Phase transformation considerations during process development and manufacture of solid oral dosage forms

A general review of the methods available for the physical characterization of pharmaceutical solids is presented. The techniques are classified as being on the molecular level (properties capable of being detected in an ensemble of individual molecules), the particulate level (properties which can be detected through the analysis of an ensemble of particles), and the bulk level (properties which can be measured only using a relatively large amount of material). The molecular-level properties discussed are infrared spectroscopy and nuclear magnetic resonance spectrometry, the particulate-level properties discussed are particle morphology, particle size distribution, powder X-ray diffraction, and thermal methods of analysis, and the bulk-level properties discussed are surface area, porosity and pore size distribution, and powder flow characteristics. Full physical characterization of three modifications of lactose (hydrous, anhydrous, and Fast-Flo) is presented to illustrate the type of information which can be obtained using each of the techniques discussed.

Physical characterization of pharmaceutical solids.

On the physical characterization of pharmaceutical solids

Spectral Methods for the Characterization of Polymorphs and Solvates

Water associated with polymeric pharmaceutical excipients derived from cellulose and starch can have a profound effect on the properties of the excipient and on the other ingredients making up a solid dosage form. Important questions which need to be addressed include How much water will be sorbed or desorbed at various relative humidities and temperatures? and What is the thermodynamic state of water associated with the solid as a function of moisture content? A critical review of the literature is presented to demonstrate the most likely answers to these questions. It appears that water exists in at least three thermodynamic states in starch, cellulose, and their derivatives: (1) water directly and tightly bound, with a stoichiometry of one water molecule per anhydroglucose unit; (2) water in a relatively unrestricted form, approaching the properties of bulk or pure liquid water; and (3) water in an intermediate state or states, with properties reflecting a much higher level of structure than bulk water but less than that of tightly bound water. Some implications of such behavior for pharmaceutical systems are discussed.

The interactions of water with cellulose- and starch-derived pharmaceutical excipients.

(1984). Solid State Reactions - Theoretical and Experimental Aspects. Drug Development and Industrial Pharmacy: Vol. 10, No. 8-9, pp. 1175-1276.

Lynn Van Campen

Papers

Solid State Reactions - Theoretical and Experimental Aspects