Section 7.3.2 Solids Dispersion

If the drug and polymer are miscible in their Luid state, then as discussed in Section Thermodynamic Perspective of Miscibility and Phase Separation in Solid Dispersions, the mixture may or may not undergo phase separation during solidiLcation, thereby inLuencing the structure of solid dispersion. 

Karanth et al. have reviewed various approaches that may be utilized in the manufacturing of solid dispersions [30], In this section, selected examples of techniques that have potential for commercial-scale manufacturing of solid dispersions are presented. 

Various techniques available for characterization of solid-state properties of raw materials and Ln-ished solid dispersions are presented in this section. In most cases, solid dispersions are process into Lnished dosage forms using conventional approaches such as tabletting, encapsulation, and < forth, and the characterization of such Lnished dosage formulations are not presented here. 

Nanoparticles are frequently used as a suspension in some kind of solvent. This is a two phase mixture of suspended solid and liquid solvent and is thus an example of a colloid. The solid doesn t separate out as a precipitate partially because the nanoparticles are so small and partially because they are stabilised by coating groups that prevent their aggregation into a precipitate and enhance their solubility. Colloidal gold, which has a typical red colour for particles of less than 100 nm, has been known since ancient times as a means of staining glass. Colloid science is a mature discipline that is much wider than the relatively recent field of nanoparticle research. Strictly a colloid can be defined as a stable system of small particles dispersed in a different medium. It represents a multi-phase system in which one dimension of a dispersed phase is of colloidal size. Thus, for example, a foam is a gas dispersed in a liquid or solid. A liquid aerosol is a liquid dispersed in gas, whereas a solid aerosol (or smoke) is a solid dispersed in a gas. An emulsion is a liquid dispersed in a liquid, a gel is liquid dispersed in a solid and a soils a solid dispersed in a liquid or solid. We saw in Section 14.7 the distinction between sol and gel in the sol gel process. 

As described in the previous section, solid particles can be broken up if the applied shear stresses are sufficiently large. In contrast, however, liquid droplets cannot be dispersed under certain conditions, even in shear fields with very large shear stresses. The Weber number We is often used to characterize the dispersion of droplets (another notation often used instead... 

To couple the intrinsic coke burning kinetics described in Section II.B with gas and solid flow models, the simplest approach is provided by the one-dimensional solid dispersion model based on following assumptions ... 

The purpose of this section is to define the various parameters that are measured by DSC. The types of thermal events, exothermic or endothermic, that can be measured by DSC are reported in Table 1. The following sections will describe some of the more fundamental thermal events. Examples from the pharmaceutical field will be given to illustrate the techniques. The examples will be based on either single components such as drug substance and bulk excipients or on a mixture of components such as physical blends of drugs and excipients, solid dispersions, formulated drugs after granulation, and/or compression. 

Depending on the similarity in size and structure to the host molecules, guest additive (impurity) molecules may be taken up into the host crystal lattice to form solid solutions (see Section 1.1.4). In cases of additive molecules that do not satisfy the general incorporation criteria for solid solution formation (e.g., for large polymers of distinctly different chemical structures), forced coprecipitation of the additives with the host molecules will lead to the formation of solid dispersions. Such dispersion systems are highly unstable thermodynamically and will revert back to the stable state, resulting in phase separation. 

This section discusses dispersive SPE, matrix solid phase dispersion, solid phase micro-extraction, micro-extraction by packed sorbent, stir-bar sorbent extraction, and the restricted-access materials. ... 

Sections 7.3.1 to 7.3.4 consider solids suspension, solids dispersion, solids dissolving, and solids flocculating respectively. General issues related to mixing using a fluidized bed are given in Section 7.3.5. 

In the section on Dispersion in Chapter 8, we considered how to make stable colloidal dispersions of solid and found that, for stability, it was necessary to keep the particles apart. We learned that aqueous pigment dispersions could be stabilized by adsorbed surfactant molecules, which ionized in the water to produce an electrical charge barrier around the particle (ionic stabilization). This could also be done by using polymer molecules, anchored strongly to the particle, but also extending out into the solvent, in which they are soluble. These polymer molecules provide a steric barrier around the particle and this method of stabilization is called steric stabilization. Exactly the same techniques are used to stabilize emulsions. 

Reactor conditions for the FRRPP of VDC were deduced from Table 1.1.2 for azeotropic t-butanol/MEK as a suitable solvent/precipitant. Section 3.2.5 presented the reactor procedure for the formation of the PVDC material. The range of starting concentration of VDC was 31-83%. After polymerization for 5 h with AIBN as initiator, percent conversion values fell on a range of 1-13% at 120°C. Such a result is similar to conversion results for FRRPP of S in ether. The difference in the FRRPP of VDC was that the PVDC is a fine brown solid dispersion when it was removed from the reactor. 

The following sections will give a detailed overview on the downstream processing of the amorphous solid dispersions manufactured by different technologies. Overall, it can be concluded that the downstream process should avoid the use of water, higher temperatures and pressures as much as possible. 

Dissolution of the salt of an acidic compound has its own complications. The salt is likely to convert to the free acid. When this happens, the liberated free acid may coat the surface of the remaining drug particles or nucleate on other particle surfaces, leading to a slowdown of dissolution (Wei-Qin 2(X)9). As described in the earlier sections, weak acids may rapidly precipitate/crystallize or gel in stomach before transit to the lower GI. It is therefore important to select amorphous solid dispersion and downstream technology, yielding a drug product with optimal supersaturation at physiologically relevant pH for absorption. 

The items listed in the second section are related to the manufacturing process, as the polymer should be easily dissolved in a suitable solvent to prepare a solid dispersion (slurry) to be coated on the metal support by means of different techniques. The electrode should have enough mechanical stability in order to be machinable during the different phases of cell assembly process as pressing, slitting, winding. 

The latex form of Heveaplus is compounded in the usual way with dispersions of required additives to formulations as exemplified in a latter section. Solid Heveaplus MG is best milled on a two-roll mill to bring about some breakdown and elimination of gel material before dissolving in solvent. The degree of milling should be carefully controlled, as excessive milling will lead to the elimination of grafted material and increase the amount of homopolymer. A recommended solvent is made of... 

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