Solid dispersion classification

In Chapter 1 the importance of the various classes of colloidal systems to modern science and technology was indicated in a general way. Because of the wide variety of colloidal systems one encounters, each having certain unique features that distinguish it from the others, it is convenient to discuss each major classification separately. For that reason, chapters have been devoted to specific systems such as solid dispersions, aerosols, emulsions, foams, lyophilic colloids (i.e., polymer solutions), and association colloids. There is a great deal of overlap in many aspects of the formation, stabilization, and destruction of those systems, and an effort will be made not to repeat more than is necessary. However, for purposes of clarity, some repetition is unavoidable. 

Fig. 2.4 Classification of solid dispersions. (Adapted from Vasconcelos et al. 2007)...

Baird JA, Taylor LS (2012) Evaluation of amorphous solid dispersion properties using thermal analysis techniques. Adv Drug Deliv Rev 64(5) 396-421 Baird JA, Van Eerdenbrugh B, Taylor LS (2010) A classification system to assess the crystallization tendency of organic molecules from undercooled melts. J Pharm Sd 99(9) 3787-3806 Barandiaran JM, Colmenero J (1981) Continuous cooling approximation for the formation of a glass. J Non-Cryst Solids 46(3) 277-287... 

Process technology selection for the manufacture of amorphous solid dispersions requires consideration of the particular complexities of the drug and excipients. HME offers the possibility to manufacture drug products in a continuous, cost-effective manner, yet it presents unique challenges that must be tackled. Noting the significant interplay between formulation and process, a risk-based classification system has been developed to aid in the early assessment of dispersion success using melt extrusion. 

Solid dispersion is defined as one type of method to produce an amorphous compound by incorporating a hydrophobic drug into a hydrophilic carrier (Chiou and Riegelman 1971). It is one of the most studied methods to solubilize and to enhance dissolution rate of biopharmaceutical classification system (BCS) class 2 compounds. For instance, a solid dispersion of ritonavir (Law et al. 2001), ER-3421 (a dual 5-lipoxygenase/cyclooxygenase inhibitor Kushida et al. 2002), was found to have a much higher dissolution rate than the crystalline counterpart and resulted in higher area under curve (AUC) and Cmax in the in vivo study. 

Spray Dryers A spray diyer consists of a large cyhndrical and usu ly vertical chamber into which material to be dried is sprayed in the form of small droplets and into which is fed a large volume of hot gas sufficient to supply the heat necessary to complete evaporation of the liquid. Heat transfer and mass transfer are accomphshed by direct contact of the hot gas with the dispersed droplets. After completion of diying, the cooled gas and solids are separated. This may be accomplished partially at the bottom of the diying chamber by classification and separation of the coarse dried particles. Fine particles are separated from the gas in external cyclones or bag collectors. When only the coarse-particle fraction is desired for fini ed product, fines may be recovered in wet scrubbers the scrubber liquid is concentrated and returned as feed to the diyer. Horizontal spray chambers are manufactured with a longitudinal screw conveyor in the bottom of the diying chamber for continuous removal of settled coarse particles. 

It is classification by contacting method that provides the two principal categories into which leaching equipment is divided (I) that in which the leaching is accomphshed oy percolation and (2) that in which particulate solids are dispersed into a hquid and subsequently separated from it. Each includes batch and continuous units. Materials which disintegrate during leaching are treated in equipment of the second class. 

Disperse systems can be classified in various ways. Classification based on the physical state of the two constituent phases is presented in Table 1. The dispersed phase and the dispersion medium can be either solids, liquids, or gases. Pharmaceutically most important are suspensions, emulsions, and aerosols. (Suspensions and emulsions are described in detail in Secs. IV and V pharmaceutical aerosols are treated in Chapter 14.) A suspension is a solid/liquid dispersion, e.g., a solid drug that is dispersed within a liquid that is a poor solvent for the drug. An emulsion is a li-quid/liquid dispersion in which the two phases are either completely immiscible or saturated with each other. In the case of aerosols, either a liquid (e.g., drug solution) or a solid (e.g., fine drug particles) is dispersed within a gaseous phase. There is no disperse system in which both phases are gases. 

The classification system introduced by Carr [29,30] was used to evaluate the flow properties of the sorbitol powders. In Carr s system, a flowable powder is defined as free flowing and will tend to flow steadily and consistently. This is to be contrasted with a floodable powder, which will exhibit an unstable, discontinuous, and gushing type of flow. The parameters in Carr s system include the angle of repose, angle of spatula, compressibility, cohesion, and dispersibility. Based on these parameters, flowability and floodability indices are calculated to determine the handling properties of bulk solids. 

There are no standard engineering classification methods for mixing equipment, and often, quite different types of mixers can fulfill the same mixing task. Nevertheless, we can subdivide mixers used in processing into three broad categories particulate solids mixers, laminar distributive mixers, and laminar dispersive mixers. This classification, on the basis of application, is supported by the nature of the primary mixing mechanism taking place in them. 

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