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AAPS PharmSciTech

, 21:10 | Cite as

Implication of Coformer Structural Diversity on Cocrystallization Outcomes of Telmisartan with Improved Biopharmaceutical Performance

  • Jamshed Haneef
  • Poonam Arora
  • Renu ChadhaEmail author
Research Article
  • 3 Downloads

Abstract

Crystal engineering approach was utilized for the development of different multicomponent solid forms of telmisartan (TEL) to improve its oral bioavailability. In this context, two cocrystals, gentisic acid (GA) and maleic acid (MA), while two eutectic mixtures, para-aminobenzoic acid (PABA) and adipic acid (AA), were successfully prepared and characterized by different analytical tools. Both the cocrystals exhibited characteristic heterosynthons, viz. OHacid⋯Narom and OHacid⋯O, to propagate new network. Structural features of coformers has been correlated with the outcomes of cocrystallization approach. Coformers having auxiliary functionality in addition to complementary functional groups have high propensity to generate cocrystals. However, multicomponent where auxiliary functionality is lacking, such combinations, is shown to form eutectic mixtures owing to strong homomeric interaction. Besides, the developed cocrystals and eutectic mixtures showed higher aqueous solubility (3–5.5-fold) and intrinsic dissolution rate (1–2.6-fold) over pure TEL. In vivo studies also revealed significant improvement in relative bioavailability (2–2.6-fold). The study also shed light on the implications of eutectic mixtures in mitigating the solubility issues of drugs which are often considered negative results of cocrystallization strategy.

KEY WORDS

bioavailability cocrystals crystal engineering eutectic mixtures multicomponent solid forms 

Notes

Acknowledgements

Mr. Jamshed Haneef is highly thankful to the Department of Science and Technology (DST), New Delhi, India, for providing the Inspire fellowships. Authors are also thankful for the services provided by the Sophisticated Analytical Instrumentation Facility (SAIF), Panjab University, India, to carry out the analysis of the sample.

Supplementary material

12249_2019_1559_MOESM1_ESM.docx (1.3 mb)
ESM 1 Supporting information contains Figure 1: Overlay of FTIR spectra of TEL, GA and TEL-GA; Figure 2: Overlay of FTIR spectra of TEL, MA and TEL-MA; Figure 3: Overlay of 13C SSNMR spectra of TEL, GA and TEL-GA; Figure 4: Overlay of 13C SSNMR spectra of TEL, MA and TEL-MA; Figure 5: Overlay of experimental and simulated PXRD patterns of TEL-GA cocrystal; Figure 6: Overlay of experimental and simulated PXRD patterns of TEL-MA cocrystal; Figure 7: Overlay of PXRD patterns of cocrystals (TEL-MA & TEL-GA) before and after stability study; Figure 8: Overlay of PXRD patterns of eutectic mixtures (TEL-PABA & TEL-AA) before and after stability study. Table 1: Multicomponent solid form screening of telmisartan using various coformers. Crystallographic information can be obtained from www.ccdc.cam.ac.uk/data (CCDC nos. 1868619 &1868609) (DOCX 1302 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and ResearchJamia HamdardNew DelhiIndia
  2. 2.University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Studies (CAS), Sector 14Panjab UniversityChandigarhIndia
  3. 3.Chitkara College of Pharmacy, Chitkara UniversityRajpura, PatialaIndia

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