止吐药多潘立酮的新药-药物和药物-营养盐：新盐的结构和理化方面,CrystEngComm

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止吐药多潘立酮的新药-药物和药物-营养盐：新盐的结构和理化方面
CrystEngComm ( IF 2.6 ) Pub Date : 2024-01-04 , DOI: 10.1039/d3ce01000g
Sunil Kumar Nechipadappu _{1,

2} , Debasish Swain _{2,

3}

Affiliation

药品中的药物-药物多组分晶体（共晶体/盐）可能会在未来几年加剧固定剂量组合（FDC）的主要挑战。与 FDC 相关的挑战，例如药物不相容性、溶解度差异和稳定性问题，可以通过盐/共结晶来克服。在此，作者报道了止吐药多潘立酮 (DOM) 与各种药物共形成物的八种药物-药物/药物-营养盐，例如烟酸 (NCA)、DL-扁桃酸 (MAA)、水杨酸 (SLA)、乳清酸（OTA）和阿司匹林（ASP）。单晶 X 射线衍射研究揭示了 DOM-NCA 和 DOM-MAA 盐中存在多种固体形式，这些形式因水的存在而不同。这些盐，即 DOM-MAA、DOM-OTA 和 DOM-ASP，结晶为无水盐。基于 CrystalCMP 软件，发现盐 DOM–NCA I、DOM–SLA 和 DOM–MAA I 在晶体堆积方面相似。与 DOM 和共形成物（DOM-OTA 除外）相比，制备的盐显示出较低的熔化温度。制备的盐在三种不同缓冲介质中的溶解度表明 DOM 在 pH 6.8 和 1.2 缓冲液中的溶解度有所增强。与母体 DOM 相比，DOM 在盐中的溶解度在醋酸盐缓冲液 (pH 4.6) 中显着降低。pH 6.8 缓冲液中的溶出研究表明，盐中的药物释放速度更快。制备的盐在加速湿度条件（40°C，70-75% RH）下表现出稳定性 30 天，证明了进一步开发这些药物-药物/药物-营养盐的可能性。

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New drug–drug and drug–nutraceutical salts of anti-emetic drug domperidone: structural and physicochemical aspects of new salts

The drug–drug multicomponent crystals (cocrystal/salt) in pharmaceutical products may boost the major challenges of fixed-dose combinations (FDCs) in coming years. The challenges associated with FDCs such as drug incompatibility, solubility differences, and stability issues can be overcome by salt/cocrystallization. Herein, the authors report eight drug–drug/drug–nutraceutical salts of the anti-emetic drug domperidone (DOM) with various drug coformers such as nicotinic acid (NCA), DL-mandelic acid (MAA), salicylic acid (SLA), orotic acid (OTA), and aspirin (ASP). The single-crystal X-ray diffraction study revealed multiple solid forms in DOM–NCA and DOM–MAA salts which differ by the presence of water. The salts, namely, DOM–MAA, DOM–OTA and DOM–ASP crystallized as anhydrous salts. The salts DOM–NCA I, DOM–SLA, and DOM–MAA I were found to be similar in crystal packing based on CrystalCMP software. The prepared salts showed lower melting temperatures as compared to DOM and coformers except for DOM–OTA. The solubility of the prepared salts in three different buffer media revealed enhancement in the solubility of DOM in pH 6.8 and 1.2 buffers. The solubility of DOM in the salts was drastically reduced in the acetate buffer (pH 4.6) as compared to the parent DOM. The dissolution study in pH 6.8 buffer demonstrated the faster drug release in the salts. The prepared salts exhibited stability under accelerated humidity conditions (40 °C, 70–75% RH) for 30 days, demonstrating the possibility of further developing these drug–drug/drug–nutraceutical salts.

更新日期：2024-01-04

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