A combined spectroscopic and chromatographic approach has been employed to study the products of allomerization of chlorophyll a (chl a), bacteriochlorophyll a (bchl a) and bacterioviridin (bvir) under a variety of conditions. Using high-performance liquid chromatography, mass spectrometry (MS), tandem-MS, NMR spectroscopy, UV-VIS absorption spectroscopy and protected surface-enhanced resonance Raman spectroscopy we have identified the allomers formed under all the conditions. Analysis of the different product distributions enables us to reach conclusions about the reaction mechanism. Water is identified as the source of hydroxyl in the allomerization reaction and it is firmly established that a C(13 2 )-CO 2 Me group is required for allomerization to occur. Under identical allomerization conditions, bchl a yields a distribution of products that is different from those given by chl a and bvir. This observation has allowed us to demonstrate that it is the bonding at the C(7)᎐C(8) position of chlorophylls and not the presence of a conjugated carbonyl functionality that influences the reactivity in ring E.
This manuscript represents the view of the Dissolution Working Group of the IQ Consortium on the challenges of and recommendations on solubility measurements and development of dissolution methods for immediate release (IR) solid oral dosage forms formulated with amorphous solid dispersions. Nowadays, numerous compounds populate the industrial pipeline as promising drug candidates yet suffer from low aqueous solubility. In the oral drug product development process, solubility along with permeability is a key determinant to assure sufficient drug absorption along the intestinal tract. Formulating the drug candidate as an amorphous solid dispersion (ASD) is one potential option to address this issue. These formulations demonstrate the rapid onset of drug dissolution and can achieve supersaturated concentrations, which poses significant challenges to appropriately characterize solubility and develop quality control dissolution methods. This review strives to categorize the different dissolution and solubility challenges for ASD associated with 3 different topics: (i) definition of solubility and sink conditions for ASD dissolution, (ii) applications and development of non-sink dissolution (according to conventional definition) for ASD formulation screening and QC method development, and (iii) the advantages and disadvantages of using dissolution in detecting crystallinity in ASD formulations. Related to these challenges, successful examples of dissolution experiments in the context of control strategies are shared and may lead as an example for scientific consensus concerning dissolution testing of ASD.
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