1,720,999 research outputs found
Ointments: towards the understanding of structure, stability and processing
No full textThe majority of the research on dermatological products and excipients was conducted before the 1980’s. Since then, the analytical techniques have significantly improved. Despite this increase in investigational possibilities, there is hardly any recent innovation in dermatological products. It is expected that a more thorough understanding of the physical properties of excipients and formulations will eventually lead to dermatological product innovation. For one of the major ointment excipients, petrolatum (or Vaseline®), the critical properties were studied, such as its consistency. Synchrotron small- and wide-angle X-ray scattering, pulsed NMR, microscopy and rheometry were used to elucidate the petrolatum structure on nano-, micro- and macrometer scale. The combination of these techniques shows that petrolatum is composed of 21 % solid material at room temperature. This solid fraction consists of lamellar sheets which are packed in stacks. These lamellar sheets are formed during cooling. The rheological differences in petrolatum can be explained by the number of lamellar stacks present. When more lamellar stacks are present, the petrolatum is more rigid. Furthermore, the influence of individual variables in the production process on ointment yield stress, a measure for spreadability, was studied. A design of experiments (DoE) approach was used. It was shown that by varying parameters in the production process substantial differences in the yield stress of the ointment were observed. Only 5 of the 14 produced batches were within the pre-defined requirements for yield stress. It was found that mixing rate and filling temperature significantly influence ointment yield stress (p = 0.0013 and 0.0065 respectively). The outcomes of this study were subsequently evaluated on industrial production scale. Similar impact of ointment filling temperature on product yield stress was found. Additionally, the chemical stability of a corticosteroid, triamcinolone acetonide (TCA) in an ointment formulation was studied. The degradation mechanism of TCA and similar corticosteroids was elucidated. Interestingly, it is shown that the ointment excipients lanolin and petrolatum influence TCA degradation significantly. Lanolin and petrolatum contain small traces (few ppm) of metals such as copper, iron and nickel. These metals were shown to accumulate in the propyleneglycol phase in the ointment formulation. This is the phase in which TCA resides. The increase in trace metal content causes a significant increase in TCA degradation. Furthermore, the degradation pathway for TCA was elucidated. The alcohol group in the 20-keto-21-hydroxyl sidechain of TCA first oxidizes to an aldehyde. This compound subsequently degrades to four other degradation products. Interestingly, the 20-keto-21-hydroxyl side chain is not unique for TCA but rather common for corticosteroids. Therefore, hydrocortisone (HC), desoximethasone (DS) and TCA were studied likewise. These all have the C17 bound 20-keto-21-hydroxyl group in common. However, in addition to the 20-keto-21-hydroxyl group, different groups are bound to this C17 atom. It was shown that this group influences both the qualitative and the quantitative degradation of these corticosteroids. In general, seven degradation products are formed for these corticosteroids. Especially HC was shown to degrade into the largest variety of degradation products (five in total) and generally showed the highest degradation constants
Ointments: towards the understanding of structure, stability and processing
No full textThe majority of the research on dermatological products and excipients was conducted before the 1980’s. Since then, the analytical techniques have significantly improved. Despite this increase in investigational possibilities, there is hardly any recent innovation in dermatological products. It is expected that a more thorough understanding of the physical properties of excipients and formulations will eventually lead to dermatological product innovation. For one of the major ointment excipients, petrolatum (or Vaseline®), the critical properties were studied, such as its consistency. Synchrotron small- and wide-angle X-ray scattering, pulsed NMR, microscopy and rheometry were used to elucidate the petrolatum structure on nano-, micro- and macrometer scale. The combination of these techniques shows that petrolatum is composed of 21 % solid material at room temperature. This solid fraction consists of lamellar sheets which are packed in stacks. These lamellar sheets are formed during cooling. The rheological differences in petrolatum can be explained by the number of lamellar stacks present. When more lamellar stacks are present, the petrolatum is more rigid. Furthermore, the influence of individual variables in the production process on ointment yield stress, a measure for spreadability, was studied. A design of experiments (DoE) approach was used. It was shown that by varying parameters in the production process substantial differences in the yield stress of the ointment were observed. Only 5 of the 14 produced batches were within the pre-defined requirements for yield stress. It was found that mixing rate and filling temperature significantly influence ointment yield stress (p = 0.0013 and 0.0065 respectively). The outcomes of this study were subsequently evaluated on industrial production scale. Similar impact of ointment filling temperature on product yield stress was found. Additionally, the chemical stability of a corticosteroid, triamcinolone acetonide (TCA) in an ointment formulation was studied. The degradation mechanism of TCA and similar corticosteroids was elucidated. Interestingly, it is shown that the ointment excipients lanolin and petrolatum influence TCA degradation significantly. Lanolin and petrolatum contain small traces (few ppm) of metals such as copper, iron and nickel. These metals were shown to accumulate in the propyleneglycol phase in the ointment formulation. This is the phase in which TCA resides. The increase in trace metal content causes a significant increase in TCA degradation. Furthermore, the degradation pathway for TCA was elucidated. The alcohol group in the 20-keto-21-hydroxyl sidechain of TCA first oxidizes to an aldehyde. This compound subsequently degrades to four other degradation products. Interestingly, the 20-keto-21-hydroxyl side chain is not unique for TCA but rather common for corticosteroids. Therefore, hydrocortisone (HC), desoximethasone (DS) and TCA were studied likewise. These all have the C17 bound 20-keto-21-hydroxyl group in common. However, in addition to the 20-keto-21-hydroxyl group, different groups are bound to this C17 atom. It was shown that this group influences both the qualitative and the quantitative degradation of these corticosteroids. In general, seven degradation products are formed for these corticosteroids. Especially HC was shown to degrade into the largest variety of degradation products (five in total) and generally showed the highest degradation constants
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
New Insights into Drug Absorption from Oil Depots
No full textSustained delivery formulations are used in order to prolong the pharmacological activity of a drug. A commonly used parenteral sustained delivery formulation is an oil depot which consists of a solution of lipophilic molecules in a vegetable oil. These are normally administered either intramuscularly (i.m.) or subcutaneously (s.c.). The idea of the formulation approach is that a substance that is far better soluble in oil than in water tends to stay in the oil phase. The exact mechanism of drug absorption from these formulations is not fully understood however. The aim of this dissertation was to obtain more understanding about the way a drug is absorbed from an oil depot into the human body. It is generally assumed that the drug release from the oil is mainly determined by the substance’s partition coefficient, i.e. the ratio between lipid and aqueous solubilities of the drug. In the human body, the aqueous phase is represented by the interstitial fluid, which is located between cell tissue at the site of injection. Logically, the higher the affinity for oil, the lower the tendency a drug will have to leave the oil phase. Consequently, a more pronounced sustained drug release is obtained by an increase of the drugs lipophilicity (i.e. higher partition coefficient). A drug can be made more lipophilic through esterification of the molecule with a fatty acid. This esterified compound is inactive as such and is therefore referred to as prodrug. After release from the oil it is activated by hydrolysis, resulting in the so-called parent compound or active substance, which is responsible for the pharmacological effect. The papers that have been published until now can be distinguished into two different focus points: On the one hand, in vitro models examined the prodrug release from the oil depot, which is basically nothing else than a diffusion process through an interface. On the other hand, other studies focused mainly on the pharmacokinetic profiles, i.e. the plasma concentrations of the parent compound. Clearly, the appearance of the parent compound in the blood stream must be considered as a result of a sequence of steps including release out of the oil, hydrolysis of the prodrug and transport to the central circulation. These steps, i.e. the exact fate of the prodrug once released from the oil depot has remained relatively uninvestigated. Therefore, the specific aim of this dissertation is to assess what happens with the prodrug once it is released out of the oil depot. In my dissertation, it is presented what the new insights are of drug absorption from oil depots. It has been examined what the role of the excipient benzyl alcohol was on the absorption of nandrolone and how the oil is distributed over the injection site. Finally, I have studied where activation of the inactive drugs takes place in the body. These fundamental aspects on drug absorption from oil depots are relevant for the therapeutic efficacy in patients
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Tumor targeted drug delivery: fate of the encapsulated and released drug
No full textIn this research the selective delivery of drug by liposomes to solid tumors as compared to healthy tissues is studied. Liposomes are small spheres (typically about 30-500 nm in diameter and preferably about 200 nm or less) in which drugs can be encapsulated. As long as the drug is encapsulated it cannot cause toxic and therapeutic effects. The drug has to be released from the liposomes to do so. Therefore, knowledge of the individual encapsulated and released drug concentrations is essential to understand and improve drug delivery by liposomes. While such individual concentrations in plasma have been reported, these are rarely measured in tumor and healthy tissues due to practical complications. In this study, such individual concentrations in murine blood and tissues were measured by using liposomes containing prednisolone phosphate as a model formulation. The rapid conversion of prednisolone phosphate into prednisolone after release of prednisolone phosphate from the liposomes enables the separate quantification of encapsulated and released drug, respectively. The corresponding analytical methodology was appropriately developed and validated to obtain reliable results. Implementation of the methodology shows that, from a quantitative point of view, the availability of released drug in the tumor is not pronounced as compared to the liver, spleen and kidneys. However, extended drug release is observed in the tumor and probably contributes to the beneficial effect. The probably rapid redistribution of prednisolone from the tissues after drug release from the liposomes highlights the impact of the properties of the drug compound itself on the liposomal drug delivery effect. It is therefore suggested that, from a pharmacodynamic point of view, further research should focus on released drug concentrations instead of the drug release
New Insights into Drug Absorption from Oil Depots
No full textSustained delivery formulations are used in order to prolong the pharmacological activity of a drug. A commonly used parenteral sustained delivery formulation is an oil depot which consists of a solution of lipophilic molecules in a vegetable oil. These are normally administered either intramuscularly (i.m.) or subcutaneously (s.c.). The idea of the formulation approach is that a substance that is far better soluble in oil than in water tends to stay in the oil phase. The exact mechanism of drug absorption from these formulations is not fully understood however. The aim of this dissertation was to obtain more understanding about the way a drug is absorbed from an oil depot into the human body. It is generally assumed that the drug release from the oil is mainly determined by the substance’s partition coefficient, i.e. the ratio between lipid and aqueous solubilities of the drug. In the human body, the aqueous phase is represented by the interstitial fluid, which is located between cell tissue at the site of injection. Logically, the higher the affinity for oil, the lower the tendency a drug will have to leave the oil phase. Consequently, a more pronounced sustained drug release is obtained by an increase of the drugs lipophilicity (i.e. higher partition coefficient). A drug can be made more lipophilic through esterification of the molecule with a fatty acid. This esterified compound is inactive as such and is therefore referred to as prodrug. After release from the oil it is activated by hydrolysis, resulting in the so-called parent compound or active substance, which is responsible for the pharmacological effect. The papers that have been published until now can be distinguished into two different focus points: On the one hand, in vitro models examined the prodrug release from the oil depot, which is basically nothing else than a diffusion process through an interface. On the other hand, other studies focused mainly on the pharmacokinetic profiles, i.e. the plasma concentrations of the parent compound. Clearly, the appearance of the parent compound in the blood stream must be considered as a result of a sequence of steps including release out of the oil, hydrolysis of the prodrug and transport to the central circulation. These steps, i.e. the exact fate of the prodrug once released from the oil depot has remained relatively uninvestigated. Therefore, the specific aim of this dissertation is to assess what happens with the prodrug once it is released out of the oil depot. In my dissertation, it is presented what the new insights are of drug absorption from oil depots. It has been examined what the role of the excipient benzyl alcohol was on the absorption of nandrolone and how the oil is distributed over the injection site. Finally, I have studied where activation of the inactive drugs takes place in the body. These fundamental aspects on drug absorption from oil depots are relevant for the therapeutic efficacy in patients
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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