preload the LSZ into liposomes prior to spray-drying process.     

Optimization of spray-drying conditions for the large-scale preparation of Bacillus thuringiensis var. israelensis after downstream processing

Reduction of water activity in the formulations of mosquito biocontrol agent, Bacillus thuringiensis var. israelensis is very important for long term and successful storage. A protocol for spray drying of B. thuringiensis var. israelensis was developed through optimizing parameters such as inlet temperature and atomization type. A indigenous isolate of B. thuringiensis var. israelensis (VCRC B-17) was dried by freeze and spray drying methods and the moisture content and mosquito larvicidal activity of materials produced by the two methods were compared. The larvicidal activity was checked against early fourth instars Aedes aegypti larvae. Results showed that the freeze-dried powders retained the larvicidal activity fairly well. The spray-dried powder moderately lost its larvicidal activity at different inlet temperatures. Between the two types of atomization, centrifugal atomization retained more activity than the nozzle type atomization. Optimum inlet temperature for both centrifugal and nozzle atomization was 160 degrees C. Keeping the outlet temperature constant at 70 degrees C the moisture contents for the spray-dried powders through centrifugal atomization and freeze-dried powders were 10.23% and 11.80%, respectively. The LC(50) values for the spray-dried and freeze-dried powders were 17.42 and 16.18 ng/mL, respectively. Spore count of materials before drying was 3 x 10(10) cfu/mL and after spray drying through nozzle and centrifugal atomization at inlet and outlet temperature of 160 degrees C/70 degrees C were 2.6 x 10(9) and 5.0 x 10(9) cfu/mL, respectively.     

Spray drying of lipid-based systems loaded with Camellia sinensis polyphenols

In this work, spray-dried lipid systems based on soy phosphatidylcholine, cholesterol and lauroyl polyoxylglycerides for entrapping Green tea polyphenols were produced. The aim was to study the effects of the encapsulating composition and spray drying conditions on the system performance and physicochemical product properties. The spray dryer powder production yield falls around 50.7?±?2.8%, which is typical for lab scale spray dryers. Wrinkled and rounded particles, with low surface porosities were generated, independent of the drying carriers (trehalose or lactose) used. The product showed high encapsulation efficiency of Green tea polyphenols, which was promptly redispersible in water. It presented low density, and good compressive and flow properties. The results herein reported confirm the feasibility of the entrapment of Green tea polyphenols in lipid-based compositions by spray drying in presence of the drying carriers evaluated. The spray-dried microparticles show high potential to be used as additive in food, nutraceutical and pharmaceutical products.     

Evidence of membrane damage in Lactobacillus bulgaricus following freeze drying

The mechanism of inactivation of Lactobacillus bulgaricus due to freeze drying was investigated. Cells were freeze-dried in skim milk powder, maltodextrin, glycerol, trehalose and water. Results are presented confirming previous authors'observations regarding membrane damage during freeze drying. In an attempt to define more clearly the nature of this damage, further experiments were carried out. Results show that following freeze drying changes occur in the unsaturated: saturated fatty acid ratio, a decrease in the activity of the membrane-bound enzyme ATPase and a loss of ΔpH.     

Rheological properties of water-soluble spruce O-acetyl galactoglucomannans

The thermal and rheological properties of spray-dried, ethanol-precipitated, purified, and deacetylated spruce galactoglucomannans (GGM) were investigated by rheological measurements and differential scanning calorimetry. The shear rate dependence of viscosity and the effects of the drying method, temperature, ionic strength, and deacetylation on rheological properties were studied. GGM solutions exhibited a shear thinning behaviour. GGM solutions did not obey the Cox–Merz rule. The storage modulus of GGM solutions increased with an increase in concentration; gradually until a concentration of 5%, but rapidly at higher concentrations. Ethanol-precipitated GGM solutions showed a more elastic behaviour than spray-dried GGM solutions. Deacetylation caused an increase in apparent viscosity and more significantly in storage modulus. The storage modulus increased slightly with a decrease in temperature. A small amount addition of NaCl slightly changed the oscillatory behaviour. The effects of above factors were discussed in terms of molecular interactions. The rheological measurements of GGM solutions provide the basis of functionalities of GGM solutions.     

Effect of sucrose and maltodextrin on the physical properties and survival of air-dried Lactobacillus bulgaricus: an in situ fourier transform infrared spectroscopy study

The effect of sucrose, maltodextrin and skim milk on survival of L. bulgaricus after drying was studied. Survival could be improved from 0.01% for cells that were dried in the absence of protectants to 7.8% for cells dried in a mixture of sucrose and maltodextrin. Fourier transform infrared spectroscopy (FTIR) was used to study the effect of the protectants on the overall protein secondary structure and thermophysical properties of the dried cells. Sucrose, maltodextrin and skim milk were found to have minor effects on the membrane phase behavior and the overall protein secondary structure of the dried cells. FTIR was also used to show that the air-dried cell/protectant solutions formed a glassy state at ambient temperature. 1-Palmitoyl 2-oleoyl phosphatidyl choline (POPC) was used in order to determine if sucrose and maltodextrin have the ability to interact with phospholipids during drying. In addition, the glass transition temperature and strength of hydrogen bonds in the glassy state were studied using this model system. Studies using poly-L-lysine were done in order to determine if sucrose and maltodextrin are able to stabilize protein structure during drying. As expected, sucrose depressed the membrane phase transition temperature (Tm) of POPC in the dried state and prevented conformational changes of poly-L-lysine during drying. Maltodextrin, however, did not depress the Tm of dried POPC and was less effective in preventing conformational changes of poly-L-lysine during drying. We suggest that when cells are dried in the presence of sucrose and maltodextrin, sucrose functions by directly interacting with biomolecules, whereas maltodextrin functions as an osmotically inactive bulking compound causing spacing of the cells and strengthening of the glassy matrix.     

Agglomerated Oral Dosage Forms of Artemisinin/β-Cyclodextrin Spray-Dried Primary Microparticles Showing Increased Dissolution Rate and Bioavailability

Artemisinin, a poorly water-soluble antimalarial drug, presents a low and erratic bioavailability upon oral administration. The aim of this work was to study an agglomerated powder dosage form for oral administration of artemisinin based on the artemisinin/β-cyclodextrin primary microparticles. These primary microparticles were prepared by spray-drying a water–methanol solution of artemisinin/β-cyclodextrin. β-Cyclodextrin in spray-dried microparticles increased artemisinin water apparent solubility approximately sixfold. The thermal analysis evidenced a reduction in the enthalpy value associated with drug melting, due to the decrease in drug crystallinity. The latter was also evidenced by powder X-ray diffraction analysis, while ¹³C-NMR analysis indicated the partial complexation with β-cyclodextrin. Agglomerates obtained by sieve vibration of spray-dried artemisinin/β-cyclodextrin primary microparticles exhibited free flowing and close packing properties compared with the non-flowing microparticulate powder. The in vitro dissolution rate determination of artemisinin from the agglomerates showed that in 10 min about 70% of drug was released from the agglomerates, whereas less than 10% of artemisinin was dissolved from raw material powder. Oral administration of agglomerates in rats yielded higher artemisinin plasma levels compared to those of pure drug. In the case of the agglomerated powder, a 3.2-fold increase in drug fraction absorbed was obtained.