Buspirone Hydrochloride Polymorphism: Stability, Solubility, Flow Properties, and Manufacturing Implications

Buspirone hydrochloride, an anxiolytic agent, has two interconvertible polymorphic forms that may affect its physicochemical properties and therapeutic efficacy. Despite this relevance, polymorphism is often neglected in pharmaceutical analyses, potentially leading to inconsistent results and compromised drug performance. This study investigates the polymorphism, stability, solubility, and flow properties of commercial samples of buspirone hydrochloride, focusing on how polymorphic transformations affect pharmaceutical performance. Samples from two international suppliers were stored under controlled and stress conditions (humidity and temperature) in open and closed vials. Structural characterization used Fourier-transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction, while flow and density properties were determined by Carr index and Hausner ratio. Solubility of pure polymorphic Forms 1 and 2 was evaluated in physiologically relevant pH media using high-performance liquid chromatography. The Indian sample contained a mixture of Forms 1 and 2, whereas the Finnish sample consisted exclusively of Form 2. Under stress, Form 2 converted to Form 1, completely in open vials and partially in closed ones, confirming the greater thermodynamic stability of Form 1. Among the analytical methods, differential scanning calorimetry proved to be the most effective in distinguishing polymorphic forms and identifying mixtures. Both forms showed pH-dependent solubility, with peak dissolution at pH 1.2, and very poor flow properties, requiring formulation adjustments. Solubility data supported a preliminary classification of both polymorphs as Biopharmaceutics Classification System Class I or Class III, although permeability differences remain unexplored. These findings advance the understanding of buspirone hydrochloride's polymorphic properties, supporting the development of more effective formulations.