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The objective of this study is to achieve a fundamental understanding of polymorphic interconversion during the tableting process, including during compaction, dwell, decompression/unloading, and ejection using an in situ mechanical Raman spectroscopy. The fit-for-purpose in situ mechanical Raman spectroscopy developed herein can provide simultaneous measurement of Raman spectra and densification for the powder compacts. Chlorpropamide (CPA), an antidiabetic drug, was selected as a model pharmaceutical compound because of its mechanical shear-induced polymorphic conversions. The results confirm that CPA polymorph A (CPA-A) was transformed to CPA polymorph C (CPA-C) under different compaction stresses. We also observed that the converted polymorph CPA-C could be reverted to the CPA-A due to the elastic recovery of powder compacts as detected during dwelling and unloading. This study is the first depiction of the dynamics of CPA polymorphic interconversion during compression, dwell, unloading, and ejection. Mechanistically, this study illustrates a correlation between the change in the powder compact's relative density and polymorphic interconversion of the drug substance in different solid-state forms. The present research suggests that the process-induced polymorph conversion is a complicated dynamic process, which could be affected by the compaction pressure, the elasticity/plasticity of the material, the level of elastic recovery, and the dissipation of residual stress. In summary, this study demonstrates that the in situ mechanical Raman spectroscopy approach enables the simultaneous detection of mechanical and chemical information of the powder compact throughout the tableting process.

A novel design for thermally activated delayed fluorescence (TADF) emitters was developed by decorating dibenzofuran with four carbazole type electron donors and two CN electron withdrawing units. The four carbazole type donors were attached to one side of the dibenzofuran, and two CN units were introduced on the other side of the dibenzofuran for highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) separation. The HOMO and LUMO were largely separated, and they were overlapped in the dibenzofuran due to aromatic nature of dibenzofuran. Two TADF emitters, DBFCzCN and DBFtCzCN, were built on the design platform decorating the dibenzofuran, and they showed high EQEs of 25.2% and 17.4% in the vacuum deposited TADF devices. Additionally, the DBFtCzCN emitter showed a high EQE of 13.9% in the solution processed TADF devices.

PURPOSE: This study aims to understand the impact of spray drying nozzles on particle surface composition and aerosol stability. METHODS: The combination formulations of colistin and azithromycin were formulated by 2-fluid nozzle (2N) or 3-fluid (3N) spray drying in a molar ratio of 1:1. A 3-factor, 2-level (2(3)) factorial design was selected to investigate effects of flow rate, inlet temperature and feed concentration on yield of spray drying and the performance of the spray dried formulations for the 3N. RESULTS: FPF values for the 2N formulation (72.9 ± 1.9% for azithromycin & 73.4 ± 0.8% for colistin) were higher than those for the 3N formulation (56.5 ± 3.8% for azithromycin & 55.1 ± 1.6% for colistin) when stored at 20% RH for 1 day, which could be attributed to smaller physical size for the 2N. There was no change in FPF for both drugs in the 2N formulation after storage at 75% RH for 90 days; however, there was a slight increase in FPF for colistin in the 3N formulation at the same storage conditions. Surface enrichment of hydrophobic azithromycin was measured by X-ray photoelectron spectroscopy for both 2N and 3N formulations and interactions were studied using FTIR. CONCLUSIONS: The 3-fluid nozzle provides flexibility in choosing different solvents and has the capability to spray dry at higher feed solid concentrations. This study highlights the impact of hydrophobic azithromycin enrichment on particle surface irrespective of the nozzle type, on the prevention of moisture-induced deterioration of FPF for hygroscopic colistin.

Three novel green thermally activated delayed fluorescence (TADF) materials, (5,5′-bis(4-(9,9-dimethylacridin-10(9H)-yl)phenyl)-2,2′-bipyrimidine (22bpmAc), 10,10′-([2,5′-bipyrimidine]-2′,5-diylbis(4,1-phenylene))bis(9,9-dimethyl-9,10-dihydroacridine) (25bpmAc), and 2,2′-bis(4-(9,9-dimethylacridin-10(9H)-yl)phenyl)-5,5′-bipyrimidine (55bpmAc)) based on bipyrimidine cores as the new electron-accepting units and acridine as the electron-donating unit were designed, synthesized, and applied as green emitters in TADF devices. The TADF emitters were designed to have different nitrogen orientations in the bipyrimidine core. Two emitters, 25bpmAc and 55bpmAc, showed higher quantum efficiencies and narrower emission spectra relative to 22bpmAc. The former emitters have restricted geometry by hydrogen-bonding interactions on a central core, whereas the latter emitter does not have hydrogen bonding. The intramolecular hydrogen-bonding interaction suppressed a nonradiative mechanism in the 25bpmAc and 55bpmAc TADF e...

Solution-processed high-efficiency fluorescent organic light-emitting diodes with an external quantum efficiency over 18% were developed by engineering a host material and device structure designed for solution process. A high triplet energy host material designed for the solution process, (oxybis(3-(tert-butyl)-6,1-phenylene))bis(diphenylphosphine oxide) (DPOBBPE), worked efficiently as the host of blue fluorescent devices because of good solubility, high photoluminescence quantum yield, and good film properties. The DPOBBPE host enabled a high external quantum efficiency of 18.8% in the fluorescent organic light-emitting diodes by the solution process. Moreover, 25.8% external quantum efficiency in the soluble blue thermally activated delayed fluorescent devices was also realized. The 25.8% external quantum efficiency of the DPOBBPE delayed fluorescent device and 18.8% external quantum efficiency of the fluorescent device are the highest efficiency values achieved in the solution-processed blue fluorescent organic light-emitting diodes. Moreover, the solution-processed fluorescent device showed an improved blue color coordinate of (0.14, 0.20) compared to (0.17, 0.31) of the delayed fluorescent device.

A high triplet energy material with the ability to suppress intermolecular interactions was synthesized as a host for a blue thermally activated delayed fluorescence (TADF) emitter for blue-shifted emission color and high quantum efficiency in solution-processed TADF organic light-emitting diodes. The host material, (5-(tert-butyl)-2-(4-(tert-butyl)phenoxy)phenyl)diphenylphosphine oxide (POBBPE), was designed to have a phenoxyphenyl core structure for high triplet energy, a diphenylphosphine oxide group for electron transport, and two tert-butyl units to prevent intermolecular interaction. Solution-processed blue TADF devices were developed using the POBBPE host and 2,3,4,5,6-penta(9H-carbazol-9-yl)benzonitrile (5CzCN) as the emitter, and a high quantum efficiency of 23.3% was achieved. In particular, the color coordinates of the solution-processed POBBPE:5CzCN devices were (0.16, 0.23), which were significantly blue-shifted compared to the color coordinates of (0.17, 0.31) from a previous 5CzCN device fabricated using a well-known bis[2-(diphenylphosphino)phenyl]ether oxide host.

INTRODUCTION: Dry powder inhalers (DPIs) are popular for pulmonary drug delivery. Various techniques have been employed to produce inhalation drug particles and improve the delivery efficiency of DPI formulations. Physical stability of these DPI formulations is critical to ensure the delivery of a reproducible dose to the airways over the shelf-life. AREAS COVERED: This review focuses on the impact of solid-state stability on aerosolization performance of DPI drug particles manufactured by powder production approaches and particle engineering techniques. It also highlights the different analytical tools that can be used to characterize the physical instability originating from production and storage. EXPERT OPINION: A majority of the DPI literature focuses on the effects of physico-chemical properties such as size, morphology and density on aerosolization. While little has been reported on the physical stability, particularly the stability of engineered drug particles for use in DPIs. Literature data have shown that different particle engineering methods and storage conditions may cause physical instability of dry powders for inhalation and can significantly change the aerosol performance. A systematic examination of physical instability mechanisms in DPI formulations is necessary during formulation development in order to select the optimum formulation with satisfactory stability. In addition, the use of appropriate characterization tools are critical to detect and understand physical instability during the development of DPI formulations.

Homogeneous mixing of 2 cohesive jet-milled drug powders is a challenge for pharmaceutical manufacturing on account of their cohesive nature resulting in the formation of strong and random agglomerates. In this study, colistin and ciprofloxacin were co-jet milled to develop combination alantibiotic dry powder formulations for inhalation. The properties of particle size, morphology, content uniformity, and in vitro aerosolization were evaluated. The distribution of 2 drugs in the co-jet milled powders was assessed using time-of-flight secondary ion mass spectrometry. The co-jet milled powders demonstrated an acceptable content uniformity indicating homogeneity. In general, time-of-flight secondary ion mass spectrometry images showed relatively homogeneous distributions of ciprofloxacinand colistin in the co-milled formulations. Importantly, the 2 drugs generally had the similar fineparticle fraction and deposition behavior in each combinational formulation supporting that the particlemixtures were relatively homogenous and could maximize the antimicrobial synergy. In conclusion, cojetmilling could be a viable technique to produce the combination powders for inhalation. Refereed/Peer-reviewed

New green thermally activated delayed fluorescence (TADF) materials built on a directly coupled dual emitting core based backbone structure were designed, synthesized, and applied as green dopants in TADF devices. An ortho-linkage between a carbazole or 3,6-di-tert-butylcarbazole donor and a triazine acceptor facilitated the TADF emission, and direct coupling of the two TADF emitting cores more than doubled the external quantum efficiency of the TADF devices. The TADF emitter based on the directly coupled dual emitting core design exhibited a green emission with a CIE coordinate of (0.23, 0.52) and a maximum external quantum efficiency of 20.8% compared with less than 10% efficiency of a conventional TADF emitter with the corresponding chemical structure.

Co-jet-milling drugs and lubricants may enable simultaneous particle size reduction and surface coating to achieve satisfactory aerosolization performance. This study aims to establish the relationship between surface lubricant coverage and aerosolization behavior of a model drug (ciprofloxacin HCl) co-jet-milled with lubricants [magnesium stearate (MgSt) or L-leucine]. The co-jet-milled formulations were characterized for their particle size, morphology, cohesion, Carr’s index, and aerosolization performance. The surface lubricant coating was assessed by probing surface chemical composition using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary-ion mass spectrometry (ToF-SIMS). The effects of co-jet-milling on the surface energy and in vitro dissolution of ciprofloxacin were also evaluated. Our results indicated that, in general, ciprofloxacin co-jet-milled with L-leucine at > 0.5% w/w showed a significant higher fine particle fraction (FPF) compared with the ciprofloxacin jet-milled alone. The FPF values plateau at or above 5 % w/w for both MgSt and L-leucine. We have established the quantitative correlations between surface lubricant coverage and aerosolization in the tested range for each of the lubricants. More importantly, our results suggest different mechanisms to improve aerosolization for MgSt-coating and L-leucine-coating, respectively: MgSt-coating reduces inter-particulate interactions through the formation of low surface energy coating films, while L-leucine-coating not only reduces the surface energy but also creates rough particle surfaces that reduce inter-particulate contact area. Furthermore, surface coatings with 5% w/w MgSt (which is hydrophobic) did not lead to substantial changes in in vitro dissolution. Our findings have shown that the coating structure/quality and their effects could be highly dependent on the process and the coating material. The findings from this mechanistic study provide fundamental understanding of the critical effects of MgSt and L-leucine surface coverages on aerosolization and powder flow properties of inhalation particles.

This study shows a molecular design strategy for controlling the dihedral angle of two carbazole donors linked to a 2,4-diphenyl-1,3,5-triazine acceptor by a phenyl unit. Using this approach, six thermally activated delayed fluorescence emitters were synthesized with donors placed in various positions around a central phenyl core, and the photophysical relationship between the donor position and its dihedral angle was investigated. We demonstrate that this angle can affect both the strength of the charge transfer state and the conjugation across the entire molecule, effectively changing the singlet-triplet energy gap of the system. We conclude that materials containing two substituted -ortho donors or one -ortho and an adjacent -meta have the smallest energy gaps and the shortest delayed fluorescence lifetimes. On the other hand, emitters with no -ortho substituted donors have larger energy gaps and slow-to-negligible delayed fluorescence. When applying these materials to organic light-emitting diodes, these blue-emitting devices have a range of electrical properties, the best producing efficiencies as high as 21.8% together with high resistance to roll-off that correlate with the reverse intersystem crossing rates obtained.

Poor water solubility and poor bioavailability are problems with many pharmaceuticals. Increasing surface area by micronization is an effective strategy to overcome these problems, but conventional techniques often utilize solvents and harsh processing, which restricts their use. Newer, green technologies, such as supercritical fluid (SCF)-assisted particle formation, can produce solvent-free products under relatively mild conditions, offering many advantages over conventional methods. The antisolvent properties of the SCFs used for microparticle and nanoparticle formation have generated great interest in recent years, because the kinetics of the precipitation process and morphologies of the particles can be accurately controlled. The characteristics of the supercritical antisolvent (SAS) technique make it an ideal tool for enhancing the solubility and bioavailability of poorly water-soluble drugs. This review article focuses on SCFs and their properties, as well as the fundamentals of overcoming poorly water-soluble drug properties by micronization, crystal morphology control, and formation of composite solid dispersion nanoparticles with polymers and/or surfactants. This article also presents an overview of the main aspects of the SAS-assisted particle precipitation process, its mechanism, and parameters, as well as our own experiences, recent advances, and trends in development.

To achieve a deeper and more uniform impregnation of water-soluble phosphorous-based fire retardants (WPFRs), in this work several physical pretreatment methods were developed including kerfing, boring, and the combination of both for structural square-wood posts in wooden buildings. Research was performed on three wood species, sugi (Cryptomeria japonica), larch (Larix olgensis), and Douglas fir (Pseudotsuga menziesii Franco), which are generally recognized as refractory wood species. The effects of pretreatment method on chemical uptake, chemical penetration, and mechanical properties were evaluated. The methods were compared with the incising method, a traditional method used for wood preservation. The results indicated that the pretreatments effectively increased the chemical uptake and penetration, especially in larch wood. Although the traditional incising method also increased the chemical uptake, it decreased the modulus of rupture (MOR) and compressive strength. The boring and combined method with a boring diameter less than 12 mm are recommended for WPFR wood impregnation.

거대억새의 활용방안을 찾기 위하여 거대억새 파티클로 보드를 제조한 후 수지함침율 50%일 때 탄화온도 600∼1,200°C별로, 탄화온도 800°C일 때 수지함침율 30∼60%별로 탄화하여 세라믹을 제조한 후 물성을 조사하였다. 탄화온도가 증가함에 따라 탄화 후 밀도, 두께감소율, 길이감소율 및 중량감소율도 증가하였다. 수지함침율이 증가함에 따라 탄화 후 밀도, 길이감소율 및 중량 감소율은 증가하였으나 두께감소율은 감소하였다.

To clarify the mechanical behaviour differences between earlywood and latewood, separated the early- wood and the latewood specimens loaded to the rupture with tensile load parallel to the grain. The separated test specimens for tensile test were prepared from douglas fir (Pseudotsuga menziesii) and stress-strain relation was evaluated by optical measurement system using the Digital Image Correlation (DIC), which can visualize strain during the tensile test. The results are summarized as follows: The estimated strain data by universal testing machine show good accordance with that estimated by DIC. There was a difference in the fracture pattern of the earlywood and the latewood of douglas fir that the surface of ruptured earlywood typically simple while that of was somewhat complicate. The longitudinal tensile strength of earlywood specimens of douglas fir at wood height from ground 12.8 m, 9.8 m, 6.7 m and 0.9 m were 51 MPa, 69 MPa, 110 MPa and 114 MPa, while those of latewood were 208 MPa, 234 MPa, 247 MPa and 198 MPa. Elastic modulus in the longitudinal tensile of earlywood speci- mens of douglas fir at wood height from ground 12.8 m, 9.8 m, 6.7 m and 0.9 m were 5458 MPa, 7202 MPa, 9705 MPa and 8761 MPa, while those of latewood were 13747 MPa, 19405 MPa, 17365 MPa and 14044 MPa.

The characteristic of vegetation mat prepared from miscanthus, waste wood chip, perlite and pulp slurry was investigated. The pore rate was increased with amount of pulp slurry. The hydraulic conductivity decreased with the amount of miscanthus in the condition mixed with each other raw materials. With the miscanthus amount, the soil hardness was increased. The peel strength decreased with the mount of miscanthus amount in all case. Hydrogen ion concentration (pH) was the overall alkaline. The MOR of miscanthus based vegetation mat was decreased with the amount miscanthust.

Junsung Park,1,2,* Wonkyung Cho,1,2,* Hee Jun Park,1,2 Kwang-Ho Cha,1,2 Dae-Chul Ha,2,5 Youn-Woong Choi,5 Ha-Young Lee,3 Sun-Hang Cho,5 Sung-Joo Hwang1,41Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; 2College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 3Biomaterials Laboratory, Korea Research Institutes of Chemical Technology, Daejeon, Republic of Korea; 4College of Pharmacy, Yonsei University, Incheon, Republic of Korea; 5Korea United Pharm Inc, Seoul, Republic of Korea *These authors contributed equally to this workObjectives: The purpose of this study was to observe the pharmacokinetic behavior of newly synthesized biocompatible polymers based on polyhydroxyethylaspartamide (PHEA) to be used to coat an iron oxide core to make superparamagnetic iron oxide nanoparticles (SPION).Materials and methods: The isotopes [14C] and [59Fe] were used to label the polymer backbone (CLS) and iron oxide core (FLS), respectively. In addition, unradiolabeled cold superparamagnetic iron oxide nanoparticles (SPION/ULS) were synthesized to characterize particle size by dynamic light scattering, morphology by transmission electron microscopy, and in vivo magnetic resonance imaging (MRI). CLS and FLS were used separately to investigate the behavior of both the synthesized polymer and [Fe] in Sprague Dawley (SD) rats, respectively. Because radioactivity of the isotopes was different by β for CLS and γ for FLS, synthesis of the samples had to be separately prepared.Results: The mean particle size of the ULS was 66.1 nm, and the biodistribution of CLS concentrations in various organs, in rank order of magnitude, was liver > kidney > small intestine > other. The biodistribution of FLS concentrations was liver > spleen > lung > other. These rank orders show that synthesized SPION mainly accumulates in the liver. The differences in the distribution were caused by the SPION metabolism. Radiolabeled polymer was metabolized by the kidney and excreted mainly in the urine; [59Fe] was recycled for erythrocyte production in the spleen and excreted mainly in the feces. The MR image of the liver after intravenous injection demonstrated that [Fe] effectively accumulated in the liver and exhibited high-contrast enhancement on T2-weighted images.Conclusion: This newly synthesized, polymer-coated SPION appears to be a promising candidate for use as a liver-targeted, biocompatible iron oxide MR imaging agent.Keywords: SPION, radiolabeled, polyhydroxyethylaspartamide, pharmacokinetic, liverCorrigendum for this paper has been published

Larch bark was liquefied in the presence of phenol and the obtained liquefied resultant was reacted with formaldehyde to prepare the liquefied bark-modified phenol formaldehyde resin (BPF) in an attempt to apply for preparing straw boards. The dynamic wettability of the BPF resin was evaluated on the surfaces of rice straw; either on the alkali solution treated or untreated rice straw surfaces. A new wetting model was employed to quantify the resins’ penetration performances using the spreading–penetration parameters (K value) as a constant to characterize penetration rate. The bigger the K value was, the stronger the penetration and spreading capacity was. Moreover, the curing kinetics of the BPF resin was also investigated with dynamic differential scanning calorimetry. The results showed that the K value of BPF resin was the highest, followed by those of BPF mixed with polymethylene diphenyl diisocyanate PMDI resin and conventional phenol formaldehyde (PF) resin, indicating that the BPF resin had the best wettability. The activation energy of BPF was close to that reported for wood/phenol/formaldehyde resins, but was higher than that of PF resin. The curing reaction was almost complete at 40 % conversion.

Changes in the physical and mechanical properties and anatomical structures of spruce (Picea) and larch (Larix) specimens before and after fire-retardant impregnation were studied. Results indicated that the static modulus of elasticity (MOE), dynamic modulus of elasticity (DMOE), and the Brinell hardness of the specimens decreased for both wood species upon post-treatment. This could be accounted for by the degradation of hemicelluloses by the phosphorus-based compound, the minute cracks in the latewood cell wall, and the enlarged width of the cell lumen of the specimen resulting from the vacuum-pressure treatment. However, the decreased ratio of the MOR and DMOE to density contributed to lower sound transmission, which is expected to be important in a housing environment.

Miscanthus sacchariflorus straw was used as a raw material for the manufacture of Miscanthus–wood particle composite board with Douglas-fir particles in ratios of 100/0, 80/20, 60/40, 40/60, 20/80, and 0/100. A commercial phenol–formaldehyde resin was used as a binder at 9 and 11 % for target densities of 0.50 and 0.65 g/cm3, respectively. The effects of the Miscanthus/wood particle ratio on the composite board properties were investigated. In addition, the density profile was also examined to improve the understanding of the composite board manufacturing process. Results indicate that the internal bonding value increased drastically in the board containing up to 50 % wood particles, providing a valuable parameter for subsequent research. The board properties were greatly improved with increasing density and binder addition level.

적절한 용도개발이 필요한 조선산업 폐합판의 흡음성능과 기계적 성질을 파악하고자 메이플과 메란티 폐합판을 적층하고 재단하여 폐합판재활용보드를 만들어 전달함수법으로 흡음율을 측정하고 휨강도를 측정하였다. 메이플과 메란티에서 제작된 폐합판 적층 보드의 최대강도는 각각 534와 414 kgf/ $cm^2$ 으로 나타나 상용합판과 비교하여 비슷한 강도성능을 나타내었다. 측정주파수범위에서 메란티 폐합판재활용보드의 흡음율은 0.25 전후의 수치를 나타내어 비교 대상인 섬유판과 신갈나무 시험편보다 높은 흡음율을 나타내었다. 폐합판 재활용보드의 측면을 슬라이스절삭하여 제작한 보드는 우수한 강도적 성능과 흡음성능으로 실내장식재로의 재활용이 기대되었다. 【Sound absorption capability and bending strength of laminated ship-building plywood waste of maple and melanti wood were estimated. Sound absorption coefficients of wood had been measured by the two microphone transfer function method and bending strength examined by three point loading. The maximum strength in bending of laminated ship-building plywood waste of maple and melanti wood were 534 and 414 kgf/ $cm^2$ , respectively. The sound absorption coefficients of laminated ship-building plywood waste were higher than mongolian oak and fiber board, well used construction material. Especially, in the case of laminated ship-building plywood waste of melanti wood, average sound absorption coefficient was about 0.25. It was surmised that the laminated ship-building plywood waste can be used as interior materials because of its good mechanical and sound absorption properties.】

Wood is widely used as a housing material because of its environmental superiority, good mechanical properties, fine appearance, and high thermal insulation properties. However, wood is a sound reflecting material with a relatively low sound absorption capability. It is recognized that the sound absorption capability of wood is influenced by air permeability that varies by the sound incident surface structure. Wood is a porous material which has numerous cylindrical pores in the fiber direction. However, the permeability of wood is relatively low because there are very few continuous pores in wood. The pores in wood are classified into three types: through, blind, and closed. Among these pores, only the through pore has continuous vessel elements that readily permit fluid flow. Furthermore, the formation of pit–aspirations in softwoods or tylosis in hardwoods restricts the air or liquid flow in wood. Improving the permeability of wood has been an interest of many wood researchers because highly permeable solid wood can be treated easily by a functional treatment that allows the good dimensional stability, fire proofing, and other traits. It is generally recognized that wood treatability increases with permeability. Several treatments, such as steaming, extraction with solvents, and degradation with enzymes or microorganisms, have been attempted to increase the permeability of wood. However these treatments did not have a sufficient effect on increasing permeability, and a useful method has not yet been developed. In a previous paper, Kang et al. (2008 a) reported that the delignification treatment by Wise’s method improved wood permeability in the fiber direction, and that the sound absorption capability on the cross sectional surface of Larix kaemferi increased, as compared with the control wood. Also, it was found that the sound absorption capability of a mushroom bed log of Mongolian oak degraded by fungus over four years was 2–3 times higher than that of control wood (Kang et al., 2008 b). On the other hand, steam explosion is used in the field of pulp and fiberboard manufacturing or the wood– based biomass industry and is exposure to violent pressure and temperature changes via steam. For this treatment, the target material is mounted in a closed chamber, and then superheated steam is introduced from a boiler. The superheated steam heats the chamber and target material to a high temperature and pressure, which is maintained for a moment and then discharged abruptly by a blasting device. By this process, high–pressure Changes in Permeability and Sound Absorption Capability of Yellow Poplar Wood by Steam Explosion Treatment

【The objectives of this study were to evaluate the effect of formulation ingredients on the drug release and to optimize the novel sustained release matrix tablet formulations of bupropion hydrochloride. A three factor, three-level Box-Behnken design was used for the optimization procedure, with the amounts of PEO ( $X_1$ ), citric acid ( $X_2$ ) and Compritol 888 ATO ( $X_3$ ) as the independent variables. The selected dependent variables were the cumulative percentage values of bupropion hydrochloride that had dissolved after 1, 4 and 8 hr. Various dissolution profiles of the drug from sustained release matrix tablets were obtained. Optimization was performed for $X_1$ , $X_2$ and $X_3$ using the following target ranges; $30%{\leq}Y_1{\leq}45%$ ; $70{\leq}Y_2{\leq}85%$ ; $85%{\leq}Y_3{\leq}100%$ . The optimized formulation for bupropion hydrochloride was achieved with 12.5% PEO ( $X_1$ ), 2.5% citric acid ( $X_2$ ) and 10% Compritol 888 ATO ( $X_3$ ). The sustained release matrix tablets with the optimized formulation provided a release profile that was close to predicted values. In addition, the dissolution profiles of the sustained release matrix tablet with the optimized formulation were similar to those of the commercial product Wellbutrin $^{(R)}$ SR tablets ( $f_2$ =79.8 79.83).】

Microcrystals of megestrol acetate (MA), a poorly water-soluble drug, were successfully prepared using an antisolvent precipitation technique for improving the dissolution rate. The effective hydrophilic polymers and surfactants used were screened for their abilities to produce smaller particle sizes. Raw micronized MA and processed MA microcrystals were ranked by the Student-Newman-Keuls test in order of increasing particle size and SPAN values as follows: processed MA microcrystals in the presence of polymer and surfactant (mean diameter 1048nm)

This study was aimed at offering basic data to develop a new use of sawdust and rice husk. The results of this study were as follows: In surface temperature of ceramics by resin impregnation rate, the velocity was great in the early time of heat transfer because the temperature precipitously increased to 10 minutes elapsed. Also, the surface temperature of ceramics manufactured in resin impregnation rate of 60~70% indicated the highest. Heat transfer was fast in terms of the changes in surface temperature of ceramics according to the carbonization temperature, as because the density of ceramics made on condition of the carbonization temperature of and was high. Moreover, ceramics maintained heat for a long time because the descent velocity of surface temperature of ceramics was slower than that of heater.

The purpose of this study was to develop and optimize oral controlled-release formulations for tamsulosin hydrochloride using a combination of two cellulose ester derivatives, hydroxypropyl methylcellulose (HPMC) and hydroxypropyl methylcellulose phthalate (HPMCP), with Surelease as a coating material. A three-factor, three-level Box-Behnken design was used to prepare systematic model formulations, which were composed of three formulation variables, the content of HPMC (X(1)) and HPMCP (X(2)) and the coating level (X(3)), as independent variables. The response surface methodology (RSM) and multiple response optimization utilizing the polynomial equation were used to search for the optimal coating formulation with a specific release rate at different time intervals. The drug release percentages at 2, 3 and 5h were the target responses and were restricted to 15-30% (Y(1)), 50-65% (Y(2)) and 80-95% (Y(3)), respectively. The optimal coating formulation was achieved with 10% HPMC and 20% HPMCP at a coating level of 25%, and the observed responses coincided well with the predicted values from the RSM optimization technique. The drug release from pellets coated with the optimized formulation showed a controlled-release pattern (zero-order), in comparison with a commercial product (Harunal capsule). In conclusion, a novel, oral, controlled-release delivery system for tamsulosin hydrochloride was successfully developed by incorporating HPMC and HPMCP as coating additives into Surelease aqueous ethylcellulose dispersion.

The effect of compatibilizing agents on mechanical properties and morphology of a lignocellulosic material-thermoplastic polymer composite was examined. Using rice-husk flour as the reinforcing filler and polypropylene as the thermoplastic matrix polymer, a particle-reinforced composite was prepared, and its mechanical and morphological properties examined as a function of the amount of compatibilizing agent used. In the sample preparation, four levels of filler loading (10, 20, 30 and 40 wt%) and three levels of compatibilizing agent content (1, 3 and 5 wt%) were used, and in the tensile test, six test temperatures (−30, 0, 20, 50, 80 and 110 °C) and five crosshead speeds (2, 10, 100, 500 and 1500 mm/min) were used. The tensile strengths of the composites decreased as the filler loading increased, but the tensile properties were significantly improved with the addition of the compatibilizing agent. Both the notched and unnotched Izod impact strengths were almost the same with the addition of compatibilizing agent. A morphological study revealed that the positive effect of compatibilizing agent on interfacial bonding.

To determine certain physical properties, viz. the thickness swelling and water absorption, and mechanical properties, viz. the tensile strength and Izod impact strength, of lignocellulosic filler reinforced polyolefin bio-composites, polyolefin was used as the matrix polymer and rice-husk flour as the reinforcing filler. Wood flour was also used as a reinforcing filler, and commercial particleboard, medium-density fiberboard and solid woods (red pine and birch) were also included in this study, in order to obtain comparative water absorption behavior measurements. Test samples were prepared, in order to determine the physical and mechanical properties of the bio-composites as a function of filler loading and according to filler type as well as with respect to the thermoplastic polymer itself. The thickness swelling and water absorption of the bio-composites slightly increased as the filler loading increased, but to a negligible extent as compared with the wood-based composites (particleboard and fiberboard) and the solid woods (red pine and birch). The mechanical properties of the composites decreased as the filler loading increased, but the composites had an acceptable strength level. It was concluded that these bio-composites are suitable to be used for the interior of bathrooms, wood decks, food packaging, etc.

The micron or nano-sized lysozyme as a model protein drug was prepared using solution enhanced dispersion by supercritical fluid (SEDS) process at various conditions (e.g., solvent, temperature and pressure) to investigate the feasibility of pulmonary protein drug delivery. The lysozyme particles prepared were characterized by laser diffraction particle size analyzer, scanning electron microscopy (SEM) and powder X-ray diffractometry (PXRD). The biological activity of lysozyme particles after/before SEDS process was also examined. Lysozyme was precipitated as spherical particles. The precipitated particles consisted of 100 - 200 nm particles. Particle size showed the precipitates to be agglomerates with primary particles of size . The biological activity varied between 38 and 98% depending on the experimental conditions. There was no significant difference between untreated lysozyme and lysozyme after SEDS process in PXRD analysis. Therefore, the SEDS process could be a novel method to prepare micron or nano-sized lysozyme particles, with minimal loss of biological activity, for the pulmonary delivery of protein drug.

To determine the possibility of using lignocellulosic materials as reinforcing fillers in the thermoplastic polymer composite, polypropylene as the matrix and rice-husk flour as the reinforcing filler were used to prepare a particle-reinforced composite in order to determine testing data for the physical, mechanical and morphological properties of the composite according to the filler loading in respect to thermoplastic polymer. In the sample preparation, four levels of filler loading (10, 20, 30 and 40 wt.%) were designed. In the tensile test, six levels of test temperature (−30, 0, 20, 50, 80 and 110 °C) and five levels of crosshead speed (2, 10, 100, 500 and 1500 mm/min) were designed. Tensile strengths of the composites slightly decreased as the filler loading increased. Tensile modulus improved with increasing filler loading. Notched and unnotched Izod impact strengths were lowered by the addition of rice-husk flour. The composite became brittle at higher crosshead speed, and showed plastic deformation with increasing test temperature.

The overall aim of this study was to prepare a nasal powder formulation of salmon calcitonin (sCT) using an absorption enhancer to improve its bioavailability. In this work, powder formulations for nasal delivery of sCT were studied using various absorption enhancers and stabilizers. Powders were prepared by two different methods: conventional spray-drying (SD) and novel supercritical fluid-assisted spray-drying (SASD) to investigate the role of CO2 in the particle formation process. The prepared sCT powder formulations were characterized by several analyses; powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), and the Fourier transform infrared (FT-IR) spectroscopy method. The particle size distribution was also evaluated. In vivo absorption tests were carried out in Sprague-Dawley rat using the prepared powder formulations, and the results were compared to those of raw sCT. Quantitative analysis by high-performance liquid chromatography (HPLC) indicated that sCT was chemically stable after both the SD and SASD processes. Results of PXRD, SEM, and FT-IR did not indicate a strong interaction or defragmentation of sCT. The in vivo absorption test showed that SD- and SASD-processed sCT powders increased the bioavailability of the drug when compared to the nasal administration of raw sCT. In addition, SASD-processed sCT exhibited higher nasal absorption when compared with SD-processed sCT in all formulations due to a reduction of particle size. The results from this study illustrate that the preparation of nasal powders using the SASD process could be a promising approach to improve nasal absorption of sCT.

Wonkyung Cho,1,2 Min-Soo Kim,3 Jeong-Soo Kim,2 Junsung Park,1,2 Hee Jun Park,1,2 Kwang-Ho Cha,1,2 Jeong-Sook Park,2 Sung-Joo Hwang1,4 1Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; 2College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 3Department of Pharmaceutical Engineering, Inje University, Gimhae, Republic of Korea; 4College of Pharmacy, Yonsei University, Incheon, Republic of Korea Background: The aim of this study was to develop an optimized solid self-microemulsifying drug delivery system (SMEDDS) formulation for sirolimus to enhance its solubility, stability, and bioavailability. Methods: Excipients used for enhancing the solubility and stability of sirolimus were screened. A phase-separation test, visual observation for emulsifying efficiency, and droplet size analysis were performed. Ternary phase diagrams were constructed to optimize the liquid SMEDDS formulation. The selected liquid SMEDDS formulations were prepared into solid form. The dissolution profiles and pharmacokinetic profiles in rats were analyzed. Results: In the results of the oil and cosolvent screening studies, Capryol™ Propylene glycol monocaprylate (PGMC) and glycofurol exhibited the highest solubility of all oils and cosolvents, respectively. In the surfactant screening test, D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) was determined to be the most effective stabilizer of sirolimus in pH 1.2 simulated gastric fluids. The optimal formulation determined by the construction of ternary phase diagrams was the T32 (Capryol™ PGMC:glycofurol:vitamin E TPGS = 30:30:40 weight ratio) formulation with a mean droplet size of 108.2 ± 11.4 nm. The solid SMEDDS formulations were prepared with Sucroester 15 and mannitol. The droplet size of the reconstituted solid SMEDDS showed no significant difference compared with the liquid SMEDDS. In the dissolution study, the release amounts of sirolimus from the SMEDDS formulation were significantly higher than the raw sirolimus powder. In addition, the solid SMEDDS formulation was in a more stable state than liquid SMEDDS in pH 1.2 simulated gastric fluids. The results of the pharmacokinetic study indicate that the SMEDDS formulation shows significantly greater bioavailability than the raw sirolimus powder or commercial product (Rapamune® oral solution). Conclusion: The results of this study suggest the potential use of a solid SMEDDS formulation for the delivery of poorly water-soluble drugs, such as sirolimus, through oral administration. Keywords: sirolimus, solubility, stability, bioavailability, self-emulsifying drug delivery systems, microemulsion

Pankaj Ranjan Karn,1,3 Wonkyung Cho,1,3 Hee-Jun Park,1,3 Jeong-Sook Park,3 Sung-Joo Hwang1,21Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Yeonsu-gu, Incheon, Republic of Korea; 2College of Pharmacy, Yonsei University, Yeonsu-gu, Incheon, Republic of Korea; 3College of Pharmacy, Chungnam National University, Yuseong-gu, Daejeon, Republic of KoreaAbstract: A novel method to prepare cyclosporin A encapsulated liposomes was introduced using supercritical fluid of carbon dioxide (SCF-CO2) as an antisolvent. To investigate the strength of the newly developed SCF-CO2 method compared with the modified conventional Bangham method, particle size, zeta potential, and polydispersity index (PDI) of both liposomal formulations were characterized and compared. In addition, entrapment efficiency (EE) and drug loading (DL) characteristics were analyzed by reversed-phase high-performance liquid chromatography. Significantly larger particle size and PDI were revealed from the conventional method, while EE (%) and DL (%) did not exhibit any significant differences. The SCF-CO2 liposomes were found to be relatively smaller, multilamellar, and spherical with a smoother surface as determined by transmission electron microscopy. SCF-CO2 liposomes showed no significant differences in their particle size and PDI after more than 3 months, whereas conventional liposomes exhibited significant changes in their particle size. The initial yield (%), EE (%), and DL (%) of SCF-CO2 liposomes and conventional liposomes were 90.98 ± 2.94, 92.20 ± 1.36, 20.99 ± 0.84 and 90.72 ± 2.83, 90.24 ± 1.37, 20.47 ± 0.94, respectively, which changed after 14 weeks to 86.65 ± 0.30, 87.63 ± 0.72, 18.98 ± 0.22 and 75.04 ± 8.80, 84.59 ± 5.13, 15.94 ± 2.80, respectively. Therefore, the newly developed SCF-CO2 method could be a better alternative compared with the conventional method and may provide a promising approach for large-scale production of liposomes.Keywords: supercritical carbon dioxide, liposome, chemical stability, physical stability

Articular cartilage has a limited capacity to heal itself and thus focal defects often result in the development of osteoarthritis. Current cartilage tissue engineering strategies seek to regenerate injured tissue by creating scaffolds that aim to mimic the unique structure and composition of native articular cartilage. Decellularization is a novel strategy that aims to preserve the bioactive factors and 3D biophysical environment of the native extracellular matrix while removing potentially immunogenic factors. The purpose of this study was to develop a procedure that can enable decellularization and recellularization of intact articular cartilage matrix. Full-thickness porcine articular cartilage plugs were decellularized with a series of freeze-thaw cycles and 0.1% (w/v) sodium dodecyl sulfate detergent cycles. Chondroitinase ABC (ChABC) was applied before the detergent cycles to digest glycosaminoglycans in order to enhance donor chondrocyte removal and seeded cell migration. Porcine synovium-derived mesenchymal stem cells were seeded onto the decellularized cartilage scaffolds and cultured for up to 28 days. The optimized decellularization protocol removed 94% of native DNA per sample wet weight, while collagen content and alignment were preserved. Glycosaminoglycan depletion prior to the detergent cycles increased removal of nuclear material. Seeded cells infiltrated up to 100 μm into the cartilage deep zone after 28 days in culture. ChABC treatment enhances decellularization of the relatively dense, impermeable articular cartilage by reducing glycosaminoglycan content. ChABC treatment did not appear to affect cell migration during recellularization under static, in vitro culture, highlighting the need for more dynamic seeding methods.

The wet granulation method was successfully used to manufacture amorphous telmisartan tablets (CNU) for comparison with the spray-drying method, used for Pritor™. Drug crystallinity in the tablet was characterized using differential scanning calorimetry and powder X-ray diffraction, and pharmaceutical properties of the tablets such as hardness, friability, water absorption, and in vitro dissolution in pH 1.2, 4.0, 6.8 and 7.5 were characterized. Especially with regard to the water absorption feature, the CNU tablets showed better performance by maintaining their original structures and by absorbing less water. Since both Pritor™ and CNU tablets had similar physical properties of crystallinity, hardness, friability, and > 50 f2 value in an in vitro dissolution study, the bioequivalence of CNU tablets should be analyzed in a future in vivo study. Therefore, telmisartan tablets can be produced using a more economical and easier method than that used to produce Pritor™ tablets.

The aim of this study was to investigate the effects of micronization and amorphorization of cefdinir on solubility and dissolution rate. The amorphous samples were prepared by spray-drying (SD) and supercritical anti-solvent (SAS) process, respectively and their amorphous natures were confirmed by DSC, PXRD and FT-IR. Thermal gravimetric analysis was performed by TGA. SEM was used to investigate the morphology of particles and the processed particle had a spherical shape, while the unprocessed crystalline particle had a needle-like shape. The mean particle size and specific surface area were measured by dynamic light scattering (DLS) and BET, respectively. The DLS result showed that the SAS-processed particle was the smallest, followed by SD and the unprocessed cefdinir. The BET result was the same as DLS result in that the SAS-processed particle had the largest surface area. Therefore, the processed cefdinir, especially the SAS-processed particle, appeared to have enhanced apparent solubility, improved intrinsic dissolution rate and better drug release when compared with SD-processed and unprocessed crystalline cefdinir due not only to its amorphous nature, but also its reduced particle size. Conclusions were that the solubility and dissolution rate of crystalline cefdinir could be improved by physically modifying the particles using SD and SAS-process. Furthermore, SAS-process was a powerful methodology for improving the solubility and dissolution rate of cefdinir.

According to expansion of the market for portable products such as mobile phone, digital camera and PMP, adoption of WLP for various devices was increasing. Recently, WLP was being applied to higher pin count device as well as lower pin count device. In case that WLP is applied to higher pin count device, various reliability issues are expected from large die size and fine solder ball pitch. The more die size increase and contact area decrease, the more solder joint is fragile, especially at the outermost. To apply the WLP to mobile application, the reliability of various types of WLP in terms of die size, UBM (Under Bump Metallurgy) type, solder material and solder ball pitch have been evaluated at package and board level. First, the reliability for WLP of 3 mm ? 3 mm size and 0.5 mm solder ball pitch using solder ball with Sn3.0Ag0.5Cu solder composition on electroplated Cu/Ni/Au UBM had been evaluated by employing TC (Thermal Cycling) and HTS (High Temperature Storage) at package level and passed TC 2000cycles and HTS 1000hrs. Second, the reliability for WLP of 3.7 mm ? 3.9 mm size and 0.5 mm solder ball pitch using solder ball with Sn3.0Ag0.5Cu solder composition on electroplated Cu/Ni/Au UBM had been evaluated at package level and passed TC 500cycles, HTS 1000hrs and PCT 168hrs. Third, the reliability for WLP of 4 mm ? 4 mm size and 0.4 mm solder ball pitch using Sn3.0Ag0.5Cu on electroplated Ni UBM and ENIG (Electroless Nickel Immersion Gold) finished substrate has been evaluated by employing TC, THT (Temperature Humidity Test), 4-point bending and Drop test at board level. All items electrically passed except the one TC sample without underfill. As a result of cross-section analysis of TC samples without underfill, some solder crack on PCB side were found. For the 4-point bending samples, separation between Cu pad and TiW were found at die side of outermost row and crack between IMC and Ni Pad was found at PCB side of outermost. In case of drop test, there was no issue except the PCB resin crack under the outermost bonding pad. Finally, WLP of 6 mm ? 6 mm size and 0.4 mm solder ball pitch has fabricated and the reliability of TC, HTS, PCT, drop and electro-migration are being evaluated.

The purpose of this study was to prepare microspheres loaded with hydrophilic drug, bupivacaine HCl using poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). Microspheres were prepared with varying the PLGA/PLLA ratio with two different levels of bupivacaine HCl (5 and 10%) using a supercritical anti-solvent (SAS) technique. Microspheres ranging from 4-10 microm in geometric mean diameter could be prepared, with high loading efficiency. Powder X-ray diffraction (PXRD) revealed that bupivacaine HCl retained its crystalline state within the polymer and was present as a dispersion within the polymer phase after SAS processing. The release of bupivacaine HCl from biodegradable polymer microspheres was rapid up to 4 h, thereafter bupivacaine HCl was continuously and slowly released for at least 7 days according to the PLGA/PLLA ratio and the molecular weight of PLLA.

Kwang-Ho Cha,1,3 Kyung-Jin Cho,3 Min-Soo Kim,4 Jeong-Soo Kim,3 Hee Jun Park,1,3 Junsung Park,1,3 Wonkyung Cho,1,3 Jeong-Sook Park,3 Sung-Joo Hwang1,21Yonsei Institute of Pharmaceutical Sciences, 2College of Pharmacy, Yonsei University, Incheon, Republic of Korea; 3College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 4Department of Pharmaceutical Engineering, Inje University, Gimhae, Republic of KoreaBackground: The aim of this study was to enhance the bioavailability of fenofibrate, a poorly water-soluble drug, using a melt-adsorption method with supercritical CO2.Methods: Fenofibrate was loaded onto Neusilin® UFL2 at different weight ratios of fenofibrate to Neusilin UFL2 by melt-adsorption using supercritical CO2. For comparison, fenofibrate-loaded Neusilin UFL2 was prepared by solvent evaporation and hot melt-adsorption methods. The fenofibrate formulations prepared were characterized by differential scanning calorimetry, powder x-ray diffractometry, specific surface area, pore size distribution, scanning electron microscopy, and energy-dispersive x-ray spectrometry. In vitro dissolution and in vivo bioavailability were also investigated.Results: Fenofibrate was distributed into the pores of Neusilin UFL2 and showed reduced crystal formation following adsorption. Supercritical CO2 facilitated the introduction of fenofibrate into the pores of Neusilin UFL2. Compared with raw fenofibrate, fenofibrate from the prepared powders showed a significantly increased dissolution rate and better bioavailability. In particular, the area under the drug concentration-time curve and maximal serum concentration of the powders prepared using supercritical CO2 were 4.62-fold and 4.52-fold greater than the corresponding values for raw fenofibrate.Conclusion: The results of this study highlight the usefulness of the melt-adsorption method using supercritical CO2 for improving the bioavailability of fenofibrate.Keywords: fenofibrate, melt adsorption, supercritical CO2, bioavailability

Min-Soo Kim1, Jeong-Soo Kim1, Hee Jun Park1, Won Kyung Cho1,3, Kwang-Ho Cha1,3, Sung-Joo Hwang2,31College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea, 2College of Pharmacy, 3Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of KoreaBackground: The aim of this study was to improve the physicochemical properties and bioavailability of poorly water-soluble sirolimus via preparation of a solid dispersion of nanoparticles using a supercritical antisolvent (SAS) process.Methods: First, excipients for enhancing the stability and solubility of sirolimus were screened. Second, using the SAS process, solid dispersions of sirolimus-polyvinylpyrrolidone (PVP) K30 nanoparticles were prepared with or without surfactants such as sodium lauryl sulfate (SLS), tocopheryl propylene glycol succinate, Sucroester 15, Gelucire 50/13, and Myrj 52. A mean particle size of approximately 250 nm was obtained for PVP K30-sirolimus nanoparticles. Solid state characterization, kinetic solubility, powder dissolution, stability, and pharmacokinetics were analyzed in rats.Results: X-ray diffraction, differential scanning calorimetry, and high-pressure liquid chromatography indicated that sirolimus existed in an anhydrous amorphous form within a solid dispersion of nanoparticles and that no degradation occurred after SAS processing. The improved supersaturation and dissolution of sirolimus as a solid dispersion of nanoparticles appeared to be well correlated with enhanced bioavailability of oral sirolimus in rats. With oral administration of a solid dispersion of PVP K30-SLS-sirolimus nanoparticles, the peak concentration and AUC0→12h of sirolimus were increased by approximately 18.3-fold and 15.2-fold, respectively.Conclusion: The results of this study suggest that preparation of PVP K30-sirolimus-surfactant nanoparticles using the SAS process may be a promising approach for improving the bioavailability of sirolimus.Keywords: sirolimus, solubility, bioavailability, supercritical antisolvent, nanoparticles