The amorphization of the readily crystallizable therapeutic ingredient and food additive, menthol... more The amorphization of the readily crystallizable therapeutic ingredient and food additive, menthol, was successfully achieved by inclusion of neat menthol in mesoporous silica matrixes of 3.2 and 5.9 nm size pores. Menthol amorphization was confirmed by the calorimetric detection of a glass transition. The respective glass transition temperature, Tg = -54.3 °C, is in good agreement with the one predicted by the composition dependence of the Tg values determined for menthol:flurbiprofen therapeutic deep eutectic solvents (THEDESs). Nonisothermal crystallization was never observed for neat menthol loaded into silica hosts, which can indicate that menthol rests as a full amorphous/supercooled material inside the pores of the silica matrixes. Menthol mobility was probed by dielectric relaxation spectroscopy, which allowed to identify two relaxation processes in both pore sizes: a faster one associated with mobility of neat-like menthol molecules (α-process), and a slower, dominant one due to the hindered mobility of menthol molecules adsorbed at the inner pore walls (S-process). The fraction of molecular population governing the α-process is greater in the higher (5.9 nm) pore size matrix, although in both cases the S-process is more intense than the α-process. A dielectric glass transition temperature was estimated for each α (Tg,dielc(α)) and S (Tg,dielc(S)) molecular population from the temperature dependence of the relaxation times to 100 s. While Tg,dielc(α) agrees better with the value obtained from the linearization of the Fox equation assuming ideal behavior of the menthol:flurbiprofen THEDES, Tg,dielc(S) is close to the value determined by calorimetry for the silica composites due to a dominance of the adsorbed population inside the pores. Nevertheless, the greater fraction of more mobile bulk-like molecules in the 5.9 nm pore size matrix seems to determine the faster drug release at initial times relative to the 3.2 nm composite. However, the latter inhibits crystallization inside pores since its dimensions are inferior to menthol critical size for nucleation. This points to a suitability of these composites as drug delivery systems in which the drug release profile can be controlled by tuning the host pore size.
Page 1. Molecular motions in solid chloropentamethylbenzene: A thermally stimulated depolarisatio... more Page 1. Molecular motions in solid chloropentamethylbenzene: A thermally stimulated depolarisation currents study Nata lia T. Correia, Joa8o M. Campos and Joaquim J. Moura-Ramos* Centro Complexo I, IST , Av. Rovisco ...
... experiment. In this context, we showed how to calculate the temperature variation of the Debo... more ... experiment. In this context, we showed how to calculate the temperature variation of the Deborah number, D, associated with a TSDC peak, and concluded that, at the maximum of the peak, the value of D should be unity. This ...
The significance of the amorphous state in pharmaceuti-cal systems has been underlined in relativ... more The significance of the amorphous state in pharmaceuti-cal systems has been underlined in relatively recent works (1,2). The time scales of molecular motions are necessary to effectively characterize the properties of amorphous pharma-ceutical solids (3,4). The fragility index ...
It is well known that the dissolution rate and therapeutic activity of a drug depend on its physi... more It is well known that the dissolution rate and therapeutic activity of a drug depend on its physical state and, particu-larly, on its degree of crystallinity. The significance of the amorphous state in pharmaceutical systems has been under-lined in recent works (1,2). A disordered ...
The present paper focuses on the high temperature form I of caffeine and on its low temperature m... more The present paper focuses on the high temperature form I of caffeine and on its low temperature metastable form. Structural, dynamic, and kinetic information has been obtained by X-ray, dielectric, and calorimetric investigations. This study shows the following features: (1) The high temperature phase (I) of caffeine is in a state of dynamically orientationally disordered crystalline state (so-called "plastic, or rotator, phase"). (2) This high-symmetry hexagonal phase can be maintained at low temperature in a metastable situation. (3) Under deep undercooling of form I a glass transition occurs in the disordered crystalline state near room temperature. It is associated with the orientational freezing in of the molecular motions. Otherwise stated, the metastable state I enters into a nonergodic unstable state, so-called "glassy crystal" state. These findings rationalize the difficulties seen with caffeine in pharmaceutical science.
Page 1. Polymer International 33 (1994) 293-302 Molecular Motions in Poly(viny1 acetate) Revisite... more Page 1. Polymer International 33 (1994) 293-302 Molecular Motions in Poly(viny1 acetate) Revisited. A Thermally Stimulated Current Study Ana B. Dias," Natalia T. Correia," Joaquim J. Moura-Ramosa* & Anabela C. Fernandesb ...
Acta Crystallographica Section B Structural Science, 2005
The high-temperature phase I of anhydrous caffeine was obtained by heating and annealing the puri... more The high-temperature phase I of anhydrous caffeine was obtained by heating and annealing the purified commercial form II at 450 K. This phase I can be maintained at low temperature in a metastable state. A powder X-ray diffraction pattern was recorded at 278 K with a laboratory diffractometer equipped with an INEL curved position-sensitive detector CPS120. Phase I is dynamically orientationally disordered (the so-called plastic phase). The Rietveld refinements were achieved with rigid-body constraints. It was assumed that on each site, a molecule can adopt three preferential orientations with equal occupation probability. Under a deep undercooling of phase I, below 250 K, the metastable state enters in a glassy crystal state.
The journal of physical chemistry. B, Jan 27, 2006
Molecular mobility in crystalline anhydrous caffeine was studied by the dielectric technique of t... more Molecular mobility in crystalline anhydrous caffeine was studied by the dielectric technique of thermally stimulated depolarization currents (TSDC). Two relaxational processes were found, one appearing at approximately -10 degrees C that is ascribed to a reorientational glass transition, and a higher temperature one that probably arises from local molecular motions that are precursors of diffusion and sublimation. The experimental results suggest that both crystalline phases II and I of caffeine, that have distinct crystal structures, are solid rotator phases. Furthermore, this dynamic reorientational disorder shows a reorientational glass transition at the same temperature in phase II and in metastable phase I.
The amorphization of the readily crystallizable therapeutic ingredient and food additive, menthol... more The amorphization of the readily crystallizable therapeutic ingredient and food additive, menthol, was successfully achieved by inclusion of neat menthol in mesoporous silica matrixes of 3.2 and 5.9 nm size pores. Menthol amorphization was confirmed by the calorimetric detection of a glass transition. The respective glass transition temperature, Tg = -54.3 °C, is in good agreement with the one predicted by the composition dependence of the Tg values determined for menthol:flurbiprofen therapeutic deep eutectic solvents (THEDESs). Nonisothermal crystallization was never observed for neat menthol loaded into silica hosts, which can indicate that menthol rests as a full amorphous/supercooled material inside the pores of the silica matrixes. Menthol mobility was probed by dielectric relaxation spectroscopy, which allowed to identify two relaxation processes in both pore sizes: a faster one associated with mobility of neat-like menthol molecules (α-process), and a slower, dominant one due to the hindered mobility of menthol molecules adsorbed at the inner pore walls (S-process). The fraction of molecular population governing the α-process is greater in the higher (5.9 nm) pore size matrix, although in both cases the S-process is more intense than the α-process. A dielectric glass transition temperature was estimated for each α (Tg,dielc(α)) and S (Tg,dielc(S)) molecular population from the temperature dependence of the relaxation times to 100 s. While Tg,dielc(α) agrees better with the value obtained from the linearization of the Fox equation assuming ideal behavior of the menthol:flurbiprofen THEDES, Tg,dielc(S) is close to the value determined by calorimetry for the silica composites due to a dominance of the adsorbed population inside the pores. Nevertheless, the greater fraction of more mobile bulk-like molecules in the 5.9 nm pore size matrix seems to determine the faster drug release at initial times relative to the 3.2 nm composite. However, the latter inhibits crystallization inside pores since its dimensions are inferior to menthol critical size for nucleation. This points to a suitability of these composites as drug delivery systems in which the drug release profile can be controlled by tuning the host pore size.
Page 1. Molecular motions in solid chloropentamethylbenzene: A thermally stimulated depolarisatio... more Page 1. Molecular motions in solid chloropentamethylbenzene: A thermally stimulated depolarisation currents study Nata lia T. Correia, Joa8o M. Campos and Joaquim J. Moura-Ramos* Centro Complexo I, IST , Av. Rovisco ...
... experiment. In this context, we showed how to calculate the temperature variation of the Debo... more ... experiment. In this context, we showed how to calculate the temperature variation of the Deborah number, D, associated with a TSDC peak, and concluded that, at the maximum of the peak, the value of D should be unity. This ...
The significance of the amorphous state in pharmaceuti-cal systems has been underlined in relativ... more The significance of the amorphous state in pharmaceuti-cal systems has been underlined in relatively recent works (1,2). The time scales of molecular motions are necessary to effectively characterize the properties of amorphous pharma-ceutical solids (3,4). The fragility index ...
It is well known that the dissolution rate and therapeutic activity of a drug depend on its physi... more It is well known that the dissolution rate and therapeutic activity of a drug depend on its physical state and, particu-larly, on its degree of crystallinity. The significance of the amorphous state in pharmaceutical systems has been under-lined in recent works (1,2). A disordered ...
The present paper focuses on the high temperature form I of caffeine and on its low temperature m... more The present paper focuses on the high temperature form I of caffeine and on its low temperature metastable form. Structural, dynamic, and kinetic information has been obtained by X-ray, dielectric, and calorimetric investigations. This study shows the following features: (1) The high temperature phase (I) of caffeine is in a state of dynamically orientationally disordered crystalline state (so-called "plastic, or rotator, phase"). (2) This high-symmetry hexagonal phase can be maintained at low temperature in a metastable situation. (3) Under deep undercooling of form I a glass transition occurs in the disordered crystalline state near room temperature. It is associated with the orientational freezing in of the molecular motions. Otherwise stated, the metastable state I enters into a nonergodic unstable state, so-called "glassy crystal" state. These findings rationalize the difficulties seen with caffeine in pharmaceutical science.
Page 1. Polymer International 33 (1994) 293-302 Molecular Motions in Poly(viny1 acetate) Revisite... more Page 1. Polymer International 33 (1994) 293-302 Molecular Motions in Poly(viny1 acetate) Revisited. A Thermally Stimulated Current Study Ana B. Dias," Natalia T. Correia," Joaquim J. Moura-Ramosa* & Anabela C. Fernandesb ...
Acta Crystallographica Section B Structural Science, 2005
The high-temperature phase I of anhydrous caffeine was obtained by heating and annealing the puri... more The high-temperature phase I of anhydrous caffeine was obtained by heating and annealing the purified commercial form II at 450 K. This phase I can be maintained at low temperature in a metastable state. A powder X-ray diffraction pattern was recorded at 278 K with a laboratory diffractometer equipped with an INEL curved position-sensitive detector CPS120. Phase I is dynamically orientationally disordered (the so-called plastic phase). The Rietveld refinements were achieved with rigid-body constraints. It was assumed that on each site, a molecule can adopt three preferential orientations with equal occupation probability. Under a deep undercooling of phase I, below 250 K, the metastable state enters in a glassy crystal state.
The journal of physical chemistry. B, Jan 27, 2006
Molecular mobility in crystalline anhydrous caffeine was studied by the dielectric technique of t... more Molecular mobility in crystalline anhydrous caffeine was studied by the dielectric technique of thermally stimulated depolarization currents (TSDC). Two relaxational processes were found, one appearing at approximately -10 degrees C that is ascribed to a reorientational glass transition, and a higher temperature one that probably arises from local molecular motions that are precursors of diffusion and sublimation. The experimental results suggest that both crystalline phases II and I of caffeine, that have distinct crystal structures, are solid rotator phases. Furthermore, this dynamic reorientational disorder shows a reorientational glass transition at the same temperature in phase II and in metastable phase I.
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