Solid dispersions excipients

Nalidixic acid is another example of BCS class II drug, with oral bioavailability limited by poor solubility and slow dissolution (40). Compared to drug powder alone, the solid dispersion of nalidixic acid with P-cyclodextrin or PYP or sodium starch glycolate had much faster dissolution. X-ray diffraction studies revealed the formation of amorphous areas and less degree of crystallinity in the solid dispersion of nalidixic acid with excipients. 

Due to their large surface area for adsorption, porous materials are useful excipients for solid dispersions. For example, 2-naphthoic acid (2-NPA) solid dispersion with porous crystalline cellulose (PCC) has been successfully prepared by heat treatment of 2-NPA and PCC mixture. " PCC is derived from MCC, but with a larger surface area. Different from 2-NPA mixed with PCC, 2-NPA mixed with MCC still maintained a crystalline form under the same mixing and heating conditions. Various experimental data such as X-ray powder diffraction, Fourier transform infrared (FT-IR) spectroscopy, and solid-state fluorescence measurements suggest that 2-NPA is adsorbed onto the surface of PCC and becomes molecularly dispersed into the system. 

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. 

Recent advances in the scientific understanding of the in vivo performance, the role of supersaturation, and advanced manufacturing technologies will likely render solid solutions and solid dispersions more commercially successful. Excipients used in solid solutions and solid dispersions include polyvinylpyrrolidone, PEG 4,000, PEG 8,000, Gelucire 50/13, and Gelucrie 44/14. Solid solutions are molecular mixtures of a drug dissolved in a solid at a concentration below supersaturation and are thus thermodynamically stable, compared to solid dispersions, which are thermodynamically unstable amorphous drug dispersed within a solid matrix susceptible to crystallization. 

Hulsmann et al. in 2000 investigated the use of HME techniques to increase the solubility and dissolution rate of a poorly water-soluble drug, 17-estradiol hemihydrate by preparing solid dispersions of the drug into different compositions of excipients such as PEG 4000, PVP K 30, Kollidon, Sucroester ... 

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