Sudarshan Mahapatra

Crystal packing and melting temperatures of small oxalate esters: the role of C—H⋯O hydrogen bonding

The simple dialkyl oxalates are generally liquids at room temperature except for dimethyl and di-tert-butyl oxalate which melt at 327 and 343 K. The crystal structures of diethyl, di-iso-propyl, di-n-butyl, di-tert-butyl and methyl ethyl oxalates were determined. The liquid esters were crystallized using the cryocrystallization technique. A comparison of the intermolecular interactions and packing features in these crystal structures was carried out. The crystal structure of dimethyl oxalate was redetermined at various temperatures. The other compounds were also studied at several temperatures in order to assess the attractive nature of the hydrogen bonds therein. A number of moderate to well defined C-H···O interactions account for the higher melting points of the two solid esters. Additionally, a diminished entropic contribution ΔS(m) in di-tert-butyl oxalate possibly increases the melting point of this compound further.

Quinoxaline: Z′ = 1 form

A new Z′ = 1 crystal structure of quinoxaline (or 1,4-diazanaphthalene), C8H6N2, with one-fifth the volume of the earlier known Z′ = 5 structure was obtained by means of an in situ cryocrystallization technique.

3-(2-Bromo­acet­yl)-6-fluoro-2H-chromen-2-one

The non-H atoms of the title compound, C11H6BrFO3, are essentially coplanar (r.m.s. deviation for all non-H atoms = 0.074 Å). In the crystal, the molecules are linked by C—H⋯O and C—H⋯Br interactions.

Development of pharmaceutically acceptable crystalline forms of APIs

Vamsi Krishna Mudapaka1, Srividya Ramakrishnan1, Sesha Reddy Yarraguntla1, Subba Reddy Peddireddy1, Sundara Lakshmi Kanniah2, Lalita Kanwar3, Sudarshan Mahapatra1, Amjad Basha Mohammad1, Vishweshwar Peddy1, Peter W Stephens4 1Integrated Product Development, Dr. Reddys Laboratories Ltd, Hyderabad, India, 2TEVA API, Plot No. 2-G, 2-H, 2-I, Ecotech-II, Udyog Vihar, Greater Noida, India, 3IP-38, IIT Delhi Campus, Hauz Khas, New Delhi-110016, India, 4Department of Physics and Astronomy, Stony Brook University, Stony Brook, New York 11794-3800, United States E-mail: mudapakavamsi@live.com

Unusual polymorphs of thymine

Susanta Kumar Nayak1, Ramanaiah Chennuru2, Prakash Muthudoss2, Srividya Ramakrishnan2, Amjad B. Mohammad2, R. Ravi Chandra Babu3, Sudarshan Mahapatra2 1Department Of Chemistry, Visvesvaraya National Institute Of Technology(VNIT), Nagpur, India, 2Integrated Product Development (IPDO), Dr. Reddy’s Laboratories Ltd., Bachupally, Hyderabad, India, 3Department Of Chemistry, College Of Science, GITAM University, Visakhapatnam, India E-mail: nksusa@gmail.com

Advantages of amorphous DRL-X over the marketed form

Solubility and dissolution play a pivotal role in an oral drug bioavailability. In addition to this pharmaceutical process parameters are also crucial for physical stability and drug development. DRL-X is a tyrosine kinase inhibitor drug belonging to Biopharmaceutics Classification System (BCS) class II. An amorphous form of DRL-X is prepared using spray drying technique and characterized by PXRD, DSC, and TGA etc. Various pharmaceutical properties of this amorphous form is compared against the marketed form of DRL-X. Current study indicates an enhanced apparent solubility over biological pH range 1.2 to 6.8, improved dissolution rate and IDR (Intrinsic Dissolution Rate) in OGD (Office of Generic Drugs) media for the synthesized amorphous form of DRL-X. Further this amorphous form is a stable glass with high glass transition temperature providing a better physical stability. This is further supported by the evidence of better tolerance to high compression, milling and aqueous granulation processes. Discovery of a novel amorphous form of DRL-X showing better physical stability, enhanced apparent solubility and dissolution will be a part of the presentation/discussion.

Designed crystallization via sublimation

Crystal structure determination of organic compounds is essential to understand structure-property correlation and is of specific importance in the pharmaceutical industries. In particular, the structure determination is unambiguously carried out using data obtained from a single crystal. One of the essentials for a successful structure determination is the requirement of a good quality single crystal or a single phase polycrystalline sample of the given material. Often crystals are formed with the incorporation of the solvent in the lattice during crystallization. In order to obtain crystal structures of anhydrous compounds, a novel approach is required where intervention of solvent can be entirely eliminated. There are a large number of methods to synthesize single crystals of a required compound like for example slow evaporation, vapour diffusion, solvent diffusion, sublimation, convection, and zone melting. Out of these techniques, slow solvent evaporation from a solution is frequently adopted to grow single crystals of organics, and this leads to the incorporation of the solvent in the crystal structure. On the other hand sublimation technique is found to be less explored towards single crystal generation and discovery of novel polymorphs. Designing of apparatus for single crystal growth assisting anhydrous crystal structure determination of different pharmaceutical compounds and generation of polymorphs will be a part of the discussion and presentation.

Crystal structure of 3-bromo-acetyl-6-chloro-2H-1-benzo-pyran-2-one.

In the title compound, C11H6BrClO3, the benzopyran ring system is essentially planar, with a maximum deviation of 0.036 (2) Å for the O atom. The Cl and Br atoms are displaced by −0.0526 (8) and 0.6698 (3) Å, respectively, from the mean plane of this ring system. In the crystal, two pairs of weak C—H⋯O hydrogen bonds to the same acceptor O atom link molecules into inversion dimers.

N-(2-Amino-3,5-dibromo-benz-yl)-N-methyl-cyclo-hexan-1-aminium p-toluenesulfonate.

The title compound, C14H21Br2N2 +·C7H7O3S−, features a salt of protonated bromhexine, a pharmaceutical used in the treatment of respiratory disorders, and the p-toluenesulfonate anion. The crystal packing is stabilized by intermolecular N—H⋯O, N—H⋯Br and C—H⋯O hydrogen bonds.

A novel approach to specifically crystallize anhydrous compounds: crystal structure of adenine

Crystallization without solvent incorporation is a key requirement to study anhydrous forms of compounds. The structures of all the anhydrous nucleobases were not available as adenine was very hard to crystallize without solvent incorporation. X-ray powder diffraction data both from conventional source as well as synchrotron radiation was found inadequate to solve the structure in the anhydrous form. Crystals of anhydrous adenine were grown by a new approach using the principle of sublimation and gradient cooling. Anhydrous adenine crystallizes in a monoclinic space group P21/c with a=7.891(3), b=22.242(8), c=7.448(3)Å, β =113.193(5)°, V=1201 .6 (3 )Å 3 and Z=8 . There are two molecules in the asymmetric unit linked via N-H···N hydrogen bonds. The crystal structure is stabilized by two additional sets of N-H···N hydrogen bonds, one across the center of symmetry connecting the imidazole moiety to the pyridine moiety and the other linking the next asymmetric unit resulting in a sheet motif.