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.

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 solidstate 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 characterized by powder X-ray diffraction analysis, DSC, scanning electron microscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, and solid-state 13 C nuclear magnetic resonance spectroscopy. Intramolecular hydrogen bonding interactions in salicylic acid and weaker intermolecular interactions between hydroxyl (-OH) group present at the ortho position of salicylic acid with the keto (-CO) group of curcumin result in a generation of eutectic, whereas strong hydrogen bonding interactions between hydroxyl -OH groups present in hydroxyquinol molecule and curcumin molecule result in formation of cocrystal upon melting and recrystallization. These curcumin−salicylic acid eutectic and curcumin−hydroxyquinol cocrystals show faster powder dissolution rates than raw curcumin. In the case of curcumin−hydroxyquinol cocrystals, cocrystals containing a curcumin mole fraction of 0.33 showed enhanced dissolution than cocrystals containing a curcumin mole fraction of 0.5.

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 drug due to its use in pre-eclampsia and ovarian cancer treatments. This mixture was found to have an increased dissolution rate when compared with curcumin. After 1 h, 175 mg/L of curcumin was dissolved from the coamorphous mixture, while only 45 mg/L was dissolved from curcumin Form I. The coamorphous mixture is stable as it was shown to keep its amorphous behavior after 24 h in solution at elevated temperatures. Curcumin formed a eutectic with suberic acid at a mole fraction of 0.2, whereas it remained as a physical mixture with dextrose. Also, solution crystallization of curcumin with dextrose at a mole fraction of 0.5 resulted into a form II curcumin polymorph.

This work focuses on the synthesis of oil-layered microbubbles using two microfluidic T-junctions in series and evaluation of the effectiveness of these 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 drugladen 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

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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.

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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-inflammatory, antitumor, and anticancer properties. Its use in pharmaceutical applications has been limited because of its poor aqueous solubility and hence poor bioavailability. In this work, attempts were made to formulate new solid forms of Curcumin with several coformers, mainly to enhance the dissolution rate of curcumin in aqueous medium. Ibuprofen, succinic acid, paracetamol, carbamazepine, ethyl paraben, glycine, tyrosine, N-acetyl D,Ltryptophan and biotin are the coformers investigated in this study. Binary phase diagrams were constructed for each binary system which helped in identifying the nature and the composition of the solid phase. All binary systems except curcumin−ibuprofen exhibited eutectic formation. The curcumin−ibuprofen system resulted in a physical mixture. These solid phases were further characterized through powder X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy and Raman spectroscopy. Dissolution studies conducted for eutectics showed enhanced dissolution rates as compared to raw curcumin. The results obtained were compared with the literature reports to present a consolidated account of research being conducted to enhance aqueous solubility of curcumin by developing new solid forms of curcumin such as eutectics, coamorphous solids, and cocrystals. Further, attempts have been made to understand how molecular geometry and intermolecular interactions influence the formation of a specific solid form.