Background

Cocrystallization by solvent evaporation was used to enhance the dissolution, physicochemical properties, and bioavailability of nimodipine (NMD). Here, we aimed to develop NMD cocrystals with improved solubility and dissolution. Thereafter, our objective was to check the changes in brain tissue concentrations before and after the cocrystal formation of NMD.

Methods

A 3²-factor design was used for product optimization by determining the desirability function. Differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy were used to confirm the formation of cocrystals.

Results

The saturation solubility study of NMD:SA cocrystals resulted in 9.52 mg/ml, which is 128-fold higher than that of pure NMD (0.074 mg/ml). In vitro dissolution and permeability studies showed an improvement in the percentage of drug release and permeability of NMD from cocrystals as compared to pristine NMD. An in vivo study of oral bioavailability in Wistar rats demonstrated higher plasma and brain tissue concentrations of NMD in the cocrystal form than in the conventional oral suspension.

Discussions

The findings of this study showed a positive correlation between nimodipine solubility, improvement in dissolution, and its effect on brain tissue concentration in Wistar rats. The improved solubility of nimodipine may lead to increased dissolution rates, which can enhance its bioavailability and therapeutic efficacy in the treatment of cerebral vasospasms.

中文翻译：

---

通过共结晶研究尼莫地平（BCS II 类）溶解度、溶出度改善与脑组织浓度之间的相关性

背景

通过溶剂蒸发共结晶来增强尼莫地平 (NMD) 的溶出度、理化性质和生物利用度。在这里，我们的目标是开发具有改善的溶解度和溶出度的 NMD 共晶体。此后，我们的目的是检查 NMD 共晶形成前后脑组织浓度的变化。

方法

通过确定合意性函数，使用3 ^{2因素设计来优化产品。}使用差示扫描量热法、粉末X射线衍射和扫描电子显微镜来确认共晶的形成。

结果

NMD:SA 共晶的饱和溶解度研究结果为 9.52 mg/ml，比纯 NMD (0.074 mg/ml) 高 128 倍。体外溶出度和渗透性研究表明，与原始 NMD 相比，共晶 NMD 的药物释放百分比和渗透性有所改善。Wistar 大鼠口服生物利用度的体内研究表明，共晶形式的 NMD 血浆和脑组织浓度高于传统口服混悬液。

讨论

这项研究的结果表明，尼莫地平的溶解度、溶出度的改善及其对 Wistar 大鼠脑组织浓度的影响之间存在正相关。尼莫地平溶解度的提高可能导致溶出速率增加，从而增强其治疗脑血管痉挛的生物利用度和疗效。