• Journal of the Korean Society of Safety
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• v.36 no.3
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• pp.24-30
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• 2021

Heat is generated during the synthesis and mixing process of chemical compounds due to a change in activation energy during the reaction. A runaway reaction occurs when sufficient heat is not removed during the heat control process within a reactor, rapidly increasing the temperature, reaction speed, and rate of heat generation inside the reactor. A risk assessment was executed using an RC-1 (Reaction Calorimeter) during Friedel-Crafts acylation. Friedel-Crafts acylation runs the risk of rapid heat generation during Active Pharmaceutical Ingredient (API) manufacturing; it was used to confirm the risk of a runaway reaction at each synthesis stage and during the mixing process. This study used experimental data to develop a safety efficiency improvement plan to control the risks of runaway and other exothermic reactions, which was implemented at the production site of a chemical plant.

• Journal of the Korean Institute of Gas
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• v.22 no.4
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• pp.49-54
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• 2018

In the Active Pharmaceutical Ingredient(API) manufacturing company, since the product is produced by the chemical reaction, fire and explosion are frequently occurred in the process of inputting the raw powder as the chemical reaction stage. There are not many studies on safety measures through analysis of cause of accident in the actual chemical reaction stage. In this study, we investigated the heat flow in the boron removal reaction process to investigate the risk in the chemical reaction stage. The study reaction process was performed by using the reaction calorimeter for the products synthesized at the actual raw material in pharmaceutical factory. The risk was estimated by comparing the maximum temperature of the synthesis reaction, which can generate heat due to the failure of cooling in the actual manufacturing process, and the technical temperature. These results are applied to commercial manufacturing sites and safety measures to control the risk of runaway reaction due to reaction heat are suggested.

• Journal of Pharmaceutical Investigation
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• v.24 no.1
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• pp.33-40
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• 1994

In order to develop a broad-spectrum veterinary anthelmintic, a combined preparation of nitroxynil and levamisole was formulated for subcutaneous injection. The preformulation studies on solubilization, physicochemical stability and toxicity of combined preparation were performed. The combined preparation of nitroxynil-N-ethylglucamine and levamisole base could be solubilized up to 50.3%(w/v) of active ingredient concentration in propylene glycol/water system. Injectable solutions were most stable at $4^{\circ}C$. Local toxicities such as flare and edema were not shown when the usual dose of the combined preparation was injected subcutaneously to the rats.

• Journal of Pharmaceutical Investigation
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• v.6 no.2
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• pp.58-68
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• 1976

120 tablets of 25mg phenformin hydrochloride tablet and 4mg chlorpheniramine maleate tablet, respectively, were assayed and analyzed to obtain basic data on the content uniformity of domestic pharmaceuticals. All of the tablets of phenformin hydrochloride and that of chlorpheniramine maleate were met the requirements of the test for weight variation and content but no regularity was found in the content unformity specifications. In case of chlorpheniramine maleate tablets, standard deviation of active ingredient content of B maker was 4.1% and that of C maker 7.1%.

• Analytical Science and Technology
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• v.24 no.6
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• pp.519-526
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• 2011

Chemometrics using near-infrared (NIR) and Raman spectroscopy have found significant uses in a variety quantitative and qualitative analyses of pharmaceutical products in complex matrixes. Most of the pharmaceutical can be measured directly with little or no sample preparation using these spectroscopic methods. During pharmaceutical manufacturing process, analytical techniques with no or less sample preparation are very critical to confirm the quality. This study showed NIR and Raman spectroscopy with principal component analysis (PCA) was very effective for the blending processing control. It is of utmost importance to evaluate critical parameters related to quality of products during pharmaceutical processing. The blending is confirmed by off-line determination of active pharmaceutical ingredient (API) by a conventional method such as high performance liquid chromatography (HPLC) and UV spectroscopy. These analytical methods are time-consuming and ineffective for real time control. This study showed the possibility for the determination of blend uniformity end-point of CR tablets with the use of both NIR and Raman spectroscopy. The samples were acquired from six positions during blending processing with U-type blender from 0 to 30 min. Using both collected NIR and Raman spectral data, principal component analysis (PCA) was used to follow the uniformity of blending and finally determine the end-point. The variation of homogeneity of six samples during blending was clearly found and blend uniformity end-point was successfully confirmed in the domains of principal component (PC) scores.

• Journal of Pharmaceutical Investigation
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• v.41 no.5
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• pp.263-272
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• 2011

Tablet dosage forms have been preferred over other formulations for the oral drug administration due to their low manufacturing costs and ease of administrations, especially controlled-release applications. Controlled-release tablets are oral dosage forms from which the active pharmaceutical ingredient (API) is released over an intended or extended period of time upon ingestion. This may allow a decrease in the dosing frequency and a reduction in peak plasma concentrations and hence improves patient compliance while reducing the risk of undesirable side effects. Conventional singlelayered matrix tablets have been extensively utilized to deliver APIs into the body. However, these conventional single-layered matrix tablets present suboptimal delivery properties, such as non-linear drug delivery profiles which may cause higher side effects. Recently, a multi-layered technology has been developed to overcome or eliminate the limitations of the singlelayered tablet with more flexibility. This technology can give a good opportunity in formulating new products and help pharmaceutical companies enhancing their life cycle management. In this review, a brief overview on the multi-layered tablets is given focusing on the various tablet designs, manufacturing issues and drug release profiles.

• Archives of Pharmacal Research
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• v.26 no.2
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• pp.157-161
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• 2003

The major ingredient of Persicae Semen is a cynogenic compound, amygdalin (D-mandelonitrile-$\beta$-gentiobioside). Controversial results on the anticancer activity of amygdalin were reported due to its conversion to its inactive isomer, neoamygdalin. In order to inhibit the epimerization of amygdalin, we used newly developed simple acid boiling method in preparation of Persicae Semen extract. HPLC analysis revealed most of amygdalin in Persicae Semen extract was active D-form. Persicae Semen extract was used to analyze its effect on cell proliferation and induction of apoptosis in human promyelocytic leukemia (HL-60) cells. Persicae Semen extract was cytotoxic to HL-60 cells with $IC_{50}$ of 6.4 mg/mL in the presence of 250 nM of $\beta$-glucosidase. The antiproliferative effects of Persicae Semen extract appear to be attributable to its induction of apoptotic cell death, as Persicae Semen extract induced nuclear morphology changes and internucleosomal DNA fragmentation.

• Journal of Marine Bioscience and Biotechnology
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• v.10 no.2
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• pp.62-72
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• 2018

An active ingredient with hyaluronidase (HAse) inhibitory effect is one of the anti-aging approaches in cosmeceuticals. Here, red sea cucumbers (RSCs), Stichopus japonicus, from Jeju Island were evaluated to examine their HAse inhibitory and antioxidant activity effect. In this study, RSCs were extracted by six enzymatic hydrolysis (Alcalase; Al, Trypsin; Try, Neutrase; Neu, Pepsin; Pep, Alpha-chymotrypsin; Chy and Protamex; Pro). Alcalase hydrolysate (AlH) showed the highest antioxidant capacities for both of oxygen radical absorbance capacity (ORAC) and trolox equivalent antioxidant capacity (TEAC) methods, compared to those of other hydrolysates, at $66.59{\pm}0.78{\mu}M\;TE/mg$ and $135.78{\pm}3.24{\mu}M\;TE/mg$, respectively. Furthermore, AlH performed the highest capacity of HAse inhibitory with $IC_{50}$ value of 3.21 mg/ml. Thus, RSCs hydrolyzed by Al were chosen to determine the cellular antioxidant activity and hyaluronic acid (HA) production effect on Human immortalized keratinocyte cell line (HaCaT). The results showed that AlH improved the cell viabilities and intracellular reactive oxygen species (ROS) induced by 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) were significantly decreased. In addition, AlH increased HA amount by regulating HYAL2 and HAS2 expressions in the HaCaT cells. Taken together, AlH of RSCs collected from Jeju Island showed HAse inhibitory and antioxidant activities against skin-aging which shows its potentials can be an optional natural bioactive ingredient for novel cosmeceuticals.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.417-424
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• 2023

Parkinson's disease (PD) which has various pathological mechanisms, recently, it is attracting attention to the mechanism via microbiome-gut-brain axis. 6-Shogaol, a representative compound of ginger, have been known for improving PD phenotypes by reducing neuroinflammatory responses. In the present study, we investigated whether 6-shogaol and ginger attenuate degeneration induced by Proteus mirabilis (P. mirabilis) on the intestine and brain, simultaneously. C57BL/6J mice received P. mirabilis for 5 days. Ginger (300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage feeding for 22 days including the period of P. mirabilis treatment. Results showed that 6-shogaol and ginger improved motor dysfunction and dopaminergic neuronal death induced by P. mirabilis treatment. In addition, they suppressed P. mirabilis-induced intestinal barrier disruption, pro-inflammatory signals such as toll-like receptor and TNF-α, and intestinal α-synuclein aggregation. Moreover, ginger and 6-shogaol significantly inhibited neuroinflammation and α-synuclein in the brain. Taken together, 6-shogaol and ginger have the potential to ameliorate PD-like motor behavior and degeneration of dopaminergic neurons induced by P. mirabilis in mice. Here, these findings are meaningful in that they provide the first experimental evidence that 6-shogaol might attenuate PD via regulating gut-brain axis.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.187.2-187.2
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• 2003

The cyclin-dependent kinases (CDKs), a group of serine/threonine kinases that form active heterodimeric complexes binding to cyclins, are key regulators of the cell cycle. The role of cyclin dependent kinases(CDKs) in cell cycle regulation has stimulated an interest in them as potential targets for proliferative diseases such as cancer, psoriasis, and chemotherapeutic agent-induced alopecia. Indirubin, an active ingredient of a traditional Chinese recipe Danggui Longhui Wan, are potent CDK inhibitors competing with ATP for binding to the catalytic site of the CDKs. (omitted)