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Title: Modulation of morphology and efficacy of new CB1 receptor antagonist using simple and benign polymeric additives
Authors: Banerjee, Kaushik
Patel, Darshit R
Kulshrestha, Anchal
Joshipura, Dhawal
Joharapurkar, Amit
Ghoshdastidar, Krishnarup
Jain, Mukul R
Srivastava, Brijesh Kumar
Chakraborty, Mukut
Pattanayak, Sutanuka
Ballabh, Amar
Keywords: Obesity;CB1 antagonist;crystallography;morphology;in vivo efficacy
Issue Date: Jul-2021
Publisher: NIScPR-CSIR, India
Abstract: The compound 1, [(1H-[1]benzoxepino[5,4-c]pyrazole-3-carboxamide, 8-chloro-1-(2,4-dichlorophenyl)-4,5-dihydro-N- 1-piperidinyl], a known CB1 modulator has been synthesized and characterized by IR, NMR and single Crystal X-ray study. The single crystal study of 1 displays a number of halogen bonds leading to 1-D network along with other weak noncovalent interactions. The CB1 modulator 1 inherently possesses extremely low solubility in water, which makes its application as drug difficult, and this may be attributed to multiple halogen bonds present in the crystal structure. A series of polymer additives, which are Generally Regarded As Safe (GRAS), have been explored to investigate whether they can modulate the halogen bond present in 1 through formation of various non-bonded interactions. Surprisingly, these polymers are found to change crystal morphology, crystal packing while retaining efficacy and bioavailability. The polymer molecular weight is found to play a significant role in crystal morphology modification especially in case of polyethylene glycol (PEG). The formation of new polymorphic forms of 1 and modification of halogen bond has been established using powder X-ray diffraction and IR study, respectively, in case of PEG 4000, PVPK-30, PVA polymers and compound 1 adducts.
Page(s): 1014-1021
ISSN: 0975-0983(Online); 0376-4699(Print)
Appears in Collections:IJC-B Vol.60B(07) [July 2021]

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