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Sundaramurthi P.,University of Minnesota | Sundaramurthi P.,Hughes Inc. | Suryanarayanan R.,University of Minnesota
Pharmaceutical Research | Year: 2010

Purpose: To study the influence of crystallizing and non-crystallizing cosolutes on the crystallization behavior of trehalose in frozen solutions and to monitor the phase behavior of trehalose dihydrate and mannitol hemihydrate during drying. Methods: Trehalose (a lyoprotectant) and mannitol (a bulking agent) are widely used as excipients in freeze-dried formulations. Using differential scanning calorimetry (DSC) and X-ray diffractometry (XRD), the crystallization behavior of trehalose in the presence of (i) a crystallizing (mannitol), (ii) a non-crystallizing (sucrose) solute and (iii) a combination of mannitol and a model protein (lactose dehydrogenase, catalase, or lysozyme) was evaluated. By performing the entire freeze-drying cycle in the sample chamber of the XRD, the phase behavior of trehalose and mannitol were simultaneously monitored. Results: When an aqueous solution containing trehalose (4% w/v) and mannitol (2% w/v) was cooled to -40°C at 0.5°C/min, hexagonal ice was the only crystalline phase. However, upon warming the sample to the annealing temperature (-18°C), crystallization of mannitol hemihydrate was readily evident. After 3 h of annealing, the characteristic XRD peaks of trehalose dihydrate were also observed. The DSC heating curve of frozen and annealed solution showed two overlapping endotherms, attributed by XRD to the sequential melting of trehalose dihydrate - ice and mannitol hemihydrate - ice eutectics, followed by ice melting. While mannitol facilitated trehalose dihydrate crystallization, sucrose completely inhibited it. In the presence of protein (2 mg/ml), trehalose crystallization required a longer annealing time. When the freeze-drying was performed in the sample chamber of the diffractometer, drying induced the dehydration of trehalose dihydrate to amorphous anhydrate. However, the final lyophiles prepared in the laboratory lyophilizer contained trehalose dihydrate and mannitol hemihydrate. Conclusions: Using XRD and DSC, the sequential crystallization of ice, mannitol hemihydrate, and trehalose dihydrate was observed in frozen solutions. Mannitol, by readily crystallizing as a hemihydrate, accelerated trehalose dihydrate crystallization in frozen solutions. However, by remaining amorphous, sucrose completely inhibited trehalose dihydrate crystallization. Crystallization of the lyoprotectantt in the model protein formulations might have serious implications on protein stability. © 2010 Springer Science+Business Media, LLC.


Sundaramurthi P.,University of Minnesota | Sundaramurthi P.,Hughes Inc. | Suryanarayanan R.,University of Minnesota
Pharmaceutical Research | Year: 2011

Purpose: To effectively inhibit succinate buffer crystallization and the consequent pH changes in frozen solutions. Methods: Using differential scanning calorimetry (DSC) and X-ray diffractometry (XRD), the crystallization behavior of succinate buffer in the presence of either (i) a crystallizing (glycine, mannitol, trehalose) or (ii) a non-crystallizing cosolute (sucrose) was evaluated. Aqueous succinate buffer solutions, 50 or 200 mM, at pH values 4.0 or 6.0 were cooled from room temperature to -25°C at 0.5°C/min. The pH of the solution was measured as a function of temperature using a probe designed to function at low temperatures. The final lyophiles prepared from these solutions were characterized using synchrotron radiation. Results: When the succinic acid solution buffered to pH 4.0, in the absence of a cosolute, was cooled, there was a pronounced shift in the freeze-concentrate pH. Glycine and mannitol, which have a tendency to crystallize in frozen solutions, remained amorphous when the initial pH was 6.0. Under this condition, they also inhibited buffer crystallization and prevented pH change. At pH 4.0 (50 mM initial concentration), glycine and mannitol crystallized and did not prevent pH change in frozen solutions. While sucrose, a non-crystallizing cosolute, did not completely prevent buffer crystallization, the extent of crystallization was reduced. Sucrose decomposition, based on XRD peaks attributable to β-D-glucose, was observed in frozen buffer solutions with an initial pH of 4.0. Trehalose completely inhibited crystallization of the buffer components when the initial pH was 6.0 but not at pH 4.0. At the lower pH, the crystallization of both trehalose dihydrate and buffer components was evident. Conclusion: When retained amorphous, sucrose and trehalose effectively inhibited succinate buffer component crystallization and the consequent pH shift. However, when trehalose crystallized or sucrose degraded to yield a crystalline decomposition product, crystallization of buffer was observed. Similarly, glycine and mannitol, two widely used bulking agents, inhibited buffer component crystallization only when retained amorphous. In addition to stabilizing the active pharmaceutical ingredient, lyoprotectants may prevent solution pH shift by inhibiting buffer crystallization. © 2010 Springer Science+Business Media, LLC.


Patent
Hughes Inc. | Date: 2012-11-21

A separator assembly comprises a vertical vessel including a fluid inlet for receiving a fluid including a gas, at least two liquids, and solids, at least two liquid outlets for discharging the liquids, a gas outlet at an upper end thereof for discharging gas, and a solids outlet at a lower end thereof for discharging solids. A baffle plate extends across the vessel, and cooperates with the vessel to define an upper section and a lower section, and has a first conduit extending downwardly so that liquids and solids may flow into the lower section, and a second conduit extending upwardly so that gases may flow from the lower section to the upper section. A backpressure valve is in fluid communication with the gas outlet and is configured to discharge gas while maintaining a selected level of pressure inside the vessel.


Patent
Hughes Inc. | Date: 2012-12-11

Provided are methods, systems, and apparatuses for telematics navigation.


Trademark
Hughes Inc. | Date: 2015-03-23

Software for use in the research and design of the built environment including building life-cycle for fire protection systems design and analysis, code consulting, risk assessment, commissioning, emergency management and security and alarm systems.


Trademark
Hughes Inc. | Date: 2016-10-14

Exercise equipment, namely, foam rollers.


R

Trademark
Hughes Inc. | Date: 2016-04-20

Matrix code labels.


Trademark
Hughes Inc. | Date: 2016-04-20

Computer software applications for handheld computing devices, namely, software for providing access to an online database featuring information about food ingredients; computer software applications for handheld computing devices, namely, software for providing access to an online database for the storage and retrieval of information, including text, electronic documents, graphics, and audio visual information.


Trademark
Hughes Inc. | Date: 2015-03-23

Software for use in the research and design of the built environment including building life-cycle for fire protection systems design and analysis, code consulting, risk assessment, commissioning, emergency management and security and alarm systems.


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