127 research outputs found

    Comparative static curing versus dynamic curing on tablet coating structures

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    International audienceCuring is generally required to stabilize film coating from aqueous polymer dispersion. This post-coating drying step is traditionally carried out in static conditions, requiring the transfer of solid dosage forms to an oven. But, curing operation performed directly inside the coating equipment stands for an attractive industrial application. Recently, the use of various advanced physico-chemical characterization techniques i.e., X-ray micro-computed tomography, vibrational spectroscopies (near infrared and Raman) and X-ray microdiffraction, allowed new insights into the film-coating structures of dynamically cured tablets. Dynamic curing end-point was efficiently determined after 4 h. The aim of the present work was to elucidate the influence of curing conditions on film-coating structures. Results demonstrated that 24 h of static curing and 4 h of dynamic curing, both performed at 60 degrees C and ambient relative humidity, led to similar coating layers in terms of drug release properties, porosity, water content, structural rearrangement of polymer chains and crystalline distribution. Furthermore, X-ray microdiffraction measurements pointed out different crystalline coating compositions depending on sample storage time. An aging mechanism might have occur during storage, resulting in the crystallization and the upward migration of cetyl alcohol, coupled to the downward migration of crystalline sodium lauryl sulfate within the coating layer. Interestingly, this new study clearly provided further knowledge into film-coating structures after a curing step and confirmed that curing operation could be performed in dynamic conditions

    Comprehensive study of dynamic curing effect on tablet coating structure

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    International audienceThe dissolution method is still widely used to determine curing end-points to ensure long-term stability of film coatings. Nevertheless, the process of curing has not yet been fully investigated. For the first time, joint techniques were used to elucidate the mechanisms of dynamic curing over time from ethylcellulose (Aquacoat (R))-based coated tablets. X-ray micro-computed tomography (X mu CT), Near Infrared (NIR), and Raman spectroscopies as well as X-ray microdiffraction were employed as non-destructive techniques to perform direct measurements on tablets. All techniques indicated that after a dynamic curing period of 4 h, reproducible drug release can be achieved and no changes in the microstructure of the coating were any longer detected. X mu CT analysis highlighted the reduced internal porosity, while both NIR and Raman measurements showed that spectral information remained unaltered after further curing. X-ray microdiffraction revealed densification of the coating layer with a decrease in the overall coating thickness of about 10 pm as a result of curing. In addition, coating heterogeneity attributed to cetyl alcohol was observed from microscopic images and Raman analysis. This observation was confirmed by X-ray microdiffraction that showed that crystalline cetyl alcohol melted and spread over the coating surface with curing. Prior to curing, X-ray microdiffraction also revealed the existence of two coating zones differing in crystalline cetyl alcohol and sodium lauryl sulfate concentrations which could be explained by migration of these constituents within the coating layer. Therefore, the use of non-destructive techniques allowed new insights into tablet coating structures and provided precise determination of the curing end-point compared to traditional dissolution testing. This thorough study may open up new possibilities for process and formulation control

    Process Analytical Technology : suivi en temps rĂ©el d’une opĂ©ration d’enrobage et de curing et nouvelles avancĂ©es dans la caractĂ©risation du film polymĂšre

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    Implementation of PAT (Process Analytical Technology) approach has recently been promoted by the FDA (Food and Drug Administration) within the pharmaceutical industry. A desired goal of the PAT framework is to enhance understanding and control of the manufacturing process through timely measurements, during processing, to ensure final product quality. Real-time monitoring of a coating operation was performed from in-line Near Infrared (NIR) measurements inside a pan coater. Mass of coating materials, determined by simple and fast weighing but depending on core tablet weight uniformity, and film coating thickness, obtained from accurate and non-destructive Terahertz Pulsed Imaging (TPI) measurements, were used as reference values to calibrate NIR spectral information. In both cases, these two critical quality attributes were predicted with low predictive errors, which were found to be similar. In addition, real-time predictions of drug release from cured tablets were carried out by in-line NIR measurements. The coating operation was successfully stopped when desired dissolution criteria were achieved. A post-coating thermal treatment, known as curing, is generally required to stabilize film coating from aqueous polymer dispersion. Innovative techniques were jointly used to elucidate the underlying mechanisms of film formation along the curing process. This study provided a new insight into the tablet coating structure, highlighting a reduced internal coating porosity, a decrease in water content and showing a better structural rearrangement of polymer chains, with dynamic curing. All investigated techniques confirmed that a stabilized state was reached after a 4 h dynamic curing in comparison with a reference curing carried out in an oven for 24 h. Interestingly even prior to curing, new findings were pointed out, during coated tablets storage, related to the crystallisation and the upward migration of cetyl alcohol, coupled to the downward migration of sodium lauryl sulfate within the coating layer.La mise en place de la dĂ©marche PAT (Process Analytical Technology), initiĂ©e par la FDA (Food and Drug Administration) s’est dĂ©veloppĂ©e au cours de ces derniĂšres annĂ©es, au sein de l’industrie pharmaceutique. GrĂące Ă  des contrĂŽles en continu au coeur des procĂ©dĂ©s de fabrication, elle permet une meilleure comprĂ©hension et une maĂźtrise de la formulation et du procĂ©dĂ©, afin d’assurer la qualitĂ© finale des mĂ©dicaments.A travers ce travail, nous avons mis en place un suivi en temps rĂ©el, par spectroscopie proche infrarouge, d’une opĂ©ration d’enrobage suite Ă  l’intĂ©gration d’une sonde Ă  l’intĂ©rieur d’une turbine d’enrobage. La quantitĂ© d’enrobage, dĂ©terminĂ©e par une simple et rapide pesĂ©e mais nĂ©anmoins soumise Ă  la variabilitĂ© de la masse des comprimĂ©s nus, ainsi que l’épaisseur du film, obtenue avec prĂ©cision par imagerie tĂ©rahertz ont servi de valeurs de rĂ©fĂ©rence pour calibrer l’information spectrale. Dans les deux cas, ces deux attributs qualitĂ© critiques ont Ă©tĂ© prĂ©dits avec de faibles erreurs de prĂ©diction, qui se sont rĂ©vĂ©lĂ©es ĂȘtre similaires. Par ailleurs, la prĂ©diction en temps rĂ©el des propriĂ©tĂ©s de dissolution de comprimĂ©s prĂȘts Ă  ĂȘtre libĂ©rĂ©s, Ă  partir de spectres acquis in-line, a permis de dĂ©terminer l’arrĂȘt optimal de l’opĂ©ration d’enrobage.Suite Ă  un enrobage rĂ©alisĂ© Ă  partir d’une dispersion aqueuse de polymĂšre une Ă©tape supplĂ©mentaire de traitement thermique ou curing est gĂ©nĂ©ralement nĂ©cessaire afin de stabiliser le film d’enrobage. Un travail de caractĂ©risation menĂ© Ă  partir de techniques innovantes a permis d’apporter un nouvel Ă©clairage sur la comprĂ©hension des phĂ©nomĂšnes impliquĂ©s dans la formation du film au cours du curing. La caractĂ©risation approfondie de la structure d’enrobage de comprimĂ©s soumis Ă  un curing en turbine (conditions dynamiques) a mis en Ă©vidence la diminution de la porositĂ©, couplĂ©e Ă  l’évaporation de l’eau et Ă  une meilleure organisation des chaĂźnes de polymĂšre au cours du curing. L’étude de comprimĂ©s soumis Ă  un curing de rĂ©fĂ©rence en Ă©tuve durant 24 h (conditions statiques) a confirmĂ© l’obtention d’un film stable aprĂšs 4 h de curing dynamique. De nouveaux phĂ©nomĂšnes, indĂ©pendants du curing, liĂ©s Ă  la cristallisation et Ă  la migration de l’alcool cĂ©tylique, couplĂ©e Ă  la migration du lauryl sulfate de sodium, au sein de la couche d’enrobage ont Ă©tĂ© dĂ©tectĂ©s au cours de la conservation des comprimĂ©s enrobĂ©s

    Process Analytical Technology : real-time monitoring of coating and curing operation and new insight into polymer film characterisation

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    La mise en place de la dĂ©marche PAT (Process Analytical Technology), initiĂ©e par la FDA (Food and Drug Administration) s’est dĂ©veloppĂ©e au cours de ces derniĂšres annĂ©es, au sein de l’industrie pharmaceutique. GrĂące Ă  des contrĂŽles en continu au coeur des procĂ©dĂ©s de fabrication, elle permet une meilleure comprĂ©hension et une maĂźtrise de la formulation et du procĂ©dĂ©, afin d’assurer la qualitĂ© finale des mĂ©dicaments.A travers ce travail, nous avons mis en place un suivi en temps rĂ©el, par spectroscopie proche infrarouge, d’une opĂ©ration d’enrobage suite Ă  l’intĂ©gration d’une sonde Ă  l’intĂ©rieur d’une turbine d’enrobage. La quantitĂ© d’enrobage, dĂ©terminĂ©e par une simple et rapide pesĂ©e mais nĂ©anmoins soumise Ă  la variabilitĂ© de la masse des comprimĂ©s nus, ainsi que l’épaisseur du film, obtenue avec prĂ©cision par imagerie tĂ©rahertz ont servi de valeurs de rĂ©fĂ©rence pour calibrer l’information spectrale. Dans les deux cas, ces deux attributs qualitĂ© critiques ont Ă©tĂ© prĂ©dits avec de faibles erreurs de prĂ©diction, qui se sont rĂ©vĂ©lĂ©es ĂȘtre similaires. Par ailleurs, la prĂ©diction en temps rĂ©el des propriĂ©tĂ©s de dissolution de comprimĂ©s prĂȘts Ă  ĂȘtre libĂ©rĂ©s, Ă  partir de spectres acquis in-line, a permis de dĂ©terminer l’arrĂȘt optimal de l’opĂ©ration d’enrobage.Suite Ă  un enrobage rĂ©alisĂ© Ă  partir d’une dispersion aqueuse de polymĂšre une Ă©tape supplĂ©mentaire de traitement thermique ou curing est gĂ©nĂ©ralement nĂ©cessaire afin de stabiliser le film d’enrobage. Un travail de caractĂ©risation menĂ© Ă  partir de techniques innovantes a permis d’apporter un nouvel Ă©clairage sur la comprĂ©hension des phĂ©nomĂšnes impliquĂ©s dans la formation du film au cours du curing. La caractĂ©risation approfondie de la structure d’enrobage de comprimĂ©s soumis Ă  un curing en turbine (conditions dynamiques) a mis en Ă©vidence la diminution de la porositĂ©, couplĂ©e Ă  l’évaporation de l’eau et Ă  une meilleure organisation des chaĂźnes de polymĂšre au cours du curing. L’étude de comprimĂ©s soumis Ă  un curing de rĂ©fĂ©rence en Ă©tuve durant 24 h (conditions statiques) a confirmĂ© l’obtention d’un film stable aprĂšs 4 h de curing dynamique. De nouveaux phĂ©nomĂšnes, indĂ©pendants du curing, liĂ©s Ă  la cristallisation et Ă  la migration de l’alcool cĂ©tylique, couplĂ©e Ă  la migration du lauryl sulfate de sodium, au sein de la couche d’enrobage ont Ă©tĂ© dĂ©tectĂ©s au cours de la conservation des comprimĂ©s enrobĂ©s.Implementation of PAT (Process Analytical Technology) approach has recently been promoted by the FDA (Food and Drug Administration) within the pharmaceutical industry. A desired goal of the PAT framework is to enhance understanding and control of the manufacturing process through timely measurements, during processing, to ensure final product quality. Real-time monitoring of a coating operation was performed from in-line Near Infrared (NIR) measurements inside a pan coater. Mass of coating materials, determined by simple and fast weighing but depending on core tablet weight uniformity, and film coating thickness, obtained from accurate and non-destructive Terahertz Pulsed Imaging (TPI) measurements, were used as reference values to calibrate NIR spectral information. In both cases, these two critical quality attributes were predicted with low predictive errors, which were found to be similar. In addition, real-time predictions of drug release from cured tablets were carried out by in-line NIR measurements. The coating operation was successfully stopped when desired dissolution criteria were achieved. A post-coating thermal treatment, known as curing, is generally required to stabilize film coating from aqueous polymer dispersion. Innovative techniques were jointly used to elucidate the underlying mechanisms of film formation along the curing process. This study provided a new insight into the tablet coating structure, highlighting a reduced internal coating porosity, a decrease in water content and showing a better structural rearrangement of polymer chains, with dynamic curing. All investigated techniques confirmed that a stabilized state was reached after a 4 h dynamic curing in comparison with a reference curing carried out in an oven for 24 h. Interestingly even prior to curing, new findings were pointed out, during coated tablets storage, related to the crystallisation and the upward migration of cetyl alcohol, coupled to the downward migration of sodium lauryl sulfate within the coating layer

    Process Analytical Technology : suivi en temps rĂ©el d’une opĂ©ration d’enrobage et de curing et nouvelles avancĂ©es dans la caractĂ©risation du film polymĂšre

    No full text
    Implementation of PAT (Process Analytical Technology) approach has recently been promoted by the FDA (Food and Drug Administration) within the pharmaceutical industry. A desired goal of the PAT framework is to enhance understanding and control of the manufacturing process through timely measurements, during processing, to ensure final product quality. Real-time monitoring of a coating operation was performed from in-line Near Infrared (NIR) measurements inside a pan coater. Mass of coating materials, determined by simple and fast weighing but depending on core tablet weight uniformity, and film coating thickness, obtained from accurate and non-destructive Terahertz Pulsed Imaging (TPI) measurements, were used as reference values to calibrate NIR spectral information. In both cases, these two critical quality attributes were predicted with low predictive errors, which were found to be similar. In addition, real-time predictions of drug release from cured tablets were carried out by in-line NIR measurements. The coating operation was successfully stopped when desired dissolution criteria were achieved. A post-coating thermal treatment, known as curing, is generally required to stabilize film coating from aqueous polymer dispersion. Innovative techniques were jointly used to elucidate the underlying mechanisms of film formation along the curing process. This study provided a new insight into the tablet coating structure, highlighting a reduced internal coating porosity, a decrease in water content and showing a better structural rearrangement of polymer chains, with dynamic curing. All investigated techniques confirmed that a stabilized state was reached after a 4 h dynamic curing in comparison with a reference curing carried out in an oven for 24 h. Interestingly even prior to curing, new findings were pointed out, during coated tablets storage, related to the crystallisation and the upward migration of cetyl alcohol, coupled to the downward migration of sodium lauryl sulfate within the coating layer.La mise en place de la dĂ©marche PAT (Process Analytical Technology), initiĂ©e par la FDA (Food and Drug Administration) s’est dĂ©veloppĂ©e au cours de ces derniĂšres annĂ©es, au sein de l’industrie pharmaceutique. GrĂące Ă  des contrĂŽles en continu au coeur des procĂ©dĂ©s de fabrication, elle permet une meilleure comprĂ©hension et une maĂźtrise de la formulation et du procĂ©dĂ©, afin d’assurer la qualitĂ© finale des mĂ©dicaments.A travers ce travail, nous avons mis en place un suivi en temps rĂ©el, par spectroscopie proche infrarouge, d’une opĂ©ration d’enrobage suite Ă  l’intĂ©gration d’une sonde Ă  l’intĂ©rieur d’une turbine d’enrobage. La quantitĂ© d’enrobage, dĂ©terminĂ©e par une simple et rapide pesĂ©e mais nĂ©anmoins soumise Ă  la variabilitĂ© de la masse des comprimĂ©s nus, ainsi que l’épaisseur du film, obtenue avec prĂ©cision par imagerie tĂ©rahertz ont servi de valeurs de rĂ©fĂ©rence pour calibrer l’information spectrale. Dans les deux cas, ces deux attributs qualitĂ© critiques ont Ă©tĂ© prĂ©dits avec de faibles erreurs de prĂ©diction, qui se sont rĂ©vĂ©lĂ©es ĂȘtre similaires. Par ailleurs, la prĂ©diction en temps rĂ©el des propriĂ©tĂ©s de dissolution de comprimĂ©s prĂȘts Ă  ĂȘtre libĂ©rĂ©s, Ă  partir de spectres acquis in-line, a permis de dĂ©terminer l’arrĂȘt optimal de l’opĂ©ration d’enrobage.Suite Ă  un enrobage rĂ©alisĂ© Ă  partir d’une dispersion aqueuse de polymĂšre une Ă©tape supplĂ©mentaire de traitement thermique ou curing est gĂ©nĂ©ralement nĂ©cessaire afin de stabiliser le film d’enrobage. Un travail de caractĂ©risation menĂ© Ă  partir de techniques innovantes a permis d’apporter un nouvel Ă©clairage sur la comprĂ©hension des phĂ©nomĂšnes impliquĂ©s dans la formation du film au cours du curing. La caractĂ©risation approfondie de la structure d’enrobage de comprimĂ©s soumis Ă  un curing en turbine (conditions dynamiques) a mis en Ă©vidence la diminution de la porositĂ©, couplĂ©e Ă  l’évaporation de l’eau et Ă  une meilleure organisation des chaĂźnes de polymĂšre au cours du curing. L’étude de comprimĂ©s soumis Ă  un curing de rĂ©fĂ©rence en Ă©tuve durant 24 h (conditions statiques) a confirmĂ© l’obtention d’un film stable aprĂšs 4 h de curing dynamique. De nouveaux phĂ©nomĂšnes, indĂ©pendants du curing, liĂ©s Ă  la cristallisation et Ă  la migration de l’alcool cĂ©tylique, couplĂ©e Ă  la migration du lauryl sulfate de sodium, au sein de la couche d’enrobage ont Ă©tĂ© dĂ©tectĂ©s au cours de la conservation des comprimĂ©s enrobĂ©s

    Process Analytical Technology (suivi en temps réel d'une opération d'enrobage et de curing et nouvelles avancées dans la caractérisation du film polymÚre)

    No full text
    La mise en place de la dĂ©marche PAT (Process Analytical Technology), initiĂ©e par la FDA (Food and Drug Administration) s est dĂ©veloppĂ©e au cours de ces derniĂšres annĂ©es, au sein de l industrie pharmaceutique. GrĂące Ă  des contrĂŽles en continu au coeur des procĂ©dĂ©s de fabrication, elle permet une meilleure comprĂ©hension et une maĂźtrise de la formulation et du procĂ©dĂ©, afin d assurer la qualitĂ© finale des mĂ©dicaments.A travers ce travail, nous avons mis en place un suivi en temps rĂ©el, par spectroscopie proche infrarouge, d une opĂ©ration d enrobage suite Ă  l intĂ©gration d une sonde Ă  l intĂ©rieur d une turbine d enrobage. La quantitĂ© d enrobage, dĂ©terminĂ©e par une simple et rapide pesĂ©e mais nĂ©anmoins soumise Ă  la variabilitĂ© de la masse des comprimĂ©s nus, ainsi que l Ă©paisseur du film, obtenue avec prĂ©cision par imagerie tĂ©rahertz ont servi de valeurs de rĂ©fĂ©rence pour calibrer l information spectrale. Dans les deux cas, ces deux attributs qualitĂ© critiques ont Ă©tĂ© prĂ©dits avec de faibles erreurs de prĂ©diction, qui se sont rĂ©vĂ©lĂ©es ĂȘtre similaires. Par ailleurs, la prĂ©diction en temps rĂ©el des propriĂ©tĂ©s de dissolution de comprimĂ©s prĂȘts Ă  ĂȘtre libĂ©rĂ©s, Ă  partir de spectres acquis in-line, a permis de dĂ©terminer l arrĂȘt optimal de l opĂ©ration d enrobage.Suite Ă  un enrobage rĂ©alisĂ© Ă  partir d une dispersion aqueuse de polymĂšre une Ă©tape supplĂ©mentaire de traitement thermique ou curing est gĂ©nĂ©ralement nĂ©cessaire afin de stabiliser le film d enrobage. Un travail de caractĂ©risation menĂ© Ă  partir de techniques innovantes a permis d apporter un nouvel Ă©clairage sur la comprĂ©hension des phĂ©nomĂšnes impliquĂ©s dans la formation du film au cours du curing. La caractĂ©risation approfondie de la structure d enrobage de comprimĂ©s soumis Ă  un curing en turbine (conditions dynamiques) a mis en Ă©vidence la diminution de la porositĂ©, couplĂ©e Ă  l Ă©vaporation de l eau et Ă  une meilleure organisation des chaĂźnes de polymĂšre au cours du curing. L Ă©tude de comprimĂ©s soumis Ă  un curing de rĂ©fĂ©rence en Ă©tuve durant 24 h (conditions statiques) a confirmĂ© l obtention d un film stable aprĂšs 4 h de curing dynamique. De nouveaux phĂ©nomĂšnes, indĂ©pendants du curing, liĂ©s Ă  la cristallisation et Ă  la migration de l alcool cĂ©tylique, couplĂ©e Ă  la migration du lauryl sulfate de sodium, au sein de la couche d enrobage ont Ă©tĂ© dĂ©tectĂ©s au cours de la conservation des comprimĂ©s enrobĂ©s.Implementation of PAT (Process Analytical Technology) approach has recently been promoted by the FDA (Food and Drug Administration) within the pharmaceutical industry. A desired goal of the PAT framework is to enhance understanding and control of the manufacturing process through timely measurements, during processing, to ensure final product quality. Real-time monitoring of a coating operation was performed from in-line Near Infrared (NIR) measurements inside a pan coater. Mass of coating materials, determined by simple and fast weighing but depending on core tablet weight uniformity, and film coating thickness, obtained from accurate and non-destructive Terahertz Pulsed Imaging (TPI) measurements, were used as reference values to calibrate NIR spectral information. In both cases, these two critical quality attributes were predicted with low predictive errors, which were found to be similar. In addition, real-time predictions of drug release from cured tablets were carried out by in-line NIR measurements. The coating operation was successfully stopped when desired dissolution criteria were achieved. A post-coating thermal treatment, known as curing, is generally required to stabilize film coating from aqueous polymer dispersion. Innovative techniques were jointly used to elucidate the underlying mechanisms of film formation along the curing process. This study provided a new insight into the tablet coating structure, highlighting a reduced internal coating porosity, a decrease in water content and showing a better structural rearrangement of polymer chains, with dynamic curing. All investigated techniques confirmed that a stabilized state was reached after a 4 h dynamic curing in comparison with a reference curing carried out in an oven for 24 h. Interestingly even prior to curing, new findings were pointed out, during coated tablets storage, related to the crystallisation and the upward migration of cetyl alcohol, coupled to the downward migration of sodium lauryl sulfate within the coating layer.PARIS11-SCD-Bib. Ă©lectronique (914719901) / SudocSudocFranceF

    Plateau technique de synthÚses et de caractérisations physico-chimiques de matériaux

    No full text
    Journées Scientifiques et technologiques GabÚs/CÎtes dÁrmor ; 2 pages; GabÚs (Tunisie); 7-9 mai 200
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