Solution Crystallization Method Research Articles

Revealing the mechanism of polymer inhibition of 2,4-dichlorophenoxyacetic acid Polymorphs phase transition by experimental and molecular dynamics simulation

It is well-established that the occurrence of solution-mediated phase transformation makes the precise preparation of pure metastable forms of drugs by solution crystallization methods extremely challenging. This paper demonstrates that the polyvinylpyrrolidone (PVP) and N-vinyl-2-pyrrolidone and vinylacetate (PVPVA) polymers can effectively prevent crystal form transformation of the 2,4-dichlorophenoxyacetic acid (2,4-D) in the solution. We performed the induction time and crystal growth rate experiments at different supersaturation levels. The results showed that the polymer additives can significantly prolong the induction time and have an inhibition effect on crystal nucleation. The PVP and PVPVA almost completely inhibited the crystal growth in both the length and width directions. Molecular dynamics simulations reveal that the interaction energy between the polymer and crystal face determines the magnitude of the inhibition effect on the crystal growth of stable polymorph Form I. These results suggest that polymorph control during the solution crystallization process can be achieved by adding polymer additives.

Glutaric acid purification by coupled solution crystallization and melt crystallization

The mixed dibasic acids (DBA) is a by-product during adipic acid (ADA) production by oxidation of cyclohexanol or cyclohexanone, which contains large amount of glutaric acid (GA) with ADA and succinic acid (SA). In this work, we have explored the feasibility of the coupled solution crystallization and melt crystallization for the purification of GA. To obtain fundamental thermodynamic properties for the process design, the gravimetric method was used to measure the solubility of the three dibasic acids in water from 293.15 K to 345.15 K at atmospheric pressure. The results showed that GA was the most soluble component while all solubility increased with increasing temperature. Therefore, it is reasonable to concentrate GA in the liquid phase by cooling crystallization. Similarly, the ternary solid-liquid melt equilibrium phase diagram was constructed based on the experimental data of the three binary subsystems (GA-ADA, GA-SA, ADA-SA). It was found that the concentrated GA after solvent evaporation could be purified by melt crystallization efficiently. Thus a coupled solution crystallization and melt crystallization process was designed. With the operated operating parameters, the purity of GA could reach 99.06% by secondary melt crystallization. Overall, the coupled solution crystallization and melt crystallization method to separate DBA has proven to be effective.

Highly Efficient Production of Desired Solid Forms of Drugs with Improved Mechanical Properties via an Organic Solvent-Free Sublimation Process

The pharmaceutical industry is required to constantly broaden its development areas and accelerate technical transformation because of the continued global rise in medicine consumption. However, the usage of organic solvents in pharmaceutical production results in up to 20 million tons annually of chemical waste, causing a serious environmental problem. Here, we proposed a solvent-free sustainable chemical technology, sublimation crystallization, for highly efficient screening and preparation of pharmaceutical solid forms (i.e., polymorphs), which eliminates the wastes associated with solvent use from the source. By adjusting the parameters of sublimation crystallization, we have obtained multiple polymorphs of several important drugs, including the antituberculosis drug pyrazinamide (PZA) and nonsteroidal anti-inflammatory drugs (NSAIDs), flufenamic acid (FFA) and mefenamic acid, particularly γ form of PZA and polymorphs IV and VII of FFA, which are difficult to produce from conventional solution crystallization methods. Mechanical property measurements from both powder and single crystal tests reveal that the γ form of PZA readily prepared by sublimation crystallization has the most excellent tabletability properties. In situ crystal growth observations indicate a direct vapor-to-crystal growth mechanism for the sublimation crystallization process consistent with conventional vapor phase deposition. Furthermore, the governing factors and growth mechanisms of sublimation and solution crystallization processes were analyzed and discussed, and it was found that the rate-limiting step of crystal growth is the surface-integration process in solution crystallization, whereas it becomes the surface diffusion process in sublimation crystallization. Overall, our developed sublimation crystallization provides a promising green technology for the development and production of (new) drugs, broadening the thinking behind the development of sustainable chemicals.

Modified luminescent properties from green afterglow to efficient orange emission in zirconium-based organometallic chloride scintillator by Sb3+ doping

Zero-dimension (0D) metal halides based on metals with the 5s2 lone pair have attracted great attentions due to their strong triplet broadband emission. However, the conversion from weak afterglow to efficient and fast photoluminescence by regulating the composition of 0D metal halides is still a tough challenge. Herein, Sb3+ ions-doped 0D (Ph4P)2ZrCl6·4CH3CN metal halides were synthesized by a simple solution crystallization method. Compared with the weak triplet green 560 nm afterglow from the organic Ph4P+ components, the emission of the Sb3+-doped material exhibits a strong orange photoluminescence at 660 nm with a high photoluminescence quantum yield of 72% by a host to dopant energy transfer process. In addition, a flexible large-sized X-ray scintillator screen with an area of 16 cm2 was prepared using polydimethylsiloxane as the host matrix, which exhibits excellent scintillation properties with light yields of 8,290 photons/MeV, low detectable limits of 0.986 μGy/s, and a near-infrared broadband emission from 600 nm to 850 nm under steady-state X-ray excitation, which is highly compatible with the response range of the long-wave sensitive silicon-based photodetectors. Therefore, this work not only provides a deep insight into the energy transfer process in the 0D metal halide materials but also opens an alternative approach to realize flexible large-size near-infrared X-ray imaging based on the 0D metal halide scintillator.

Tailoring Crystallization Growth of Small‐Molecule Organic Semiconductors by Modification with Conjugated Polymers for Organic Field‐Effect Transistors

AbstractBy investigating a typical small molecule, 6,13‐bis(triisopropylsilylethynyl) pentacene (TIPS), the crucial influence of conjugated polymers as additives on modulating the crystallization processes, crystalline structures, and carrier transport is unraveled. The conjugated polymer additives including poly[2,5‐bis(3‐alkylthio‐phen‐2‐yl)thieno(3,2‐b)thiophene (PBTTT) and poly(9,9‐di‐n‐octylfluorene‐alt‐benzothiadiazole) (F8BT) via a solution crystallization method can bring in crystalline structures that are not accessible by nonconjugated polymers, demonstrating superior order and enhanced carrier transport without external treatments. In such cases, polymorphism of the small molecules is manipulated by the features of conjugated polymers in the blend. According to optical microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X‐ray diffraction (XRD), different crystalline morphologies such as fibrous crystals from TIPS/PBTTT and rod‐like crystals from TIPS/F8BT are observed, which is determined by the crystalline habitats and solubility of conjugated polymers in small‐molecule/polymer blends. Meanwhile, organic field‐effect transistors (OFETs) based on TIPS/PBTTT and TIPS/F8BT blends are prepared for the purpose of exploring the electrical characteristics, yielding the mobility of 0.3 and 3.53 cm2 V−1 s−1, respectively. The conjugated‐polymer‐mediated polymorphism of small molecules can provide an attractive platform to explore the fundamental relationship between crystal stacking and electrical behaviors without altering the chemical structure.

Co-crystals of ezetimibe: design, formulation and evaluation

Crystallization is a very promising approach to design solid-state properties with desired physicochemical properties. The objective of the present research work was to design, formulate and evaluate Ezetimibe cocrystals. In the present study, Cocrystals of Biopharmaceutics Classification System (BCS) Class II drug, Ezetimibe using 3-pyridine carboxamide as coformer were prepared. 3-pyridine carboxamide was selected as suitable coformer from initial screening. Cocrystals of Ezetimibe with 3-pyridine carboxamide were obtained in 1:1 ratio by solution crystallization method. Hot stage microscopy indicated interaction among drug and coformer. Differential scanning calorimetry spectra of formulated cocrystals reflected shift in endotherm corresponding to melting point in comparison to Ezetimibe, coformer and physical mixture. Fourier transform infrared (FTIR) spectra indicated towards shifting in specific bands characteristic of Ezetimibe. X-Ray Powder Diffraction pattern pointed towards crystallinity and difference in 2θ values of characteristic peaks. The cocrystals showed faster dissolution rate in comparison to Ezetimibe and marketed sample. Pharmacodynamic investigation reveals that cocrystals reduced lipid levels in serum in comparison to pure drug. Pharmaceutical Cocrystals of Ezetimibe with 3-pyridine carboxamide represented a promising approach to improve bioavailability of Ezetimibe drug.

Poly (3-hexylthiophene) (P3HT) Crystalsomes: Tiling 1D Polymer Crystals on a Spherical Surface.

Polymer crystalsomes are a class of hollow crystalline polymer nanoparticles with shells formed by single crystals with broken translational symmetry. They have shown intriguing mechanical, thermal, and biomedical properties associated with spherical packing. Previously reported crystalsomes are formed by quasi-2D lamellae which can readily tile on a spherical surface. In this work, the formation of polymer crystalsomes formed by 1D polymer crystals is reported. Poly (3-hexylthiophene) (P3HT) is chosen as the model polymer because of its 1D growth habit. P3HT crystalsomes are successfully fabricated using a miniemulsion solution crystallization method, as confirmed by scanning electron microscopy and transmission electron microscopy. X-ray diffraction (XRD) and selected area electron diffraction experiments confirm that P3HT crystallized into a Form I crystal structure. XRD, differential scanning calorimetry and UV-Vis results reveal curvature-dependent structural, thermal and electro-optical properties.

Glibenclamide–malonic acid cocrystal with an enhanced solubility and bioavailability

Objective The objective of the work is to enhance the solubility, dissolution, and pharmacokinetic properties of glibenclamide (GLB) via cocrystallization technique. Significance Glibenclamide is an oral hypoglycemic agent used for treating non-insulin-dependent (type II) diabetes mellitus. It exhibits poor aqueous solubility and oral bioavailability, thereby compromising its therapeutic effect. Therefore, utilizing cocrystal approach for enhancing the solubility will modulate the physicochemical properties of GLB without altering its molecular structure. Methods Cocrystal was prepared by solution crystallization method using coformer malonic acid. The cocrystal was characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FT-IR) studies. The prepared cocrystal was subjected to solubility, in vitro dissolution, and pharmacokinetic studies. Results The DSC endotherms, PXRD patterns, and the FT-IR spectra of the cocrystal established the formation of a cocrystal. The formation of eutectic mixture was refuted upon comparing the DSC endotherm and PXRD pattern of the cocrystal with that of the physical mixture. GLB showed a twofold enhancement in solubility and a significant improvement in the rate of dissolution (p < 0.05, independent t-test) after cocrystallization. The pharmacokinetic parameters on male Sprague Drawly rats showed 1.45 enhancement in AUC0–24 and 1.36-fold enhancement in the C max of GLB as compared to the pure drug. Conclusion These findings demonstrate that cocrystallization technique was able to tailor the solubility and dissolution profile of GLB leading to an enhanced pharmacokinetic property.

A Novel Co-crystallization Technique to enhance the Physicochemical property of BCS Class-II drugs using Efavirenz as a model drug

Pharmaceutical co-crystallization, a novel technique, provides for alteration and tailoring of physicochemical properties of active pharmaceutical ingredients (API) notwithstanding maintaining the intrinsic activity of the drug molecule. In the present work, co-crystals of efavirenz (EFA) were prepared with selected conformers of GRAS (Generally Recognized as Safe) status wise salicylic acid (SA) and benzoic acid (BA) using solution crystallization method to improve its dissolution. The assembly of crystal structure was evaluated by means of fourier transformation infrared spectroscopy (FTIR), x-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and nuclear magnetic resonance (NMR). Saturation solubility and in vitro dissolution studies were further employed to investigate co-crystals. Equilibrium solubility profile of EFA-SA and EFA-BA exhibits an enhancement of 1.60 and 1.29 folds of solubility of efavirenz co-crystals as compared to the pure drug. Pharmacokinetic study performed in rats showed AUC0-∞ for co-crystals formulation was higher (13.15±0.02µg hmL−1) than the pure drug suspension formulation 7.85±0.03µg hmL−1. Statistically, AUC0-t of the co-crystal formulation was significantly higher (p&lt;0.05) as compared to pure drug suspension formulation. Higher amount of drug concentration in blood indicated better systemic absorption of efavirenz from co-crystals formulation as compared to the pure drug suspension formulation.

Morphological and Chemical Analysis of Low-Density Polyethylene Crystallized on Carbon and Clay Nanofillers.

Interest in carbon and clay-based nanofillers has grown in recent years. The crystallization behavior of low-density polyethylene (LDPE) was studied using a variety of notable nanofillers used in engineering applications and prepared using a solution crystallization method. Carbon nanotubes (CNTs), graphene oxide nano-platelets, clay (montmorillonite), and modified clay (surface-modified with trimethyl stearyl ammonium) were used to induce heterogeneous crystallization of LDPE. The crystallized LDPE samples, imaged using scanning and transmission electron microscopy, revealed different microstructures for each nanohybrid system, indicating these various nanofillers induce LDPE lamellae ordering. The underlying interactions between polymer and nanofiller were investigated using FTIR spectroscopy. X-ray diffraction (XRD) was used to determine crystallinity. This work examines how the differences in morphology and chemical structure of the nanofillers induce changes in the nucleation and growth of polymer crystals. These results will provide guidance on functional design of nano-devices with controlled properties.

Perovskite (PEA)2Pb(I1-xBrx)4 single crystal thin films for improving optoelectronic performances

Single crystal perovskites have become advanced materials in many applications due to their excellent optoelectronic properties and stability. However, bulk single crystal with unsatisfactory thickness would limit its application in flexible optoelectronic devices. Here, large-area two-dimensional perovskite (PEA) 2 Pb(I 1-x Br x ) 4 (x = 0–1) single crystal thin films (SCTFs) were prepared with a space-confined solution temperature-lowering crystallization method. Through rational control of halide compositions, we succeeded in growing (PEA) 2 Pb(I 1-x Br x ) 4 SCTFs with x increased from 0 to 1, which achieved band gap fine-tuning from 2.28 to 2.95 eV, corresponding to the edge of the absorption spectrum adjusted from green to blue. Using the excellent (PEA) 2 Pb(I 1-x Br x ) 4 SCTFs properties, a series of photodetectors were designed. The photodetector based on the I-rich composition (x = 0.1) exhibits optimum photosensitivity ( I light / I dark = 2 × 10 4 ) at wavelength of 473 nm (0.52 mW cm −2 ), while the photodetector based on the Br-rich component (x = 0.8) has the highest I light / I dark ratio (~1.6 × 10 4 ) under 405 nm (0.52 mW cm −2 ), showing the selectivity in light detection. At the same time, those devices show extremely low dark current, high specific detectivity (~10 13 Jones) and excellent stability. • Perovskite (PEA) 2 Pb(I 1-x Br x ) 4 (x = 0–1) SCTFs are prepared with a space-confined solution crystallization method. • Uniform Br doping in (PEA) 2 Pb(I 1-x Br x ) 4 (x = 0–1) SCTFs is evaluated by EDS analysis and elemental mapping. • Perovskite (PEA) 2 Pb(I 1-x Br x ) 4 (x = 0–1) SCTFs achieve band gap fine-tuning from 2.28 to 2.95 eV by Br doping. • Perovskite (PEA) 2 Pb(I 1-x Br x ) 4 SCTFs photodetectors show the selectivity in light detection under different wavelength.

Anomalous sensitivity related to crystal characteristics of 2,6-diamino-3,5-dinitropyrazing-1-oxide (LLM-105)

Sensitivity is one of the greatest concerns in explosive materials, and its underlying mechanism remains ambiguous. In this study, 2,6-diamino-3,5- dinitropyrazine -1-oxide (LLM-105) crystals with different morphologies, such as crosswise, needle, plate, block, diamond, and spherical shapes, were prepared using a solution crystallization method, and their crystal characteristics and sensitivity were investigated. It was found that the H50 values (impact sensitivity) of LLM-105 vary within an extremely wide range of 33.8–112.2 cm and are mainly influenced by the particle morphology, crystal integrity, particle surface defects, and roughness, but are mostly independent of intracrystalline defects and particle sizes. The friction sensitivities of all samples are zero and are unaffected by the crystal characteristics. The G50 values (shock sensitivity) are within the range of 0–6.9 mm, increasing with decreasing particle sizes and the apparent crystal density. Notably, LLM-105 crystals with a spherical shape, good integrity, smooth surface, and fewer defects are insensitive to impact and shock impulse. The relationships between the crystal characteristics and the sensitivity of LLM-105 are extremely complex and show some abnormal phenomena, which can be attributed to the crystal packing style and aggregated microstructures of LLM-105.

Confined Crystal Melting in Edgeless Poly(l-lactic acid) Crystalsomes.

Polymer single crystals tend to be quasi two-dimensional (2D) lamellae and their small lateral surfaces are the starting points of lamella melting and thickening. However, the recently discovered crystalsomes, which are defined for hollow single crystal-like spherical shells, are edgeless, self-confined, and incommensurate with translational symmetry. This work concerns the structure and melting behavior of these edgeless crystalsomes. Poly(l-lactic acid) crystalsomes were grown using a miniemulsion solution crystallization method. Differential scanning calorimetry and in situ wide-angle X-ray diffraction were used to follow the structural evolution of the crystalsomes upon heating. Our results demonstrated that the structure and melting behavior of crystalsomes are curvature-dependent and significantly different from their flat crystal counterpart.

Pharmaceutical Cocrystal: A Novel Approach to Tailor the Biopharmaceutical Properties of a Poorly Water Soluble Drug.

The present study reports the formation of a cocrystal of candesartan with the coformer methyl paraben, its characterization and determination of its bioavailability. Candesartan is a poorly water-soluble drug having an anti-hypertensive activity. The recent patents on the cocrystals of the drugs Progesterone (US9982007B2), Epalrestat (EP2326632B1), Gefitinib (WO2015170345A1), and Valsartan (CN102702118B) for enhancement of solubility, helped in selection of the drug for this work. Candesartan cocrystal was prepared by solution crystallization method. The formation of a new crystalline phase was characterized by Differential Scanning Calorimetry (DSC), Fourier Transform Infrared (FTIR) and Powder X-ray Diffraction (PXRD) studies. Saturation solubility studies were carried out in ethanol: water (50:50 % v/v) mixture. The dissolution studies were conducted in 900 ml of phosphate buffer at pH 7.4(I.P.) with 0.7% w/w of Tween 20 at 50 rpm, maintained at a temperature of 37±0.5°C in a USP type II dissolution apparatus. The pharmacokinetic behavior of candesartan and its cocrystal was thereof investigated in male Wistar rats. There was 6.94 fold enhancement in the solubility of candesartan after its cocrystallization. The dissolution profile of the cocrystal exhibited significant improvement in solubility at 60 and 120 minutes and it remained stable in ethanol: water (50:50%v/v) mixture for 48 h as confirmed by PXRD studies. The AUC0-24of the cocrystal was found to be increased by 2.9 fold in terms of bioavailability as compared to the pure drug. The prepared cocrystal was found to be relatively more soluble than the pure drug and also showed an enhanced oral bioavailability as compared to the pure drug.

Bamboo-like ultra-high molecular weight polyethylene fibers and their epoxy composites

It is important for most structural material to achieve both good strength and toughness. However, they are generally mutually exclusive, which is the lower-strength, and hence higher-toughness. Ultra-high molecular weight polyethylene (UHMWPE) fibers have excellent mechanical properties, unfortunately, the interfacial adhesion of UHMWPE fiber reinforced polymer composites is extremely low. Inspired by the shape of bamboo in nature, we herein designed and prepared UHMWPE fiber with new structure. UHMWPE fibers were periodically decorated with polymer lamellar crystals using a polymer solution crystallization method, resulting in bamboo-like structure. It was showed that the strength and toughness of bamboo-like UHMWPE fibers reinforced epoxy (EP) composites were improved simultaneously, which were attributed to the special interface structure between UHMWPE fibers and EP. The strengthening mechanism of the composites is mainly due to the bamboo-like crystals on the fiber surface, which plays a role of pinning and increases the crack propagation path.

Determination of Solubility and Nucleation Kinetics of Valnemulin Hydrochloride Solvate

Dissolution and nucleation are the two indispensable processes to be investigated in order to understand crystallization behavior of a compound. In this study, the crystalline valnemulin hydrochloride water–ethanol solvate (VHWES) was successfully prepared by the solution crystallization method. The solubility of VHWES in ethanol + water binary solvents was measured at eight different temperatures from 278.15 to 313.15 K using a static analytical method, and these solubility data was correlated by several different thermodynamic models. The model parameters were calculated and analyzed based on the difference between calculated results and measured solubility data. It was found that the results correlated by thermodynamic models are in good agreement with the measured solubilities. Furthermore, the nucleation process of VHWES in the ethanol + water (molar ratio of 1:1) system was investigated in detail. The induction times of nucleation and metastable zone width were measured at various temperatures under different supersaturations, and interfacial energies were calculated using classical nucleation theory. The results reveal that homogeneous nucleation predominates under high supersaturation while heterogeneous nucleation predominates under low supersaturation.

Naringenin Cocrystals Prepared by Solution Crystallization Method for Improving Bioavailability and Anti-hyperlipidemia Effects.

Naringenin exerts anti-inflammatory, hypolipidemic, and hepatoprotective effects; however, it shows low oral bioavailability because of poor water solubility. In this work, cocrystals of naringenin were formed to address these issues. Using the solution crystallization method, various naringenin cocrystals were prepared with different cocrystal coformers, including naringenin-nicotinamide, naringenin-isonicotinamide, naringenin-caffeine, naringenin-betaine, and naringenin-L-proline. The formation of these cocrystals was assayed by using DSC, XRD, and FT-IR spectroscopy. The stoichiometric ratio of naringenin and the CCFs in the corresponding cocrystals was investigated by NMR. The solubility of naringenin, as well as its dissolution rate, was markedly improved by forming cocrystals. The oral bioavailability of naringenin administered as naringenin-L-proline and naringenin-betaine cocrystals was achieved significantly greater than that of pure naringenin (p < 0.05). In particular, the Cmax of naringenin-L-proline and naringenin-betaine cocrystals were 2.00-fold and 3.35-fold higher, and the AUC of naringenin-L-proline and naringenin-betaine cocrystals were 2.39-fold and 4.91-fold, respectively, higher than pure naringenin in rats. With the naringenin-betaine cocrystals for oral delivery, the drug distribution in the liver was significantly increased compared to pure naringenin. Accordingly, the naringenin-betaine cocrystals showed improved anti-hyperlipidemia effects on the C57 BL/6J PNPLA3 I148M transgenic mouse hyperlipidemia model. Collectively, cocrystal formation is a promising way to increase the bioavailability of naringenin for treating hyperlipidemia.

Water droplet on inclined dusty hydrophobic surface: influence of droplet volume on environmental dust particles removal.

A water droplet's behavior on an inclined hydrophobic surface in the presence of environmental dust particles is considered and the droplet's dynamics are analyzed pertinent to self-cleaning applications. A polycarbonate wafer is crystallized using the solution-crystallization method to generate hierarchically distributed micro/nano-sized spherules and pillars on the surface. To improve the wetting state and lower the contact angle hysteresis, functionalized silica particles are synthesized and, later, deposited on the crystallized surface. Environmental dust particles are collected and characterized in terms of elemental composition, size and shape. A high-speed camera is used to monitor a water droplet's behavior on the inclined hydrophobic surface with and without the presence of dust particles. The influence of droplet volume on the dust particle removal rate from the inclined hydrophobic surface is assessed. It is found that the functionalized silica particles deposited on the surface result in a droplet contact angle in the order of 158 ± 2° and contact angle hysteresis of 2 ± 1°. The water droplet mainly rolls on the inclined hydrophobic surface and the sliding velocity remains almost 13% of the transverse velocity of the droplet. Droplet wobbling is influenced by the dust particles and the droplet size; in which case, increasing the droplet volume enhances the droplet puddle thickness on the hydrophobic surface. The cloaking of the droplet fluid onto the dust particles causes mixing of the dust particles with the droplet fluid while enhancing the particle removal from the hydrophobic surface. Increasing the droplet volume slightly enhances the size of the area of the cleaned surface.

Enhanced Solubility of Telmisartan Phthalic Acid Cocrystals within the pH Range of a Systemic Absorption Site.

Telmisartan (TLM), a nonpeptide angiotensin II antagonist, is widely prescribed for treating arterial hypertension and marketed by the innovator with the trade name of Micardis and Micardis plus. Telmisartan exhibits low aqueous solubility in the pH range of 3–7, which is the physiological pH. For addressing the issue of poor solubility of TLM, its commercial form makes use of inorganic alkalinizers. The present work illustrates the attempt to improve the solubility of telmisartan via a crystal engineering approach. A novel solid form of telmisartan with phthalic acid was obtained through the solution crystallization method (TPS) and the reaction crystallization method (TPR). Both the forms (TPS and TPR) were thoroughly characterized by powder diffraction X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, and 1H NMR and were identified to be two different crystalline forms. Solubility studies of TPS and TPR were conducted at varying pH of phosphate buffer, and they exhibited 11-fold and 22-fold increased solubility, respectively, when compared to that of the pure drug at pH 5, which is within the pH of small intestine at which telmisartan is best absorbed orally from the systemic circulation.

(Keynote) Physics, Materials and Applications of High-Mobility Organic Transistor Circuits

Development of functional materials and understanding of the microscopic mechanisms mutually benefit through their close interaction. To accelerate development of organic semiconductor devices for industrial application to flexible and printed electronics, it has been essential to understand the mechanism of charge transport in conjunction with molecular-scale charge transfer. We examine the idea that high-mobility charge transport in newly developed solution-crystalized organic transistors is caused by band-like charge transport, using several different methods to probe coherence in the electronic charge. These materials, being essentially different from conventional organic semiconductors with basically incoherent hopping-like transport, often show high values of mobility exceeding 10 cm2/Vs so that high-speed organic transistor circuits are realized. We first employ Hall-effect measurement which differentiates the coherent band transport from site-to-site hopping. Rubrene single crystal transistors were the first to show the Hall voltage obviously indicating the band transport with the mobility exceeding 10 cm2/Vs, whereas the result of pentacene single crystal transistors with the mobility around 1 cm2/Vs suggested somewhat intermediate between coherent and incoherent charge transport. An interesting crossover from hopping-like to band-like transport is also found by gradually changing temperature and external pressure, clearly indicating involvement of intermolecular phonons. Stimulated by the experiments in the early stage, such materials as decyldinaphthobenzo-dithiophene derivatives (Cn-DNBDT) are newly synthesized to stabilize the molecular position in the crystal form by introducing steric hindrance in their p-conjugated cores. With the development of solution-crystallization method, arrays of the single crystal transistors are formed to the size of wafer scale on plastic substrates. The mobility is as high as 20 cm2/Vs for p-type compound and 4 cm2/Vs for an n-type compound. We measured spin relaxation time of the electric-field induced carriers down to 4.2 K using the large-area ultra-thin single-crystal transistors, so that electron-spin relaxiation is precisely investigated. We found that the spin-relaxation follows the Elliott-Yafet mechanism so that the spin life time is consistently elongated at low temperatures due to reduced phonon scattering via spin-orbit coupling. The result suggest that charge carrier mobility can as high as 650 cm2/Vs with minimized phonon scattering at the low temperature. This presentation also focuses on recent development of key technologies for printed LSIs which can provide future low-cost platforms for RFID tags, AD converters, data processors, and sensing circuitries. Such prospect bears increasing reality because of recent research innovations in the field of material chemistry, charge transport physics, and solution processes of printable organic semiconductors. With excellent chemical and thermal stability in recently developed new materials, we are developing simple integrated devices based on CMOS using p-type and n-type printed organic FETs. Particularly important are new processing technologies for continuous growth of the organic single-crystalline semiconductor “wafers” from solution and for lithographical patterning of semiconductors and metal electrodes. Successful rectification and identification are demonstrated at 13.56 MHz with printed organic CMOS circuits.