• Journal of the Korean Crystal Growth and Crystal Technology
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• v.26 no.6
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• pp.232-237
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• 2016

Cocrystallization of active pharmaceutical ingredients has been widely recognized as a versatile tool to regulate the physical properties of pharmaceutical compounds through designed crystal structures. Grinding or milling has been especially useful to screen the feasibility of cocrystal formation, and the addition of a small amount of liquid is routinely necessary. In the present study, the effect of temperature was studied for the milling cocrystallization of ibuprofen and nicotinamide to establish a liquid-free method. The milling-induced cocrystallization was more effective with liquid nitrogen cooling than at room temperature, which was confirmed by XRD and DSC analyses. This behavior was attributed to the limited molecular mobility below the glass transition temperatures of the cocrystal components, which made it effective to destruct the crystals of raw materials and consequently form the ibuprofen/nicotinamide cocrystal. Further studies would be necessary to establish the utility of the current conclusion to the field of pharmaceutical crystallization.

• Korean Journal of Plant Resources
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• v.31 no.6
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• pp.695-703
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• 2018

Previously, we have reported a plant extract isolated from Lysimachia foenum gracum Herba as a new environment friendly biopesticide that has the mycelial growth inhibition effect on Magnaporthe oryzae, the pathogenic fungus of the rice blast disease. For the finding of additional biopesticide candidate, we tested the mycelial growth inhibitory effects about 700 species of plant extracts on PDA media. Among them, the extract of Anemarrhena asphodeloides showed prominent inhibitory effect of which $IC_{50}$ was $139.7{\mu}g/ml$. Mycelial radii of M. oryzae were measured on PDA medium containing the four organic solvent fractions isolated from total extract from A. asphodeloides. Ethyl acetate fraction showed the impressive inhibitory effect of $IC_{50}$, $54.12{\mu}g/ml$. In the subsequent rice field test for the total extract of A. asphodeloides, we obtained encouraging 62.0% control rate of rice blast disease without any phytotoxicity. It is almost equivalent to that of chemical pesticides implying the applicability of the extract as a new biopesticide. In further study, the analysis of active ingredients of the extract would be necessary for the development of a new biopesticide and for the verification of cellular mechanism by which the mycelial growth of M. oryzae inhibited.

• CELLMED
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• v.8 no.3
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• pp.11.1-11.6
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• 2018

In vitro anti-obesity effects of anti-cancer (AC) functional kimchi in differentiated 3T3-L1 adipocytes were studied. We constructed three experimental groups: Control, standardized kimchi (SK), and AC functional kimchi (A-FK) that included active ingredients and Lactobacillus plantarum. Kimchi extracts did not show any cytotoxicity in pre-adipocytes in the concentration range of 1 - 5 mg/mL. A-FK significantly reduced fat droplet formation and absorbance in differentiated 3T3-L1 adipocytes, as shown by Oil red O staining, compared to Control and SK (P < 0.05). SK and A-FK reduced adipo-/lipogenesis related genes such as $C/EBP{\alpha}$, SREBP-1, LPL, and $LXR{\alpha}$ compared to Control (P < 0.05). Especially, A-FK more greatly reduced SREBP-1 and LPL compared to SK (P < 0.05). A-FK up-regulated the ${\beta}$-oxidation related gene CPT-1c and down-regulated the pro-inflammatory cytokine IL-6 compared to Control (P < 0.05). Based on the results, A-FK exhibited anti-obesity effects by inhibiting fat droplet formation and adipo-/lipogenesis related genes by regulating the ${\beta}$-oxidation related gene CPT-1c and pro-inflammatory cytokine IL-6. In previous studies, A-FK kimchi already exhibited a strong anti-cancer effect. These results indicate that A-FK increased anti-obesity activity in this model system due to its functional ingredients and anti-cancer functionality.

• Korean Chemical Engineering Research
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• v.48 no.6
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• pp.757-762
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• 2010

Since the quality and performance of medicinal products are heavily dependent upon the size, shape and polymorphism of active pharmaceutical ingredients(APIs), their crystallization has been regarded as one of the most important pharmaceutical processes. In this study, NIR-based inline measurements were employed to monitor key attributes of API particles real-time during the crystallization process. Principal component analysis(PCA) method was selected to correlate inline NIR spectra while the well-known aspirin was studied as a model drug. According to our characterization results, the ratio of ethanol to acetone did not cause any change in polymorphism, but resulted in a significant difference in the nucleation time, crystal growth and crystal shape. These phenomenological changes were well correlated with the PCA's implications. It turned out that the NIR-based inline monitoring technology can be employed well in observing and predicting key quality attributes such as crystal size during pharmaceutical crystallization processes.

• KSBB Journal
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• v.16 no.3
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• pp.233-236
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• 2001

Because of casehardenign effect of amorphous paclitaxel, residual solvents, methylene chloride and emthanol could not be reduced to the maximum value allowed, 600 ppm and 3,000 ppm, in accord with the guidelines issued by the International Conference on Harmonization (ICH, 1997), using rotary evaporation and successive drying in a vacuum oven. However, methylene chloride and methanol were reduced to 486 ppm and 403 ppm, respectively using supercritical $CO_2$ on purified paclitaxel. The optimum pressure and operating time were 80 bar and 30 min at fixed operating temperature ($40^{circ}C$). This approach serves as a novel application of supercritical fluid extraction to remove residual solvents from active pharmaceutical ingredients.

• Natural Product Sciences
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• v.12 no.1
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• pp.55-61
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• 2006

A description of simple, isocratic and precise reversed phase HPLC methods is given for simultaneous quantification of pholcodine and ephedrine hydrochloride together with either carbinoxamine maleate or terfenadine in antitussive-antihistaminic oral pharmaceutical formulations. Separations were carried out on X-Terra and symmetry shield C18 column $(250\;{\times}\;4.6\;mm,\;5\;{\mu}m)$. The used isocratic elution systems were either $0.02\;M\;KH_2PO_4-acetonitrile$ in the ratio of 75 : 25 and pH adjusted to 7.70 with orthophosphoric acid or sodium hydroxide, for syrup (method A), or 0.02 octanesulphonic acid sodium salt solution-acetonitrile-acetic acid in the ratio of 75 : 25 : 0.5 for suspension (method B). The elution of both mixtures was achieved with a flow rate of 1 ml/min. Detection was carried out by UV absorbance at wavelengths of 220 and 250 nm for syrup and suspension, respectively. The quantification of the components in synthetic mixtures and actual syrup and suspension were calculated using the internal standard technique with metoclopramide HCl and codeine phosphate as internal standards (IS), respectively. The methods, for both mixtures, were validated and met all the requirements for the quality control analysis recommended by FDA and ICH.

• Biomolecules & Therapeutics
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• v.11 no.1
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• pp.51-57
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• 2003

General pharmacological properties of ADP, a new pharmaceutical composition, which contains a mixed water extract obtained from the mixture of Phellodendron cortex (Phellodendron amurense) and Anemarrhena rhizoma (Anemarrhena asphodeloides), as the active ingredients, were investigated in experimental animals administering orally and in vitro test system. ADP had no influences on general behavior, pentobarbital sleeping time, spontaneous motor activity, motor coordination of mice, normal body temperature, chemoshock produced by pentylenetetrazole and writhing syndromes induced by 0.8% acetic acid at the dose of 150 and 1500 mg/kg. Gastric secretion of rats and intestinal motility of mice were not also influenced by the administration of ADP at doses of 150 and 1500 mg/kg, with the exception of the significant decrease of free HCI concentration at a dose of 1500 mg/kg in rats. ADP (150 and 1500 mg/kg) did not alter mean arterial blood pressure and heart rate in conscious rats. ADP given to anesthetized rats showed no effect on respiratory rate at the same doses. In in vitro experiments, ADP at the concentration of 150 mg/L did not show direct effect and inhibitory or augmentative action on histamine- or acetylcholine-induced contractions in the isolated ileum of guinea-pig. Taken together, these results indicate that ADP does not induce any adverse effects in experimental animals.

• Journal of Pharmaceutical Investigation
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• v.26 no.2
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• pp.91-98
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• 1996

Precipitation was formed during the preparation of decoction from a mixure of Scutellariae Radix and Coptidis Rhizoma or Phellodendri Cortex according to the prescription of Hwang-ryean-hae-dog-tang. Baicalin and berberine, the active ingredients of the two herbal medicine were identified in coprecipitated product. Pills were prepared using the coprecipitated product and various binders. The dissolution rate of baicalin and berberine from pills was increased in at pH1.2 when acacia or tragacanth was used. The absorption rate of baicalin from the coprecipitated product was faster than that from Scutellaria extract, but the absorption of berberine from CPP was slower in stomach, duodenum and jejunum of rats compared with Coptis extract. The time required for the maximum serum concentration (Cmax) of baicalin and berberine from CPP in mice were 150 and 200 min after oral administration, respectively. The maximum serum concentration of baicalin from CPP in mice was higher than Scutellaria extract, but the concentration of berberine was lower compared with Coptis extract. The minimum inhibitory concentration of CPP was below $50\;{\mu}g/ml$ against gram positive bacteria, and was higher than that against gram negative bacteria. The antibacterial activity of CPP was lower than that of herberine, but was more potent than Scutellaria extract. It was found that the inhibition rates of growth by CPP against S. epidermidis, K. pneumoniae, B. cereus and S.aureus were 60.0, 51.1, 45.4 and 39.9%, respectively.

• Journal of Pharmaceutical Investigation
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• v.39 no.4
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• pp.263-267
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• 2009

The purpose of this study is to evaluate the efficacy of stipulated cleaning process, and the prohibition of cross-contamination and microbiological contamination, which inadequate cleaning in multi-production could occur, through cleaning validation of multi-purpose facility used to produce five biopharmaceutical products as sterile injection. After production of five biopharmaceutical products such as hGH, rhGCSF, rhEPO, rhFSH and rhIFN using vial filling machine, the cleaning validation such as residual analysis of active ingredients or human serum albumin, measurement of total organic carbon (TOC), residual analysis of detergent and microbiological contamination were carried out. In the case of rhGH and rhGCSF clean validations, drug residues were not detected. Furthermore, in the case of rhEPO, rhFSH and rhIFN clean validations, human serum albumin residues were not detected. At TOC (total organic carbon) analysis, all clean validations gave the TOC of about average 137.93%, not more than 150% of acceptance criteria. At sodium analysis for the checking of residues of cleaning agent, sodium residues were not detected. In sterility test, they showed no microbiological contamination of bacteria and fungi. Thus, this cleaning validation was determined as successful in protection of cross-contamination and induction of safety in multi-purpose facility.

• Korean Journal of Clinical Pharmacy
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• v.23 no.3
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• pp.239-247
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• 2013

Background: Fixed drug combinations are formulations containing two or more active ingredients in a single dosage form. Such combination therapies are commonly applied to improve efficacy, reduce adverse events and replace co-administration, etc. National and international guidelines for hypertension treatment recommend addition of other classes of antihypertensive drugs rather than incremental dose of mono-therapy, when blood pressure is not adequately controlled. Thus, many dual combinations of antihypertensive drugs have been approved and pharmaceutical companies are recently interested in developing antihypertensive triple combinations. Clinical trial designs for the fixed combinations are various depending on the target patients, dosage and clinical endpoints. Thereby, further discussions for the clinical trials of antihypertensive triple therapies are required regarding the indication claimed. Conclusion: This article provides a review for the assessment of the label and medical reports of the clinical trials on antihypertensive triple therapies in advanced foreign countries.