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Musical Rhythms can be modeled in different ways. Usually the models rely on certain temporal divisions and time discretization. We have proposed a generative model based on Deep Reinforcement Learning (Deep RL) that can learn musical... more
Musical Rhythms can be modeled in different ways. Usually the models rely on certain temporal divisions and time discretization. We have proposed a generative model based on Deep Reinforcement Learning (Deep RL) that can learn musical rhythmic patterns without defining temporal structures in advance. In this work we have used the Dr. Squiggles platform, which is an interactive robotic system that generates musical rhythms via interaction, to train a Deep RL agent. The goal of the agent is to learn the rhythmic behavior from an environment with high temporal resolution, and without defining any basic rhythmic pattern for the agent. This means that the agent is supposed to learn rhythmic behavior in an approximated continuous space just via interaction with other rhythmic agents. The results show significant adaptability from the agent and great potential for RL-based models to be used as creative algorithms in musical and creativity applications.
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Excipients are crucial components of most pharmaceutical formulations. In the case of a solid oral dosage formulation containing the salt form of a weakly ionizable drug, excipient selection is critical, as some excipients are known to... more
Excipients are crucial components of most pharmaceutical formulations. In the case of a solid oral dosage formulation containing the salt form of a weakly ionizable drug, excipient selection is critical, as some excipients are known to cause salt disproportionation (conversion of salt to the free form). Therefore, robust formulation design necessitates an in-depth understanding of the factors impacting salt disproportionation during processing or storage as this can negatively impact product quality and performance. To date, there is an incomplete understanding of key excipient properties influencing salt disproportionation. Specifically, the potential roles of amorphous excipient glass transition temperature and excipient hygroscopicity, if any, on salt disproportionation are still not well understood. Furthermore, the relationship between the compression and the extent of salt disproportionation is an unknown factor. Herein, by utilizing various grades of polyvinylpyrrolidone (PVP...
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This work critically evaluates a number of machine learning approaches for predicting the crystallization propensity of active pharmaceutical ingredients using a real-world dataset.
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Caffeine-oxalic acid cocrystal, widely reported to be stable under high humidity, dissociated in the presence of numerous pharmaceutical excipients. In cocrystal-excipient binary systems, the water mediated dissociation reaction occurred... more
Caffeine-oxalic acid cocrystal, widely reported to be stable under high humidity, dissociated in the presence of numerous pharmaceutical excipients. In cocrystal-excipient binary systems, the water mediated dissociation reaction occurred under pharmaceutically relevant storage conditions. Powder X-ray diffractometry was used to identify the dissociated products obtained as a consequence of coformer-excipient interaction. The proposed cocrystal dissociation mechanism involved water sorption, dissolution of cocrystal and excipient in the sorbed water, proton transfer from oxalic acid to the excipient, and formation of metal salts and caffeine hydrate. In compressed tablets with magnesium stearate, the cocrystal dissociation was readily discerned from the appearance of peaks attributable to caffeine hydrate and stearic acid. Neutral excipients provide an avenue to circumvent the risk of water mediated cocrystal dissociation.
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Approximately 50% of solid oral dosage forms utilize salt forms of the active pharmaceutical ingredient (API). A major challenge with the salt form is its tendency to disproportionate to produce the unionized API form, decreasing the... more
Approximately 50% of solid oral dosage forms utilize salt forms of the active pharmaceutical ingredient (API). A major challenge with the salt form is its tendency to disproportionate to produce the unionized API form, decreasing the solubility and negatively impacting product stability. However, many of the factors dictating the tendency of a given salt to undergo disproportionation remain to be elucidated. In particular, the role of the solid-state properties of the salt on the disproportionation reaction is unknown. Herein, various solid forms of a model salt, miconazole mesylate (MM), were evaluated for their tendency to undergo disproportionation when mixed with basic excipients, namely tribasic sodium phosphate dodecahydrate (TSPd) and croscarmellose sodium (CCS), and exposed to moderate relative humidity storage conditions. It was observed that the rate and extent of salt disproportionation were significantly different for the various solid forms of MM. As expected, the amorp...
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Punch sticking is a complex phenomenon influenced primarily by particle size, tooling surface roughness, tooling design, and tooling construction material. When particle and environmental factors are controlled, compaction pressure has a... more
Punch sticking is a complex phenomenon influenced primarily by particle size, tooling surface roughness, tooling design, and tooling construction material. When particle and environmental factors are controlled, compaction pressure has a distinct effect on punch sticking behavior for a given active pharmaceutical ingredient (API). This research focuses on the effect of compaction pressure on punch sticking using five compounds with different sticking propensities. The results collectively show that sticking tends to be more problematic under higher compaction pressures and for more ductile compounds. This is attributed to the greater punch surface coverage by the API and the stronger cohesion of API to the existing API layer on the punch.
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Nanoindentation and atomic force microscopy (AFM) are two surface techniques used to study mechanical and surface properties of solids. One area where these two approaches are not widely employed, however, is the discrimination of... more
Nanoindentation and atomic force microscopy (AFM) are two surface techniques used to study mechanical and surface properties of solids. One area where these two approaches are not widely employed, however, is the discrimination of polymorphs, for which methods such as single crystal XRD, PXRD, spectroscopy, DSC and ss-NMR are more commonly used. The main advantage of the surface techniques is that a single micron-sized crystal is sufficient for analysis. Here we discuss the application of nanoindentation, AFM height imaging and force–distance measurements to distinguish two polymorphs of a pharmaceutical cocrystal containing caffeine and glutaric acid.
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Research Interests: Chemistry, Water, Powder Diffraction, Crystallization, Medicine, and 12 moreSynchrotron Radiation, Micelle, Pharmaceutical Sciences, Temperature, Phase transition, X ray diffraction, Phase Behavior, Hydrate, Polarized Light Microscopy, Liquid Crystalline, Pharmacology and pharmaceutical sciences, and phase diagram
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Adherence of powder onto tablet tooling, known as punch sticking, is one of the tablet manufacturing problems that need to be resolved. An important step toward the resolution of this problem is to quantify sticking propensity of... more
Adherence of powder onto tablet tooling, known as punch sticking, is one of the tablet manufacturing problems that need to be resolved. An important step toward the resolution of this problem is to quantify sticking propensity of different active pharmaceutical ingredients (APIs) and understand physicochemical factors that influence sticking propensity. In this study, mass of adhered material onto a removable upper punch tip as a function of number of compression is used to monitor sticking kinetics of 24 chemically diverse compounds. We have identified a mathematical model suitable for describing punch sticking kinetics of a wide range of compounds. Chemical analyses have revealed significant enrichment of API content in the adhered mass. Based on this large set of data, we have successfully developed a new punch sticking model based on a consideration of the interplay of interaction strength among API, excipient, and punch surface. The model correctly describes the general shape of sticking profile, that is, initial rise in accumulated mass followed by gradual increase to a plateau. It also explains why sometimes sticking is arrested after monolayer coverage of punch surface by API (punch filming), while in other cases, API buildup is observed beyond monolayer coverage.
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Crystalline mesophases, which are commonly classified according to their translational, orientational, and conformational order as liquid crystals, plastic crystals, and conformationally disordered crystals, represent a common state of... more
Crystalline mesophases, which are commonly classified according to their translational, orientational, and conformational order as liquid crystals, plastic crystals, and conformationally disordered crystals, represent a common state of condensed matter. As an intermediate state between crystalline and amorphous materials, crystalline mesophases resemble amorphous materials in relation to their molecular mobility, with the glass transition being their common property, and at the same time possessing a certain degree of translational periodicity (with the exception of nematic phase), with corresponding narrow peaks in X-ray diffraction patterns. For example, plastic crystals, which can be formed both by near-spherical molecules and molecules of lower symmetry, such as planar or chain molecules, can have both extremely sharp X-ray diffraction lines and exhibit glass transition. Fundamentals of structural arrangements in mesophases are compared with several types of disorder in crystalline materials, as well as with short-range ordering in amorphous solids. Main features of the molecular mobility in crystalline mesophases are found to be generally similar to amorphous materials, although some important differences do exist, depending on a particular type of mobility modes involved in relaxation processes. In several case studies reviewed, chemical stability appears to follow the extent of disorder, with the stability of crystalline mesophase found to be intermediate between amorphous (least stable) and crystalline (most stable) materials. Finally, detection of crystalline mesophases during manufacturing of two different types of dosage forms is discussed.
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Crystalline mesophases, which are commonly classified according to their translational, orientational, and conformational order as liquid crystals, plastic crystals, and conformationally disordered crystals, represent a common state of... more
Crystalline mesophases, which are commonly classified according to their translational, orientational, and conformational order as liquid crystals, plastic crystals, and conformationally disordered crystals, represent a common state of condensed matter. As an intermediate state between crystalline and amorphous materials, crystalline mesophases resemble amorphous materials in relation to their molecular mobility, with the glass transition being their common property, and at the same time possessing a certain degree of translational periodicity (with the exception of nematic phase), with corresponding narrow peaks in X-ray diffraction patterns. For example, plastic crystals, which can be formed both by near-spherical molecules and molecules of lower symmetry, such as planar or chain molecules, can have both extremely sharp X-ray diffraction lines and exhibit glass transition. Fundamentals of structural arrangements in mesophases are compared with several types of disorder in crystalline materials, as well as with short-range ordering in amorphous solids. Main features of the molecular mobility in crystalline mesophases are found to be generally similar to amorphous materials, although some important differences do exist, depending on a particular type of mobility modes involved in relaxation processes. In several case studies reviewed, chemical stability appears to follow the extent of disorder, with the stability of crystalline mesophase found to be intermediate between amorphous (least stable) and crystalline (most stable) materials. Finally, detection of crystalline mesophases during manufacturing of two different types of dosage forms is discussed.
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ABSTRACT Simple group contribution methods which incorporate nonadditive, nonconstitutive properties are proposed to predict normal boiling points and melting points for aliphatic, non-hydrogen-bonding compounds. Boiling points and... more
ABSTRACT Simple group contribution methods which incorporate nonadditive, nonconstitutive properties are proposed to predict normal boiling points and melting points for aliphatic, non-hydrogen-bonding compounds. Boiling points and melting points are estimated from the ratio of the enthalpy of transition and the entropy of transition. The enthalpy of transition is assumed to be equal to the summation of group values. The entropy of boiling is estimated using a modification of Trouton's rule, while the entropy of melting is estimated using a modification of Walden's rule. The root mean square errors for the estimation of boiling points and melting points are 14.4 K and 34.3 K, respectively.
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The percent hemolysis induced by various surfactants was determined as a function of the formulation composition and formulation: blood contact time using the dynamic in vitro method of Krzyzaniak et al. (1). The amount of hemolysis... more
The percent hemolysis induced by various surfactants was determined as a function of the formulation composition and formulation: blood contact time using the dynamic in vitro method of Krzyzaniak et al. (1). The amount of hemolysis induced by nonionic surfactant formulations is shown to be relatively low and to increase only slightly with contact time. However, when ionic surfactant formulations are used, hemolysis is shown to increase dramatically with surfactant concentration and to be sigmoidally related to the logarithm of contact time. Since surfactant-induced hemolysis is dependent on both the surfactant concentration and the contact time, intravascular hemolysis must be evaluated using an in vitro method that simulates the intravenous injection site. With this information, hemolytically safe surfactant formulations can be developed for intravenous administration.
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... with an intravenous injection. In an attempt to develop a more physiologically realistic model, Reed and Yalkowsky (1985)first determined that in vitro hemolysis is dependent on the formulation:blood ratio. They developed an ...
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The percent hemolysis induced by various surfactants was determined as a function of the formulation composition and formulation: blood contact time using the dynamic in vitro method of Krzyzaniak et al. (1). The amount of hemolysis... more
The percent hemolysis induced by various surfactants was determined as a function of the formulation composition and formulation: blood contact time using the dynamic in vitro method of Krzyzaniak et al. (1). The amount of hemolysis induced by nonionic surfactant formulations is shown to be relatively low and to increase only slightly with contact time. However, when ionic surfactant formulations are used, hemolysis is shown to increase dramatically with surfactant concentration and to be sigmoidally related to the logarithm of contact time. Since surfactant-induced hemolysis is dependent on both the surfactant concentration and the contact time, intravascular hemolysis must be evaluated using an in vitro method that simulates the intravenous injection site. With this information, hemolytically safe surfactant formulations can be developed for intravenous administration.