Co-formability, solubility enhancement and stability of olanzapine co-amorphous systems produced with different co-formers

Introduction Strategies to address the problem of poorly water-soluble drugs encompass conversion a crystalline drug into an amorphous form promote its apparent solubility and dissolution. Co-amorphous systems (CAMs) incorporate low molecular mass molecules (co-formers), which are mixed with one single phase [1 Blaabjerg LI, Lindenberg E, Rades T, et al. Influence preparation pathway on glass forming ability. Int J Pharm. 2017;521(1–2):232–239.[Crossref], [PubMed] , [Google Scholar],2 Dengale SJ, Grohganz H, Recent advances in co-amorphous formulations. Adv Drug Deliv Rev. 2016;100:116–125.[Crossref], [PubMed], [Web Science ®] Scholar]]. The aim this study is understand capability different co-formers (amino, carboxylic sulphonic acids), production CAMs olanzapine by ball milling, solvent evaporation quench cooling.Materials methods Mixtures (2 g) (OLZ) each co-former [l-aspartate (ASP); l-tryptophan (TRY); l-arginine (ARG); l-proline (PRO); citric acid (CIT); tartaric (TAR); oxalic (OXA); saccharine (SAC); potassium acessulfame (ACE); cyclamic (CYC)] 1:1 molar ratios were submitted milling (BM), (SE) cooling (QC). evaluated for OLZ increase, co-formability storage stability over time, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) Fourier-transform infra-red spectroscopy (FTIR).Results BM technique presented most promising results followed QC SE (Table 1), since more produced. All acids (SAC, CYC ACE) formed regardless used, presenting complete amorphization probably due their higher ability produce intermolecular interactions, like hydrogen-bonding, thus increasing (more than 8 weeks at 25 °C/11 53% RH). Conversely, amino least efficient producing CAMs. Crystalline (40.1 mg/L) water general increase was observed. Carboxylic (TAR, CIT, OXA) achieved biggest (up 269 times, TART) 199 SAC), unveiling possibility improved dissolution profiles bioavailability. Discussion conclusions: has shown converting entity, particularly when presence stabilise structures formed. In fact, acids, both BM, successfully stabilised obtained. Due noteworthy solubility, resulting from co-amorphization, considered be adequate process active compounds poor such as OLZ.Co-formability, enhancement produced co-formersAll authorsAna C. Bastos, Inês A. Santos, João F. Pinto & Ana I. Fernandeshttps://doi.org/10.1080/07853890.2021.1896099Published online:28 September 2021Table 1. Comparison co-amorphization using techniques co-formers. Download CSVDisplay Table