JPH04127057A - Method for measuring degree of crystallization of drug preparation - Google Patents
Method for measuring degree of crystallization of drug preparationInfo
- Publication number
- JPH04127057A JPH04127057A JP24976890A JP24976890A JPH04127057A JP H04127057 A JPH04127057 A JP H04127057A JP 24976890 A JP24976890 A JP 24976890A JP 24976890 A JP24976890 A JP 24976890A JP H04127057 A JPH04127057 A JP H04127057A
- Authority
- JP
- Japan
- Prior art keywords
- crystallization
- degree
- compound
- crystallinity
- measuring
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 25
- 239000003814 drug Substances 0.000 title abstract description 12
- 238000002425 crystallisation Methods 0.000 title abstract description 10
- 230000008025 crystallization Effects 0.000 title abstract description 10
- 229940079593 drug Drugs 0.000 title abstract description 8
- 238000002360 preparation method Methods 0.000 title abstract description 7
- -1 beta-lactam compound Chemical class 0.000 claims abstract description 13
- XIURVHNZVLADCM-IUODEOHRSA-N cefalotin Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CC1=CC=CS1 XIURVHNZVLADCM-IUODEOHRSA-N 0.000 claims description 13
- 229960000603 cefalotin Drugs 0.000 claims description 13
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 abstract description 29
- 238000011088 calibration curve Methods 0.000 abstract description 3
- 238000005259 measurement Methods 0.000 description 9
- 238000004108 freeze drying Methods 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000004020 luminiscence type Methods 0.000 description 3
- 238000002076 thermal analysis method Methods 0.000 description 3
- 238000005979 thermal decomposition reaction Methods 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- 230000004913 activation Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
Landscapes
- Cephalosporin Compounds (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】 (産業上の利用分野) 本発明は、医薬品製剤の結晶化度の測定方法。[Detailed description of the invention] (Industrial application field) The present invention is a method for measuring the degree of crystallinity of a pharmaceutical preparation.
特にβ−ラクタム化合物の結晶化度の測定方法に関する
。In particular, it relates to a method for measuring the degree of crystallinity of a β-lactam compound.
(従来の技術)
医薬品として使用される化合物の多くは、−旦、それを
結晶として単離している。その主な理由は、一般に結晶
質の化合物が非晶質の化合物に比べてその精製度合が高
く、安定であるからである。経口投与製剤等の場合には
、そのまま製剤化される事も多いが、注射用製剤の場合
には粉末充填時に異物混入の恐れがあることから、−旦
、結晶性粉末を水溶液として、フィルターで異物除去し
たのち凍結乾燥する手法が採用されることが多い。(Prior Art) Many compounds used as pharmaceuticals are first isolated as crystals. The main reason for this is that crystalline compounds generally have a higher degree of purification and are more stable than amorphous compounds. In the case of oral preparations, they are often formulated as they are, but in the case of injection preparations, there is a risk of contamination with foreign substances during powder filling, so first, the crystalline powder is made into an aqueous solution and filtered. A method of freeze-drying after removing foreign substances is often adopted.
凍結乾燥法は異物除去には最適であるが、非晶質の存在
割合が高くなる欠点があり、結晶化度(化合物全量に対
する結晶性化合物の割合)を高める凍結乾燥法が種々提
案されている。例えば、セファロチンナトリウム(商品
名:ケフリン■、塩野義製薬@)は結晶化度がほぼ10
0%の凍結乾燥製剤として供給されている。Although the freeze-drying method is optimal for removing foreign substances, it has the disadvantage of increasing the proportion of amorphous substances, and various freeze-drying methods have been proposed to increase the degree of crystallinity (the ratio of crystalline compounds to the total amount of compounds). . For example, cephalothin sodium (trade name: Kefrin■, Shionogi & Co., Ltd.) has a crystallinity of approximately 10.
Supplied as a 0% lyophilized formulation.
以上述べたように、各種医薬品化合物の結晶化度と安定
性には密接な関係があり、結晶化度を簡便にかつ高精度
で測定する方法が望まれていた。As described above, there is a close relationship between the crystallinity and stability of various pharmaceutical compounds, and a method for measuring the crystallinity easily and with high accuracy has been desired.
従来、これらの測定はX線解析法や熱分析法などによっ
て行われていたが、操作が繁雑であり比較的長時間を要
するなどの欠点があった。Conventionally, these measurements have been carried out by X-ray analysis, thermal analysis, etc., but these have disadvantages such as complicated operations and relatively long time requirements.
(発明が解決しようとする課題)
本発明は、上記従来の課題を解決するものであリ、その
目的とするところは、各種医薬品製剤。(Problems to be Solved by the Invention) The present invention is intended to solve the above-mentioned conventional problems, and its purpose is to provide various pharmaceutical preparations.
とりわけβ−ラクタム化合物の結晶化度を簡便にかつ精
度よく測定する方法を提供することにある。In particular, it is an object of the present invention to provide a method for easily and accurately measuring the crystallinity of a β-lactam compound.
本発明方法を用いれば、凍結乾燥直後の製品の品質管理
を容易に行うことが可能であり、また、製品保存中に生
じる製品劣化を容易に追跡チエツクして行くことも可能
である。By using the method of the present invention, it is possible to easily control the quality of the product immediately after freeze-drying, and it is also possible to easily track and check product deterioration that occurs during product storage.
(課題を解決するための手段) 本発明の医薬品製剤の結晶化度の測定方法は。(Means for solving problems) A method for measuring the degree of crystallinity of a pharmaceutical formulation of the present invention is as follows.
該医薬品製剤の極微弱化学発光強度を測定することを包
含する。It includes measuring the extremely weak chemiluminescence intensity of the pharmaceutical formulation.
好適な実施態様においては、上記医薬品製剤は。In a preferred embodiment, the pharmaceutical formulation is:
β−ラクタム化合物であり、好ましくはセファロチンナ
トリウムである。A β-lactam compound, preferably cephalothin sodium.
本発明の方法により医薬品製剤、特にβ−ラクタム化合
物の結晶化度を測定するには、まず、既知の結晶化度の
該化合物の極微弱化学発光(extraweak ch
emiluminescence ; CL)を適当な
手段で測定する。例えば、所定時間における該化合物か
らの受光量を光電子増倍管で増幅し、光電子パルス数と
して計測表示記録することの可能な化学発光測定装置が
利用され得る。このような装置としては1例えば、東北
電子産業■製のChemiluminescence
analyzer 0X−70型が用いられ得る。上記
化合物の結晶化度は、あらかじめ既知の結晶化度測定装
置1例えば、X線解析装置、熱分析結晶化度解析装置な
どにより測定され得る。In order to measure the crystallinity of a pharmaceutical formulation, particularly a β-lactam compound, by the method of the present invention, firstly, the ultraweak chemiluminescence (extraweak chemiluminescence) of the compound of known crystallinity is measured.
eluminescence; CL) is measured by an appropriate means. For example, a chemiluminescence measurement device that can amplify the amount of light received from the compound in a predetermined time using a photomultiplier tube and measure, display and record the photoelectron pulse number can be used. Examples of such devices include 1, for example, Chemiluminescence manufactured by Tohoku Denshi Sangyo ■.
Analyzer model 0X-70 can be used. The crystallinity of the above compound can be measured in advance using a known crystallinity measuring device 1, such as an X-ray analyzer or a thermal analysis crystallinity analyzer.
上記結晶化度と化学発光強度とは所定の関係を有する。The crystallinity and chemiluminescence intensity have a predetermined relationship.
例えば、結晶化度を横軸に、そして発光強度(例えば、
平均時間あたりの発光量)を縦軸に取ると、第1図に示
すような直線が得られる。For example, the crystallinity is plotted on the horizontal axis, and the luminescence intensity (e.g.
If the vertical axis is the average amount of light emitted per hour, a straight line as shown in FIG. 1 is obtained.
これを検量線とすると、結晶化度の未知の上記化合物の
サンプルの発光強度を測定することにより。Using this as a calibration curve, the luminescence intensity of a sample of the above compound with unknown crystallinity is measured.
容易に結晶化度を算出することが可能となる。It becomes possible to easily calculate the degree of crystallinity.
これまで個々の化合物について、上記C’Lが存在する
ことは知られていた。これは、該化合物が大気中の酸素
により酸化され、化学発光を普遍的に生じるためと考え
られていた。例えば、水柱らは。It has been known that the above C'L exists in individual compounds. This was thought to be because the compound is oxidized by oxygen in the atmosphere and universally produces chemiluminescence. For example, Water Pillar et al.
薬学雑誌105 (4) 401−406 (1985
)において1種々の医薬品化合物の[’L値を種々の温
度で測定して、 CLと該化合物の酸化性との関係を考
案している。さらに、水柱らは、東北電子産業レポート
、株式会社東北電子産業、仙台、 1985年、1〜6
頁、において、化合物の種類や測定温度によりCL値が
異なること、不安定な化合物のCL値が高いこと、そし
て、測定温度が高い程CL値が高いことを示している。Pharmaceutical Journal 105 (4) 401-406 (1985
), the ['L values of various pharmaceutical compounds were measured at various temperatures, and the relationship between CL and the oxidizing properties of the compounds was devised. Furthermore, Mizuhira et al., Tohoku Electronic Industry Report, Tohoku Electronic Industry Co., Ltd., Sendai, 1985, 1-6.
Page shows that the CL value differs depending on the type of compound and the measurement temperature, that the CL value of unstable compounds is high, and that the higher the measurement temperature, the higher the CL value.
そして、上記現象は、油脂や食品が劣化によりCLを生
じるのと同様の原理で生じ、医薬品についてもその成分
が酸化をうけてCLを放出するためCL値が高くなると
結論づけている。このように。The authors concluded that the above phenomenon occurs on the same principle as that of fats and oils and foods that produce CL due to deterioration, and that the CL value of pharmaceuticals also increases because their components undergo oxidation and release CL. in this way.
CLは、主として酸化反応により生じ、温度が高くなる
とCL値がより高くなることは知られていたが。It was known that CL is mainly produced by oxidation reactions, and that the higher the temperature, the higher the CL value.
特定の化合物が生じるCLと、該化合物の結晶化度との
関係は全く知られていなかった。The relationship between the CL produced by a specific compound and the crystallinity of the compound was completely unknown.
これに対して1発明者らは、所定の化合物、特にβ−ラ
クタム化合物のCL値と結晶化度とは、温度が一定であ
れば所定の関係を有するという、従来では全く知られて
いなかった事実を見い出し。In contrast, the inventors discovered that the CL value and crystallinity of a given compound, especially a β-lactam compound, have a certain relationship as long as the temperature is constant, which was completely unknown in the past. Find the facts.
本発明を完成するに至った。一般の医薬品、特にβ−ラ
クタム化合物については結晶化度が低い程不安定である
ことが知られている。従って1本発明方法によりある化
合物のCL値を測定し、結晶化度を算出することができ
れば、その化合物の安定性を評価することが可能となる
。本発明方法について、以下の実施例において、セファ
ロチンナトリウムを例に挙げて説明する。本発明方法は
、セファロチンナトリウムに特定されず、他のβ−ラク
タム化合物、さらに他の医薬品についても適用が可能で
ある。他の医薬品についても結晶化度と該医薬品との関
係が明らがであれば2本法を用いてCL値を測定するこ
とにより、結晶化度、さらには、該医薬品の安定性を評
価することが可能となる。The present invention has now been completed. It is known that general pharmaceuticals, especially β-lactam compounds, are more unstable as the degree of crystallinity is lower. Therefore, if the CL value of a certain compound can be measured by the method of the present invention and the degree of crystallinity can be calculated, it becomes possible to evaluate the stability of that compound. The method of the present invention will be explained in the following examples using cephalothin sodium as an example. The method of the present invention is not limited to cephalothin sodium, but can be applied to other β-lactam compounds and even other pharmaceuticals. If the relationship between crystallinity and the drug is clear for other drugs, the CL value can be measured using two methods to evaluate the crystallinity and further the stability of the drug. becomes possible.
(実施例) 以下に本発明の実施例を示す。(Example) Examples of the present invention are shown below.
実施例1
精製セファロチンナトリウムの原末(塩野義製薬■から
提供)を120メツシユの標準篩で篩過し。Example 1 Purified bulk powder of cephalothin sodium (provided by Shionogi & Co., Ltd.) was sieved through a 120 mesh standard sieve.
これをサンプル1とした。次に、同一ロットの上記セフ
ァロチンナトリウム原末280gを局方蒸留水720g
に50℃で加熱溶解させた。この溶液を直ちに5℃に冷
却した後、0.22μmのメンブランフィルタ−で加圧
濾過し、28%水溶液とした。この水溶液を、容量14
−のバイアルに3.3mfずつ分注し。This was designated as sample 1. Next, 280 g of the above cephalothin sodium bulk powder from the same lot was added to 720 g of pharmacopoeically distilled water.
The mixture was heated and dissolved at 50°C. This solution was immediately cooled to 5° C. and filtered under pressure through a 0.22 μm membrane filter to obtain a 28% aqueous solution. Add this aqueous solution to a volume of 14
- Dispense 3.3 mf into each vial.
次の方法により凍結乾燥した。まず、−40℃にて1時
間保持して凍結させ(第1凍結工程)、−5℃に異通し
て所定の時間(0,0,5,10,または15時間)保
持しく晶析工程)、 再び一40℃にて2時間保持しく
第2凍結工程)9次いで、0.2ミlJバールの減圧下
で、30℃(柵温)にて25時間乾燥させた(乾燥工程
)。晶析工程に要した時間が15時間、10時間、0.
5時間、および0時間のサンプルを、それぞれサンプル
2.3.4.および5とした。It was freeze-dried by the following method. First, freeze by holding at -40°C for 1 hour (first freezing step), then hold at -5°C for a predetermined time (0, 0, 5, 10, or 15 hours) (crystallization step). The sample was then kept at -40° C. for 2 hours (second freezing step) and then dried at 30° C. (temperature) for 25 hours under a reduced pressure of 0.2 ml J bar (drying step). The time required for the crystallization process was 15 hours, 10 hours, and 0.
The 5 hour and 0 hour samples were labeled as samples 2.3.4., respectively. and 5.
サンプル1〜5の結晶化度を熱分析により、薬学雑誌v
ol、 109.388 (1988)の方法に従い9
次のようにして測定した。測定機器としては、理学電気
■製のTG−DTAを使用した。上記サンプル1〜5を
5 mgずつ秤取し、1.25℃/分の定速昇温過程に
おける熱分解による重量減少量をTG法により測定し。The crystallinity of samples 1 to 5 was determined by thermal analysis according to Pharmaceutical Journal v
9 according to the method of OL, 109.388 (1988).
It was measured as follows. As a measuring instrument, TG-DTA manufactured by Rigaku Denki ■ was used. 5 mg of each of the above samples 1 to 5 was weighed out, and the amount of weight loss due to thermal decomposition during a constant temperature increase process of 1.25° C./min was measured by the TG method.
次式により結晶化度 (αg)を算出した。Crystallinity is determined by the following formula: (αg) was calculated.
βg=(△Gl+ΔG2)/Σ△G1−3αg= (1
−βg)
△G1.ΔG2:サンプルの非晶質および擬結晶の各成
分の熱分解による重量減少量Σ△G1−3:サンプルの
擬結晶および結晶の各成分の熱分解による重量減少量の
合計値その結果、各サンプルの結晶化度は次のとおりで
あった:サンプルl:99.0冗、サンプル2:92.
3%、サンプル3ニア5.0%;サンプル4:58.0
%;サンプル5:4.0%。βg=(△Gl+ΔG2)/Σ△G1-3αg= (1
-βg) △G1. ΔG2: Amount of weight loss due to thermal decomposition of each component of the amorphous and pseudocrystal of the sample Σ△G1-3: Total value of weight loss due to thermal decomposition of each component of the pseudocrystal and crystal of the sample As a result, each sample The crystallinity of sample 1: 99.0, sample 2: 92.
3%, sample 3 near 5.0%; sample 4: 58.0
%; Sample 5: 4.0%.
次に、これらの化学発光強度(単位時間あたりの発光量
;CL値として示す)を次の方法により測定した。まず
、サンプルを直径53mm、高さ13mmステンレス製
プレートに入れ、東北電子産業11mchemi1um
inescence analyzer 0X−70型
にセットし9次のようにして23℃にて測定を行った。Next, the chemiluminescence intensity (amount of luminescence per unit time; shown as a CL value) of these samples was measured by the following method. First, the sample was placed in a stainless steel plate with a diameter of 53 mm and a height of 13 mm.
The sample was set in an inescence analyzer 0X-70 model, and measurements were performed at 23° C. in the following manner.
まず、試料をセット後1通気シャッターを閉じた状態で
10秒間隔で連続10回測定を行い、ダークカラン)
(dark count)を求め、次いでシャッターを
開けた状態で10秒間隔で連続5分間測定して定常状態
となた後連続6回測定を行い、平均値を求めた。このと
きの測定値(平均値)からダークカウントを引いた値を
試料のCL値とした。First, after setting the sample, measurements were taken 10 times in a row at 10 second intervals with the ventilation shutter closed.
(dark count) was determined, and then measurements were taken continuously for 5 minutes at 10 second intervals with the shutter open, and after reaching a steady state, measurements were taken 6 times in a row, and the average value was determined. The value obtained by subtracting the dark count from the measured value (average value) at this time was defined as the CL value of the sample.
サンプルNα1〜5のCL値を表1に示す。Table 1 shows the CL values of samples Nα1 to Nα5.
(以下余白)
表1
回帰分析の結果:
Y切片
Y評価値の標準誤差
R2乗
標本数
自由度
21578、610
813、50771
0.9925069
X係数
X係数の標準誤差
213、5030
10、710436
上記各サンプルの結晶化度と、 CL値との関係を第1
図に示す。第1図から、サンプルの結晶化度が低い程C
L値は高くなり、該結晶化度とCL値とは。(Space below) Table 1 Results of regression analysis: Standard error of Y intercept Y evaluation value R square Number of samples Degrees of freedom 21578, 610 813, 50771 0.9925069 X coefficient Standard error of X coefficient 213, 5030 10, 710436 Each sample above The relationship between the degree of crystallinity and the CL value is expressed as
As shown in the figure. From Figure 1, the lower the crystallinity of the sample, the more C
The L value increases, and what is the crystallinity and CL value?
良好な直線関係を示すことがわかる。これを検量線とし
て使用すれば、未知の結晶化度のセファロチンナトリウ
ムのCL値を測定することにより結晶化度を算出するこ
とが可能となる。It can be seen that a good linear relationship is shown. If this is used as a calibration curve, it becomes possible to calculate the degree of crystallinity by measuring the CL value of cephalothin sodium with an unknown degree of crystallinity.
実施例2
実施例のサンプルNrJ、1.2および5の新たなサン
プルを3個ずつ準備した。これらのサンプルのCL値を
、27℃、47℃および67℃において測定した。Example 2 Three new samples each of samples NrJ, 1.2 and 5 of the example were prepared. The CL values of these samples were measured at 27°C, 47°C and 67°C.
但し、 CL値の測定においては、サンプルをセットし
てから10分間、10秒間隔で連続測定した後、10回
測定した値を使用した。その結果を表2に示す。However, in measuring the CL value, continuous measurements were taken at 10 second intervals for 10 minutes after setting the sample, and then the values measured 10 times were used. The results are shown in Table 2.
さらに、測定温度(1/TX 103)とCL値との関
係を第2図に示す。Furthermore, the relationship between the measured temperature (1/TX 103) and the CL value is shown in FIG.
(以下余白)
表2
表2および第2図から、絶対温度の逆数とCL値の対数
とは直線関係を示すことがわかる。そこでアレニウスの
式に適用し、化学発光反応の活性化エネルギーを算出し
た。その結果を表3に示す。(Margins below) Table 2 From Table 2 and FIG. 2, it can be seen that the reciprocal of the absolute temperature and the logarithm of the CL value show a linear relationship. Therefore, we applied the Arrhenius equation to calculate the activation energy of the chemiluminescent reaction. The results are shown in Table 3.
表3
10.94
11.36
6.05
表3から、結晶化度の低いセファロチンナトリウムは結
晶性のセファロチンナトリウムに比べて活性化エネルギ
ーが小さく、熱に不安定であることが明らかである。Table 3 10.94 11.36 6.05 From Table 3, it is clear that cephalothin sodium with low crystallinity has a lower activation energy and is unstable to heat than crystalline cephalothin sodium. .
(発明の効果)
本発明によれば、このように、医薬品製剤、特にβ−ラ
クタム化合物の極微弱化学発光強度を測定することによ
り該化合物の結晶化度が短時間のうちに精度良く測定さ
れる。一般に、結晶化度の高い化合物はど安定性が高い
ため1本法により医薬品製剤の結晶化度を測定すること
により、該製剤の安定性を評価することが可能となる。(Effects of the Invention) According to the present invention, as described above, by measuring the extremely weak chemiluminescence intensity of a pharmaceutical preparation, particularly a β-lactam compound, the degree of crystallinity of the compound can be measured with high precision in a short time. Ru. In general, compounds with a high degree of crystallinity have high stability, so by measuring the degree of crystallinity of a pharmaceutical preparation using a single method, it is possible to evaluate the stability of the drug preparation.
第1図は、セファロチンナトリウムの結晶化度と該化合
物の単位時間あたりの化学発光量との関係を示すグラフ
、そして、第2図は、セファロチンナトリウムを種々の
温度で測定したときの温度と単位時間あたりの化学発光
量との関係を示すグラフである。
以上Figure 1 is a graph showing the relationship between the crystallinity of cephalothin sodium and the amount of chemiluminescence per unit time of the compound, and Figure 2 is a graph showing the relationship between the crystallinity of cephalothin sodium and the amount of chemiluminescence per unit time of the compound, and Figure 2 shows the temperature when cephalothin sodium was measured at various temperatures. It is a graph showing the relationship between the amount of chemiluminescence and the amount of chemiluminescence per unit time. that's all
Claims (1)
薬品製剤の結晶化度測定法。 2、前記医薬品製剤がβ−ラクタム化合物である請求項
1に記載の測定法。 3、前記β−ラクタム化合物がセファロチンナトリウム
である請求項2に記載の測定法。[Scope of Claims] 1. A method for measuring crystallinity of pharmaceutical preparations, which includes measuring extremely weak chemiluminescence intensity. 2. The measuring method according to claim 1, wherein the pharmaceutical preparation is a β-lactam compound. 3. The measuring method according to claim 2, wherein the β-lactam compound is cephalothin sodium.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP24976890A JPH04127057A (en) | 1990-09-18 | 1990-09-18 | Method for measuring degree of crystallization of drug preparation |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP24976890A JPH04127057A (en) | 1990-09-18 | 1990-09-18 | Method for measuring degree of crystallization of drug preparation |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH04127057A true JPH04127057A (en) | 1992-04-28 |
Family
ID=17197941
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP24976890A Pending JPH04127057A (en) | 1990-09-18 | 1990-09-18 | Method for measuring degree of crystallization of drug preparation |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH04127057A (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5452948A (en) * | 1994-10-07 | 1995-09-26 | The Whitaker Corporation | Apparatus and method for electronically controlled hydraulic actuator |
JP2015206603A (en) * | 2014-04-17 | 2015-11-19 | 鹿島建設株式会社 | Coated film weather-resistance prediction method |
-
1990
- 1990-09-18 JP JP24976890A patent/JPH04127057A/en active Pending
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5452948A (en) * | 1994-10-07 | 1995-09-26 | The Whitaker Corporation | Apparatus and method for electronically controlled hydraulic actuator |
JP2015206603A (en) * | 2014-04-17 | 2015-11-19 | 鹿島建設株式会社 | Coated film weather-resistance prediction method |
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