The U.S. Food and Drug Administration is alerting drug and dietary supplement  manufacturers, compounding pharmacies, and distributors of Povidone analogs (Povidone/Copovidone/Crospovidone), that the agency recently detected excessive levels of peroxide in one lot of Crospovidone (cross linked polyvinyl N-pyrrolidone) manufactured by China-based Tianjin Boai NKY International Ltd1.  The peroxide level found by the FDA in the lot was more than four (4) times the maximum level of peroxide (400 ppm) allowed by global compendial monographs.  

Other lots of Povidone analogs2 manufactured by this firm may also contain excessive levels of peroxide. An Import Alert has been issued to prevent further entry of Tianjin Boai NKY International Ltd Crospovidone into the U.S. market.

To date, the FDA is not aware of any illnesses in the United States stemming from peroxide contamination. The level of peroxide found in this particular lot does not appear, on its own, to pose a significant health risk in drugs or dietary supplements. The FDA nonetheless remains concerned that elevated levels of peroxide can cause subpotent finished products. 

Crospovidone is a very common ingredient in drugs and dietary supplements. Peroxide is a potential impurity from the polymerization step involved in the manufacturing of Povidone analogs. Residual peroxide levels of <100 ppm have been reported to cause oxidative degradation.The FDA is concerned that drug manufacturers using excipients containing high levels of peroxides will observe a loss of drug potency and the formation of excessive impurities during the product shelf life.

It is essential that users and distributors implement robust supplier management programs to assure that peroxide levels in Povidone analogs are in control for each batch received. Manufacturers using such excipients should employ sound risk management principles in establishing appropriate scrutiny (including peroxide testing regimen) and actions to take for a given supplier, including but not limited to the following:  

(a) review supplier history, including any relevant information on manufacturing reliability;
(b) assess peroxide levels obtained from testing4 of past batches of Povidone analogs;

(c) determine reliability of results reported on Certificates of Analysis;

(d) consider information obtained from ongoing communications with suppliers; and

(e) determine whether the quality of any finished product has been impacted.
Manufacturers who use ingredients that might contain elevated levels of peroxide are advised to notify the FDA if they become aware of any further findings of quality problems or potentially related adverse events.


May also do business as Friends Union Enterprise (Jianjin) Ltd, Boai New Kaiyuan Pharmaceutical Company, Boai NKY Pharmaceuticals Ltd or Bluetech Chemicals Limited.


A recently published study also found elevated levels of peroxide in multiple lots of Povidone analogs, consistent with the FDA’s findings. (Silverstein, PhD, Irwin, Pharmaceutical Technology, Vol. 33, Issue 10, pp. 84-88, October 02, 2009. “The Case for Supplier Qualification.”)

 Hartauer, et al, Pharm. Dev. Technol. 2000;5(3):303-10. “Influence of peroxide impurities in povidone and crospovidone on the stability of raloxifene hydrochloride in tablets: identification and control of an oxidative degradation product.”

4 A peroxide test is not currently listed in the USP monographs for crospovidone and povidone. However, a non-specific USP/EP method (see Copovidone NF) can be used to readily detect peroxide present at 400 ppm in Povidone analogs. Alternatively, a validated method shown to be specific for peroxide and having at least the same sensitivity as the compendial method may be used.

Crospovidone 交聯聚維酮 是什麼東西呢?

其實就是優碘的賦形劑povidone的類似物,

想認識優碘,可以參考這篇:陰道灌洗

其實這個東西,在你常常看見的健康食品裡面都有

例如善存:

CN-001.jpg

預覽“VitaminC購物網 銀寶善存 (285錠)”.png

也不是只有保健食品才有,藥物也會用到:

螢幕快照 2010-10-23 上午10.59.33.png  

最後,附上一些賦形劑的介紹:

螢幕快照 2010-10-22 下午11.37.48.png螢幕快照 2010-10-22 下午11.40.06.png 

CAS數字: 9003-39-8

分子式: C6H9

默克 13, 7783

MFCD : MFCD00149016

1-Ethenyl-2-pyrrolidoinone均聚物(IUPAC); 多[1 (2含氧的1 pyrrolidinyl)乙烯]; polyvidone; 聚乙烯吡咯烷酮; PVP; 1乙烯基2pyrrolidinone聚合物

 

物產

PVP是可溶解於水以及極性的溶劑. 在水中它會形成黏性物質. 乾燥時是一粒輕的片狀粉末,會吸收大氣水中,大約可以佔本身質量的18%。有優秀的保溼性及包覆性,使它被利用來作為塗層或添加劑。

 

用途

單體有可能為致癌物質而且毒性高,彈在水中形成聚合物PVP後,不僅很安全,而且還可以食用,在二次大戰期間,也被拿來做代用血漿。

在藥物致祭學方面,被利用來作用賦形劑,主要是因為對人體呈現惰性,只會簡單的經過身體,然後被代謝掉,最常見的就是優碘:PVP增加 碘 形成複合體(Povidone碘 )具有殺菌的功能。其實這類的產品很多,像是軟膏,,子宮托,液體肥皂和外科洗刷。

PVP為極性分子,所以也應用為相片噴墨紙和有時候也會添加在一些配方的墨水中。

PVP也用於個人產品,例如 洗髮精還有牙膏、油漆和黏著劑,甚至像是郵票背面,也用在隱形眼鏡和製鋼過程。目前有些還會用在髮膠上面。

 PVP也可以作為食品添加劑和安定劑,用數字E分類:E1201. PVPP是 E1202. 也用於製酒業,作為 澄清劑。

在 分子生物學PVP可以使用作為封堵劑,分析作為Denhardt的緩衝成分。對於分析鑑定,尤其是洗DNA或是將植物多酚分離出來時,都可以用到PVP。

PVP也用於許多技術應用:

  • 作為膠粘劑
  • 作為特別添加劑,像電池, 陶瓷, 玻璃纖維, 墨水還有噴墨機紙
  • 乳化劑幫助分解質聚合化
  • 光致抗蝕劑,利用在陰極射線管 (CRT)
  • 用途在含水金屬的冷卻,鋼練造等等
  • 可以生產膜製品,例如透析過濾器
  • 當黏合劑和絡合代理在agro應用例如 莊稼的保護,種子治療和塗層
  • 作為在牙漂白膠凝體的一個變厚的基質
  • 作為援助為增加藥物的可溶性以液體和半流質的劑量表(糖漿軟的明膠 膠囊)和作為抗化劑 再結晶

交互相聯的衍生物

 交互相聯PVP的形式在藥劑學也使用作崩散劑,例如聚乙烯Polypyrrolidone (PVPP), crospovidone, crospolividone。 基本上, PVPP是PVP的一個高度被交互相聯的結構使它不能溶解在水中,但它吸收水并且非常迅速地仍然膨脹。所以可以使用來加速藥物崩散,除此之外,也可以用來提取雜質。利用相同的原理,可以在生產啤酒時,除掉一些多酚類的雜質,讓啤酒可以產生穩定的泡泡。

PVPP可以作為錠劑或是懸浮液,或是利用他吸收化合物,進行腹瀉治療,就像活性炭一樣。

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