Alan P. MacKenzie

Effect of Solute on Ice-Solution Interfacial Free Energy; Calculation from Measured Homogeneous Nucleation Temperatures

Among the forms of the water polymer interface of interest to low temperature scientists one distinguishes in particular the common surfaces separating ice from solid polymer and ice from aqueous polymer solution. The ice — solid polymer interface has been the subject of considerable attention; it was, for example, discussed at the Sapporo Conference on the Physics of Snow and Ice in 1966 /1/ and was the subject of a symposium chaired by Dr. H. H. G. Jellinek in 1967 /2/. Studies on the ice — aqueous solution interface have, in contrast, been limited largely to the interpretation of growth rate measurements in dilute salt solutions /3/, where the physical characteristics of the solution dominate the contribution from the surface effects.

Interactions in the Water-Polyvinylpyrrolidone System at Low Temperatures

Great interest has attached to the hydration of macromolecular species and to the state of water molecules in hydrophilic polymer systems in particular. Bull /1/ and Hoover and Mellon /2/ reported the sorption of water by cellulose, cellulose acetate, nylon, and numerous proteins, applying equations developed originally to describe the binding of monatomic gases and small molecules to free surfaces. Bull determined the method of Brunauer, Emmett and Teller /3/ to suffice at 25 and 40°C. from 0.05 to 0.50 water activity (denoted hereafter by the symbol ‘aW’). Hoover and Mellon applied Bradley’s isotherm /4,5/ very successfully throughout the range of aW’ s (0.06 to 0.93) encompassed in their studies. Bull, and Hoover and Mellon each determined that water became attached to certain sites on the macromolecules, also that additional water molecules became attached to the first to form layer-like structures.

Stability, Characterization, Formulation, and Delivery System Development for Transforming Growth Factor-Beta 1

This chapter has reviewed the multifunctional role that the TGF-β play with diverse proliferative and suppressive effects on many different cell types. The various in vitro and in vivo effects of TGF-β was discussed with emphasis on the therapeutic potential of this growth factor in areas such as wound healing and bone regeneration. The structure and properties of TGF-β were presented, followed by a more detailed description of the characterization and stabilization of TGF-β1) in both the liquid and lyophilized state. The chapter concluded with a review of some of the different controlled release systems that have been utilized for the delivery of TGF-β1 to various preclinical models. Clearly the therapeutic potential for TGF-β1) is great. Both the formulation and delivery of this growth factor will play an important role in its eventual clinical success

Water Clusters in Amorphous Pharmaceuticals

Amorphous materials, although lacking the long-range translational and rotational order of crystalline and liquid crystalline materials, possess certain local (short-range) structure. This paper reviews the distribution of one particular component present in all amorphous pharmaceuticals, that is, water. Based on the current understanding of the structure of water, water molecules can exist in either unclustered form or as aggregates (clusters) of different sizes and geometries. Water clusters are reported in a range of amorphous systems including carbohydrates and their aqueous solutions, synthetic polymers, and proteins. Evidence of water clustering is obtained by various methods that include neutron and X-ray scattering, molecular dynamics simulation, water sorption isotherm, concentration dependence of the calorimetric Tg , dielectric relaxation, and nuclear magnetic resonance. A review of the published data suggests that clustering depends on water concentration, with unclustered water molecules existing at low water contents, whereas clusters form at intermediate water contents. The transition from water clusters to unclustered water molecules can be expected to change water dependence of pharmaceutical properties, such as rates of degradation. We conclude that a mechanistic understanding of the impact of water on the stability of amorphous pharmaceuticals would require systematic studies of water distribution and clustering, while such investigations are lacking.

Extremophile extracts and enhancement techniques show promise for the development of a live vaccine against Flavobacterium columnare.

The effects of temperature, ionic strength, and new cryopreservatives derived from polar ice bacteria were investigated to help accelerate the development of economical, live attenuated vaccines for aquaculture. Extracts of the extremophile Gelidibacter algens functioned very well as part of a lyophilization cryoprotectant formulation in a 15-week storage trial. The bacterial extract and trehalose additives resulted in significantly higher colony counts of columnaris bacteria (Flavobacterium columnare) compared to nonfat milk or physiological saline at all time points measured. The bacterial extract combined with trehalose appeared to enhance the relative efficiency of recovery and growth potential of columnaris in flask culture compared to saline, nonfat milk, or trehalose-only controls. Pre-lyophilization temperature treatments significantly affected F. columnare survival following rehydration. A 30-min exposure at 0 degrees C resulted in a 10-fold increase in bacterial survival following rehydration compared to mid-range temperature treatments. The brief 30 and 35 degrees C pre-lyophilization exposures appeared to be detrimental to the rehydration survival of the bacteria. The survival of F. columnare through the lyophilization process was also strongly affected by changes in ionic strength of the bacterial suspension. Changes in rehydration constituents were also found to be important in promoting increased survival and growth. As the sodium chloride concentration increased, the viability of rehydrated F. columnare decreased.

Considerations in determination of residual moisture in lyophilized demineralized bone matrix: the role of residual moisture analyzers

The objective of this study is to determine whether a residual moisture analyzer (RMA) can be an acceptable instrument for measuring the residual moisture in lyophilized demineralized bone matrix (DBM). Instruments from two different manufacturers with differing configurations and controls were compared: the Ohaus MB45 and Arizona Instrument MAX4000XL. The effects of various factors such as test temperature, drying profile, end point criteria, lift compensation, chamber configuration, and rehydration on residual moisture (RM) are examined. The performance of the RMAs is based on their ability to reproduce RM results obtained by the current standard gravimetric method. RMAs provide reliable, accurate and reproducible results in a number of industries that rely on the determination of RM. We hypothesize that RMAs are suitable for measuring RM in DBM and provide validation study data with optimized settings for these two instruments. Potentially, such studies will provide justification for allowance of this methodology as an acceptable alternative to the current gravimetric method allowed by American Association of Tissue Banks Standards.