Vlachou M et al. Antitubercular Adamantane Derivatives … Drug Res Original Article Thieme Introduction Tuberculosis (TB) is a highly infectious disease, caused by the path- ogen Mycobacterium tuberculosis (Mtb), which is one of the most serious public health issues nowadays. TB mostly afects develop- ing nations, especially in Africa and Asia, where the highest inci- dence of the disease has been recorded [1, 2]. In recent years a wide range of factors has led to the resurgence of TB. The causative path- ogen Mtb aficts more frequently patients with weakened immune system and thus, TB is signifcantly hazardous to those who sufer from the human immune defciency virus (HIV) [3–7]. Poor patient compliance due to the long treatment regimen (6–9 months) has resulted in emergence of both multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. In addition, the high cost of conventional therapy constitutes a serious problem. Hence, it is obvious that there is an imperative need to design new agents with antitubercular activity in order not only to tackle the resistant strains of Mtb, but also to reduce the therapy period [3–7]. Adamantan-2-yl- N'-[( E )-3,7-dimethyl-octa-2,6-dienyl] ethane-1,2-diamine (SQ109) is a promising drug candidate with an- titubercular activity against drug-resistant strains of Mtb (▶ Fig. 1). This drug candidate is considered to be an antagonist of the my- colic acid transporter, MmpL3, and as a result SQ109 inhibits the cell wall synthesis [8–10]. MmpL3 is a RND (Resistance, Nodulation and Division) transporter, which is required for the transport of my- In vitro Controlled Release of two new Tuberculocidal Adaman- tane Aminoethers from Solid Pharmaceutical Formulations (II) Authors Marilena Vlachou 1 , Angeliki Siamidi 1 , Dimitrios Spaneas 1 , Dimitrios Lentzos 1 , Polixeni Ladia 1 , Konstantina Anastasiou 1 , Ioannis Papanastasiou 2 , Angeliki-Sofa Foscolos 2 , Markos-Orestis Georgiadis 2 , Vangelis Karalis 1 , Tahsin Kellici 3 , Thomas Mavromoustakos 3 Afliations 1 School of Health Sciences, Department of Pharmacy, Section of Pharmaceutical Technology, National and Kapodistrian University of Athens, University Campus, Athens, Greece 2 School of Health Sciences, Department of Pharmacy, Section of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, University Campus, Athens, Greece 3 Department of Chemistry, Laboratory of Organic Chemistry, National and Kapodistrian University of Athens, University Campus, Athens, Greece Key words adamantane aminoethers, tuberculosis, matrix tablet formulations, in vitro release received 10.04.2017 accepted 18.06.2017 Bibliography DOI https://doi.org/10.1055/s-0043-114012 Published online: 2017 Drug Res © Georg Thieme Verlag KG Stuttgart · New York ISSN 2194-9379 Correspondence Marilena Vlachou School of Health Sciences Department of Pharmacy Section of Pharmaceutical Technology National and Kapodistrian University of Athens Panepistimioupoli-Zografou 15784, Athens Greece Tel.: + 30/210/7274 674, Fax: + 30/210/7274 674 vlachou@pharm.uoa.gr AbSTrAcT The aim of the present investigation was to develop matrix tablet formulations for the in vitro controlled release of two new tuberculocidal adamantane aminoethers (compounds III and IV), congeneric to the adamantane derivative SQ109, which is in fnal clinical trials, and aminoethers (I) and (II), using care- fully selected excipients, such as polyvinylpyrrolidone, sodium alginate and lactose. The tablets were prepared using the direct compression method and dissolution experiments were con- ducted using the US Pharmacopoeia type II apparatus (paddle method) in gastric and intestinal fuids. The results suggest that both analogues, albeit more lipophilic than SQ109, and ami- noethers (I) and (II), have the requisite in vitro release charac- teristics for oral administration. In conclusion, these formula- tions merit further assessment by conducting in vivo studies, at a later stage. Downloaded by: Cornell. Copyrighted material.