*Article* **Furosemide/Non-Steroidal Anti-Inflammatory Drug–Drug Pharmaceutical Solids: Novel Opportunities in Drug Formulation**

**Francisco Javier Acebedo-Martínez 1, Carolina Alarcón-Payer 2, Lucía Rodríguez-Domingo 1,3, Alicia Domínguez-Martín 3, Jaime Gómez-Morales <sup>1</sup> and Duane Choquesillo-Lazarte 1,\***


**Abstract:** The design of drug–drug multicomponent pharmaceutical solids is one the latest drug development approaches in the pharmaceutical industry. Its purpose is to modulate the physicochemical properties of active pharmaceutical ingredients (APIs), most of them already existing in the market, achieving improved bioavailability properties, especially on oral administration drugs. In this work, our efforts are focused on the mechanochemical synthesis and thorough solid-state characterization of two drug–drug cocrystals involving furosemide and two different non-steroidal anti-inflammatory drugs (NSAIDs) commonly prescribed together: ethenzamide and piroxicam. Besides powder and single crystal X-ray diffraction, infrared spectroscopy and thermal analysis, stability, and solubility tests were performed on the new solid materials. The aim of this work was evaluating the physicochemical properties of such APIs in the new formulation, which revealed a solubility improvement regarding the NSAIDs but not in furosemide. Further studies need to be carried out to evaluate the drug–drug interaction in the novel multicomponent solids, looking for potential novel therapeutic alternatives.

**Keywords:** drug–drug cocrystal; furosemide; ethenzamide; piroxicam; mechanochemical synthesis
