Blend Uniformity and Content Uniformity in Oral Solid Dosage Manufacturing: an IQ Consortium Industry Position Paper.

The IQ Consortium Uniformity Testing Working Group reviewed the current BU and CU testing practices among ten member companies. All ten companies presented their current approach to BU and CU testing at the three stages of Product Lifecycle Management: the Process Design Stage, the Process Qualification Stage, and the Continuous Verification Stage. With this information on hand, the Uniformity Testing Working Group members developed a risk-based approach to BU and CU testing, and proposed innovative methods to reduce or eliminate blend sampling based on risk to Uniformity of Dosage Unit (UDU) testing.

Analysis of thermolabile residual solvents in a spray dried dispersion using static headspace gas chromatography.

In this study, we discuss the development of a static headspace gas chromatography method for the analysis of residual acetone as well as its enriched impurities including mesityl oxide and diacetone alcohol, in a spray dried dispersion. The major challenges include the instability of mesityl oxide and diacetone alcohol at high temperature and peak tailing of diacetone alcohol. It was found that the headspace oven temperature has to be controlled to 150°C or below to prevent degradation beyond an acceptable level (< 1%).

Toward novel antiparasitic formulations: Complexes of Albendazole desmotropes and β-cyclodextrin.

Novel complexes of two different solid forms of Albendazol and β-cyclodextrin were investigated in an attempt to obtain promising candidates for the preparation of alternative matrices used in pharmaceutical oral formulations. The interaction between each form of Albendazol and β-cyclodextrin was studied in solution and solid state, in order to investigate their effect on the solubility and dissolution rate of Albendazol solid forms. The solid supramolecular systems were characterized using a variety of techniques including natural-abundance C cross-polarization magic-angle-spinning nuclear magnetic resonance, powder X-ray diffraction, Fourier transform-infrared spectroscopy and scanning electron microscopy.

The Bioenhancer Piperine is at Least Trimorphic.

Polymer-induced heteronucleation (PIHn), a powerful crystalline polymorph discovery method, has revealed two novel polymorphs of the low solubility bioenhancer piperine. Both of these forms exhibit enhanced solubility when compared to the commercial polymorph, thereby potentially improving the efficacy of piperine as a bioenhancer. Structural comparison of the three forms reveals that π-π interactions are only present in the two newly discovered forms.

Investigating albendazole desmotropes by solid-state NMR spectroscopy.

Characterization of the molecular structure and physicochemical solid-state properties of the solid forms of pharmaceutical compounds is a key requirement for successful commercialization as potential active ingredients in drug products. These properties can ultimately have a critical effect on the solubility and bioavailability of the final drug product. Here, the desmotropy of Albendazole forms I and II was investigated at the atomic level.

Controlling pharmaceutical crystallization with designed polymeric heteronuclei.

To investigate the hypothesis that molecules acting as crystallization inhibitors in solution could be transformed into crystallization promoters, additives were synthesized that mimic the pharmaceuticals acetaminophen and mefenamic acid and also possess polymerizable functionality. It was found that, in solution, these additives face-selectively inhibit crystal growth and lead to overall slower crystal appearance. In contrast, when the tailor-made additives were incorporated into an insoluble polymer, the induction time for the onset of crystal formation for both pharmaceuticals was substantially decreased.

Towards exhaustive and automated high-throughput screening for crystalline polymorphs.

Methods capable of exhaustively screening for crystal polymorphism remain an elusive goal in solid-state chemistry. Particularly promising among the new generation of approaches is polymer-induced heteronucleation (PIHn), a tool utilizing hundreds of unique polymers for granting kinetic access to polymorphs. Here PIHn is redeployed in a high density format in which 288 distinct polymers, each acting as a heteronucleant, are arrayed on one substrate.

insights into novel supramolecular complexes of two solid forms of norfloxacin and β-cyclodextrin.

The solid-state properties of novel complexes of β-cyclodextrin and two different solid forms of norfloxacin were investigated at the molecular level, in an attempt to obtain promising candidates for the preparation of alternative matrices used in pharmaceutical oral formulations. In order to evaluate the physical properties inherited from the different polymorphs, these supramolecular systems were characterized using a variety of spectroscopic techniques including natural-abundance (13) C cross-polarization magic-angle-spinning (CP-MAS) nuclear magnetic resonance (NMR), powder X-ray diffraction, and Fourier transform infrared spectroscopy. The intrinsic proton spin-lattice relaxation times detected in (13) C CP-MAS NMR spectra are used to confirm and distinguish the complex formation, as well as to provide better insights into the molecular fragments that are involved in the interaction with β-cyclodextrin.

Variation of mobile carbon reserves in trees at the alpine treeline ecotone is under environmental control.

In low temperature-adapted plants, including treeline trees, light-saturated photosynthesis is considerably less sensitive to temperature than growth. As a consequence, all plants tested so far show increased nonstructural carbohydrate (NSC) tissue concentrations when exposed to low temperatures. Reduced carbon supply is thus an unlikely cause for low temperature range limits of plants.