Reversible addition-fragmentation chain transfer polymerization of vinyl acetate and vinyl pivalate in supercritical carbon dioxide

Quang Long Pham,심재진,유바라즈할도라이,웬방호아,ChanKyu Kang 한국화학공학회 2014 Korean Journal of Chemical Engineering Vol.31 No.11

Two highly supercritical CO2-soluble, poly(vinyl acetate) (PVAc)-based macro-reversible addition-frag-mentation chain transfer (RAFT) agents were synthesized. The RAFT agents were used for the first time in RAFT/macromolecular design via the interchange of xanthates (MADIX) and polymerization of vinyl acetate (VAc) and vinylpivalate (VPi) in supercritical carbon dioxide (scCO2). A homopolymer PVAc and a block copolymer PVAc-b-PVPimade by RAFT/MADIX polymerization were characterized, and the effects of time and RAFT agents on polymer-ization were examined. For the 8.4 wt% RAFT agent in VAc, the molecular mass (Mn) of homopolymer PVAc was26,000 g mol−1and PDI was 1.35. For the copolymerization of VPi using 9.8 wt% PVAc-RAFT agent in VPi for 24 h,the Mn and PDI of PVAc-b-PVPi reached 32,400 g mol−1and 1.42, respectively. These results suggest that the poly-dispersity can be controlled during the clean production of PVAc and PVPi by RAFT/MADIX polymerization in scCO2.

GIAO SU KIM KI TAE -MOTNHA VIETNAM HOCTAM HUYET

Pham Quang Long,강하나 한국베트남학회 2002 베트남연구 Vol.3 No.-

Polymerization of vinyl pivalate in supercritical carbon dioxide and the saponification for the preparation of syndiotacticity-rich poly(vinyl alcohol)

Quang Long Pham,Van Hoa Nguyen,유바라즈할도라이,심재진 한국화학공학회 2013 Korean Journal of Chemical Engineering Vol.30 No.5

This paper reports a successful free-radical dispersion polymerization of vinyl pivalate in supercritical carbon dioxide using poly(1H,1H-dihydroperfluorooctyl acrylate) and dimethylsiloxane-g-pyrrolidone carboxylic acid (Monasil PCA) as stabilizers. In both cases, no spherical polymer particles were obtained, which might be due to the high solubility of poly(vinyl pivalate) (PVPi) in supercritical carbon dioxide. The effects of the reaction time, pressure,temperature, monomer loading, stabilizer concentration and initiator concentration on the polymer yield and molecular weight of PVPi were also investigated. In addition, the formation of poly(vinyl alcohol) via saponification of the resulting PVPi is described.

Population Pharmacokinetics with Genetic Variants of SLCO1B1 of Rifampin in Korean Tuberculosis Patients

( Pham Quang Hoa ),( Nguyen Phuoc Long ),( Rannissa Puspita Jayanti ),( Young-kyung Choi ),( Tae-won Jang ),( Jee Youn Oh ),( Jusang Kim ),( Hyun Kuk Kim ),( Ji Young Kang ),( Yong-soon Cho ),( Jae-go 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-

Background Rifampin (RIF) is a backbone drug of tuberculosis (TB) treatment. However, little is known for the influences of SLCO1B1 on RIF pharmacokinetics (PK) in the Asian population. The aim of this study was to investigate the effect of SLCO1B1 variants on RIF PK parameters in Korean TB patients. Methods Clinical data, SLCO1B1 genotype, and drug concentrations from a multicenter prospective cohort study conducted at 20 clinical centers in Korea were utilized for the analysis. The data was divided randomly into a training dataset (80%) and a test dataset (20%). Nonlinear mixed effect analyses were employed to develop population PK modeling and simulation. The final model was internally validated by prediction-corrected visual predictive checks and non-parametric bootstrapping and externally validated using test dataset. Results In total, 879 TB patients (560 males and 319 females) were included in our study. The one-compartment disposition model with first-order absorption and elimination, and combination of additive and proportional residual error best described the RIF PK of the training data. Bodyweight and SLCO1B1 phenotype, classified as a normal, intermediate, and low function, significantly affected the apparent clearance (CL/F). The mean of RIF clearance of the normal SLCO1B1 function group is 18.3% and 14.1% higher than the intermediate and low function group (7.63 L/h to 6.45 L/h and 6.69 L/h, respectively). The findings indicated that the efficacy and safety of an intensified RIF initial dosing strategy could be partially based on SLCO1B1 phenotype classification. Conclusions The SLCO1B1 phenotype could partially explain the variability of RIF PK on Korean TB patients. Ensuring the proper RIF model- informed initial dose and dosing adjustment based on SLCO1B1 phenotype may improve the treatment outcome of the TB patients.

Novel retrofit designs using a modified coordinate descent methodology for improving energy efficiency of natural gas liquid fractionation process

Long, Nguyen Van Duc,Minh, Le Quang,Pham, Tram Ngoc,Bahadori, Alireza,Lee, Moonyong Elsevier 2016 Journal of natural gas science and engineering Vol.33 No.-

<P><B>Abstract</B></P> <P>Tough environmental regulations, intense competition, expensive fossil energy use, and the strong growth predictions of the natural gas market have prompted efforts to retrofit the existing purification processes to reduce their energy requirements. The important goals of retrofit design are to analyze, evaluate and propose suitable technologies to improve the energy efficiency and/or increase the capacity. This paper reports the results of a techno-economic feasibility study to retrofit a natural gas liquid (NGL) fractionation process. A novel hybrid system, side reboiler and heat pump-assisted, thermally-coupled distillation sequence to maximize the energy efficiency, was proposed. Fractional utilization of the area was used as a hydraulic performance indicator to determine if a bottleneck occurs in a retrofit design. A modified coordinate descent methodology was employed to solve the optimization problem. As a result, the modified coordinate descent methodology was successful in finding the optimal proposed sequence structure and the operating variables, which resulted in operating cost savings of 44.55% compared to the representative base case. The short payback period of 14 months and reduced CO<SUB>2</SUB> emissions of up to 42.05% showed that the proposed sequence is an attractive option for retrofitting in industrial implementation. This sequence can be employed for both grass-root and retrofit designs. This study also showed that even the heat pump can reduce the energy requirements significantly, and may have higher exergy loss than the existing conventional distillation columns.</P> <P><B>Highlights</B></P> <P> <UL> <LI> An energy efficient hybrid technology was proposed for retrofit. </LI> <LI> Optimal design is efficiently done by modified coordinate descent methodology. </LI> <LI> Operating cost saving of 44.55% could be achieved. </LI> <LI> A TCDS can increase the energy efficiency of a heat pump. </LI> <LI> The proposed sequence is an attractive option for industrial implementation. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

A cost-effective retrofit of conventional distillation sequence to dividing-wall prefractionator configuration

Minh, Le Quang,Pham, Tram Ngoc,Long, Nguyen Van Duc,Shin, Joonho,Lee, Moonyong Elsevier 2018 Computers & chemical engineering Vol.110 No.-

<P><B>Abstract</B></P> <P>A dividing-wall prefractionator configuration was investigated for a safe and economic retrofit of the conventional sequence using simple distillation columns. In the proposed retrofit configuration, the first column was modified to a dividing wall column as a prefractionator to supply prefractionated multi-feeds to the subsequent column. To investigate the effectiveness of the proposed configuration, nine near-ideal feed mixtures were considered for analysis. The proposed configuration was then compared with several other alternative configurations. The proposed dividing-wall prefractionator efficiently generates prefractionated multi-feed streams avoiding feed mismatch and remixing effect with low modification cost. Moreover, because the proposed retrofit configuration allows for flexible switching between the dividing-wall prefractionator and the conventional operating mode, a safe retrofit is also ensured by reducing the operational risks. Several industrial retrofit cases were studied to validate the proposed dividing-wall prefractionator configuration.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A dividing wall prefractionator configuration (DWPC) was studied for safe and cost-effective retrofit. </LI> <LI> A combined optimization method was proposed and applied for reliable design and fair comparison. </LI> <LI> Practical guideline was developed for the potential retrofit of DWPC. </LI> <LI> The performance of proposed DWPC was illustrated through several industrial cases. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Center for Personalized Precision Medicine for Tuberculosis: Smart Research and Development Workstation

Van Lam Nguyen,안상진,Pham Quang Hoa,Nguyen Phuoc Long,안상진,조용순,신재국 대한의료정보학회 2022 Healthcare Informatics Research Vol.28 No.2

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Supercritical fluid mediated synthesis of poly(2-hydroxyethyl methacrylate)/Fe₃O₄ hybrid nanocomposite

Nguyen, Van Hoa,Haldorai, Yuvaraj,Pham, Quang Long,Shim, Jae-Jin Elsevier 2011 Materials science and engineering B. Advanced Func Vol.176 No.10

<P><B>Graphical abstract</B></P><P>We successfully developed an easier and more effective method to prepare a magnetic polymer nanocomposite by in situ radical polymerization of 2-hydroxyethyl methacrylate in the presence of the surface-modified Fe<SUB>3</SUB>O<SUB>4</SUB> nanoparticles with a coupling agent in supercritical CO<SUB>2</SUB>. FE-TEM pictures showed that the nanoparticles were well dispersed in the polymer matrix. The incorporation of Fe<SUB>3</SUB>O<SUB>4</SUB> in the nanocomposite was confirmed by FT-IR, XRD and XPS. Thermal stability and magnetic property increase with the increasing amount of Fe<SUB>3</SUB>O<SUB>4</SUB> nanoparticles in the composite. This new environmentally benign green synthetic route may offer advantages of easy separation and solvent removal.<ce:figure id='fig0005'></ce:figure></P><P><B>Highlights</B></P><P>► A magnetic polymer nanocomposite (Fe<SUB>3</SUB>O<SUB>4</SUB>-g-PHEMA) was successfully synthesized via in-situ dispersion polymerization in supercritical carbon dioxide. ► The Fe<SUB>3</SUB>O<SUB>4</SUB> nanoparticles were well dispersed in the polymer matrix. ► The resulting nanocomposites have an excellent superparamagnetic property, which is favorable for their bio-applications. ► This new environmentally benign green synthetic route offers advantages of avoiding the use of organic solvents as well as easy separation of solvent.</P> <P><B>Abstract</B></P><P>Poly(2-hydroxyethyl methacrylate) (PHEMA) and magnetic nanoparticle (Fe<SUB>3</SUB>O<SUB>4</SUB>) hybrid nanocomposite was synthesized by dispersion polymerization in supercritical carbon dioxide (scCO<SUB>2</SUB>) using a copolymeric stabilizer, poly[(2-dimethylamino)ethyl methacrylate-<I>co</I>-1<I>H</I>,1<I>H</I>-perfluorooctyl methacrylate] (PDMAEMA-co-PFOMA). Fe<SUB>3</SUB>O<SUB>4</SUB> nanoparticles were first surface-modified with a silane coupling agent methacryloxypropyltrimethoxysilane (MPTMS), which provides a reactive CC bond and can copolymerize with 2-hydroxyethyl methacrylate (HEMA). After immobilization of the silane coupling agent, polymer chains were successfully grafted onto the surface of Fe<SUB>3</SUB>O<SUB>4</SUB>, resulting in the formation of core–shell nanostructure. FE-TEM pictures showed that the nanoparticles were well dispersed in the polymer matrix. The incorporation of Fe<SUB>3</SUB>O<SUB>4</SUB> in the nanocomposite was confirmed by FT-IR, XRD and XPS. Thermal stability and magnetic property increase with the increasing amount of Fe<SUB>3</SUB>O<SUB>4</SUB> nanoparticles in the composite. This new environmentally benign green synthetic route may offer advantages of easy separation and solvent removal.</P>

NAT2 Polymorphisms Associated with Isoniazid Pharmacokinetics in Indonesia TB Patients

( Rannissa Puspita Jayanti ),( Soedarsono Soedarsono ),( Nguyen Phuoc Long ),( Pham Quang Hoa ),( Ni Made Mertanisih ),( Tutik Kusmiati ),( Ariani Permatasari ),( Yong-soon Cho ),( Jae-gook Shin ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-

Background Isoniazid (INH), a key drug for tuberculosis (TB) treatment, is eminently affected by polymorphisms in N-acetyltransferase-2 (NAT2). Nonetheless, the population pharmacokinetics (PK) studies exploring the relationship between INH PK and NAT2 polymorphisms remains unavailable in Indonesia, as the second highest burden countries of TB cases. Therefore, we aimed to develop a population PK model to estimate PK parameter, as well as characterize interindividual variability of INH withal considering the NAT2 polymorphisms in Indonesia TB patients. Method One or two occasion blood sampling from Dr. Soetomo General Hospital, Indonesia, were taken to determine INH concentrations and their clinical data were collected. The genotype of NAT2 was determined using SNaPshot method. Population PK was conducted using non-linear mixed effect method to estimate the INH PK parameters in this population. Result A total of 107 TB patients (63 males and 44 females) with 153 sampling points were enrolled in our study and used to build the model. The PK parameters of INH was well-described by one-compartment model with first-order absorption and elimination. Allometric scaling was implemented to describe the body size effects. NAT2 acetylator phenotype significantly affected the apparent clearance. The mean clearance estimated for rapid, intermediate and slow NAT2 acetylator were 55.9 L/h, 37.8 L/ h, and 17.7 L/h, respectively. According to their NAT2 acetylator phenotypes, the frequency of intermediate acetylator was dominant in our population by 45.8%. Our model was internally validated through visual predictive check and bootstrap method. Conclusion The first population PK model for INH in Indonesia TB patients has been established with NAT2 acetylator phenotype to partially explain the variability of INH clearance. Our study ensures the optimal INH dosing adjustment based on NAT2 acetylator phenotype may improve the treatment outcome and supports the importance of precision dosing in TB treatment.

Development of Population Pharmacokinetic Model for Ethambutol in Korean Patients with Tuberculosis

( Tran Minh Hung ),( Nguyen Phuoc Long ),( Pham Quang Hoa ),( Tae-won Jang ),( Jusang Kim ),( Jee Youn Oh ),( Hyun Kuk Kim ),( Ji Joung Kang ),( Yong-soon Cho ),( Jae-gook Shin ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.0

Background Ethambutol (EMB) is one of the four drugs to treat drug-susceptibility tuberculosis (TB). Therapeutic drug monitoring (TDM) is suggested to establish the safe and effective dosing of drugs in TB treatment. The population pharmacokinetic (PK) model provides a helpful tool for individualizing the treatment to minimize therapeutic failure and toxicity. This study was designed to evaluate the EMB PK parameters, characterize the interindividual variability of EMB PK parameters in Korean patients. Methods Data were collected from patients in the prospective cohort from the Center for Personalized Precision Medicine of Tuberculosis research center. The data were randomly divided into training and test sets with a ratio of 4:1. The model was developed using NONMEM version 4.7.1. Non-parametric bootstrapping and prediction-corrected visual predictive checks were used to validate the final model. Additionally, the model performance was evaluated on the test set. Results A model with two-compartment, one transit compartment prior to first-order absorption and elimination adequately described the PK profile of EMB. The estimates were 69.3 L/h for apparent clearance (CL/F), 154 L/h for apparent intercompartment clearance (Q/F), 98.8 L for apparent volume of central compartment (Vc/F), 849 L for apparent volume of peripheral compartment (Vp/F), 0.446 h-1 for rate constant of first-order absorption (Ka) and 0.719 h for mean transit time (MTT). Body weight significantly influenced CL/F and Q/F, and eGFR markedly affected CL/F. The internal and external validations indicated a satisfactory descriptive and predictive performance of the model, respectively. Conclusions We successfully established a population PK model to predict EMB concentrations for Korean TB patients. Internal and external validation confirmed that our model showed a good performance. Our model may be a valuable tool to support dose optimization according to individual patients' body weight and renal function in clinical management.