Ionic, Neutral, and Hybrid Acid鈥揃ase Crystalline Adducts of Lamotrigine with Improved Pharmaceutical Performance

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• 作者：Rajesh Thipparaboina ; Dinesh Kumar ; Sudhir Mittapalli ; Sridhar Balasubramanian ; Ashwini Nangia ; Nalini R Shastri
• 刊名：Crystal Growth & Design
• 出版年：2015
• 出版时间：December 2, 2015
• 年：2015
• 卷：15
• 期：12
• 页码：5816-5826
• 全文大小：668K
• ISSN：1528-7505

文摘

Lamotrigine (L) is a known drug in the treatment of epilepsy and bipolar disorder. Due to its unique structure and functionalities, L is able to form both salts and cocrystals. The present study reports ionic, neutral, and hybrid crystalline forms of L with improved material properties and modified drug release rates. Novel forms of L with cinnamic acid (CA), ferulic acid (FRA), salicylic acid (SAC), and vanillin (VN) were successfully prepared and characterized using single crystal XRD, SEM, FT鈥揑R, DSC, TGA, and powder XRD. LCA and LVN crystallized in P2₁/c space group, whereas LSAC crystallized in P1虆 space group. Pseudo-quadruple hydrogen bond with R₄² (16) graph set notation were observed in all three crystal structures of L. The characteristic FT鈥揑R stretching peaks at 3326.53, 3341.53, and 3340.65 cm^鈥? corresponding to N⁺鈥揌 bond were observed in LCA, LFRA, and LSAC. Comparison of dissolution profiles using similarity factor (f2) analysis revealed that the dissolution profiles of LCA, LFRA, and LVN were significantly different from that of L. LVN exhibited improved dissolution rate compared to L and LCA revealed a sustained release profile. Both these properties are important in designing oral dosage forms for neuropathic pain and bipolar disorder therapy. Further, LCA can be used in the development of extended release drug delivery systems for treating epileptic disorders.