Abstract
Freeze-drying was evaluated as a production technique for co-amorphous systems of a poorly water-soluble drug. Naproxen was freeze-dried together with arginine and lysine as co-former. To increase the solubility of naproxen in the starting solution, the applicability of five surfactants was investigated, namely sodium dodecyl sulfate, pluronic F-127, polyoxyethylene (40) stearate, tween 20 and TPGS 1000. The influence of the surfactant type, surfactant concentration and total solid content to be freeze-dried on the solid state of the sample was investigated. X-ray powder diffraction and differential scanning calorimetry showed that the majority of systems formed co-amorphous one-phase systems. However, at higher surfactant concentrations, and depending on the surfactant type, surfactant reflections were observed in the XRPD analysis upon production. Crystallization of both naproxen and amino acid occurred from some combinations under storage. In conclusion, freeze-drying was shown to be a feasible technique for the production of a selection of co-amorphous drug–amino acid formulations.
Highlights
Co-amorphous systems have gained interest as a promising system to stabilize poorly water-soluble drugs in an amorphous form over the last few years [1]
It would be of interest to investigate whether another technique that can yield amorphous products can be applicable for the production of co-amorphous systems, despite the financial costs usually associated with this method: freeze-drying
In order to truly follow the thermodynamic pathway in the establishment of a co-amorphous system, it is expected that both active pharmaceutical ingredient (API) and co-former are to be dissolved
Summary
Co-amorphous systems have gained interest as a promising system to stabilize poorly water-soluble drugs in an amorphous form over the last few years [1]. It has been shown that spray-drying is a viable technique for the production of co-amorphous systems, frequently even surpassing the results obtained via ball milling. With regard to (2), the use of buffers should be considered carefully as strong pH changes can occur due to selective freezing of the buffer salts Considering these challenges, it was decided to initiate the investigation with the application of surfactants [25]. The effects of the five surfactants, sodium dodecyl sulfate (SDS), pluronic F-127 (PF127), polyoxyethylene (40) stearate (P40S), tween 20 (T20) and TPGS 1000 (TPGS), were investigated It was the aim of this study to investigate whether freeze-drying could be a viable technique for the production of co-amorphous drug–amino acid systems and to obtain an initial overview of the influence of formulation parameters and surfactants on the product characteristics
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