Isolation and characterisation of impurities in adapalene
ABSTRACT Three impurities of structure 2-4 were isolated and characterised during the optimisation of a synthetic procedure to adapalene. Impurity 1 was a by-product of the Friedel-Crafts reaction of adamantanol with 4-bromoanisole. Impurities 3 and 4 were due to side reactions of the final Negishi coupling.
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ABSTRACT: Drug impurity profiling, i.e. identification, structure elucidation and quantitative determination of impurities and degradation products in bulk drug materials and pharmaceutical formulations is one of the most important fields of activities in modern pharmaceutical analysis. The reason for the increased importance of this area is that unidentified, potentially toxic impurities are health hazards and in order to increase the safety of drug therapy, impurities should be identified and determined by selective methods. The number of papers dealing with drug impurity profiling is high and the rate is continuously increasing. The aim of this review is to characterise the state-of-the-art in the field of impurity profiling of drugs based mainly on papers published in the last 5 years. The main areas, discussed in this review are separation and determination of impurities with known structure, off-line and on-line chromatographic – spectroscopic methods for the structure elucidation of impurities and degradation products as well as some selected topics such as impurity issues in compendia, genotoxic impurities and analytical aspects of enantiomeric purity of chiral drugs. The points of view of the selection of papers for the review and their discussion are • papers with interesting chemical background i.e. where the impurities are products of interesting side reactions of the synthesis or products of interesting degradation reactions, and • papers where up to date on-line methods (HPLC-MS, HPLC-NMR, etc.) played predominant role in the structure elucidation.Current Pharmaceutical Analysis 11/2008; 4(4):215-230. DOI:10.2174/157341208786306199 · 0.77 Impact Factor
Article: Spotlight on adapalene.[Show abstract] [Hide abstract]
ABSTRACT: In the field of dermatology, topical retinoids represent a mainstay in acne treatment. Adapalene is a naphthoic acid derivative showing some pharmacological activities similar to the regular retinoids. The drug is used singly or in combination for treating acne and a few other miscellaneous skin disorders. To critically review the pharmacokinetic, pharmacologic aspects and clinical benefits and adverse effects associated with topical adapalene. A systematic literature review was conducted primarily based on PubMed citations. Adapalene shares some biological activities in common with retinoic acid. However, it exhibits distinct physicochemical and binding properties for selective retinoic acid receptors. In acne, adapalene is expected to reduce comedogenesis, expel mature comedones and exert some anti-inflammatory effects. The drug is effective as monotherapy in mild comedonal acne and in combination with benzoyl peroxide for mild-to-moderate inflammatory acne. The safety profile of adapalene is good. Indeed, only discrete to moderate adverse events including erytheme, xerosis, itching and stinging may develop during the early treatment phase. Clinical experience has established that adapalene represents a valuable addition to the other current treatments for acne.Expert Opinion on Drug Metabolism & Toxicology 12/2009; 5(12):1565-75. DOI:10.1517/17425250903386269 · 2.93 Impact Factor
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ABSTRACT: 6[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid (Adapalene®), a synthetic aromatic retinoid specific for RARβ and RARγ receptors, has been prepared utilizing a Pd/C-mediated Suzuki coupling between 6-bromo-2-naphthoic acid and 4-methoxyphenyl boronic acid, followed by introduction of an adamantyl group in the position 3 of the formed 6-(4-methoxyphenyl)-2-naphthoic acid. The interaction of 6-(4-methoxyphenyl)-2-naphthoic acid/ethyl ester and the 3-adamantyl analogs with DNA was studied in aqueous solution at physiological conditions by UV-vis spectroscopy. The calculated binding constants K(ligand-DNA) ranged between 1.1×10(4) M(-1) and 1.1×10(5) M(-1), the higher values corresponding to those of the adamantylated compounds. Molecular modeling studies have emphasized that the intercalative binding of adapalene and its derivatives to DNA is mainly stabilized by hydrophobic interactions related to the presence of the adamantyl group.Bioorganic Chemistry 07/2011; 39(4):151-8. DOI:10.1016/j.bioorg.2011.07.003 · 2.14 Impact Factor