• Title/Summary/Keyword: T-A formulation

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Qualitative and quantitative assessment of process related impurities in Brigatinib raw material and formulations using HPLC

  • Attada Tharun;Potnuru Jagadeesh;B Srinivasa Kumar;Kota Thirumala Prasad;Venkateswara Rao Anna
    • Analytical Science and Technology
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    • v.36 no.4
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    • pp.180-190
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    • 2023
  • The presence of process related impurities in any drug or the drug product was associated with its safety, stability and efficacy. The overall literature survey proved that there is no method published on the assessment of process related impurities in brigatinib. In this study, a simple, reliable and stable HPLC qualitative method was reported for quantification of process related impurities with easy and quick extraction procedure. The impurities along with standard brigatinib was resolved on Lichrospher® C18 (250 mm × 4.6 mm; 5 ㎛ particle size) column in room temperature using methanol, acetonitrile, pH 4.5 phosphate buffer in 55:25:20 (v/v) at 1.0 mL/min as mobile phase and UV detection at 261 nm. The method produces well resolved peaks at retention time of 4.60 min, 12.28 min, 3.37 min, 7.34 min and 8.39 min respectively for brigatinib, impurity A, B, C and D. The method produces a very sensitive detection limit of 0.0065 ㎍/mL, 0.0068 ㎍/mL, 0.0053 ㎍/mL and 0.0058 ㎍/mL for impurity A, B, C and D respectively with calibration curve linear in the concentration range of 22.5-135 ㎍/mL for brigatinib and 0.0225-0.135 ㎍/mL for impurities. The method produces all the validation parameters under the acceptable level and doesn't produces any considerable changes in peak area response while minor changes in the developed method conditions. The method can effectively resolve the unknown stress degradation products along with known impurities with less % degradation. The method can efficiently resolve and quantify the impurities in formulation and hence can suitable for the routine quality analysis of brigatinib in raw material and formulation.

Robust control of linear systems under structured nonlinear time-varying perturbations I - Analysis

  • Bambang, Riyanto-T.;Shimemura, Etsujiro
    • 제어로봇시스템학회:학술대회논문집
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    • 1993.10b
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    • pp.81-87
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    • 1993
  • In this paper robust stability conditions are obtained for linear dynamical systems under structured nonlinear time-varying perturbations, using absolute stability theory and the concept of dissipative systems. The conditions are expressed in terms of solutions to linear matrix inequality(LMI). Based on this result, a synthesis methodology is developed for robust feedback controllers with worst-case H$_{2}$ perforrmance via convex optimization and LMI formulation.

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Enzymatic Glycosylation of Acrylic Acid and Methacrylic Acid (아크릴산과 메타크릴산의 효소적 배당화)

  • 박돈희;김해성
    • KSBB Journal
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    • v.16 no.1
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    • pp.82-86
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    • 2001
  • Glyco-acrylate and methacrylate were synthesized by lipase-catalyzed glycosylation of acrylic acid, methacrylic acid and their vinyl esters with $\beta$-methyl fructoside and glycerol in t-butanol as a reaction medium. At the optimum conditions for enzymatic glycosylation of acrylic acid and vinyl methacrylate, we attained up to 80% conversion for glyco-acrylate from acrylic acid and 90% conversion for glyco-methacrylate from vinyl methacrylate. The polymerizable glyco-acrylates and methacrylate have biomedical application as hydrophilic monomers and hydration modifiers to be use for hydrogel contact lens formulation.

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Biodistribution and Genotoxicity of Transferrin-Conjugated Liposomes/DNA Complexes in Mice

  • Lee Sang Mi;Kim Jin-Seok;Oh Yu-Kyoung;Lee Yong-Bok;Sah Hongkee
    • Macromolecular Research
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    • v.13 no.3
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    • pp.218-222
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    • 2005
  • Transferrin-conjugated liposomes ($T_f$-liposomes) were made and formulated with pCMVluc DNA to form a lipoplex. Among the various formulations studied, the $T_f$-liposome: pCMVluc DNA complex at a ratio of 5: 1 (wt/wt) showed the highest transfection efficiency, which was twice that of $Lipofectin^{TM}$ on HeLa cells. The maxi-mum tolerated dose (MTD) of this lipoplex formulation from a single intravenous injection was over 10 mg/kg in healthy ICR mice. The RT-PCR results showed that the highest level of luciferase mRNA was detected in the lungs, followed by the liver, spleen, heart and kidneys, after an intravenous injection into mice. Two weeks after the injection, the levels of luciferase mRNA decreased gradually in the liver, spleen, heart, and kidney, but not in the lungs. The micro-array study showed that the cancer-related genes, including the bcl 6 gene, were highly up-regulated by the treatment with $T_f$-liposome/ pCMVluc DNA complex on HeLa cells, indicating that there were possible interactions between the host chromosomal DNA and the $T_f$-liposome within the cells. The results obtained from this study are expected to be useful for designing a safe and efficient gene delivery system using transferrin-conjugated liposomes.

A New Method on the Derivation of the Thermodynamic Quantities for a System Represented by the Canonical Ensemble (Canonical Ensemble 로 代表된 系의 에너지 分布則 및 熱力學的牀態量의 道出에關하여)

  • Kim Shoon-Kyung
    • Journal of the Korean Chemical Society
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    • v.3 no.1
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    • pp.3-8
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    • 1954
  • Fowler obtained thermodynamic quantities assuming the theory which could be derived by representing the system with microcanonical ensemble, in order to introduce the temperature T of the system proper, he considered the combined systems which are composed of the system proper and another arbitrary system that is in thermal contact with the former, and represented the combined system by a microcanonical ensemble, here, he used the steepest descent method in his calculation. This Fowler's treatment is not only unsatisfactory at the point of theoretical view but also he could not make the formulation of free energy of Helmholtz's so that this formular was forced to be assumed. From the point of Quantum Statistical Mechanical view, the materially closed system which is in an equilibrium state with the temperature T is best represented by canonical ensemble. At the actual derivation of the distribution law and thermodynamic quantities, however, in order to avoid the difficulty of calculation Tolman proceeded his calculation either representing the system proper by the grand-canonical ensemble or adding a certain limitation.

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A Splitting Time Integrator for Fully Flexible Cell Molecular Dynamics (분할 적분 기법을 적용한 N-sigma-T 분자동역학 전산모사)

  • Park, Shi-Dong;Cho, Maeng-Hyo
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.31 no.8
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    • pp.826-832
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    • 2007
  • Fully flexible cell preserves Hamiltonian in structure so that the symplectic time integrator is applicable to the equations of motion. In the direct formulation of fully flexible cell N-Sigma-T ensemble, a generalized leapfrog time integration (GLF) is applicable for fully flexible cell simulation, but the equations of motion by GLF has structure of implicit algorithm. In this paper, the time integration formula is derived for the fully flexible cell molecular dynamics simulation by using the splitting time integration. It separates flexible cell Hamiltonian into terms corresponding to each of Hamiltonian term. Thus the simple and completely explicit recursion formula was obtained. We compare the performance and the result of present splitting time integration with those of the implicit generalized leapfrog time integration.

A New Formulation of Controlled Release Amitriptyline Pellets and Its In Vivo/In Vitro Assessments

  • Park, Eun-Seok;Lee, Dong-Soo;Kwon, Seok-Young;Chi, Sang-Cheol
    • Archives of Pharmacal Research
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    • v.26 no.7
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    • pp.569-574
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    • 2003
  • Controlled-release amitriptyline pellets (ATP) were formulated and its oral bioavailability was assessed in human volunteers after oral administration under fasting conditions. Core pellets were prepared using a CF granulator by two different methods (powder layering and solvent spraying) and coated with Eudragit RS or RL 100. Physical characteristics and dissolution rates of core pellets and coated pellets were evaluated to optimize the formulation. Powder layering method resulted in a better surface morphology than solvent spraying method. However, physical properties of the products were poorer when prepared by powder layering method with respect to hardness, friability and density. The dissolution profile of amitriptyline coated with Eudragit RS 100 was comparable to that of commercially available amitriptyline enteric-coated pellets ($Saroten^{\circledR}$ retard). After the oral administration of both products at the dose of 50 mg, the mean maximum concentrations ($C_{max}$) were 36.4 and 29.7 ng/mL, and the mean areas under the concentration-time curve ($AUC_{0-96}$) were 1180.2 and 1010.7 ng.h/mL for ATP and Saroten retard, respectively. The time to reach the maximum concentrations ($T_{max}$) was 6 h for both formulations. Statistical evaluation suggested that ATP was bioequivalent to Saroten retard.

Studies on the Physico-chemical Properties of Mixed Radioactive Waste Glass

  • Kim, C.W.;Choi, J.R.;Ji, P.K.;Park, J.K.;Shin, S.W.;Ha, J.H.;Song, M.J.;Hwang, T.W.;Park, S.J.
    • Journal of Radiation Protection and Research
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    • v.29 no.1
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    • pp.33-39
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    • 2004
  • In order to vitrify the W1 waste (ion-exchange resin(IER), zeolite, and dry active waste(DAW)) generated from Korean Nuclear Power Plants, a glass formulation development based on waste compositions and production rates was performed. A aluminoborosilicate glass, AG8W1, was formulated to vitrify the W1 waste in an induction cold crucible melter(CCM). The processability, product performance, and economics of the candidate glass were calculated using a computer code and were measured experimentally in the laboratory and CCM. The glass viscosity and electrical conductivity as the process parameters were in the desired ranges. Start-up and maintaining glass melt of the candidate glass were favorable in the CCM. The product quality of the glass such as chemical durability, phase stability, etc. was satisfactory. The vitrification process using the candidate glass was also evaluated to be operated as economically as possible.

Integrated Control of Vector Mosquitoes with Native Fishes (Aplocheilus and Aphyocypris) ad Bacillus thuringiensis(H-14) in Natural Rice Fields of Korea (천적포식어(Aplocheilus and Aphyocypris)와 미생물제제 Bacillus thuringiensis (H-14)의 병합처리에 의한 논에서 서식하는 질병매개모기의 종합적방제)

  • 유효석;김흥철
    • Korean journal of applied entomology
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    • v.28 no.3
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    • pp.167-174
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    • 1989
  • A confined field assessment on the integrated control of vector mosquitoes (Anopheles sinen- sis and Culex tritaent'orhynchus) was conducted by timely treatment of Bacillus thuringiensis(H-14) formulation in the presence of larvivorous fish (Aplocheilus lalipes) in natural rice fields of $30,000M^2$ at Yongam, South Korea Cholla Province from July through October in 1988. In presence of larvivorous fish (Aplocheilus) at lower density of 0.6 fish per $M^2$ water surface, mosquito vector control rates ranged 55. 0~57. 6% from July through August, and when the mosquio density started to increase with over 10 larvae on the average per sample, B.t.(H-14) formulation treatment at the rate of 1. 0 Kg/ha made 100% vectors reduc¬tion in 24 hours, the control sustained above 98% until the test was terminated on October 11th. In the fish introduced rice paddies with Aphyocypris chinensis at the density of above 1. 5 fish per $M^2$, a satisfactory degree of vector control was obtained by 88. 2~96. 7% in 2 week period until September 21st. In the absence of larvivorous fishes, B.t. (H-14) treatment made 100% control in 24 hours, however, vector population rebound appeared in day 7, required to make additional treatment to suppress population down.

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