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Similar but Not Same: Impact of Structurally Similar Coformers on Co-crystallization with Telmisartan

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Abstract

Purpose

The primary objective of this research work was to formulate crystal engineered multicomponent form of a BCS II drug, telmisartan (TEL) using crystal engineering approach to improve its aqueous solubility. Further, it was attempted to understand the co-crystallization specificity of TEL using a set of structurally similar coformers.

Methods

Preliminary structural assessment and feasibility of cocrystal formation was done using Cambridge structural database (CSD) and molecular electrostatic surface potential (MESP). The formation of cocrystals was confirmed by different characterization techniques such as differential scanning calorimetry (DSC), hot stage microscopy (HSM), Fourier transform infrared spectroscopy (FTIR), and powder x-ray diffraction (PXRD). Solubility and dissolution studies were performed in phosphate buffer 7.5 and 0.1 N HCl.

Results

TEL cocrystal with maleic acid (MA) was successfully obtained, and co-crystallization specificity was decoded at MESP. Cocrystal structure was also solved from PXRD data. A 4.27-fold and 2.8-fold improvement in the solubility was observed in phosphate buffer 7.5 and 0.1 N HCl.

Conclusion

A significant improvement in the aqueous solubility and dissolution profile was observed for the prepared cocrystals over the pure TEL. The present study was a small initiative to serve as a guidance for the rationalized screening and preparation of novel multicomponent solids with desired properties.

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Data Availability

All data generated or analyzed during this study are included in this article.

Abbreviations

TEL:

Telmisartan

DSC:

Differential scanning calorimetry

HSM:

Hot stage microscopy

FTIR:

Fourier transform infrared spectroscopy

PXRD:

Powder x-ray diffraction

API:

Active pharmaceutical ingredient

MA:

Maleic acid

FA:

Fumaric acid

MAL:

Malonic acid

MAC:

Malic acid

SA:

Succinic acid

MESP:

Molecular electrostatic surface potential

DFT:

Density functional theory

TASC:

Thermal analysis by structural characterization

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  1. Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India

    Arun Kumar & Arun Nanda

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Kumar, A., Nanda, A. Similar but Not Same: Impact of Structurally Similar Coformers on Co-crystallization with Telmisartan. J Pharm Innov 18, 1954–1965 (2023). https://doi.org/10.1007/s12247-023-09759-w

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