Substitution of concentrated sodium hydroxide with sodium hydrogen carbonate for pH adjustment in pharmaceutical production.

Number

089-EN

Section

General Section

Use

Sector

Manufacture of bulk, large scale chemicals (including petroleum products)
Manufacture of fine chemicals
Health services

Function

pH regulating agent

Process

Chemical production where opportunity for exposure arises

Product category

Processing aids such as pH-regulators, flocculants, percipitant, neutalization agents
Pharmaceuticals

Application

Production of pharmaceutical products

Abstract

Neutralisation of a product during a pharmaceutical production was earlier done by applying sodium hydroxide. Sodium hydroxide was substituted with the less hazardous alternative sodium hydrogen carbonate.

Substituted substances

Sodium hydroxide

CAS No. 1310-73-2 EC No. 215-185-5 Index No. 011-002-00-6

Chemical group

Sodium compounds; hydroxides

Classification: hazard statements

H314 Causes severe skin burns and eye damage

Alternative Substances

Sodium hydrogencarbonate

CAS No. 144-55-8 EC No. 205-633-8 Index No.

Chemical group

Sodium compounds; carbonates

Reliability of information

Evidence of implementation: there is evidence that the solution was implemented and in use at time of publication

Reason substitution

skin/respiratory sensitizing

Hazard Assessment

Substance to be substituted: Sodium hydroxide causes severe skin burns and eye damage. Alternative substance: Sodium hydrogencarbonate is not listed in the SUBSPORTplus Database and has no harmonised classification according to Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation). » Check the Substance Database according to SUBSPORTplus Screening Criteria (SDSC)

Description of Substitution

During the production of pharmaceutical products, it is often necessary to neutralise a component in a process. For this pH adjustment the company applied sodium hydroxide. Through optimisation and systematic review of well-defined and publicly available "unit operations" for the chemical industry, the company started to use sodium hydrogen carbonate for pH adjustment instead. Sodium hydroxide can cause severe burns. Moreover, the substance develops a strong heat, when it is mixed with water as opposed to sodium hydrogen carbonate. By substituting sodium hydroxide with sodium hydrogen carbonate the company eliminated the heat development, and therefore the new process is faster than the old one. In the old process it was necessary to cool the mixture down before the next process step could be performed. A by-product of the use of sodium hydrogen carbonate is development of CO2. This cools the process even more. This method can be used in many processes where neutralisation occurs. Sodium hydroxide was applied as a solution while sodium hydrogen carbonate is applied as a powder. A disadvantage with the new method is that it is easier to handle liquids as compared to powder. In addition, sodium hydrogen carbonate is more expensive than sodium hydroxide and, because of the development of CO2, exhaust ventilation is necessary.

Case/substitution evaluation

Sodium hydrogen carbonate is less hazardous than sodium hydroxide. The chemical alternative was assessed against hazards in the Hazardous Substance Database according to SUBSPORT Screening Criteria (SDSC). This case study from 2010 describes the substitution of "hydrogen chloride" by "CO2" when lowering the pH value in wastewater treatment. The BVT Information sheet "Wastewater / Waste Gas Treatment" from 2016 contains the use of "CO2" to lower the pH value, not as a substitute but as an equivalent.

State of implementation

Full capacity

Date and place of implementation

1990 Denmark

Availability ofAlternative

Alternative is available on the market.

Type of information supplier

User

Contact

www.leo-pharma.com

Date, reviewed

December 11, 2020