Optical Coherence Tomography (OCT) Freeze Drying Microscopy

Abstract

A product critical temperature during freeze drying is determined. The product is imaged using optical coherence tomography (“OCT”). The product is freeze dried while the temperature of the product is measured. The product critical temperature is the temperature at which a product structure event occurs during freeze drying.

What is claimed: 
     
         1 . A method of determining a product critical temperature during freeze drying, the method comprising:
 imaging a product using optical coherence tomography (OCT);   freeze drying the product;   measuring temperature of the product during freeze drying; and   determining the product critical temperature by determining the temperature at which a product structure event occurs during freeze drying.   
     
     
         2 . The method of  claim 1  wherein the product structure event during drying is a loss of product structure if the product is amorphous and the product critical temperature is a product collapse temperature. 
     
     
         3 . The method of  claim 1  wherein the product structure event is a loss of product structure if the product is crystalline and the product critical temperature is a product eutectic temperature. 
     
     
         4 . The method of  claim 1  further comprising freeze drying the product in a standard product vial. 
     
     
         5 . The method of  claim 1  further comprising freeze drying the product in a thin film within a vial or between glass or plastic slides. 
     
     
         6 . The method of  claim 1  further comprising freeze drying the product in a vial having a diameter of about 5 mm to about 50 mm. 
     
     
         7 . The method of  claim 1  further comprising using a thermocouple to measure the product temperature. 
     
     
         8 . The method of  claim 1  further comprising using a resistance temperature detector to measure the product temperature. 
     
     
         9 . The method of  claim 1  further comprising using infrared thermometry to measure the product temperature. 
     
     
         10 . A method of providing three-dimensional structural information about a sample during freeze drying, the method comprising:
 freeze drying the sample;   acquiring a three-dimensional image of the sample; and   determining the three-dimensional structural information about the sample from the three-dimensional image.   
     
     
         11 . The method of  claim 10  further comprising acquiring the three-dimensional image of the sample using optical coherence tomography (OCT). 
     
     
         12 . The method of  claim 10  wherein the three-dimensional structural information includes information about ice nucleation during freeze drying. 
     
     
         13 . The method of  claim 10  wherein the three-dimensional structural information includes information about sublimation of solvent from the sample during freeze drying. 
     
     
         14 . The method of  claim 10  wherein the three-dimensional structural information includes information about a loss of sample structure formed during a freezing phase of freeze drying. 
     
     
         15 . The method of  claim 8  wherein the three-dimensional structural information includes information about one or more elements forming the product solidifying and forming the product structure, while at least one or more elements forming the product remains liquid. 
     
     
         16 . The method of  claim 10  further comprising acquiring images of the sample at multiple depths.