Poster presented at the 2nd International Congress of CiiEM: “Translational Research and Innovation in Human and Health Sciences”. Egas Moniz, Caparica, Portugal, 11-13 June 2017N/

Bastos, Ana C.

Fernandes, Ana I.

Pinto, João F.

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MATERIALS AND METHODSMixtures of olanzapine and L-arginine and L-tryptophan (1:1) and paroxetin and L-arginine, L-tryptophan, L-proline, L-lysine, L-tyrosineand L-phenylalanine (1:1) were processed by ball milling and quench cooling. The new products were characterized by DifferentialScanning Calorimetry (DSC) in order to identify the formation of co-amorphous between each drug and the amino acid.DSC is a calorimetric analytical technique that looks at how a material’s heat capacity (Cp) is affected by temperature. A sample ofknown mass is heated or/and cooled and the changes in its heat capacity are tracked as changes in the heat flow. This allows thedetection of transitions such as melts (Tm) and glass transitions (Tg).RESULTS AND DISCUSSIONResults have shown that olanzapine seems to be converted into the amorphous state in combination with arginine or tryptophan, eitherby quench cooling, or ball milling (Fig 1 and 2, respectively). Olanzapine alone became amorphous by quench cooling and by millingtoo, like paroxetine. Paroxetine was converted into the amorphous form when in combination with the amino acid L-proline (Fig 3).INTRODUCTIONOrally administered drugs must have sufficient water solubility to ensure that they are absorbed in the gut, as required forbioavailability and therapeutic activity. As the number of poorly water soluble drug molecules entering the clinic rises, the strategiesto enhance solubility also become increasingly important. Conversion of a crystalline drug into the amorphous form is one way toimprove its apparent solubility and dissolution rate (a measure of bioavailability). Unfortunately, the large internal energy andmolecular movement of the molecules in the amorphous state may also cause the material to convert spontaneously back to its stablecrystalline form during processing, storage or dissolution (1,2). Co-amorphous structures containing one, or more, small molecularweight compounds, which are homogenously mixed to form a new entity with a single amorphous phase (2,3), have been shown tostabilize the amorphous form of a drug in the solid state (2). Finding low molecular weight excipients compatible with the model drugmay, however, be challenging (3). In this respect, amino acids have proved their potential to form co-amorphous systems with somedrugs and are the object of the present work (1,2). Different techniques are available to obtain co-amorphous systems, namely ballmilling or quench cooling, since these techniques inflict limited chemical degradation to the drug (1,2).Ana C. Bastos1,2,  João F. Pinto2, Ana I. Fernandes11CiiEM, Instituto Superior de Ciências da Saúde Egas Moniz, Campus Universitário, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal, 2 iMed.ULisboa, Faculdade de Farmácia, Universidade de Lisboa, Avenida Professor Gama Pinto 1649-003 Lisboa, Portugalaifernandes@egasmoniz.edu.ptPRODUCTION OF CO-AMORPHOUS MATERIALS WITH THERAPEUTIC ACTIVITYREFERENCES(1) Lobmann K., Grohganz, H., Laitinen, R., Strachan, C., & Rades, T. Amino acids as co-amorphous stabilizers for poorly water soluble drugs - Part 1: Preparation, stability and dissolution enhancement.Eur J Pharm Biopharm. 2013; 85: 873-81.(2) Dengale, S. J., Grohganz, H., Rades, T., & Löbmann, K. Recent advances in co-amorphous drug formulations. Adv Drug Deliv Rev. 2016; 100: 116-25.(3) Jensen, K. T., Larsen, F. H., Löbmann, K., Rades, T., & Grohganz, H. Influence of variation in molar ratio on co-amorphous drug-amino acid systems. Eur J Pharm Biopharm. 2016; 107: 32-9.ACKNOWLEDGEMENTFundação para a Ciência e a Tecnologia (PTDC/DTP-FTO/1057/2012) is acknowledged for funding.CONCLUSIONThe study has shown that the conversion of crystalline drugs into the amorphous state is dependent on their chemical structures andinteractions with other chemical entities. For the model drugs studied the use of specific amino acids, in combination with theappropriate processing technique, has confirmed the potential to form co-amorphous systems. The use of amino acids seems to be apromising approach, worth to be explored further, provided the right combination (drug:amino acid) and processing technique havebeen identified.Fig 2 – Thermogram of the co-amorphous olanzapine and L-tryptophan produced by ball milling (6h at 650rpm)Fig 1 – Thermogram of the co-amorphous olanzapine and L-arginine produced by quench coolingFig 3 – Thermogram of the co-amorphous paroxetine and L-proline produced directly on the DSC1st run – heating         and cooling2nd run – heating        and coolingRecrystallization events are circled in greenLEGEND TO FIGURESTgTmTgTmTgThermal analysis suggested the presence of co-amorphous species in homogenous mixtures, by the presence of Tg and absence of Tm

Production of co-amorphous materials with therapeutic activity

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Production of co-amorphous materials with therapeutic activity

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