Several reports on degradation of Hyaluronic Acid (HA) involving microwaves, UV or γ-rays have been published. Rheological studies also show that Hyaluronic Acid (HA) solutions degrade at high temperature: viscosity of the solutions decreases in time as a function of temperature. Therefore, the thermal sterilization treatment of Hyaluronic Acid (HA) solutions represents a great challenge. An optimized moist-heat sterilization cycle can minimize product degradation (and change of molecular weight) maintaining the required viscosity for the specific application.
KEYWORDS: Dynamic viscosity determination, Peak cycle, Counterpressure treatment, Moist-heat sterilization, Sodium Hyaluronate, Pre-filled Syringes (PFS).
1. SODIUM HYALURONATE PFS
The Sodium Hyaluronate used to prepare the batch had an average molecular weight equal to 1.6 x 106 Dalton. The formulations were prepared by hydrating the polysaccharide in a physiological phosphate buffer solution for 12 hours at 50°C. The bulk preparations were divided in pre-filled syringes. Prefilled syringes with Hyaluronate Sodium provided by IBSA.
2. PROCESS SELECTED
Samples were treated using an Air over Steam autoclave (Fedegari FOA); this process equipment works with counterpressure in the chamber to balance pressure increase inside the syringes during the sterilization and to
avoid the risk of plunger movement.
The air initially contained in the chamber is not extracted – as in a pure saturated steam cycle – but it is only “controlled” by increasing or decreasing its quantity (i.e. the pressure) during the heating/sterilization/cooling
phase according to the characteristics of the load. The pressure of chamber air increases as it heats (with the relation of the absolute sterilization and cycle start temperatures).
The total pressure in the chamber during the sterilization phase is given by the partial pressure of the heated air plus the partial steam pressure; the final pressure in the chamber will be therefore much higher than the one obtained with pure saturated steam autoclaves.
The counter-pressure inside the autoclave was adjusted by setting the air pressure correction coefficient at 1.2. This value is a little higher than the standard value (1.08) to avoid plunger expulsion. At 121°C, 115°C and 130°C, the pressure of the vessel was 3.56 abs, 3.18 abs, and 4.25 abs, respectively. These values were calculated by using the counter-pressure equation (equation 1) and also verifying the results on Thema 4 in the final phase data section.[…]