The Effect of Water Plasticization on the Molecular Mobility and Crystallization Tendency of Amorphous Disaccharides

Heljo, Petteri; Nordberg, Antti; Tenho, Mikko; Virtanen, Tommi; Jouppila, Kirsi; Salonen, Jarno; Maunu, Sirkka Liisa; Juppo, Anne

doi:10.1007/s11095-011-0658-4

Cited by 49 publications

(31 citation statements)

References 36 publications

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“…The presence of extra water in the PVP K12 ASD might have resulted in much lower T g value compared to PVP VA64 ASD. When the PVP K12 ASD was dried to low moisture content and DSC analysis was reconducted, the T g value for PVP K12 ASD increased to 93°C, confirming that absorbed water can lower the T g of an amorphous dispersion due to plasticizing effect similar to the observations made by other researchers (26,27). The dissolution analysis of PVP K12 ASD indicated an increase in compound X release to 70% in simulated intestinal buffer compared to crystalline tablet formulation (Fig.…”

Section: Pvp Containing Amorphous Solid Dispersionssupporting

confidence: 84%

“…The PVP K12 containing ASD was found to be more hygroscopic compared to PVP VA64 containing ASD. A bsorption of excess moisture on stability can negatively impact the physical stability of ASD as the absorbed water can plasticize the system and further reduce the T g of an ASD (26,27). Thus, due to lower bioavailability and physical stability, the PVP K12 containing ASD of compound X was not further studied.…”

Section: Chemical and Physical Stability Assessment Of Amorphous Solimentioning

confidence: 99%

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Hot Melt Extrusion: Development of an Amorphous Solid Dispersion for an Insoluble Drug from Mini-scale to Clinical Scale

2015

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Abstract. The objective of the study was to develop an amorphous solid dispersion (ASD) for an insoluble compound X by hot melt extrusion (HME) process. The focus was to identify material-sparing approaches to develop bioavailable and stable ASD including scale up of HME process using minimal drug. Mixtures of compound X and polymers with and without surfactants or pH modifiers were evaluated by hot stage microscopy (HSM), polarized light microscopy (PLM), and modulated differential scanning calorimetry (mDSC), which enabled systematic selection of ASD components. Formulation blends of compound X with PVP K12 and PVP VA64 polymers were extruded through a 9-mm twin screw mini-extruder. Physical characterization of extrudates by PLM, XRPD, and mDSC indicated formation of single-phase ASD's. Accelerated stability testing was performed that allowed rapid selection of stable ASD's and suitable packaging configurations. Dissolution testing by a discriminating two-step non-sink dissolution method showed 70-80% drug release from prototype ASD's, which was around twofold higher compared to crystalline tablet formulations. The in vivo pharmacokinetic study in dogs showed that bioavailability from ASD of compound X with PVP VA64 was four times higher compared to crystalline tablet formulations. The HME process was scaled up from lab scale to clinical scale using volumetric scale up approach and scale-independent-specific energy parameter. The present study demonstrated systematic development of ASD dosage form and scale up of HME process to clinical scale using minimal drug (∼500 g), which allowed successful clinical batch manufacture of enabled formulation within 7 months.

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Section: Pvp Containing Amorphous Solid Dispersionssupporting

confidence: 84%

Section: Chemical and Physical Stability Assessment Of Amorphous Solimentioning

confidence: 99%

Hot Melt Extrusion: Development of an Amorphous Solid Dispersion for an Insoluble Drug from Mini-scale to Clinical Scale

2015

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“…Moreover, the T g s of the HMPC films were decreased with increases in water content (W c ) because of the plasticizing effects of water in the microstructure (Fig. 10b) (35,36). These changes in physical state and microstructure could affect the thermal and mechanical properties of the polymers.…”

Section: Thermal Behavior Of the Polymer During Dryingmentioning

confidence: 99%

Experimental Studies and Modeling of the Drying Kinetics of Multicomponent Polymer Films

2017

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Abstract.The process of drying thin polymer films is an important operation that influences the film structure and solid state, and the stability of the product. The purpose of this work was to study and model the drying kinetics of multicomponent films based on two polymers: hydroxypropyl methylcellulose (HPMC, amorphous) and polyvinyl alcohol (PVA, semicrystalline). The isothermal drying kinetics of the films at different temperatures (40, 60, and 80°C) were studied using thermo-gravimetric analysis (TGA) and convection oven methods. Solid-state characterization tools used in the study included polarization and hotstage microscopy, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). The drying kinetics of HPMC and PVA films in the TGA apparatus and convection oven were comparable. The three-parameter (W max , τ, n) Hill equation successfully modeled the experimental drying kinetics. The time factor τ in the Hill equation nicely explained two drying phases in the films. Solid-state phase changes occurring in the films during dehydration had a bearing on the drying kinetics and mechanisms. TGA can be used as a simple tool to determine the end points in drying processes using ovens or tunnels. The three-parameter Hill equation explained the drying kinetics and diffusion mechanisms of the solvent through the polymer films for the first time. This study advances our understanding of film drying, in particular for pharmaceutically relevant thin films.

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“…Proteínas e carboidratos são os constituintes principais estruturantes dos alimentos e a interação destes com a água e entre eles na água gover nam a estrutura e as relações entre os constituin tes em alimentos. A função entre a Tg e fração de volume da agua é chamada de função plasticizante (HELJO et al 2012, MATVEEV et al 2000. O comportamento que observa-se aqui consiste na capacidade das moléculas de água Tabela 1 -Temperatura de transição vítrea (Tg) para diferentes produtos …”

Section: Referencial Teóricounclassified

Soro Em Pó: Estado Vítreo E Condições De Operação Do Spray Dryer

et al. 2016

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RESUMOO conhecimento sobre a secagem de soro mudou significativamente nos últimos 20 anos. As indústrias começaram a utilizar em maior escala conhecimentos técnicos e científicos para a produção do soro em pó. Os principais problemas em soro em pó são: a adesão e o empedramento durante a fabricação e estocagem levando a diminuição do rendimento industrial. Estes problemas baseiam-se no controle do estado vítreo durante o processo de secagem e estocagem. Devido a importância da transição vítrea, os parâmetros de operação do spray dryer devem ser ajustados para melhorar o soro em pó. Esta revisão destaca os trabalhos científicos que abordam o impacto destes fatores sobre a secagem do soro. Como conclusão visando a melhoria do processo de secagem de soro recomenda-se que as indústrias: apliquem termohigrômetros para determinar as propriedades do ar, estabeçam a relação entre a atividade de água e a umidade relativa do ar de saída e ajustem os parâmetros de secagem baseados nas propriedades do ar e do soro.Palavras-chave: transição vítrea; diagrama de Mollier; adesão; empedramento. ABSTRACTThe knowledge on spray drying of whey has significantly changed during the last 20 years. Industries started to apply more technical and scientific information for whey powder production. The main problems in whey powder are: sticking and

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The Effect of Water Plasticization on the Molecular Mobility and Crystallization Tendency of Amorphous Disaccharides

Cited by 49 publications

References 36 publications

Hot Melt Extrusion: Development of an Amorphous Solid Dispersion for an Insoluble Drug from Mini-scale to Clinical Scale

Hot Melt Extrusion: Development of an Amorphous Solid Dispersion for an Insoluble Drug from Mini-scale to Clinical Scale

Experimental Studies and Modeling of the Drying Kinetics of Multicomponent Polymer Films

Soro Em Pó: Estado Vítreo E Condições De Operação Do Spray Dryer

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