PubMed Health⌕ Search

Biomedical subjects

Takehiro Okumura

Publications and source records attributed to Takehiro Okumura.

6 recordsLinked to original sources

An accurate quantitative analysis of polymorphs based on artificial neural networks.

Measurement precision based on homogeneous and accurate standard samples has been reported to result in significant improvement in the sensitivity and accuracy of the quantitative analysis of polymorphic mixtures. The purpose of this study was to further improve the accuracy of the quantitation based on data processing by artificial neural networks (ANNs), using such high quality standard samples. Homogeneous powder mixtures of alpha- and gamma-forms of indomethacin (IMC) at various ratios (0-50% alpha-form content) were subjected to X-ray powder diffractometry. The two diffraction peaks selected as the best combination in multiple linear regression (MLR) were used in the ANN with an extended Kalman filter as a training algorithm. The results obtained by ANN had better predictive accuracy at lower contents (0-5%) compared to those of MLR. ANNs for the diffraction data based on high quality standard samples provide an extremely precise and accurate quantification for polymorphic mixtures.

Algorithms↗

Polymorphic transformation of indomethacin under high pressures.

To study the effect of pressure on polymorphic transformation, intact powder, and ethanol slurry of alpha, gamma, and amorphous forms of indomethacin (IMC) were compressed under high pressures. A quantifying method for the percentages of these three constituents in sample powder was established. Using this method, analysis of compressed samples revealed that alpha form, which is difficult to prepare in stable form under atmospheric pressure, was easily obtained in stable form from the ethanol slurry of the amorphous IMC, which does not include any specific crystalline forms. In the ethanol slurry of gamma form, transformation to alpha form was observed: a reciprocal phenomenon under atmospheric pressure. These results can be rationally explained as follows: alpha form is more easily crystallized than gamma form in the ethanol solution, the more closely-packed crystal structure of alpha form is thermodynamically predominant over gamma form under high pressure, and pressure-induced amorphization occurs. This study indicates that crystallization experiments from the slurry of amorphous samples under various pressures can be useful in screening polymorphic or other solid states.

Calorimetry, Differential Scanning↗

Malignant pleural mesothelioma in a 14-year-old boy with right aortic arch.

We report successful surgery for malignant pleural mesothelioma (MPM) in a 14-year-old boy with right aortic arch. Pleural biopsy by video-assisted thoracic surgery yielded a diagnosis of MPM, epithelial type. As the disease was not changed after combination chemotherapy with three cycles of cisplatin and gemcitabine, we performed left extrapleural pneumonectomy, including resection of the pericardium and diaphragm for MPM, and aortopexy for right aortic arch. The postoperative course was uneventful, and the patient has remained alive without disease for 10 months postoperatively.

Adolescent↗

Evaluation of the microcrystallinity of a drug substance, indomethacin, in a pharmaceutical model tablet by chemometric FT-Raman spectroscopy.

PURPOSE: To establish a chemometric method for the precise evaluation of the microcrystallinity of indomethacin (IMC) in a pharmaceutical model tablet, based on FT-Raman spectroscopy. METHODS: Standard sample powders of homogeneous mixtures of amorphous and crystalline IMC were prepared in various proportions. A calibration model for the crystallinity of IMC was constructed by partial least-square (PLS) analysis based on the multiplicative scatter correction (MSC)+second-derivative transformed Raman spectra. A calibration model for the crystallinity of IMC in a model pharmaceutical product (IMC/mannitol=1:9 wt/wt) was also constructed using homogeneous standard sample powders of various degrees of crystallinity of IMC. RESULTS: This technique was validated to detect to 2% an amorphous or crystalline material in IMC contained in the model product (0.2% of the total mass of the tablet). Using this technique, not only pressure-induced amorphization but also the difference in microcrystallinity of IMC at the surface and interior of a model product tablet was elucidated after compaction of the tablet. CONCLUSIONS: The established technique is ideally suited for precise quantification of microanalysis of drug substances and drug products, particularly at the surface and interior of the tablet.

Anti-Inflammatory Agents, Non-Steroidal↗

A novel standard sample powder preparation method for quantitative analysis of polymorphs.

The purpose of this study was to improve the sensitivity and accuracy of the quantitative analysis of polymorphic mixtures. Calibration curve reliability has been improved through the advancement of standard mixture preparation techniques whereby samples at scales of several grams are homogeneously and accurately prepared without decrease in crystallinity. Crystalline powders are first micronized to anisotropic, nearly equal-sized (<10 microm) particles of almost random orientation in an air jet mill. These powders are then mixed in a vibration mill that includes rubber balls as mixing media. Using this technique, alpha and gamma forms of indomethacin (IMC) were prepared in various proportions from 0.5% to 50% alpha content and subjected to X-ray powder diffraction analysis. The validation data showed that these precisely prepared standard mixtures resulted in superior analytical sensitivity and accuracy compared to those prepared by agate mortar.

Calibration↗

Surgical treatment for metastatic malignancies. Pulmonary metastasis: indications and outcomes.

Surgical resection is an important modality in the treatment of pulmonary metastases from various solid tumors. The criteria for pulmonary metastasectomy are as follows: (1) the patient must be a good risk for surgical intervention; (2) the primary malignancy is controlled; (3) there is no other, extrapulmonary, metastasis; and (4) the pulmonary lesions are thought to be completely resectable. The appropriate selection of candidates according to these criteria leads to an overall 5-year survival after pulmonary metastasectomy of about 30%-40%. However, most of the reported results are retrospective analyses, and the significance of pulmonary metastasectomy seems to vary according to the primary malignancy. To clarify the significance of surgical treatment for pulmonary metastases, we need further analysis of various prognostic factors, with special reference to each primary malignancy, as well as a multiinstitutional study, and randomized prospective studies, if possible.

Humans↗