Drying and gas or vapor contact with solids – Process – Freeze-drying
Reexamination Certificate
1999-12-16
2001-05-08
Wilson, Pamela (Department: 3749)
Drying and gas or vapor contact with solids
Process
Freeze-drying
C034S292000, C034S293000, C034S407000, C034S403000
Reexamination Certificate
active
06226887
ABSTRACT:
TECHNICAL FIELD
This invention relates generally to freeze drying apparatus and associated lyophilization procedures, and more particularly, to a vapor flow detector and vacuum control system for improved monitoring and control of the lyophilization process.
BACKGROUND OF THE INVENTION
Freeze drying has been used for the preservation of a wide variety of foods, pharmaceutical, and biological products. Freeze drying enables the removal through sublimation of solvents, including water, from a substance without destroying its cellular structure. Through sublimation, the substance being freeze dried remains in a frozen, solid form until it is dried, i.e., until all liquid is removed from the substance.
During freeze drying, a constantly changing state of unbalance must exist between product ice and system pressure/temperature conditions. The migration of water vapor from the product ice interface occurs only if this state of unbalance exists and the product ice is at a higher energy level than the rest of the system. Freeze drying equipment is designed to present an isolated set of controlled conditions effecting and maintaining the optimum temperature pressure differences for a given product, thereby drying the product in a least amount of time.
The limit of unbalance is determined by the maximum amount of heat which can be applied to the product without causing a change from solid to liquid state (i.e., “melt back”). This may occur even though the chamber pressure is low since the product dries from the surface closest to the area of lowest pressure. This surface is called the ice interface. The arrangement of the drying, solid particles above this interface offers resistance to the vapors released from below raising the product pressure/temperature. To avoid “melt back”, heat energy applied to the product must not exceed the rate at which water vapor leaves the product. Another limit is the rate at which heat energy applied to the product ice (and carried away by the migrating vapors) is removed by the condenser refrigeration system. Only by maintaining a low condenser temperature can vapors be trapped as ice particles and effectively removed from the system, thereby greatly reducing and simplifying the vacuum pumping requirement. Air, and other non-condensible molecules within the chamber, as well as mechanical restrictions located between the product ice and the condenser, offer additional resistance to the movement of vapors migrating towards the condenser.
Four conditions are essential for freeze drying. These conditions must be met in the following order: (1) the product must be solidly frozen below its eutectic point or glass transition temperature; (2) a condensing surface capable of reaching temperatures approximately 20° colder than any ice interface temperature must be provided (typically lower than −40° C.); (3) the system must be capable of evacuation to an absolute pressure of between 5 and 25 microns of Hg; and, (4) a source of heat input to the product, controlled between −40° C. and +65° C., must be employed to provide the heat required to drive water from the solid to the vapor state (heat of sublimation).
The physical arrangement of equipment designed to satisfy the above four conditions varies widely, and includes individual flask freeze drying apparatus and batch process freeze drying apparatus.
When process results must be exacting and when process control is important, such as in the chemical and pharmaceutical industry, including the research and development aspects thereof, freeze drying processes are carried out in chambers on a batch basis. This allows an operator to more precisely control what occurs to the product being sublimed. Monitor and control of the freeze drying process continue to be significant issues within the industry.
For example, the temperature level within product containers used for freeze drying is critical to proper sublimation. During the freeze drying operation, the temperature of the substance within at least one container is often monitored by a temperature sensor, such as a thermocouple. Various devices for positioning a temperature sensor in a freeze drying container are described in the art. In this regard, reference commonly assigned U.S. Pat. No. 5,689,895, by Sutherland et al. entitled “Probe Positioning Device For A Flask For Freeze Drying.”
Although valuable, temperature measurement by itself may be inaccurate, depending upon placement of the thermocouple, and has certain inherent limitations. For example, temperature measurement might be used to note a point of transition from primary drying to secondary drying, but is unable to accurately identify the rate of drying or whether the freeze drying process is in fact complete.
In view of the above, any control improvements which can be used to enhance commercial operation of a freeze drying apparatus are of significant interest to the industry. The present invention is directed to meeting these needs for various monitoring and control enhancements to the freeze drying process.
DISCLOSURE OF THE INVENTION
Briefly summarized, this invention comprises in one aspect a freeze drying apparatus including a process chamber for accommodating a plurality of product containers, and a condenser chamber in communication with the process chamber via a channel. A vacuum source produces a vacuum on the condenser chamber and the process chamber. A vapor flow detector is disposed to monitor vapor flow to the condenser chamber, thereby providing information on the rate of freeze drying, as well as completion of freeze drying processing. As an enhanced embodiment, the vapor flow detector comprises a windmill sensor disposed within the channel interconnecting the process chamber and the condenser chamber.
In another aspect, the invention comprises a freeze drying apparatus for freeze drying product adapted to be contained in a frozen state in at least one flask. The freeze drying apparatus includes a manifold presenting a sealed interior chamber and at least one port adapted to receive the at least one flask to place the interior of the flask and the product therein in gaseous communication with the interior chamber of the manifold. The apparatus also includes a condenser and a vacuum pump. The condenser is associated with the interior chamber of the manifold for condensing condensible vapors present in the interior chamber. The vacuum pump produces a vacuum within the interior chamber of the manifold for reducing ambient pressure in the interior chamber. A vacuum flow detector is disposed to monitor vapor flow from product. in at least one flask coupled to the manifold during freeze drying processing.
In still another aspect, the invention again comprises a freeze drying apparatus for freeze drying product. This apparatus includes a process chamber for accommodating a plurality of product containers, and a condenser chamber in gaseous fluid communication with the process chamber. A vacuum pump produces a vacuum on the condenser chamber and process chamber, and a process controller is connected to the vacuum pump. The process controller monitors freeze drying within the freeze drying apparatus, and during freeze drying processing, selectively disconnects the vacuum pump from the condenser and process chambers without impairing freeze drying processing.
In a further aspect, a method for freeze drying product in a process chamber (coupled via a channel to a condenser chamber) is provided. The method includes: establishing frozen product to undergo lyophilization in the process chamber; establishing a condenser within the condenser chamber and subjecting the process chamber and condenser chamber to evacuation, whereby a very low atmosphere approaching a vacuum is maintained within the process chamber; performing freeze drying processing on the product within the process chamber; and monitoring vapor flow from product exposed in the process chamber.
In a still further aspect, a method for freeze drying product employing a process chamber is described which includes: sealing the
Bart, Jr. Siegfried G.
Tenedini Kenneth J.
Heslin & Rothenberg, P.C.
S.P. Industries, Inc., The Virtis Division
Wilson Pamela
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