## 2 Chemical Structure  
Ciclopirox, chemically known as 6-cyclohexyl-1-hydroxy-4-methylpyridin-2(1H)-one (Figure 1a), is a cyclic hydroxamic acid. Specifically, it is a 1-hydroxypyridin-2(1H)-one where the hydrogen atoms at positions 4 and 6 are replaced by methyl and cyclohexyl groups, respectively. Its olamine (ethanolamine) salt form is known as ciclopirox olamine (6-cyclohexyl-1-hydroxy-4-methylpyridin-2-one and 2-aminoethanol) (Figure 1b). The reference standard for ciclopirox olamine is listed in the United States Pharmacopeia (USP) and the European Pharmacopoeia (ref. no. 1302), and it is also available as a reference standard from Sigma Aldrich, St. Louis and Burlington, MA, USA (CAS 29342-05-0). The European Pharmacopoeia describes the drug substance in detail. The formula of ciclopirox olamine is C\({}_{14}\)H\({}_{24}\)N\({}_{2}\)O\({}_{3}\), and it has a molecular mass of 268.4 g/mol. Its CAS registry number is 41621-49-2 and its EC number is 255-464-9. It is a white to off-white crystalline substance and is freely soluble in water. In terms of stability, ciclopirox olamine is considered stable under normal temperatures and pressures. It does not readily react with other groups, nor does it decompose readily. It is also non-volatile, meaning it does not easily vaporize into the air. Figure 1: Chemical structure of ciclopirox (**a**) and ciclopirox olamine (**b**). In terms of content, the dried substance contains 76.0 per cent to 78.5 per cent ciclopirox (C\({}_{12}\)H\({}_{17}\)NO\({}_{2}\); M, 207.3) and 22.2 per cent to 23.3 per cent 2-aminoethanol (C\({}_{2}\)H\({}_{7}\)NO; M, 61.1). The pyridin-2(1H)-one core of ciclopirox, which is a six-membered aromatic ring, plays a crucial role in its chemical stability. The hydroxamic acid group at position 1 can participate in hydrogen bonding due to the lone pair of electrons on the nitrogen, as well as resonance delocalization within the ring. Ciclopirox could potentially exist in the following two tautomeric forms: the keto form (pyridinone), where the double bond is localized in the ring; and the enol form (hydroxypyridine), where the hydroxyl group is attached to the nitrogen. The interconversion between these forms is influenced by environmental factors such as pH, and the tautomeric balance, which may play a role in its interactions with biological targets [10; 11]. Ciclopirox is a lipophilic molecule with a log \(p\) value of 2.73, determined computationally using the iLOGP method [12]. The cyclohexyl group at position 6 introduces a bulky, non-polar, hydrophobic element, which influences the molecule's overall lipophilicity and may affect its membrane permeability. The methyl group at position 4 is relatively small but contributes to the hydrophobic nature of the molecule, affecting interactions with biological targets [1]. The conformational analysis of the cyclohexyl ring system aligns with the typical behavior of cyclohexane derivatives, which adopt a chair conformation to minimize steric strain and optimize 1,3-diaxial interactions. In ciclopirox, the bulky substituent at position 6 likely assumes an equatorial position to reduce steric hindrance, consistent with the related systems [13]. The olamine form of ciclopirox, which includes 2-aminoethanol, enhances the solubility of the drug in water and improves its bioavailability. This salt formation increases stability and allows for better absorption in biological systems, making it a preferred formulation in topical treatments. Ciclopirox olamine demonstrates improved water solubility and greater stability compared to other forms, largely due to the presence of 2-aminoethanol, which facilitates its delivery and increases bioactivity in biological organisms. Stability studies indicate that ciclopirox olamine maintains stability under standard environmental conditions (normal temperatures and pressures). However, prolonged exposure to light or moisture may affect its stability over time.