Functionalization of Polymeric Materials to Control the Kinetics of Pharmaceutical Crystallization

Frank, Derek S ProQuest Dissertations & Theses University of Mich 2019 해외박사(DDOD)

Crystallization is ubiquitous in the pharmaceutical industry and is employed in the design, development, and manufacturing of drugs. In particular, controlling the kinetics of crystallization can improve the efficiency of batch crystallization processes and ensure the physical stability of metastable drug products. Although the crystallization rate of a small-molecule pharmaceutical is often tuned by altering parameters such as pharmaceutical concentration, temperature, or solvent, there is a considerable demand for additives that can alter crystallization kinetics without changing the thermodynamic solubility of a pharmaceutical. However, the relationship between the molecular structure and impact of an additive on crystallization kinetics is still poorly understood. This dissertation presents structure-function relationships dictating how polymers can be engineered to most effectively increase or decrease the crystallization rate of small-molecule pharmaceuticals in solution and in the amorphous phase. Insoluble, crosslinked polymers are demonstrated to accelerate acetaminophen nucleation in solution. Maximizing interaction strength between polymer and acetaminophen while minimizing interaction strength between polymer and water leads to polymers best able to induce crystallization. These insoluble crystallization accelerators are leveraged to discover water-soluble polymers to inhibit crystallization. Functionalities that rapidly accelerate crystallization when tethered to soluble polymers are shown to be strong inhibitors of crystallization when attached to water-soluble polymers. This methodology of screening functionalities on insoluble polymers to determine their interaction strength with a target pharmaceutical streamlines the discovery of polymers to inhibit crystallization. The relationship between polymers designed to inhibit crystallization in solution and in the solid-state is also explored. Using a common set of polymeric materials, it is shown that increasing polymer hydrophobicity improves both the physical stability of supersaturated solutions and the physical stability of amorphous solid dispersions. Finally, the relationship between polymer functionality and physical stability is investigated for amorphous solid dispersions of the hydrophobic drug nabumetone. The solubility of polymer excipient in amorphous nabumetone is demonstrated to have a crucial effect in determining the ability of polymers to stabilize amorphous solid dispersions. Throughout all of these studies, postpolymerization functionalization is used to synthesize libraries of polymers containing a range of functional group chemistry without changing physical parameters of polymers such as number-average chain length or backbone chain chemistry to isolate the effects of polymer chemistry on the ability of a polymer to alter crystallization rates. Fundamental parameters, including interaction strength between polymer and drug, interaction strength between polymer and solvent, and cohesive polymer-polymer interactions, are shown to dictate the ability of a polymer to speed or slow crystallization, and the effect of polymers to either speed or slow crystallization is compared and contrasted for crystallizations in solution and in the amorphous phase.

BOF 슬래그 및 화학적으로 변형된 BOF 슬래그를 활용한 결정화 유리의 결정화 거동

최민우 포항공과대학교 철강대학원 2017 국내박사

전로 공정의 부산물인 BOF 슬래그는, 중금속의 환경 유해성과 처리공간의 부족 등으로, 발생 후 처리에 곤란함을 겪는 물질이다. 그럼에도, 화학 조성상 충분히 재활용 가능한 여지가 있기 때문에, 이 물질을 건축 자재나 결정화 유리 등 여러 방면으로 재활용하려는 노력이 이어져 왔다. 그 중에서, 본 연구는 BOF 슬래그를 결정화 유리로 활용하는 데에 궁극적인 목적을 두었다. 이 목적에 따라, 슬래그를 활용 가능하게 구성 성분을 변형시키는 방안과, 변형시킨 다음의 슬래그의 결정화 현상을 밝혀냄으로써, 보다 효율적인 BOF 슬래그의 활용 방안을 찾고자 하였다. BOF 슬래그를 효과적으로 재활용하기 위해서는, BOF 슬래그 내의 산화철 성분을 제거해야 한다. 비교적 간단한 열처리 공정으로 산화철을 축적시켜 물리적으로 제거할 수 있는 가능성을 기대하고, 첫 번째 연구에서는 용융된 상태의 BOF 슬래그를 냉각시키는 속도가 냉각 과정 동안의 결정화 현상에 어떠한 영향을 미치는지를 알아보았다. 먼저, 용융 상태의 BOF 슬래그를 일정한 냉각 속도로 냉각하는 조건에서 DSC 실험을 수행하였다. 냉각 과정 중 결정화에 의한 내부 구조의 변화를 알아보기 위해서는 XRD 및 EDS 분석을 이용하였다. 위의 관찰 결과들로부터, 냉각 속도는 BOF 슬래그의 결정화 과정에 영향을 주지 못함을 밝혀내었다. 비록 냉각 속도에 따라 결정상의 형태 및 크기가 조금의 차이를 보이기는 하였지만, 의미 있는 차이는 아니었다. 이 연구로부터, BOF 슬래그를 실제로 활용할 때, 냉각 속도를 이용하여 결정화 과정을 조절하여, Fe가 포함된 상을 축적시킨 후 물리적으로 분리하는 방법은 효과가 없음을 확인하였다. 그러므로, BOF 슬래그의 산화철 성분은, 불가피하게 화학적으로 변형하게 되었다. 두 번째 연구는, 바로 이산화규소를 첨가하여 환원 반응을 통해 산화철을 화학적으로 제거한 BOF 슬래그가 유리상으로부터 결정화되는 과정을 밝히는 것이다. 위의 유리 샘플이 결정화되는 과정은, 일정한 승온 속도로 승온하는 조건에서의 DSC와, 공초점 현미경 관찰로 관찰되었으며, 결정화 과정 중 샘플 내부 구조의 변화는 XRD 및 EPMA로 분석하였다. 관찰 결과, 이 유리 샘플은 결정화가 표면부터 일어났으며, 생성된 상으로는 akermanite, merwinite, wollastonite가 있었다. 그리고, 이 결정화 과정은 승온 속도에 의해 결정되는 핵 생성 온도에 의해 영향을 받는데, 이 온도에 따라 wollastonite와 마그네슘이 포함된 상(akermanite, wollastonite) 사이의 상대적인 핵 생성 속도 차이가 생기기 때문이다. 이 연구를 통해, 산화철을 화학적으로 제거한 BOF 슬래그는 열처리 과정에 따라 결정화 과정이 조절되므로, 다양한 물성을 가지는 결정화 유리로 활용될 수 있는 가능성이 확인되었다. 마지막 연구는, BOF 슬래그를 Petrurgic process에 적용시키는 데에 염두를 두고 진행되었다. Petrurgic process는 결정화 유리를 만드는 공정 중 하나로, 기존 공정에 비해 단축된 열처리 과정을 가져, 에너지 절약 및 환경에 친화적인 공정으로 알려져 있다. 이 공정에 BOF 슬래그를 사용할 수 있다면, BOF 슬래그의 지속적인 폐기로 생기는 문제를 동시에 해결할 수 있게 된다. 하지만, BOF 슬래그를 공정에 바로 활용하기에는, 녹는점이 지나치게 높고 산화철의 함량이 많아 어려움이 따른다. 그러므로, 이 연구에서는 위의 문제들을 해결하기 위해 BOF 슬래그를 앞에서와 같이 화학적인 변형을 가해 산화철 성분을 제거하여, 그 후에 액체 상태로부터 냉각될 때의 결정화 과정을 파악하여 Petrurgic process를 거친 다음의 결과물의 특징을 알아보고자 하였다. 그 결과, 이 샘플의 결정화 과정은 크게 두 부분으로 관찰되었다: 초기에는 액체상으로부터 공정점 반응이 일어나면서 결정화가 시작되었고, 계속적인 냉각으로 온도가 낮아지는 후기에는 확산 과정이 지배적이었다. 또한, 냉각 속도는 결정 상태의 형태에 많은 영향을 미치지만, 기본적인 결정화 메커니즘은 냉각 속도에 의해 크게 바뀌지 않음을 알 수 있었다. The BOF slag has been a problem because most of it has been still thrown away without any proper recycling process. Actually, dumping of the BOF slag has caused a serious environmental problem because of harmful elements such as heavy metals. Moreover, it causes a waste of potentially useful materials in the BOF slag without further valorization. Therefore, this research is focused on the effective valorization of BOF slag as a glass ceramic material by observing the crystallization properties of it, followed by preparing the iron oxide-devoid BOF slag and elucidating the crystallization mechanism of it. To recycle the BOF slag efficiently, the iron oxide-included phases in the slag should be eliminated. Therefore, the first research aimed to elucidate the effect of cooling rate on the crystallization mechanism of the melted BOF slag, expecting some possibility that the iron oxide-included phases in the slag could be accumulated to be physically separated only with some simple heat treatment. Firstly, the DSC analysis of the BOF slag were performed in non-isothermal condition of constant cooling from the melt. The XRD and EDS analysis of the slag were performed to observe the inner structure during crystallization. The observations confirmed that the cooling rate did not affect the crystallization mechanism of the melted BOF slag. Although the cooling rate could influence the change in the size and shape of the crystalline phases, the effect was not significant. From this research, it was shown to be impossible to physically separate iron oxide-included phases by accumulating them by controlling the crystallization process of the BOF slag. Therefore, it became unavoidable to chemically modify the BOF slag such as reducing iron oxide inside the slag, to utilize it as a valuable material. Hence, the second research attempted to prepare a glass ceramic material by reducing iron oxide from basic oxygen furnace (BOF) slag with adding SiO2 and investigate the crystallization mechanism of it. Firstly, the glass sample was prepared by adding 29 wt% of SiO2 to BOF slag, followed by eliminating iron oxide by reduction process. Non-isothermal DSC analysis together with confocal laser microscopy, XRD and EPMA mappings were carried out to observe the crystallization process. The glass sample showed that the crystallization process started from the surface where the main phases were identified to be akermanite, merwinite and wollastonite. In addition, the crystallization process was affected by the nucleation temperature which was decided by the heating rate because of the difference in the nucleation rate between wollastonite and Mg-rich phases. The current results could be used to propose the feasibility of utilizing BOF slag as glass-ceramics by chemical modification with heat treatment, which controls the crystallization behavior. The third research gave a thought to use the BOF slag in the Petrurgic process, to produce the glass-ceramic material from it. The ‘Petrurgic process’ has become a prominent process to address the energy saving issue on the glass ceramic-making process. If the BOF slag can be utilized by this process, the environmental problem caused by dumping the waste without recycling will be also resolved effectively. However, BOF slag itself has difficulties to directly use as a valuable material because of high melting point and high amount of iron oxide. Therefore, this research has focused on elucidating crystallization behavior of the iron oxide-devoid BOF slag glass melt during cooling process, for using the BOF slag to the Petrurgic process. From this research, the melted slag glass showed two processes of crystallization during cooling; the eutectic reaction at the early stage, and the diffusion process at the later stage. Also, the cooling rate did not affect the crystallization mechanism itself, although it influenced the morphologies after the crystallization.

Crystallization Control and Functional Applications of Polyurethane Composites via Molecular Design and Surface Modification

Lee, Jaeheon 서울시립대학교 일반대학원 2026 국내석사

CRYSTALLIZATION BEHAVIOR OF BISPHENOL-A POLYCARBONATE : EFFECTS OF CRYSTALLIZATION TIME, TEMPERATURE, AND MOLAR MASS

Sohn, Seung Man Virginia Polytechnic Institute and State Universit 2000 해외박사

Crystallization and multiple melting behavior of bisphenol-A polycarbonate (PC) was investigated using differential scanning calorimetry (DSC) for the monitoring of thermal behavior and atomic force microscopy (AFM) for the morphology study. The exceedingly slow crystallization kinetics of PC and the feasibility of obtaining near monodisperse fractions provide distinct advantages for the elucidation of the effects of crystallization time, temperature, and molar mass on crystallization kinetics. The effects of molar mass on the glass transition temperature (Tg) and heat capacity change at Tg, and the amorphous density of PC were investigated. Similar to many semicrystalline polymers, PC exhibits a multiple melting behavior upon heating. While for each PC sample, the coexistence of low and high temperature endothermic regions in the DSC heating traces is explained by the melting of populations of crystals with different stabilities, melting-recrystallization-remelting effects are observed only for the lowest molar mass samples. The effects of crystallization temperature and molar mass distribution on overall crystallization kinetics were studied for some of the fractions, including the commercial PC-28K (Mw = 28,000 g.mol-1) sample. Regarding the kinetics of secondary crystallization, particular attention was placed on understanding the effects of molar mass, initial degree of crystallinity prior to the secondary crystallization, and secondary crystallization time and temperature. The secondary crystallization of PC follows the same laws discovered in previous studies of PEEK, PET, it-PS and ethylene copolymers, and the results are discussed in the context of a bundle-like secondary crystallization model. During isothermal annealing of semicrystalline PC-28K around the high melting endotherm, a significant increase of melting temperature along with peak broadening with time was observed. Independently, morphological studies using AFM showed that mean lamellar thickness increases with time during isothermal annealing. These results are discussed in light of isothermal thickening of lamellar crystals. Lastly, almost 200 DSC melting traces of varying molar mass PC samples thermally treated under various conditions were analyzed to calculate crystallinity (Xc), rigid fraction (RF), and rigid amorphous fraction (RAF). The correlation between RAF vs Xc, Tg, and Tg broadening are discussed.

Crystallization process design of isosorbide recovery

이상열 Graduate School, Korea University 2020 국내석사

The solubility of isosorbide in ethylene glycol was measured and the crystallization kinetic parameters were estimated via seeded batch cooling crystallization. The saturation concentration of isosorbide was measured using a density meter, which enabled the rapid and accurate measurement of the concentration. The parameters were estimated by fitting the concentration and average crystal size changes to the simulation results by solving the population balance equation. Crystallization using continuous stirred tank reactors (CSTR) was simulated with the obtained parameters, and the reliability of the simulation was verified with experiments. The kinetic parameters estimated from seeded batch crystallization experiments can be used for the prediction of crystallization under seeded conditions, such as CSTR. The CSTR crystallizer predictions and estimated parameters are consistent with the results of CSTR experiments. The amount and composition of residue obtained from industrial poly(ethylene-co-isosorbide) terephthalate process was predicted, and recovery processes and optimum operating conditions are proposed via simulation using Aspen Plus.

Development of HAP Crystallization-Filtration (HCF) Process to Recover Phosphorus from Wastewater

장향연 과학기술연합대학원대학교 2021 국내박사

In Korea, management of phosphorus load from domestic wastewater is essential to prevent eutrophication and algal bloom. On the other hand, Korean wastewater plants have limitations to adapt advanced phosphorus treatment processes including coagulation. There are difficulties of operating coagulation process to dose coagulant, sludge treatment and recovering phosphorus. In this study, as a new alternative for tertiary phosphorus treatment and recovery, a ‘Hydroxyapatite (HAP) crystallization-filtration process’ which targets wastewater plants under 500 m3 capacity without using a coagulant was developed. In addition, a granular crystallization agent (GCA) and a ‘HAP crystallization-filtration trench utilizing GCA’ were proposed for the management of phosphorus discharge load caused by non-point pollution sources such as agricultural wastewater. The main results of this study are as follows. The column test results obtained showed that during the HCF process, high pH and excessive calcium dosage conditions were required to obtain effluents with total phosphorus (TP) and suspended solid (SS) concentrations below 0.2 and 10 mg/L, respectively, within 2 h of operation. Phosphorus was precipitated during the pre-treatment step, and thereafter, it crystallized on the surface of the fixed seed material in the HCF reactor. Furthermore, the addition of Ca2+ resulted in phosphorus removal efficiencies > 95%, and pH, residual Ca2+, filtration depth, and linear velocity were identified as the main design and operation parameters of the HCF process. According to the results of phosphorus fractionization in HCF process, the principle transitions of phosphorus condition were SRP (soluble reactive phosphorus) to TPP (total particulate phosphorus, PRP (particulate reactive phosphorus) + PnRP (particulate non-reactive phosphorus)) which was removed after filtration step. Following the operation of pilot-scale HCF process, the characterizations of pH, residual Ca2+, alkalinity, phosphorus concentration and SS were analyzed in 50 m3/d of flow rate condition. In the long-term operation of HCF process, the average concentrations of TP, PO4-P, and SS in the effluent were 0.05, 0.04, and 1.1 mg/L, respectively, corresponding to removal efficiencies of 90.9, 86.5, and 79.7% respectively. According to the results of column test, phosphorus removal fractionization and pilot-scale operation of HCF, control of pH value and Ca2+ with serial filtration process were recommended for successful operation. In addition, by successfully automating the pretreatment and backwashing operation at the pilot plant, and stably achieving the effluent standard through long-term operation, the applicability of the HCF process for small and medium-sized wastewater treatment facilities was demonstrated. In study of phosphorus removal form and sludge production factor according to pH and total carbonate concentration, the total carbonate concentration did not significantly affect the phosphorus removal efficiency. Even if the decarbonation process was omitted in the pretreatment step of the HCF, the phosphorus removal efficiency did not decrease, and the concentration of carbonate was in proportion only to the amount of sludge generated. The investigation of the backwashing sludge characteristics of the HCF process using SEM, FT-IR, EDS, and XRD analyses showed that owing to its high contents in calcite and calcite and phosphorus compounds (Ca-P-OH, Ca-CO-P-OH and Ca-P), HCF sludge could be used as an alternative soil amendment resource. To prevent eutrophication and remove phosphorus, circulating fluidized bed combustion (CFBC) ash was utilized to elute Ca2+ and OH- for hydroxyapatite (HAP) crystallization. CFBC ash was compared with the gypsum byproduct of a domestic waste incineration plant and pure CaO reagent. CFBC ash proved to be a suitable raw material to supply Ca2+ and OH- for HAP crystallization. CFBC ash was reprocessed as a granular crystallization agent (GCA) to improve its applicability to non-point pollution source control. In addition, a manufacturing procedure for a GCA utilizing 4.8% of blast furnace slag as a binder was developed based on durability and the ion elution rate in water. Column tests with sedimentation showed that 93% and 98% of TP and PO4-P were removed after 12 h of settling, respectively. In on-site filtration trench tests, filtration following crystallization with a 2 h EBCT achieved a 63.5% and 52.8% removal efficiency with respect to TP and PO4-P, respectively. After the column operation for 13 d, an increase in porosity with pore distribution on the surface of the GCA was observed. Through their long-term on-site operation, crystallization-filtration trenches using GCA provide an effective alternative process for the management of agricultural non-point source pollution. 우리나라 호수나 하천의 부영양화 및 녹조의 대발생을 방지하기 위해서는 하수처리 방류수의 인 부하 관리가 필수적이다. 또한, 현재 대규모 하수처리장에는 응집공정을 중심으로 한 인 고도처리공정이 도입되어 있지만 알루미늄이 포함된 응집 슬러지의 재활용 또는 자원화에는 여러 한계가 있다. 따라서, 본 연구에서는 인 고도처리 및 회수를 위한 새로운 대안으로서, 중소규모 하수처리시설을 대상으로 하여 응집제를 사용하지 않고 기존의 인 고도처리공정 이상의 처리효율을 갖는 “Hydroxyapatite (HAP) 결정여과공정(HAP crystallization-filtration, HCF)”을 개발하였다. 또한, 농업배수 등 비점오염원에 기인하는 인 배출부하 관리를 위하여 입상결정화재(GCA, granular crystallization agent) 및 이를 활용한 “HAP 결정화 여과수로(HAP crystallization-filtration trench)”를 제안하였다. 본 연구의 주요 결과는 다음과 같다. HCF 공정의 설계·운전인자를 검토하기 위한 칼럼테스트로부터, 높은 pH 및 칼슘이온(Ca2+)의 투여 조건에서 수리학적체류시간(HRT) 2시간 이내에 유출수의 총인(TP) 농도를 0.2 mg/L (I지역의 방류수 수질기준) 미만으로 안정적으로 저감하였다. HCF 공정에서 대부분의 인산염인(PO4-P)은 pH와 Ca2+ 농도를 조절하는 전처리 단계에서 불용화된 후, HCF 결정여과조에서 석회석계 결정화재를 통과하면서 여과 및 결정화되었다. Ca2+의 추가주입을 통해 TP 및 PO4-P의 제거효율 95% 이상을 달성하였으며, pH, Ca2+ 농도, 여과높이(filtration depth) 및 여과선속도(linear velocity)가 HCF 공정의 주요 설계·운전인자로 확인되었다. 또한, HCF 공정에서 인 분율화(phosphorus fractionization) 기법을 활용한 인 제거 메커니즘 분석을 통해, 주요 인 성분의 분율 변화는 SRP (soluble reactive phosphorus) 형태에서 TPP (total particulate phosphorus, PRP (particulate reactive phosphorus) + PnRP (particulate non-reactive phosphorus)) 형태로의 전환인 것으로 나타났다. 이상의 설계·운전인자를 바탕으로 하여 50 m3/d 용량의 파일럿 플랜트를 구축하고, HCF 공정의 연속운전을 실시하여 pH, 잔류 Ca2+, 알칼리도, 인 농도 및 부유물질(SS)의 거동을 분석하였다. HCF 파일럿 플랜트 장기 운전 결과, 유출수 내 TP, PO4-P 및 SS의 평균 농도는 각각 0.05, 0.04, 1.1 mg/L, 평균 제거효율은 각각 90.9, 86.5, 79.7%를 달성하였다. 칼럼테스트, 인 제거 메커니즘 분석 및 파일럿 플랜트 운전 결과를 통해, HCF 공정에서 양호한 인 제거성능을 확보하기 위해서는 pH, Ca2+ 농도를 동시에 제어하는 전처리공정과 생성된 TPP를 추가 제거하기 위한 후속 여과공정의 조합이 적절한 것으로 나타났다. 또한, 파일럿 플랜트 수준에서 전처리 및 역세척 운전을 성공적으로 자동화함과 동시에, 장기 운전을 통해 방류수 수질기준을 안정적으로 달성함으로써 중소규모 하수처리시설을 대상으로 한 “HCF 공정”의 적용성이 실증되었다. HCF 공정 내 pH 및 총탄산염(total carbonate, CO3T) 농도에 따른 인 분율의 거동 및 슬러지 생성량을 분석한 결과, pH 10 및 Ca2+ 100 mg/L 이상의 조건에서는 CO3T의 농도는 인 제거효율에 영향을 미치지 않았다. HCF 공정의 전처리 단계에서 탈탄산 과정을 생략하더라도 인 제거성능은 저하되지 않으며, 탄산염의 농도는 발생 슬러지량에만 비례하는 것으로 나타났다. HCF 공정의 부산슬러지를 SEM, FT-IR, EDS 및 XRD를 활용하여 분석한 결과, 주요 성분은 CaCO3와 다양한 형태의 인 화합물(Ca-P-OH, Ca-CO-P-OH 및 Ca-P)로 확인되었다. 따라서, HCF 공정의 부산슬러지는 농업분야에서 산성토양의 중화를 위한 토양개량제 및 비료로 사용될 수 있음이 시사되었다. 한편, 비점오염원에 기인하는 인 부하 관리를 위해 배연탈황설비 순환유동층(CFBC, circulating fluidized bed combustion)의 비산재(fly ash)를 활용하여 Ca2+ 및 OH-의 장기 용출능을 가진 입상의 GCA를 고안하였다. CFBC 비산재를 생활폐기물 소각장의 부산석고 및 시약급 CaO와 비교한 결과, CFBC 비산재가 Ca2+ 및 OH-의 지속적인 공급능을 갖고 있어 GCA의 원재료로 적합한 것으로 나타났다. 또한, 4.8%의 고로 슬래그(blast furnace slag)를 바인더로 활용하여 내구성과 이온 용출능을 극대화함으로써, 수처리 공정에 적용할 수 있는 GCA의 제조매뉴얼을 제시하였다. GCA의 인 제거성능을 확인하기 위한 칼럼침강실험에서 침전 개시 12시간 후에 TP와 PO4-P가 각각 93% 및 98% 제거되었다. 제조된 GCA를 HAP 결정화 여과수로 테스트베드에 적용하여 장기 현장실험을 실시한 결과, EBCT(empty bed contact time) 2시간 조건에서, TP 및 PO4-P가 평균 63.5% 및 52.8% 제거되었다. 장기간 GCA를 사용한 후 물리화학적 변화를 관찰한 결과, Ca2+ 및 OH-의 용출로 인하여 Ca(OH)2의 함량이 감소하였고, 기공률은 증가하는 것으로 나타났다. 따라서, GCA를 활용한 “HAP 결정화 여과수로”는 비점오염원에서 유출되는 인 부하를 관리하기 위한 효과적인 대안적 프로세스임이 입증되었다.

Improved crystal shape and insensitivity of high energy material in cooling crystallization

차상우 한밭대학교 대학원 2022 국내석사

Surface nanodroplets for efficient liquid-liquid microextraction and its application to crystallization of organic compounds

임은민 경북대학교 대학원 2024 국내석사

Crystallization reactions, which are challenging to control in large-scale environments, have been extensively investigated utilizing small droplets as a research medium. Crystallization using conventional droplets achieves crystal growth by relying on evaporation or dissolution, which cannot control the rate of supersaturation. Therefore, this study proposes a methodology for controlling the supersaturation and crystallization of organic molecules by inducing liquid-liquid extraction and dissolution using surface nanodroplets. Surface nanodroplets gradually dissolve in flowing aqueous solution simultaneously with liquid extraction of organic molecules, resulting in supersaturation that leads to nucleation and crystallization. Supersaturation and crystallization were regulated by controlling process parameters such as the concentration of organic molecules in the aqueous solution and the flow rate of the solution, using trimesic acid as a model material. Higher concentrations of trimesic acid (TMA) in solution result in more rapid crystallization, primarily due to the increased driving force for TMA diffusion into surface nanodroplets. In addition, the fast flow rate creates a thin concentration boundary layer around the droplet and accelerates supersaturation by dissolving the droplet faster. As an application, we demonstrated the crystallization of amiodarone in chloroform surface nanodroplets. Furthermore, in this study, multi-component nanodroplets were synthesized using an eco-friendly Green Deep Eutectic Solvent (gDES) composed of thymol and decanoic acid. The extraction performance of gDES-based nanodroplets was demonstrated through the extraction of rhodamine 6G and copper ions. Copper ions were chelated with decanoic acid – a component of gDES – facilitating the rapid crystallization of Cu(II)-decanoate crystals. The results presented in this study have revealed novel application potential for surface nanodroplets, suggesting that they may be applicable to various fields such as the pharmaceutical industry, energy devices, and semiconductors.

Pre-Crystallization을 적용한 Multi-Stage SWRO System에서의 Boron 제거

이준희 서울시립대학교 2011 국내석사

최근 인간이 사용할 수 있는 담수 사용량의 부족으로 인하여 해수담수화 시설이 증가하고 있다. 과거에는 해수담수화 시설은 Thermal 방식을 이용한 해수담수화 시설이 주를 이루었지만 요즈음에는 membrane 방식이 thermal 방식보다 비용면, 효율면에서 뛰어나 SWRO(seawater reverse osmosis) membrane을 이용한 해수담수화 시설이 증가하고 있다. SWRO membrane 1단시설의 1cycle 운전 시 회수율은 유입수의 35~40% 정도여서 회수율을 증가시키기 위해 다단식 SWRO 시스템을 적용하고 있다. 다단 SWRO 시스템은 회수율 증가, brine 압력 재사용, 농축수량의 감소 등으로 경제적으로 큰 이점을 나타내지만 먹는물 수질기준(한국) 1.0mg/L로 규제하는 boron의 농도가 초과하여 문제시 되고 있다. 그래서 본 논문에서는 다단 SWRO 시스템에서 pre- crystallization을 통해 Scale 발생물질을 제거 및 boron의 형태를 변화시켜 SWRO membrane을 이용한 제거특성을 살펴보고자 한다. 본 실험에 사용된 pre-crystallization 및 역삼투막장치는 고압펌프, 나노버블링장치, SWRO membrane 등으로 이루어져 있고 고압펌프는 maximum 100bar 까지 출력 가능한 펌프를 사용하였고, 나노버블링장치는 CO2를 사용하여 nano size의 버블을 발생시켜 주입하였고, SWRO membrane은 Vontron사의 SW21-4040을 사용하였다. 그리고 실험순서는 pre-crystallization 적용에 따른 boron의 제거영향, 운전 pH 및 pH 조절제에 따른 boron의 제거영향, CO2주입방식 및 crystal seeding에 따른 scale 유발물질 제거영향, 높은 pH에서의 운전온도 및 운전압력에 따른 제거영향, 최적 운전인자 적용 시 각 공정별 성상으로 평가하였다. 그 결과 permeate (2) 내 boron의 농도는 0.44mg/L로 WHO 수질 목표치에 만족하였고, 투과수의 pH는 8.53으로 1-stage 투과수와 혼합이 일어나 중성영역의 pH를 형성하게 되어 후처리공정 중 pH 조절 공정을 생략할 수 있을 것이라고 생각된다. 그리고 pre-crystallization을 적용한 multi-stage SWRO system에서 발생한 crystal을 정석탈인법의 정석재로 재이용하기 위해 연계실험을 진행하였는데, 그 결과 TP 농도는 0.05~0.16mg/L 로 96.2~87.2%의 제거효율을 나타내었다. 이는 폐수 방류수수질기준 0.2mg/L를 만족하는 수준을 나타내어 적용가능성을 생각할 수 있었다. Due to the shortage of usable freshwater, the numbers of desalination facilities have recently increased. Desalination facilities have historically used to the thermal methods, but the most recent facilities use the SWRO (seawater reverse osmosis) membrane method, mainly due to the drop in membrane prices and improved membrane development. The membrane method is also more effective and economical than the thermal methods. The main historical issue with the SWRO membrane was the recovery of the permeate in the desalination of seawater, with recoveries between 35 to 40% of the influent during the one cycle of a single stage SWRO system. Therefore, a multi-stage SWRO system has been applied to increase the recovery rate. A multi-stage SWRO system has economical advantages to desalination, such as high recovery rate, reuse of the brine pressure and decreased brine quantity. However, there is still the problem of the boron concentration exceeding the South Korean Drinking Water Quality Standard of 1.0mg/L. So, The purpose of this study was to discuss the removal of boron using a multi-stage SWRO system, with pre-crystallization for the removal of scale causing substances and to change the form of boron. The multi-stage SWRO system with pre-crystallization utilizes a high pressure pump, nano bubbling unit and SWRO membrane. The output capacity of the high pressure pump has a maximum pressure of 100 bar. The nano bubbling unit produces nano sized bubbles using CO2 gas. The spiral element of the SWRO membrane was a SW21-4040, Vontron. In this study, the influences of the applied pre-crystallization process, boron removal according to the operating pH and pH adjusting agent, scale according to the CO2 injection method and crystal seeding, boron removal according to the operating temperature and pressure at high pH, and optimum operating parameters of each applied process were investigated. As a result, the concentration of boron ions in the permeate (2) was 0.44 mg/L, which satisfied the WHO and Korea boron criterion. pH of the permeate (2) was weakly basic, pH 8.53; therefore, it was concluded that the pH control process would be able to be excluded from the post-treatment. And further experiment was conducted for reusing the crystals formed during the pre-crystallization process of this study by injecting the seeding material into the phosphorus crystallization method. The concentration of TP was 0.05 to 0.16 mg/L in the treated water, the removal efficiencies of 96.2 to 87.2%. So reuse of crystal is considered to be applicable the wastewater treatment plant in the coast.

Predicting Crystallization Outcomes of Chiral Molecules Using Simple Molecular Models

Carpenter, John The University of Utah ProQuest Dissertations & Th 2021 해외박사(DDOD)

The crystallization of molecules is a key process in manufacturing pesticides, fertilizers, dyes, pharmaceutical compounds, explosives, and many other materials. Moreover, the spatial arrangement of molecules in the solid state determines many of a compound’s physical properties, including its stability, hardness, hygroscopicity, and solubility. Therefore, reliably predicting the solid form of organic and inorganic molecules is of considerable practical importance across chemistry and material science. Over the last decades, computers have been used with increasing success to predict molecular crystals. Most current methods of computational crystal structure prediction (CSP) rank different polymorphs according to their lattice energy or free energy. The most advanced CSP methods now routinely furnish many of the polymorphs found in experiments. However, CSP has still not replaced expensive and time-consuming experimental screening procedures because many of the lowest-energy crystal structures predicted by CSP do not form in experiments. In addition, CSP currently cannot distinguish between molecules that crystallize easily and those that tend to form amorphous solids. These limitations of CSP are partly due to the numerical effort associated with calculating molecular interactions: Accurate free-energetic ranking of polymorphs requires numerically cumbersome electronic structure calculations or highly specialized force fields that must be generated on a case-by-case basis. The number and complexity of polymorphs that can be predicted for a given molecule are therefore limited. More importantly, most CSP methods ignore all kinetic aspects of molecular crystallization, which are at the heart of polymorphism and amorphization. While the pertinent microscopic processes involved in crystal nucleation and growth are well understood, directly evaluating the crystallization rates of many different polymorphs in molecular dynamics computer simulations is essentially impossible due to extreme computational cost. The practical impact of in-silico CSP on the targeted manufacturing of molecular crystals, therefore, remains limited.In this work, we develop a family of simple models of chiral molecules capable of reproducing the full range of crystallization behavior observed in real molecules. We develop several methods for efficiently simulating the crystallization dynamics of these models and for the fast identification of their crystal structures, including crystals with complex and large unit cells that are usually ignored by current CSP methods. Due to the numerical efficiency of our models, we thoroughly investigate the crystallization dynamics and polymorph landscapes of thousands of different molecules. Our study, for the first time, provides a statistically meaningful correlation of the thermodynamics and kinetics of molecular crystallization across a wide range of molecular shapes and interactions, allowing us to address several long-standing questions: What fraction of molecules do not form the thermodynamically stable crystal? Can the rates of crystallization of different polymorphs be estimated without numerically strenuous dynamical simulations? How can the likelihood of crystallization and chiral separation be enhanced? Why do molecules tend to form structurally simple polymorphs? This work can serve as guiding principles for the synthetic design of molecules and the prudent choice of crystallization conditions. Most importantly, we suggest conceptually simple and numerically efficient ways of accounting for kinetic effects in computational crystal structure prediction.