Saikat Roy

Polymorphism and isostructurality in sulfonylhydrazones

Five methyl and halogen derivatives of the conformationally flexible trimorphic molecule, bis(p-tolyl)ketone p-tosylhydrazone (TMSH, trimethyl sulfonylhydrazone) (Cryst. Growth Des., 2007, 7, 2047), were synthesized to understand polymorphism and isostructurality upon Cl–Me and inter-halogen exchange. The chlorodimethyl derivative CMSH (chlorodimethyl sulfonylhydrazone) is dimorphic whereas TCSH (trichloro sulfonylhydrazone), TBSH (tribromo sulfonylhydrazone), FMSH (fluorodimethyl sulfonylhydrazone), and MISH (methyldiiodo sulfonylhydrazone) have one crystal structure each. Single crystal X-ray diffraction and XPac analyses showed 3D isostructurality between CMSH form I, TCSH and TBSH, as well as for CMSH form II and FMSH. MISH has a different crystal packing compared to the other members due to the large iodo group. The conformational rigidity of the sulfonylhydrazone backbone leads to the observed isostructurality, whereas the presence of the sulfonamide dimer and catemer synthons results in different packing motifs and polymorphism.

Story of Sustentials curcumin: a more bioavailable synergistic nutraceutical combination

Nutraceuticalsonce isolated from parent food or herb matrix are often not stable and bioavailable as it is in food and natural source. Curcumin is the active ingredient of golden spice turmeric and has many therapeutic activities likeanti-oxidant, antiinflammation, anti-diabetic and many other beneficial biological actions. In this present work, curcumin molecular complexes were prepared based on crystal engineering strategies and their functional attribute studies. Curcumin molecular complexes with synergistic nutraceutiacals has shown enhancement of dispersibility and solubility by range of 200-700 times. In-vitro functional properties like dissolution, permeability, antioxidant activities have improved markedly in molecular complexes. Clinical evaluation of molecular complexes has been done on Spargue Dawley rat and Human subjects, which shows relative bioavailability improvement of 9.9 times and 4 times in one of the Curcumin-nutraceutical combination, which is branded as “SustentialsTM Curcumin”.

Crystal engineering solutions to improve pharmacokinetic properties of nutraceuticals

Gobal challenge of increasing needs with diminishing resources necessitates an innovative out-of-the-box thinking. Fortification of foods by nutraceuticals is a significant business opportunity, but one that still has significant technical challenges. Several factors are critical for the use and acceptance of nutraceuticals, such as, (a) stability at various pH, temperatures & relative humidity, (b) bioavailability, (c) organoleptic acceptance (taste masking) and (d) low cost formulation. Crystal engineering of synergistic combinations of nutraceuticals presented itself as a versatile platform for developing these formulations. Stable and taste masked epigallocatechin gallate, more bioavailable curcumin and biomimetic isoflavone cocrystals were developed at Tata Chemicals Innovation centre and their structures were analyzed by X-ray diffraction, properties by spectroscopic and thermal methods. Human clinical trials and in vitro anti-inflammatory studies of a synergistic formulation of curcumin – ‘Sustentials curcumin–G’, showed four times more bioavailability with pronounced reduction in IL-6 concentrations. A new brand for formulations based on crystal engineering platform, namely, ‘Sustentials Curcumin’ was launched in the market. A flavour of this research and the challenges in commercialisation journey will be presented with suitable examples. [1} Saikat Roy, Bhargav Meshiya, Ravindra Barhalikar, Anil Kumar [2017] WO 2017/002134 A1 [2] Saikat Roy, Bhargav Meshiya, Ravindra Barhalikar, Anil Kumar [2017] WO 2017/002133 A1