Tze Loon Neoh

Encapsulation of Proteins by Spray Drying and Crystal Transformation Method

Spray drying is commonly used as a dehydration technique in the pharmaceutical industry for making powdery products directly from liquid. It is also an attractive alternative for obtaining solid pharmaceutical molecules that are traditionally produced by freeze drying. Spray drying is often regarded as a harsh drying method, due to the high temperature of the drying gas. Therefore, some excipients were added to improve the stability in manufacturing process and storage. Emphasis was placed on the encapsulation of proteins by spray drying and crystal transformation method.

Dissociation characteristic of the inclusion complex of cyclomaltohexaose (α-cyclodextrin) with 1-methylcyclopropene in response to stepwise rising relative humidity

The dissociation of a crystalline complex of cyclomaltohexaose (alpha-cyclodextrin) and 1-methylcyclopropene has been studied in response to stepwise rising relative humidity at 50 degrees C using a dynamic vapor sorption instrument. The dissociation of the inclusion complex was monitored with a proton transfer reaction mass spectrometer. The increase in relative humidity generally triggered the complex dissociation. However, the dissociation was greatly retarded at 80% relative humidity, presumably owing to collapse of the crystalline structure. Abrupt dissociation was observed at 90% relative humidity which corresponded to complex dissolution. The changes in powder X-ray diffraction pattern of the inclusion complex during the storage period were also investigated.

Kinetic Analysis and Evaluation of Controlled Release of D-Limonene Encapsulated in Spray-Dried Cyclodextrin Powder under Linearly Ramped Humidity

A linearly ramped humidity system coupled with automatic sampling gas chromatography has been developed. The apparatus was adopted to measure the dynamic release flux of D-limonene included in spray-dried β-cyclodextrin (β-CD) and the polymer-coated counterparts under linearly ramped humidity (0.375%/min) at constant temperature (50°C). The release flux profiles of D-limonene were analyzed using a mathematical model based on an extended Arrhenius equation. The activation energy of D-limonene release flux from β-CD was 278 (kJ/mol), which was the highest among the powders and around twice as high as our previous results obtained by the conventional static method.

Improvement of Antifungal Activity of 10-Undecyn-1-ol by Inclusion Complexation with Cyclodextrin Derivatives

The inclusion complexation behavior between 10-undecyn-1-ol and cyclodextrin (CD) derivatives, namely, randomly methylated beta-CD (RM-beta-CD) and hydroxypropyl-beta-CD (HP-beta-CD), was studied in terms of solubility improvement, apparent stability constant, and the inclusion ratios of the resultant inclusion complexes. The aqueous solubility of 10-undecyn-1-ol was greatly improved through complexation with the CD derivatives. RM-beta-CD is comparatively more efficient in solubilizing 10-undecyn-1-ol with an apparent stability constant outstripping that of HP-beta-CD by about an order of magnitude. Comparative in vitro evaluations of the growth inhibition effects of inclusion complex solutions toward Rosellinia necatrix, a phytopathogenic fungus, were performed. In comparison with the positive control, appreciable improvements of the antifungal activity of 10-undecyn-1-ol through the addition of CD derivatives were observed visually. The improvement was evaluated in terms of area covered by the mycelia of Rosellinia necatrix and their growth rate. RM-beta-CD was proven to be more effective compared to HP-beta-CD with regard to the reduction of both fungal mycelium-covered area and growth rate constant, presumably owing to greater solubility enhancement by RM-beta-CD and thus the bioavailability of 10-undecyn-1-ol. Inclusion complexation of 10-undecyn-1-ol with CD derivatives suggests a potential means for production of an environmentally friendly 10-undecyn-1-ol-based fungicide to counteract R. necatrix.

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. Graphical abstract CLSM images for MDs of three DE and vacuole percentage were shown. PV changes of these powders at 60 °C were affected with these powder vacuole structures.

Encapsulation of Alcohol Dehydrogenase in Mannitol by Spray Drying

The retention of the enzyme activity of alcohol dehydrogenase (ADH) has been studied in various drying processes such as spray drying. The aim of this study is to encapsulate ADH in mannitol, either with or without additive in order to limit the thermal denaturation of the enzyme during the drying process. The retention of ADH activity was investigated at different drying temperatures. When mannitol was used, the encapsulated ADH was found inactive in all the dried powders. This is presumably due to the quick crystallization of mannitol during spray drying that resulted in the impairment of enzyme protection ability in comparison to its amorphous form. Maltodextin (dextrose equivalent = 11) was used to reduce the crystallization of mannitol. The addition of maltodextrin increased ADH activity and drastically changed the powder X-ray diffractogram of the spray-dried powders.

Formation of a Polymer-Coated Inclusion Complex of D-Limonene and β-Cyclodextrin by Spray Drying

The polymer-coated inclusion complex powder formation of D-limonene and β-cyclodextrin obtained by spray drying was investigated with respect to the effects of various types of polymer coating agents on the powder particle size and morphology. The addition of the polymer coating agent affected the average particle size, morphology, and internal structures of the spray-dried powders. The average particle diameter of the uncoated spray-dried powders was approximately 5 µm. The powder particle size increased upon the addition of a polymer coating reagent. With the addition of 9 wt% of the polymer coating agent, an average diameter of approximately 80 µm was obtained for the spray-dried powder particles. However, further addition showed a negligible effect on the particle size. Inclusion complex crystals were observed on the surface and inside of the powder particles.

Evaluation of Flavor Release From Spray-Dried Powder by Ramping with Dynamic Vapor Sorption–Gas Chromatography

The ramping method for humidity at constant temperature was used to evaluate the release of D-limonene from spray-dried powder using a handmade dynamic vapor sorption (DVS) instrument. The release fluxes of D-limonene from spray-dried powder at two different liquid feed temperatures, 40 and 80°C, were used to evaluate the flavor release properties of spray-dried powder. The flavor fluxes for 40°C of liquid feed temperature were faster than those for 80°C over the whole humidity range.

Formation of a new crystalline form of anhydrous β-maltose by ethanol-mediated crystal transformation.

β-Maltose monohydrate was transformed into an anhydrous form by ethanol-mediated method under several temperatures with agitation. A new stable anhydrous form of β-maltose (Mβ(s)) was obtained, as substantiated by the X-ray diffraction patterns. Mβ(s) obtained by this method presented a fine porous structure, resulting in greater specific surface area compared to those of β-maltose monohydrate and anhydrous β-maltose obtained by vacuum drying (Mβ(h)). The crystal transformation presumably consisted of two steps: dehydration reaction from the hydrous to amorphous forms and crystal formation from the amorphous forms to the noble anhydrous form. The kinetics of these reactions were determined by thermal analysis using Janders equation and Arrhenius plots. The overall activation energies of the dehydration reaction and the formation of anhydrous maltose were evaluated to be 100 and 90 kJ/mol, respectively.

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.