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.

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.

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.

Survival of Anisakis simplex in arrowtooth flounder (Atheresthes stomia) during frozen storage.

Survival of naturally occurring larvae of Anisakis simplex in fresh arrowtooth flounder (Atheresthes stomia) was determined after storage for specified periods at four freezing temperatures. All larvae were killed by 96, 60, 12, and 9 h at temperatures of -15, -20, -30, and -40 degrees C, respectively. The average percentages of live larvae per fillet at the next shortest holding time were as follows: 72 h at -15 degrees C, 0 to 3%; 48 h at -20 degrees C, 11 to 30%; 9 h at -30 degrees C, 5%; and 6 h at -40 degrees C, 0 to 3%. Larval survival was directly related to fillet thickness or weight (P < or = 0.05). Larval death was directly correlated to freezing temperatures. Holding time necessary to kill larval nematodes decreased as storage temperature decreased.