著者

稲津 邦平

出版者

一般社団法人日本PDA製薬学会

雑誌

日本PDA学術誌 GMPとバリデーション (ISSN:13444891)

巻号頁・発行日

vol.9, no.1, pp.52-60, 2007 (Released:2008-06-06)

参考文献数

12

著者

武田 豊彦 鈴木 裕介 稲津 邦平 坂元 照男 前川 秀幸

出版者

公益社団法人日本薬学会

雑誌

薬学雑誌 (ISSN:00316903)

巻号頁・発行日

vol.109, no.6, pp.p395-401, 1989-06

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Cephalothine sodium (CET-Na) in crystals can be obtained by freezing the aqueous solution and subsequent warming at a fixed temperature for facilitating crystallization prior to vacuum application for drying. The product has, however, been found to unavoidably contain traces of the amorphous CET-Na, which causes a rapid color development during storage. By using thermal analysis, differential scanning calorimetry (DSC), electric conductometry, and polarized light cryomicrographic techniques, the solubilities in water, freezing point, eutectic point, and melting behavior of CET-Na in aqueous solution were investigated. The investigation demonstrated that CET-Na in supersaturated aqueous solution is very stable, and that seeding with microcrystalline CET-Na to the supersaturated solution and subsequent cooling of the mixture till its freezing point gives neither any evidence for crystallization nor for growth of the seed crystals. The freeze-drying of CET-Na in the supersaturated solution after seeding has been demonstrated to give crystalline CET-Na contaning neither of amorphous nor of quasicrystalline form.

著者

稲津 邦平

出版者

一般社団法人日本PDA製薬学会

雑誌

日本PDA学術誌 GMPとバリデーション (ISSN:13444891)

巻号頁・発行日

vol.8, no.2, pp.140-145, 2006 (Released:2008-02-01)

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PDA の科学技術に関するディスカッショングループ(STDG)は,無菌医薬品技術に限らず,世界各国での医薬品製造,プロセスバリデーション,品質管理,薬事法規の分野を対象とし,自由に意見が交換できる場である。1994 年に FDA は,英国の PharmaWeb 社を支援し,PDA 会員や PDA が力を入れている製薬業界やバイオ業界に関係するテーマを対象として,使いやすいオンラインフォーラムを立ち上げた。PDA は,このフォーラムの調整も担当している。STDG へサインアップするアドレスには,次の URL を利用されたい。   http://www.pharmweb.net/pwmirror/pwq/pharmwebq2.html   イーメールで STDG へ参加するには,上記 URL にある所定の欄へ氏名とイーメールアドレスを入力して「send」ボタンをクリックするだけでよい。また,この URL では,1996 年から 2007 年 12 月までのメールを読むことができる。なお,メールを送るときには,ファイルを添付しないこと。グループのメンバーに有用と考えられる添付資料については,メンバー個々へ送信するか,もしくはその資料が掲載されている URL をグループ宛てに送信されたい。   日本 PDA 製薬学会は PDA 本部の了解を得て,最近に掲示された話題のうち,「経口固形製剤の使用期限」,「光安定性」,「医薬品質システムのマネジメント」「超低温凍結庫用センサーの校正」,「設備洗浄後の保管時間」および「GMP と cGMP との違い」に関する意見交換の内容を紹介する

著者

稲津 邦平

出版者

Parenteral Drug Association Japan Chapter

雑誌

日本PDA学術誌 GMPとバリデーション (ISSN:13444891)

巻号頁・発行日

vol.1, no.2, pp.95-96, 1999 (Released:2006-08-03)

著者

武田 豊彦 鈴木 裕介 稲津 邦平 坂元 照男 前川 秀幸

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.109, no.6, pp.395-401, 1989-06-25 (Released:2008-05-30)

参考文献数

13

被引用文献数

2 6

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Cephalothine sodium (CET-Na) in crystals can be obtained by freezing the aqueous solution and subsequent warming at a fixed temperature for facilitating crystallization prior to vacuum application for drying. The product has, however, been found to unavoidably contain traces of the amorphous CET-Na, which causes a rapid color development during storage. By using thermal analysis, differential scanning calorimetry (DSC), electric conductometry, and polarized light cryomicrographic techniques, the solubilities in water, freezing point, eutectic point, and melting behavior of CET-Na in aqueous solution were investigated. The investigation demonstrated that CET-Na in supersaturated aqueous solution is very stable, and that seeding with microcrystalline CET-Na to the supersaturated solution and subsequent cooling of the mixture till its freezing point gives neither any evidence for crystallization nor for growth of the seed crystals. The freeze-drying of CET-Na in the supersaturated solution after seeding has been demonstrated to give crystalline CET-Na contaning neither of amorphous nor of quasicrystalline form.

著者

鈴木 裕介 武田 豊彦 稲津 邦平 坂元 照男

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.110, no.11, pp.858-868, 1990-11-25 (Released:2008-05-30)

参考文献数

7

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Seeding and subsequent freeze-drying of aqueous cephalothin sodium (CET-Na) solution of supersaturated concentrations, which preliminarily received an excess of mechanical stress, have been reported to make the product unacceptable in pharmaceutical elegance and in chemical stability upon storage. In order to find out the cause, the CET-Na solution that preliminarily received mechanical stress has been examined as to its crystallization behavior during freezedrying process, by using polarizedlight cryomicroscopy, scanning electron microscopy, cryodifferential scanning calorimetry, refractometry, viscositometry, and surface tensiometry. Aqueous CET-Na solution of supersaturated concentrations, to which an excess of mechanical stress was given, has been demonstrated to exhibit the following features : in the process of seeding and subsequent freeze-drying, the solution shows an incomplete crystallization at -40°C ; in the crystal growth stage at -5°C, crystals are found to be difficult to grow sufficiently from the seeds as their nuclei. These findings indicate that the supersaturated solution has changed to an unusual state upon receiving such stress, the state being different from the state of untreated solution in that the solution thus treated shows physico-chemical properties capable of easy crystallization through a simple step of freezing. The change as such in physico-chemical properties has also been estimated to have resulted from a structural change of associated molecules of CET-Na in its supersaturated solution into a condensed state quite similarly to that of liquid crystals.

著者

鈴木 裕介 武田 豊彦 稲津 邦平 坂元 照男

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.110, no.11, pp.849-857, 1990-11-25 (Released:2008-05-30)

参考文献数

13

被引用文献数

1 2

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A method of seeding and subsequent freeze-drying of aqueous cephalothin sodium (CET-Na) of supersaturated concentrations was employed in an experiment with a regular production scale. The freeze-dried plugs of non-uniformity in appearance were consequently obtained together with those of white in color and in high uniformity in appearance. Such plugs of irregular shape have been found to show a marked color development during storage, and the reconstitution time was also prolonged. Scanning electron microscopy, powder X-ray diffractometry, and thermogravimetry have all demonstrated that the plugs of irregular appearance show dense aggregates of fine crystals of a high non-crystallinity by an incomplete crystal growth. Investigation has then been made with supersaturated CET-Na solution, which has preliminarily received varying mechanical stresses in varying time courses of temperature, similarly to a regular production program, for the purpouse of achieving the reproducibility of such unacceptable plugs. It has been demonstrated that by a more prolonged storage at a lower temperature of CET-Na in supersaturated solution the plug may surely contain aggregates of more fine crystallites of a higher non-crystallinity, accordingly have a higher irregularity in appearance and exhibit a more marked deterioration in pharmaceutical qualities.

著者

井上 正義 島 和弘 稲津 邦平

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.104, no.9, pp.973-980, 1984-09-25 (Released:2008-05-30)

参考文献数

14

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Investigation has been made to obtain the crystallinity of cephalothin sodium in seeded and frozen aqueous solution from electrical conductivity (conductivity), with a result that crystallinity (αt) can be given by the equation of αt=λT-λt/λT, where λT is the initial conductivity and λt stands for the conductivity obtained after t hours. Observed values of crystallinity by the conductivity method are in good agreement with crystallinity data by infrared method and X-ray diffraction method of the freeze-dried material. Further investigation has been made to find out whether it is possible to apply the no-seeding conductivity method for the crystallinity of dicethiamin hydrochloride in solution capable of spontaneous nucleation and transformation to its crystalline state. The result has consequently demonstrated that, in some cases of no-seeding, the phase transition is not uniform, or otherwise, the conductivity change provides an incomplete indication of nucleation and growth of perfect crystals. From the above, it may as well be said to be safe to set a limit to a seeded system, when the authors' conductivity method is applied for obtaining the crystallinity of a drug in frozen solution.

著者

井上 正義 田中 廣義 島 和弘 稲津 邦平

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.105, no.3, pp.289-295, 1985-03-25 (Released:2008-05-30)

参考文献数

16

被引用文献数

1 1

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The effect of organic solvent on the growth rate of cephalothin sodium (KF) after seeding in frozen solution was investigated. All of used solvents accelerated crystal growth of KF and it was found that the accelerative effect of solvent increased with an increase in dielectric constant of solvent. KF formed micelle in aqueous solution and the solvent lower the freezing temperature of the micelle and it can be assumed that the lowering of the freezing temperature of the micelle related to the volume of solvent existing in the micelle. Alcohol lower larger the freezing temperature of the micelle than ketone and nitrile, but the accelerative effect of alcohol on the growth rate was less than that of ketone and nitrile. The effect of the concentration of ethanol and acetone was investigated and it seemed that ethanol accelerated nucleation. Nevertheless, the accelerative effect of ethanol on the growth rate was less than that of acetone. These results suggested that simultaneous use of solvent having a different mode of action is effective for crystallization of KF in frozen solution by spontaneous nucleation.

著者

井上 正義 島 和弘 稲津 邦平

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.104, no.12, pp.1268-1274, 1984-12-25 (Released:2008-05-30)

参考文献数

10

被引用文献数

3 2

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The growth rate of cephalothin sodium (KF) after seeding in frozen solution was measured. Crystal growth of KF followed equation (1) untill α=0.98. 1-(1-α)1/3=(1/3N) (Kt)N……(1) where α is crystallinity, K is rate constant, t is time, and N is parameter depending on the freezing temperature and the amount of seed. Crystal growth of KF in the frozen solution hardly changed when the concentration of KF was in the range of 19.4% to 28.6% but it was remarkably dependent on the amount of seed at the constant freezing temperature. According to the decrease in the amount of seed at the constant freezing temperature, the value of N increased and the rate constant (K) decreased. The growth rate increased with a rise of freezing temperature, and had the maximum value at a temperature little below the eutectic temperature. The activation energy of crystal growth of KF in the range of -5°C to -14°C was 49 kcal/mol.

著者

鈴木 裕介 武田 豊彦 稲津 邦平 坂元 照男 前川 秀幸

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.109, no.6, pp.388-394, 1989-06-25 (Released:2008-05-30)

参考文献数

10

被引用文献数

1 1

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Cephalothin sodium (CET-Na) prepared according to the conventional freeze-drying methods is known to easily develop color during storage. Since amorphous CET-Na has been reported to be markedly unstable, the color development is thought to be due to the presence of traces of CET-Na in an amorphous state observed with scanning electron microscopy. Quantitation by use of the powder X-ray diffractometry of such traces of amorphous CET-Na has proved to be of little use. Thermogravimetry (TG) and differential scanning calorimetry (DSC) have demonstrated that the freeze-dried CET-Na by the conventional methods contains three types of CET-Na : amorphous (unstable phase), quasi-crystalline (metastable phase). Pyrolysis initiation temperatures of these three types of CET-Na have been demonstrated to become higher in this order. A new parameter for the evaluation of non-crystallinity of CET-Na has been introduced, in which the ratio is calculated from the data of the total weight loss observed through the pyrolysis of both amorphous and quasi-crystalline CET-Na against the total weight loss of all components during the pyrolysis of sample specimen. The ratio thus calculated is defined as "non-crystallinity". This new parameter has successfully been introduced to establish a good correlation to the degree of increasing color intensity with aging of freeze-dried CET-Na.