Ashwini Nangia

Acemetacin cocrystal structures by powder X-ray diffraction

Acemetacin cocrystals were prepared by melt crystallization and their crystal structures determined by high-resolution powder X-ray diffraction. The difficult to obtain single crystals for the acemetacin family is overcome by structure determination from powder data.

Mechanochemical synthesis of N-salicylidene­aniline: thermosalient effect of polymorphic crystals

Among the halogen derivatives of N-salicylideneaniline, polymorphs of the dichloro compound A showed the mechanical response of jumping (Forms I and III) and sudden blasting (Form II) upon heating. This difference is ascribed to the layered packing in Forms I and III such that the thermal stress acts in a unidirectional manner while for the corrugated layer structure of Form II the outcome is blasting because the thermal energy dissipates in different directions.

Polymorphism, isostructurality and physicochemical properties of glibenclamide salts

Novel salts of glibenclamide (GBA), namely glibenclamide-sodium (GBA-Na), glibenclamide-potassium (GBA-K) and glibenclamide-ammonium (GBA-NH4) were crystallized under different conditions to obtain their polymorphs, and their aqueous solubility and hydration stability studies are reported. The GBA-Na salt is dimorphic (forms I and II) and also exists as hydrate GBA-Na–H2O (form III). The GBA-K salt exists in anhydrous and hydrate forms (GBA-K, forms I and II). Crystal structure analysis of GBA-Na forms I and II showed differences in geometry of the central metal atom and ligand orientation. This kind of polymorphism of sulfonyl urea salts appears to be novel in the Cambridge Structural Database (CSD). The isostructurality of GBA-Na form I with GBA-NH4 and GBA-K form I salts is discussed. The potassium salts of GBA exhibited higher solubility compared to pure GBA. Specifically GBA-K salt forms I and II showed higher solubility by 77 fold in the water and 33 fold in phosphate buffer (pH 7) compared to the other salts. Dynamic vapor sorption (DVS) showed reversible water sorption without hysteresis for all salts, except for GBA-K form II which transformed to form I after a sorption and desorption cycle as confirmed by PXRD.

Rufinamide: Crystal structure elucidation and solid state characterization

Graphical abstract Figure. No caption available. HighlightsSingle crystals of rufinamide grown in dimethylformamide (R‐DMF) crystallized in triclinic form with P‐1 space group.Solid state characterization of R‐DMF were performed using analytical tools like DSC, PXRD, TGA and FTIR.Solubility and dissolution of R‐DMF in presence of different media was conducted.Assessment of flow and compressibility behavior of R‐DMF revealed poor flow and elastic behavior.Drug‐ excipient compatibility was determined by thermal analysis. ABSTRACT Rufinamide (R) is a triazole derivative approved for the management of partial seizures and seizures associated with Lennox‐Gastaut Syndrome, in November 2007. Crystal structure, solid state characterization, drug‐excipient compatibility and solubility play a pivotal role in formulation development. This work deals with the crystal structure elucidation of R by single crystal X‐ray diffraction and solid state characterization by thermal, spectroscopic and crystallographic techniques. Drug‐ excipient compatibility was assessed by differential scanning calorimetry (DSC). New RP‐HPLC method for quantification of R was developed with improved retention time. Solubility and dissolution of drug in different media was determined. Additionally, the flow behavior of the drug was evaluated by measuring Carrs index and Hausners ratio, while the compressibility behavior was studied using Wells protocol. R crystallized from dimethylformamide (R‐DMF) was utilized for single crystal analysis. The drug crystallized in triclinic crystal system with P‐1 space group. Asymmetric unit cell consists of two molecules of R held by intermolecular hydrogen bond (connected by N—H…O, which forms the catemeric chain). Analytical outcomes from DSC, thermogravimetric analysis (TGA) and powder X‐ray diffraction (PXRD) revealed that the drug was present in pure crystalline form and was devoid of any polymorphic or pseudopolymorphic impurities. Influence of pH on the solubility and dissolution of R‐DMF was found to be insignificant. The drug exhibited poor aqueous solubility, which was improved nearly 4.6 fold with the addition of 2% sodium lauryl sulphate (SLS). The drug exhibits poor flow and elastic compression nature. Excipients such as poly ethylene glycol (PEG) 8000, SLS, lactose monohydrate, starch and Hydroxypropyl methylcellulose (HPMC) E15 were incompatible with R‐DMF as identified by thermal analysis. It is envisaged that these information regarding solid state properties of R‐DMF would aid in identifying a logical path for formulation development.

Curcumin: pharmaceutical solids as a platform to improve solubility and bioavailability

Curcumin (CUR) is the prime curcuminoid in the Indian dietary spice turmeric, Curcuma longa, a plant of the Zingiberaceae family. CUR has promising and diverse therapeutic benefits, such as antioxidant, anti-inflammatory, antitumor, anti-hyperglycemic, antimalarial, antibacterial, and antiviral activity, including anti-Alzheimers disease. However, CUR is yet to reach the status of a therapeutic drug candidate mainly because a standard solid dosage of curcumin suffers from poor oral bioavailability (0.05 μg mL−1, less than 1%). The reasons behind its low bioavailability include poor solubility (<8 μg mL−1 in water), low permeability and absorption, and rapid metabolism (short elimination half-life of <2 h). A successful CUR therapy requires an appropriate formulation system that will enhance the bioavailability and offer greater therapeutic efficacy. This review covers a comprehensive description of the CUR pharmaceutical solids, such as polymorphs, cocrystals, eutectics, and coamorphous solid-state forms with aim to determine ways to improve its physicochemical properties, including dissolution rate, solubility, physicochemical stability, mechanical strength, compressibility for tablet formation, and oral bioavailability. The cumulative publications in the past decade have forecast a bright future for development of an oral drug formulation of curcumin.

Thermomechanical effect in molecular crystals: the role of halogen-bonding interactions

Among the halogen derivatives of salinazid, the chloro and bromo analogues show a mechanical response of jumping and breaking upon heating. Such a thermosalient response is ascribed to the sudden release of accumulated strain during the phase transition and to anisotropy in the cell parameters.

Role of hydrogen bonding in cocrystals and coamorphous solids: indapamide as a case study

The stronger sulfonamide–pyridine (SO2NH2⋯N-Py) and sulfonamide–carboxamide (SO2NH2⋯OC–NH) hydrogen bonds direct the formation of cocrystals, while the weaker sulfonamide–amine (SO2NH2⋯N–H) hydrogen bond results in coamorphous products. IDP–PIP and IDP–ARG coamorphous solids exhibit remarkable stability under accelerated conditions.