Development of L-Lysine Amino Acid-Based Co-Crystal of Telmisartan Using Crystal Engineering Approach to Improve Solubility, Dissolution, and Micrometric Properties

Abstract

Aim: To develop cocrytsal of telmisartan for enhancing its solubility in water. Background: Intermolecular interaction happens in crystal packing; it utilizes and helps us to understand the design of new solid with their respective chemical and physical properties called that crystal engineering. It is a blueprint of molecular solids with specific chemical and physical properties through an understanding and handling of intermolecular interaction for increasing solubility if poor water-soluble drugs. Objectives: The study was taken under consideration with an aim to generate and synthesize a cocrystal form of telmisartan (TEL) with L-lysine to improve its water solubility, dissolution, and micrometric properties. Methods: A dry grinding technique, solvent evaporation & cooling crystallization, the results revealed a generation of cocrystals with enhanced solubility by liquid drop grinding method. Hence, this process was further explored to investigate various formulation and process parameters that could significantly affect the crystal solubility, dissolution, and micrometric properties. Results: The solubility of TEL cocrystals was enhanced by L-lysine. Further, the optimized batch was subjected to its micrometric evaluation & physiochemical characterization like FT-IR, NMR, PXRD. The result of the micrometric evaluation showed better results as compared to standards. The dissolution studies also showed a better dissolution rate for TEL cocrystal tablets than TEL tablets formulation. Conclusion: Cocrystals of TEL with L-lysine showed better solubility and dissolution rate.

New Perspectives for Antihypertensive Sartans as Components of Co-crystals and Co-amorphous Solids with Improved Properties and Multipurpose Activity

“…This heterosynthon was confirmed in co-crystals of TEL with citric acid (CA), 157 febuxostat (FEB), 158 gentisic acid (GEN), 159 and maleic acid (MA). 159 It probably occurs in TEL co-crystals with oxalic acid (OA) 163 and L-lysine (LYS) 164 as well; however, the authors of these studies did not perform detailed analysis confirming the 3D structure of these co-crystals.…”

Molecular Insights from Spectral and Computational Studies on Crystalline and Amorphous Telmisartan

“…TEL (Figure ), characterized by high permeability and pH-dependent low aqueous solubility (0.09 μg/mL), belongs to the BCS class II drug category, with a dissolution rate-limited oral bioavailability of 40–58% . TEL is considered as a high glass forming molecule with a moderate glass stability and several strategies like use of polymers in conjunction with alkalizers, , antisolvent crystallization, development of cocrystals, − and coamorphous systems have been investigated to inhibit recrystallization of amorphous TEL (AM-TEL) to maximize its solubility and dissolution profile. Most recently, Bennett et al and Sharma et al .…”