Polymorphic phase transitions in carbamazepine and 10,11-dihydrocarbamazepine

Temperature-induced phase transitions in carbamazepine (CBZ) and 1,10-dihydrocarbamazepine (DHC) were studied by simultaneous differential scanning calorimetry - X-ray diffraction in this work. The transitions generally involve a transitional melt phase which is quickly followed by recrystallisation. The expansions of the unit cell as a function of temperature could be quantified and allow us to determine a directional order of stability in relation to the lattice constants. Dihydrocarbamazepine form II undergoes a conversion to form I by a localized melt phase. Carbamazepine (CBZ) form IV converts to form I at 182 °C, by either a solid-solid pathway or a localised intermediate melt phase. CBZ form II converted to form I at 119 °C by a pathway that appears to have included some melting, and form III underwent a part melt-recrystallisation and a part sublimation-recrystallisation to form I

Are oxygen and sulfur atoms structurally equivalent in organic crystals?

New guidelines for the design of structurally equivalent molecular crystals were derived from structural analyses of new cocrystals and polymorphs of saccharin and thiosaccharin, aided by a computational study. The study shows that isostructural crystals may be obtained through an exchange of >C?O with >C?S in the molecular components of the solids, but only if the exchanged atom is not involved in hydrogen bonding

The solid state forms of the sex hormone 17-β-estradiol

The crystal structure of the single component form of the primary female sex hormone, 17-β-estradiol (BES), is reported, solved from single crystals obtained by sublimation. The Z′ = 2 P2₁2₁2₁ structure was computationally predicted as one of the thermodynamically plausible structures. It appears that the dehydration process for the very stable hemihydrate structure is a complex process, strongly affected by particle size and conditions. An experimental polymorph screen has produced six solid forms of BES, including novel acetonitrile and highly labile ethylene dichloride solvates, and reproduced previously reported methanol and propanol solvates. These have been characterized, as far as possible given the metastability relative to the hemihydrate (BES·0.5H₂O), by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot-stage microscopy and Fourier transform infrared spectroscopy (FT-IR), sorting out some of the confusion in the earlier literature

Jet dispensing of multi-layered films for the co-delivery of three antihypertensive agents

Three-layer thin films comprising of two polymers as substrate (ethyl cellulose and, copovidone K28) and three antihypertensive agents (hydrochlorothiazide, amiloride HCl, and carvedilol) were printed using jet dispensing technology. Two film formulations with different ethyl cellulose to copovidone K28 ratio (i.e., 90/10 and 50/50 w/w) were prepared using a three-course dispensing. The films were characterized regarding surface morphology, solid-state properties, polymer-drug interactions, drug distribution in each layer, and in vitro drug release. All the components of the films were found to be in the amorphous state apart from hydrochlorothiazide which retained its crystallinity. FT-IR spectroscopy revealed hydrogen bond interactions between carvedilol and copovidone K28. Combinations of ethyl cellulose and copovidone K28 provide suitable polymeric film substrates with the ability to modify drug release. Particularly, decreased ethyl cellulose to copovidone K28 weight ratio was found to suppress the crystallization of hydrochlorothiazide and to increase the release rate of the dispensed drugs. Jet dispensing was found to be a rapid technology for the preparation of multi-layered films that can be used as personalized formulations for the delivery of combinations of drugs

Pharmaceutical applications of thermal inkjet printing

Recent trends in the area of pharmaceutical products research and development appear to be directed more towards new drug delivery systems such as oro-dispersible films, as well as new physical forms of existing drugs such as co-crystals. Adapting technologies from other fields for developing such systems can be beneficial. Thermal inkjet printing (TIJP), a technique commonly encountered in office printers, has found applications in different areas due to its advantageous properties. The aim of this work was to utilise this technique to develop oral films for personalised dosing and to investigate its potential as a rapid and inexpensive method to prepare pharmaceutical co-crystals. Two unmodified Hewlett-Packard printers were used where the ink cartridges were modified to accommodate polymeric and aqueous drug solutions. Films were successfully prepared by printing multiple layers of hydroxyl-propyl-methylcellulose solutions onto transparency films, which disintegrated faster than those prepared by solvent casting (SC). Further, the amount deposited of a model drug (salbutamol sulphate, SS) varied linearly with the feed solution concentration. This led to the preparation of oral films using edible starch paper. Good agreement between the printed and theoretical dose was achieved with single print passes. Multiple print passes resulted in a significant loss, which was predictable and the dose variation was within the BP limits for SS tablets. Polymeric films were then used as substrates to prepare oral films of clonidine. Comparison with films prepared by solvent casting in terms of their physical stability, mechanical and drug release properties was also conducted. Films prepared by TIJP were more flexible and had better dose uniformity than films prepared by SC. Nonetheless, drug release from both films was similar. Finally, the technique was investigated to prepare pharmaceutical co-crystals. This was successfully achieved by printing solutions of co-crystal formers at specific stoichiometric ratios. In conclusion, this work demonstrates the suitability of TIJP as a method to prepare oral films extemporaneously for personalised dosing as well as pharmaceutical co-crystals

Untersuchungen zur Verbesserung der Trocknungsverfahren fuer ein- und mehrwellige Wellpappe nach der Kaschierstation einer Wellpapenanlage

Available from TIB Hannover: RO 3209(1990,3) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEArbeitsgemeinschaft Industrieller Forschungsvereinigungen e.V., Koeln (Germany)DEGerman