Indumathi Sathisaran
@nitc.ac.in
Assistant Professor, School of Biotechnology
National Institute of Technology Calicut
EDUCATION
B.Tech, M.Tech, PhD
RESEARCH, TEACHING, or OTHER INTERESTS
Multidisciplinary, Biotechnology, Cancer Research, Biomaterials
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Indumathi Sathisaran and Sameer Vishvanath Dalvi
American Chemical Society (ACS)
Nevirapine (NEV) is an antiretroviral drug which falls under the Biopharmaceutics Classification System (BCS) class II category. In this work, we report the synthesis of new eutectic and cocrystal ...
Indumathi Sathisaran and Sameer Vishvanath Dalvi
Springer Science and Business Media LLC
Indumathi Sathisaran and Sameer Vishvanath Dalvi
Springer Science and Business Media LLC
In this work, carbamazepine (CBZ), an anticonvulsant drug was cocrystallized with several structurally complement coformers (coformers with amide, acid and hydrazide functional groups) to enhance its dissolution. CBZ formed a cocrystal phase with acetamide (ACE) when mixtures of CBZ and ACE (containing CBZ mole fractions, X CBZ of 0.25, 0.33, 0.5, and 0.67) were subjected to solid-state grinding (SSG), evaporative crystallization (EC), slurry conversion (SC), and slow cooling crystallization (SLC). Upon heating, the CBZ-ACE cocrystal phase formed from CBZ-ACE mixtures containing X CBZ of 0.25, 0.33 and 0.67 underwent solid-state phase transition to CBZ form I and CBZ cocrytsal phase obtained from the CBZ-ACE mixture containing X CBZ of 0.5 converted to CBZ form III. Interestingly, slow cooling cocrystallization experiments resulted in crystallization of a cocrystal as well as the CBZ dihydrate forms. The powder dissolution studies demonstrated that among the different CBZ-ACE-SSG cocrystal phases, CBZ-ACE-SSG-X CBZ -0.33 cocrystal exhibited 7.47 times improved dissolution whereas the CBZ eutectic phase with nicotinic acid hydrazide (NAH) exhibited 4.93 times increased dissolution when compared to raw CBZ.
Indumathi Sathisaran and Murugesan Balasubramanian
Elsevier BV
Polymer-based controlled-release formulations are gaining significant advantage over chemical fertilizers in recent years as they contribute to the preservation of soil fertility by reducing soil pollution in farm lands. In this work, urea (a nitrogen source fertilizer) has been entrapped within chitosan-alginate and gelatin-alginate composite beads at three different concentrations. The physical properties of the polymer composite beads namely the diameter, porosity, yield percentage, Carr's index and Hausner's ratio were determined. These fertilizer-loaded beads were also characterized by Scanning Electron Microscopy (SEM) and Fourier Transform-Infra Red (FT-IR) spectroscopy. Urea enhanced swelling of chitosan-alginate beads through the creation of pores whereas in the case of gelatin-alginate formulations, urea decreased the swelling. The swelling of the polymer composite beads was found to be maximum at pH of 5.6 when compared to that of pH conditions, 7 and 8.5. The chitosan-alginate composite beads were found to possess better fertilizer entrapping efficiency than the gelatin-alginate composite beads. The in vitro urea release studies demonstrated that the urea-entrapped gelatin-alginate beads exhibited slower urea release than that of the chitosan-alginate beads. These controlled release urea formulations were found to follow quasi-fickian diffusion mechanism.
Aaqib H. Khan, Xinyue Jiang, Swarupkumar Surwase, Merve Gultekinoglu, Cem Bayram, Indumathi Sathisaran, Dhiraj Bhatia, Jubair Ahmed, Bingjie Wu, Kezban Ulubayram,et al.
American Chemical Society (ACS)
This work focuses on evaluation of the effectiveness of double layered microbubbles loaded with doxorubicin and curcumin for cell invasion arrest from 3D spheroid models of triple negative breast cancer (TNBC), MDA-MB-231 cell line. Albumin microbubbles coated in drug-laden oil layer were synthesized using a new method of connecting two microfluidic T-mixers in series. Double-layered microbubbles thus produced consist of an innermost core of nitrogen gas encapsulated in an aqueous layer of bovine serum albumin (BSA) which in turn, is coated with an outer layer of silicone oil. In order to identify the process conditions leading to the formation of double-layered microbubbles, a regime map was constructed based on Capillary numbers for aqueous and oil phases. The microbubble formation regime transitions from double-layered to single layer microbubbles and then to formation of single oil droplets upon gradual change in flow rates of aqueous and oil phases. In-vitro dissolution studies of double-layered microbubbles in an air-saturated environment indicated that a complete dissolution of such bubbles produces an oil droplet devoid of gas bubble. Incorporation of doxorubicin and curcumin was found to produce a synergistic effect, which resulted in higher cell deaths in 2D monolayers of TNBC cells and inhibition of cell proliferation from 3D spheroid models of TNBC cells compared to control.
Indumathi Sathisaran, Dhiraj Devidas Bhatia, and Sameer Vishvanath Dalvi
Elsevier BV
Curcumin (CUR) is a Biopharmaceutics Classification System (BCS) class IV drug with poor aqueous solubility and low permeability. The dissolution of CUR can be enhanced through the cocrystallization approach. In this work, we report a new cocrystal phase of CUR with trimesic acid (TMA) with the enhanced dissolution of CUR. Cytotoxicity and cell invasion assays were conducted on (2D) monolayers and three-dimensional (3D) tumor models of triple-negative breast cancer (TNBC) cells, MDA-MB-231 using the new CUR-TMA cocrystal phase along with different CUR solid forms prepared in our previous works. The cytotoxicity and internalization assays conducted on 2D monolayers indicated that all CUR multicomponent solid forms except Curcumin-Folic Acid Dihydrate (CUR-FAD) (1:1) coamorphous solid exhibited enhanced bioavailability than unprocessed CUR. Cell invasion assay conducted on 3D tumor spheroid models showed that Curcumin-Hydroxyquinol (CUR-HXQ) cocrystal completely inhibited cell invasion whereas CUR-FAD (1:1) coamorphous solid induced enhanced invasion of cells from spheroid models.
Indumathi Sathisaran and Sameer Vishvanath Dalvi
Elsevier BV
Abstract Carbamazepine is an anticonvulsant drug which belongs to Biopharmaceutics Classification System (BCS) Class II drugs. In this work, attempts have been made to enhance the dissolution of carbamazepine (CBZ) in aqueous medium by attempting cocrystallization with the coformers such as para-hydroxybenzamide (PHBAD), salicylamide (SAL) and pyrazinamide (PRZ). Binary phase diagrams were constructed by conducting Differential Scanning Calorimetry (DSC) analysis for these CBZ-coformer pairs in order to determine the nature of the solid phase and cocrystal forming zone. CBZ formed a 1:1 cocrystal phase with PHBAD from the eutectic melts at a stoichiometric ratio of 1:1 and 1:2 whereas it formed eutectics with SAL as well as PRZ. Single crystals of CBZ-PHBAD (1:1) cocrystal phase were obtained by solvent evaporation of CBZ-PHBAD eutectic melts in Acetone-Toluene (1:1 vol ratio). Interestingly, recrystallization of eutectic melt of CBZ-PHBAD (1:1) in 1,4-Dioxane produced crystals of para-hydroxybenzamide monohydrate. Crystal structure analysis showed that CBZ-PHBAD (1:1) cocrystal and para-hydroxybenzamide monohydrate crystallized in monoclinic space groups namely P21/c and P21/n respectively. CBZ formed intermolecular interaction with two molecules of PHBAD via O-H…O hydrogen bonding and N-H...O intermolecular interaction which results into a cocrystal. Powder Dissolution (PD) studies were conducted for the CBZ-PHBAD (1:1) cocrystal, CBZ-SAL and CBZ-PRZ eutectic mixtures in Phosphate Buffer Saline (PBS) at 37 °C. Among the three carbamazepine solid forms, CBZ-PHBAD cocrystal exhibited 6.5 times higher dissolution than raw carbamazepine while the CBZ-SAL-SSG-XCBZ-0.5 eutectic and CBZ-PRZ-SSG-XCBZ-0.5 eutectic phases exhibited 2.62 and 3.05 times enhanced dissolution than raw carbamazepine.
Indumathi Sathisaran, Jenna Marie Skieneh, Sohrab Rohani, and Sameer Vishvanath Dalvi
American Chemical Society (ACS)
Curcumin is a potentially viable pharmaceutical ingredient obtained from the rhizome of a turmeric plant, Curcuma longa. It is a polyphenolic compound which is known to possess antibacterial, anti-...
Indumathi Sathisaran and Sameer Dalvi
MDPI AG
Biopharmaceutics Classification System (BCS) Class II and IV drugs suffer from poor aqueous solubility and hence low bioavailability. Most of these drugs are hydrophobic and cannot be developed into a pharmaceutical formulation due to their poor aqueous solubility. One of the ways to enhance the aqueous solubility of poorlywater-soluble drugs is to use the principles of crystal engineering to formulate cocrystals of these molecules with water-soluble molecules (which are generally called coformers). Many researchers have shown that the cocrystals significantly enhance the aqueous solubility of poorly water-soluble drugs. In this review, we present a consolidated account of reports available in the literature related to the cocrystallization of poorly water-soluble drugs. The current practice to formulate new drug cocrystals with enhanced solubility involves a lot of empiricism. Therefore, in this work, attempts have been made to understand a general framework involved in successful (and unsuccessful) cocrystallization events which can yield different solid forms such as cocrystals, cocrystal polymorphs, cocrystal hydrates/solvates, salts, coamorphous solids, eutectics and solid solutions. The rationale behind screening suitable coformers for cocrystallization has been explained based on the rules of five i.e., hydrogen bonding, halogen bonding (and in general non-covalent bonding), length of carbon chain, molecular recognition points and coformer aqueous solubility. Different techniques to screen coformers for effective cocrystallization and methods to synthesize cocrystals have been discussed. Recent advances in technologies for continuous and solvent-free production of cocrystals have also been discussed. Furthermore, mechanisms involved in solubilization of these solid forms and the parameters influencing dissolution and stability of specific solid forms have been discussed. Overall, this review provides a consolidated account of the rationale for design of cocrystals, past efforts, recent developments and future perspectives for cocrystallization research which will be extremely useful for researchers working in pharmaceutical formulation development.
Jenna Marie Skieneh, Indumathi Sathisaran, Sameer Vishvanath Dalvi, and Sohrab Rohani
American Chemical Society (ACS)
Curcumin is a naturally occurring compound derived from turmeric. Despite its many medicinal properties, such as being an antioxidant, anti-inflammatory, tumor reducer, etc., applications of curcumin are restricted due to its low aqueous solubility and consequently its poor bioavailability. By converting the solid state of poorly water-soluble active pharmaceutical ingredients to coamorphous mixtures, solvates, cocrystals, and eutectics, the solubility can be significantly improved. In this study, U. S. Food and Drug Administration approved excipients were screened for their ability to form novel solid states with curcumin to increase its aqueous solubility. Excipients were screened based on their molecular complementarity with curcumin, using Mercury software. Folic acid dihydrate (FAD), suberic acid, and dextrose are the three coformers that are investigated in this study. It was found that a coamorphous mixture can be formed between curcumin and FAD. FAD has potential as a prenatal or a women’s health ...
Indumathi Sathisaran and Sameer Vishvanath Dalvi
American Chemical Society (ACS)
Curcumin is a pharmaceutically viable ingredient derived from the rhizome of the Indian spice turmeric (Curcuma longa). However, curcumin suffers from poor water solubility, which limits its bioavailability. In this work, we report studies carried out to investigate cocrystallization of curcumin to improve its aqueous solubility. Salicylic acid and hydroxyquinol were used as coformers. Binary phase diagrams were constructed for curcumin–salicylic acid and curcumin–hydroxyquinol systems using differential scanning calorimetric (DSC) thermograms obtained for mixtures prepared by solid-state grinding. The curcumin–salicylic acid system was found to form an eutectic at a curcumin mole fraction of 0.33, whereas the curcumin–hydroxyquinol system clearly exhibited a cocrystal forming region. Out of the several curcumin to hydroxyquinol ratios studied, cocrystal formation was observed for mixtures containing curcumin mole fractions of 0.33 and 0.5. These curcumin–hydroxyquinol cocrystals were further characterize...