Maggi Lauretta, Friuli Valeria, Cerea Beatrice, Bruni Giovanna, Berbenni Vittorio, Bini Marcella
Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
Department of Information Engineering, University of Brescia, Via Branze 38, 25123 Brescia, Italy.
Molecules. 2024 May 21;29(11):2419. doi: 10.3390/molecules29112419.
Organic-inorganic hybrids represent a good solution to improve the solubility and dissolution rates of poorly soluble drugs whose number has been increasing in the last few years. One of the most diffused inorganic matrices is hydroxyapatite (HAP), which is a biocompatible and osteoconductive material. However, the understanding of the hybrids' functioning mechanisms is in many cases limited; thus, thorough physicochemical characterizations are needed. In the present paper, we prepared hybrids of pure and Mg-doped hydroxyapatite with meloxicam, a drug pertaining to the Biopharmaceutical Classification System (BCS) class II, i.e., drugs with low solubility and high permeability. The hybrids' formation was demonstrated by FT-IR, which suggested electrostatic interactions between HAP and drug. The substitution of Mg in the HAP structure mainly produced a structural disorder and a reduction in crystallite sizes. The surface area of HAP increased after Mg doping from 82 to 103 mg as well as the pore volume, justifying the slightly high drug amount adsorbed by the Mg hybrid. Notwithstanding the low drug loading on the hybrids, the solubility, dissolution profiles and wettability markedly improved with respect to the drug alone, particularly for the Mg doped one, which was probably due to the main distribution of the drug on the HAP surface.
有机-无机杂化物是提高难溶性药物溶解度和溶解速率的良好解决方案，在过去几年中，这类药物的数量一直在增加。最常见的无机基质之一是羟基磷灰石（HAP），它是一种生物相容性和骨传导性材料。然而，在许多情况下，对杂化物作用机制的了解是有限的；因此，需要进行全面的物理化学表征。在本文中，我们制备了纯羟基磷灰石和镁掺杂羟基磷灰石与美洛昔康的杂化物，美洛昔康属于生物药剂学分类系统（BCS）II类药物，即低溶解度和高渗透性药物。通过傅里叶变换红外光谱（FT-IR）证实了杂化物的形成，这表明HAP与药物之间存在静电相互作用。镁在HAP结构中的取代主要导致结构无序和微晶尺寸减小。镁掺杂后，HAP的比表面积从82增加到103 mg，孔体积也增加，这解释了镁杂化物吸附的药物量略高的原因。尽管杂化物上的药物负载量较低，但相对于单独的药物，其溶解度、溶解曲线和润湿性显著改善，特别是对于镁掺杂的杂化物，这可能是由于药物主要分布在HAP表面。
