Pharmaceutics — 05
Manufacturing process
Acetylcysteine 20% Nebulising Solution — prepared as a sterile aqueous solution, pH-adjusted to 7.0, sterile-filtered and aseptically filled with oxygen exposure minimised throughout.
Section authors · Raeesa Rashid · Sumayyah Chughtai
Batch size
100 mL
Product
20% w/v Acetylcysteine
pH
Target pH 7.0 · acceptable range 6.0–7.5
01
Process overview
The 20% w/v acetylcysteine nebulising solution is prepared as a sterile aqueous solution using Water for Injection (WFI). Disodium edetate is first dissolved in a portion of WFI, followed by the gradual addition and dissolution of acetylcysteine. The pH is then adjusted to the target of 7.0, within the acceptable range of 6.0–7.5, using sodium hydroxide and, if required, hydrochloric acid to correct an overshoot. The solution is subsequently made up to the final volume of 100 mL with WFI and mixed until uniform. Because acetylcysteine is susceptible to oxidation, exposure to oxygen is minimised during processing and filling, including the use of deaerated WFI and nitrogen protection where applicable. The bulk solution is then passed through a sterilising-grade membrane filter into sterile containers and filled aseptically, with oxygen exposure minimised during closure (USP, 2025; US8952065B2, 2015).
02
Materials
- —Acetylcysteine — 20.0 g
- —Edetate disodium — 0.05 g
- —Sodium hydroxide — q.s. to adjust pH to 7.0 (acceptable range 6.0–7.5)
- —Hydrochloric acid — q.s., if required for pH adjustment
- —Water for Injection — q.s. to 100 mL
03
Equipment
Diagram
Process flow
Preparation of WFI
≈60 mL deaerated WFI into the sterile vessel · controlled mixing begins
Dissolve edetate disodium
0.05 g added and mixed to complete dissolution
Dissolve acetylcysteine
20.0 g added gradually with continuous mixing to a homogeneous solution
pH adjustment
Make up to volume
Deaerated WFI to 100 mL · mixed to uniformity
Sterile filtration
0.22 μm sterilising-grade membrane filter into a sterile receiving vessel, aseptically
Filling & packaging
Aseptic fill into sterile single-unit containers · nitrogen headspace where used · sealed promptly and protected from light
Oxygen exposure is minimised at every stage — deaerated WFI, minimal headspace, and nitrogen protection where applicable.
Method
Steps 01–07
| No. | Step | Description |
|---|---|---|
| 01 | Preparation of WFI | Transfer approximately 60 mL of deaerated Water for Injection (WFI) into a suitable sterile compounding vessel. Begin controlled mixing and minimise exposure of the WFI to atmospheric oxygen throughout the preparation. |
| 02 | Dissolution of Edetate Disodium | Accurately weigh 0.05 g disodium edetate and add it to the initial WFI. Mix until the disodium edetate is completely dissolved. Slight heating may be used if necessary to facilitate dissolution, followed by cooling before proceeding. |
| 03 | Dissolution of Acetylcysteine | Accurately weigh 20.0 g acetylcysteine and gradually add it to the disodium edetate solution while mixing continuously. Continue mixing until the acetylcysteine is completely dissolved and a homogeneous solution is obtained. |
| 04 | pH Adjustment | Measure the pH using a calibrated pH meter. Add sodium hydroxide solution gradually while mixing until the solution reaches the target pH of 7.0, within the acceptable range of 6.0–7.5. Allow sufficient mixing before confirming the pH. If the pH exceeds the required range, hydrochloric acid may be added carefully, if required, to lower the pH back into the specified range. |
| 05 | Make-Up to Volume | Add additional deaerated WFI to the solution until the total volume reaches 100 mL. Mix thoroughly to ensure a uniform solution. Minimise exposure to atmospheric oxygen during volume make-up. |
| 06 | Processing / Sterility | Pass the prepared bulk solution through a sterilising-grade 0.22 μm membrane filter into a sterile receiving vessel under aseptic conditions. Minimise oxygen exposure during filtration and subsequent handling. |
| 07 | Filling & Packaging | Aseptically fill the sterile filtered solution into sterile, compatible single-unit containers. Minimise oxygen exposure during filling and, where nitrogen protection is used, displace the container headspace with nitrogen before closure. Seal the containers promptly and protect the finished product from light during packaging and storage. |
Notes
Key formulation and manufacturing considerations
1
Appearance
The final product should be a clear, colourless liquid.
2
Oxidation control
Acetylcysteine is highly susceptible to oxidation; therefore, a chelating agent is incorporated to help control trace metal ions, while exposure to oxygen is minimised throughout production.
3
Sterility and processing method
Sterility is essential for a product administered directly to the lungs; therefore, a sterile filtration method is selected to minimise exposure of acetylcysteine to potentially damaging high temperatures during sterilisation.