PROCESS FOR THE PREPARATION OF A PHARMACEUTICAL SOLUTION

Abstract

The invention provides a process for preparing an aqueous pharmaceutical solution of calcium gluconate. The process comprises the steps of: (i) mixing calcium gluconate, calcium saccharate and water at a mixing temperature of 60-100? C. to form a bulk solution; (ii) filling portions of the bulk solution into containers at a filling temperature of 60-100? C.; and (iii) sealing the containers with a closure. The invention also provides a batch of containers obtainable by this process.

Claims

1. A process for preparing an aqueous pharmaceutical solution of calcium gluconate, wherein the process comprises the steps of: (i) mixing calcium gluconate, calcium saccharate and water at a mixing temperature of 60-100? C. to form a bulk solution; (ii) filling portions of the bulk solution into containers at a filling temperature of 60-100? C.; and (iii) sealing the containers with a closure.

2. The process as claimed in claim 1, wherein the filling temperature is 70-90? C.

3. The process as claimed in claim 2, wherein the filling temperature is 75-85? C.

4. The process as claimed in claim 1, wherein the mixing temperature and the filling temperature are within 20? C. of each other.

5. The process as claimed in claim 1, wherein the mixing temperature is higher than the filling temperature.

6. The process as claimed in claim 1, wherein the aqueous pharmaceutical comprises 5-15% weight by volume of calcium gluconate, based on the total volume of the solution.

7. The process as claimed in claim 1, wherein the process further comprises (iv) sterilising the sealed containers.

8. The process as claimed in claim 7, wherein the sterilizing uses steam sterilization at a sterilization temperature of 110-130? C. and a sterilization time of 5-45 mins.

9. The process as claimed in claim 1, wherein the containers are 50 or 100 mL.

10. The process as claimed in claim 1, wherein the containers are plastic vials.

11. The process as claimed in claim 1, wherein the process is used to fill a batch of 500 containers or more.

12. The batch of containers obtainable by the process as claimed in claim 11.

Description

EXAMPLE

Example 1 Preparation of Aqueous Calcium Gluconate 10% w/v

[0038] Water for injection was prepared from town water by reverse osmosis followed by distillation, then sanitation.

[0039] Calcium saccharate (2.14 kg) was added to degassed water for injection (WFI, 506 kg) in a 600 L reactor at 80-85? C. Temperature was maintained using a steam jacket. Calcium gluconate (51.36 kg) was then added to the solution of calcium saccharate and WFI. The pH of the solution was checked, and adjusted as necessary. The solution was maintained at 80-85? C. and mixed until all raw materials have dissolved, and then mixed for a further 15 minutes.

[0040] The solution was then filtered and transferred into 100 mL plastic vials in portions of 107.8 g. An automated filling set up was used. Throughout filling, the solution was maintained at a temperature of 75-85? C.

[0041] The vials were stoppered and capped and filled onto autoclave trays and steam sterilised at 115? C. for 30 mins. The fill weight was checked every 500 vials, from 500-5,000, and the last vial. The variation in fill weights was reduced over runs compared to the process without maintenance of the filling temperature.