A procedure to optimize scale-up for the primary drying phase of lyophilization.

This article describes a procedure to facilitate scale-up for the primary drying phase of lyophilization using a combination of empirical testing and numerical modeling. Freeze dry microscopy is used to determine the temperature at which lyophile collapse occurs. A laboratory scale freeze-dryer equipped with manometric temperature measurement is utilized to characterize the formulation-dependent mass transfer resistance of the lyophile and develop an optimized laboratory scale primary drying phase of the freeze-drying cycle. Characterization of heat transfer at both lab and pilot scales has been ascertained from data collected during a lyophilization cycle involving surrogate material. Using the empirically derived mass transfer resistance and heat transfer data, a semi-empirical computational heat and mass transfer model originally developed by Mascarenhas et al. (Mascarenhas et al., 1997, Comput Methods Appl Mech Eng 148: 105-124) is demonstrated to provide predictive primary drying data at both the laboratory and pilot scale. Excellent agreement in both the sublimation interface temperature profiles and the time for completion of primary drying is obtained between the experimental cycles and the numerical model at both the laboratory and pilot scales. Further, the computational model predicts the optimum operational settings of the pilot scale lyophilizer, thus the procedure discussed here offers the potential to both reduce the time necessary to develop commercial freeze-drying cycles by eliminating experimentation and to minimize consumption of valuable pharmacologically active materials during process development.

Process simulation in the pharmaceutical industry: a review of some basic physical models.

This study reviews process modeling efforts which have been developed to elucidate the fundamental physical process underlying the manufacture and delivery of pharmaceutical dosage forms. Within the pharmaceutical industry, process models have been applied to a diverse array of physical processes at length and time scales that vary by orders of magnitude. As such, both large-scale continuum and particle-scale discrete approaches will be discussed in this study. Challenges associated with the practical application of process models within the pharmaceutical industry will be discussed, and opportunities for future research will be identified.

Factors defining target specificity in antibody-mediated neuropathy: density-dependent binding of anti-GD1a polyclonal IgG from a neurological patient.

IgM and IgG antibodies reacting with components of human brain gangliosides were detected in a patient bearing severe sensory ataxy. Using different chemical and immunological methods, the antigen was identified as the GD1a ganglioside. The antibodies showed antigen "density-dependent" binding, a property only observed in tumor-specific monoclonal antibodies. The relevance of this result in regard with target specificity of neuropathy-associated antibodies directed to ubiquitous glycolipids is discussed.