87 Progress in Rubber, Plastics and Recycling Technology, Vol. 32, No. 2, 2016
The Potential Use of Natural Rubber in Pharmaceutical Closures
*Author for correspondence, e-mail: trangrriv@yahoo.com
©
Smithers Information Ltd., 2016
The Potential Use of Natural Rubber in
Pharmaceutical Closures
Nguyen Ngoc Bich, Nguyen Thi Hue Trang,* Nguyen Duy Luan, and
Huynh Van Son
Rubber Research Institute of Vietnam, 236 bis Nam Ky Khoi Nghia Street, District 3,
Ho Chi Minh City, Vietnam
Received: 3 June 2013, Accepted: 30 March 2015
SUMMARY
Current manufacturing techniques could produce natural rubber closures that
meet all criteria standardized by pharmacopeias except the ultraviolet absorbance
limit in the range of 220-360 nm for the closures’ leachate. The type and the
dosage of the rubber compounds’ ingredients affected the ultraviolet absorbance
of the leachate, while rinsing the closures in water with ultrasonic waves and
ozone did not. Intensive washing of the rubber coagulum and deproteinization of
the rubber latex using bromelain reduced ultraviolet absorbance of the leachate
significantly. Further purification of natural rubber latex is necessary to enable the
use of natural rubber in pharmaceutical closures.
Keywords: Natural rubber, Pharmaceutical closures, Leachables, Ultraviolet absorbance
INTRODUCTION
Elastomeric pharmaceutical closures should not react with, absorb, or release
harmful impurities into the drug product. The possibility of rubber closures to
leach chemicals into drug compositions was noticed at early as in 1964 [1].
Vulcanization accelerators and antioxidants were found in the drug composition
[2]. Other leachables may include formaldehyde [3] and hydrogen sulfide [4].
Leachables mostly came from vulcanization activators and accelerators as
well as antioxidants [5, 6]. Leachables are not a challenge only for natural
rubber (NR); however the problem is more serious in the case of NR because
of non-rubber constituents in the NR latex. In addition, NR closures have been
observed to release allergic proteins into drug products [7]. This weakness