While the preliminary measurements could be carried out using the laboratory diffractometer, conclusive results could only be obtained by using the data collected at a synchrotron source. Two limiting factors had to be considered during the described processing: on the one hand, the unfavorable extrusion properties of NaCMC, which required a high amount of additive to enable the extrusion and on the other hand, the crystalline structure of the additives, which would lead to a crystalline product in high concentrations because of insufficient miscibility. Powder X-ray diffraction (PXRD) was applied to determine the maximum amount of additive that is still feasible for successful miscibility and an extrusion process to form an amorphous product. Another approach is the fine tuning of the extrusion process by changing screw configuration, temperature profiles or by employing different downstream processing steps. Contemporary research is primarily focused on finding new combinations of well-established polymers with plasticizers and surfactants, or even on designing new monomers for novel synthetic polymers that come with the aforementioned multiple development hurdles to reach the pharmaceutical market. However, HME formulations currently available on the market utilize only about six of the pharmaceutically accepted polymers or a combination of these. These two process techniques mostly use a combination of drug and polymeric compound. Among the different process techniques for the manufacturing of amorphous solid dispersions, hot melt extrusion (HME) and spray drying are the most common methods. One strategy is the formulation of a drug in an amorphous form as a solid dispersion, which normally leads to drug supersaturation upon oral administration to promote absorption. The rising number of poorly water-soluble drugs in the development pipelines as well as on the market encouraged the pharmaceutical industry to develop new formulation techniques. Further research is needed to harness the novel matrix with drugs in amorphous formulations. Particularly promising with NaCMC was the addition of lysine as well as meglumine. As this analysis requires probing a sample on several points and relies on high quality data, X-ray diffraction and starring techniques at a synchrotron source had to be used. Next, the obtained matrices had to be examined to ensure the homogeneous distribution of the components and the possible residual crystallinity. This was achieved by probing the matrix using several analytical techniques, such as Fourier transform infrared spectroscopy, differential scanning calorimetry, hot stage microscopy, and X-ray powder diffraction. The amount of additives had to be carefully tuned to obtain an amorphous polymer matrix. It was possible to obtain a new polyelectrolyte matrix that was viable for manufacturing by hot melt extrusion. The polyelectrolyte, carboxymethylcellulose sodium (NaCMC), was tested in combination with different additives such as amino acids, meglumine, trometamol, and urea. Therefore, this study follows an alternative approach, where new polymeric matrices are created by combining a known polymer, small molecular additives, and an initial solvent-based process step. However, their disadvantage is that they require toxicological qualification and present regulatory hurdles for their market authorization. One way around this limitation is to synthesize new polymers. A most important process technique is hot melt extrusion but process requirements limit the choice of suitable polymers. Solid dispersions are important supersaturating formulations to orally deliver poorly water-soluble drugs.
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