Implications of the Digestion of Milk-Based Formulations for the Solubilization of Lopinavir/Ritonavir in a Combination Therapy.

The development of formulation approaches to coadminister lopinavir and ritonavir antiretroviral drugs to children is necessary to ensure optimal treatment of human immunodeficiency virus (HIV) infection. It was previously shown that milk-based lipid formulations show promise as vehicles to deliver antimalarial drugs by enhancing their solubilization during the digestion of the milk lipids under intestinal conditions. In this study, we investigate the role of digestion of milk and infant formula on the solubilization behavior of lopinavir and ritonavir to understand the fate of drugs in the gastrointestinal (GI) tract after oral administration. Small angle X-ray scattering (SAXS) was used to probe the presence of crystalline drugs in suspension during digestion. In particular, the impact of one drug on the solubilization of the other was elucidated to reveal potential drug-drug interactions in a drug combination therapy. Our results showed that lopinavir and ritonavir affected the solubilization of each other during digestion in lipid-based formulations. While addition of ritonavir to lopinavir improved the overall solubilization of lopinavir, the impact of lopinavir was to reduce ritonavir solubilization as digestion progressed. These findings highlight the importance of assessing the solubilization of individual drugs in a combined matrix in order to dictate the state of drugs available for subsequent absorption and metabolism. Enhancement in the solubilization of lopinavir and ritonavir in a drug combination setting in vitro also supported the potential for food effects on drug exposure.

TAILOR-MS, a Python Package that Deciphers Complex Triacylglycerol Fatty Acyl Structures: Applications for Bovine Milk and Infant Formulas.

Liquid chromatography tandem mass spectrometry (LC/MS) and other mass spectrometric technologies have been widely applied for triacylglycerol profiling. One challenge for targeted identification of fatty acyl moieties that constitute triacylglycerol species in biological samples is the numerous combinations of 3 fatty acyl groups that can form a triacylglycerol molecule. Manual determination of triacylglycerol structures based on peak intensities and retention time can be highly inefficient and error-prone. To resolve this, we have developed TAILOR-MS, a Python (programming language) package that aims at assisting: (1) the generation of targeted LC/MS methods for triacylglycerol detection and (2) automating triacylglycerol structural determination and prediction. To assess the performance of TAILOR-MS, we conducted LC/MS triacylglycerol profiling of bovine milk and two infant formulas. Our results confirmed dissimilarities between bovine milk and infant formula triacylglycerol composition. Furthermore, we identified 247 triacylglycerol species and predicted the possible existence of another 317 in the bovine milk sample, representing one of the most comprehensive reports on the triacylglycerol composition of bovine milk thus far. Likewise, we presented here a complete infant formula triacylglycerol profile and reported >200 triacylglycerol species. TAILOR-MS dramatically shortened the time required for triacylglycerol structural identification from hours to seconds and performed decent structural predictions in the absence of some triacylglycerol constituent peaks. Taken together, TAILOR-MS is a valuable tool that can greatly save time and improve accuracy for targeted LC/MS triacylglycerol profiling.

Lipid Compositions in Infant Formulas Affect the Solubilization of Antimalarial Drugs Artefenomel (OZ439) and Ferroquine during Digestion.

Recent studies have shown that the solubilization of two antimalarial drug candidates, artefenomel (OZ439) and ferroquine (FQ), designed to provide a single-dose combination therapy for uncomplicated malaria can be enhanced using milk as a lipid-based formulation. However, milk as an excipient faces significant quality and regulatory hurdles. We therefore have investigated infant formula as a potential alternative formulation approach. The significance of the lipid species present in a formula with different lipid compositions upon the solubilization of OZ439 and FQ during digestion has been investigated. Synchrotron small-angle X-ray scattering was used to measure the diffraction from a dispersed drug during digestion and thereby determine the extent of drug solubilization. High-performance liquid chromatography was used to quantify the amount of drug partitioned into the digested lipid phases. Our results show that both the lipid species and the amount of lipids administered were key determinants for the solubilization of OZ439, while the solubilization of FQ was independent of the lipid composition. Infant formulas could therefore be designed and used as milk substitutes to tailor the desired level of drug solubilization while circumventing the variability of components in naturally derived milk. The enhanced solubilization of OZ439 was achieved during the digestion of medium-chain triacylglycerols (MCT), indicating the potential applicability of MCT-fortified infant formula powder as a lipid-based formulation for the oral delivery of OZ439 and FQ.

Low-Frequency Raman Scattering Spectroscopy as an Accessible Approach to Understand Drug Solubilization in Milk-Based Formulations during Digestion.

Techniques enabling in situ monitoring of drug solubilization and changes in the solid-state of the drug during the digestion of milk and milk-based formulations are valuable for predicting the effectiveness of such formulations in improving the oral bioavailability of poorly water-soluble drugs. We have recently reported the use of low-frequency Raman scattering spectroscopy (region of analysis <200 cm-1) as an analytical approach to probe solubilization of drugs during digestion in milk using ferroquine (SSR97193) as the model compound. This study investigates the wider utilization of this technique to probe the solubilization behavior of other poorly water-soluble drugs (halofantrine, lumefantrine, and clofazimine) in not only milk but also infant formula in the absence or presence of bile salts during in vitro digestion. Multivariate analysis was used to interpret changes to the spectra related to the drug as a function of digestion time, through tracking changes in the principal component (PC) values characteristic to the drug signals. Characteristic low-frequency Raman bands for all of the drugs were evident after dispersing the solid drugs in suspension form in milk and infant formula. The drugs were generally solubilized during the digestion of the formulations as observed previously for ferroquine and correlated with behavior determined using small-angle X-ray scattering (SAXS). A greater extent of drug solubilization was also generally observed in the infant formula compared to milk. However, in the case of the drug clofazimine, the correlation between low-frequency Raman scattering and SAXS was not clear, which may arise due to background interference from clofazimine being an intense red dye, which highlights a potential limitation of this new approach. Overall, the in situ monitoring of drug solubilization in milk and milk-based formulations during digestion can be achieved using low-frequency Raman scattering spectroscopy, and the information obtained from studying this spectral region can provide better insights into drug solubilization compared to the mid-frequency Raman region.

Impact of Ferroquine on the Solubilization of Artefenomel (OZ439) during in Vitro Lipolysis in Milk and Implications for Oral Combination Therapy for Malaria.

Milk is an attractive lipid-based formulation for the delivery of poorly water-soluble drugs to pediatric populations. We recently observed that solubilization of artefenomel (OZ439) during in vitro intestinal lipolysis was driven by digestion of triglycerides in full-cream bovine milk, reflecting the ability of milk to act as an enabling formulation in the clinic. However, when OZ439 was co-administered with a second antimalarial drug, ferroquine (FQ) the exposure of OZ439 was reduced. The current study therefore aimed to understand the impact of the presence of FQ on the solubilization of OZ439 in milk during in vitro intestinal digestion. Synchrotron small-angle X-ray scattering was used for in situ monitoring of drug solubilization (inferred via decreases in the intensity of drug diffraction peaks) and polymorphic transformations that occurred during the course of digestion. Quantification of the amount of each drug solubilized over time and analysis of their distributions across the separated phases of digested milk were determined using high-performance liquid chromatography. The results show that FQ reduced the solubilization of OZ439 during milk digestion, which may be due to competitive binding of FQ to the digested milk products. Interactions between the protonated FQ-H+ and ionized liberated free fatty acids resulted in the formation of amorphous salts, which removes the low-energy crystalline state as a barrier to dissolution of FQ, while inhibiting the solubilization of OZ439. We conclude that although milk could enhance the solubilization of poorly water-soluble OZ439 during in vitro digestion principally due to the formation of fatty acids, the solubilization efficiency was reduced by the presence of FQ by competition for the available fatty acids. Assessment of the solubilization of both drugs during digestion of fixed-dose combination lipid formulations (such as milk) is important and may rationalize changes in bioavailability when compared to that of the individual drugs in the same formulation.

Solid-State Behavior and Solubilization of Flash Nanoprecipitated Clofazimine Particles during the Dispersion and Digestion of Milk-Based Formulations.

Clofazimine, a drug previously used to treat leprosy, has recently been identified as a potential new drug for the treatment for cryptosporidiosis: a diarrheal disease that contributes to 500 000 infant deaths a year in developing countries. Rapid dissolution and local availability of the drug in the small intestine is considered key to the treatment of the infection. However, the commercially available clofazimine formulation (Lamprene) is not well-suited to pediatric use, and therefore reformulation of clofazimine is desirable. Development of clofazimine nanoparticles through the process of flash nanoprecipitation (FNP) has been previously shown to provide fast and improved drug dissolution rates compared to clofazimine crystals and Lamprene. In this study, we investigate the effects of milk-based formulations (as possible pediatric-friendly vehicles) on the in vitro solubilization of clofazimine formulated as either lecithin- or zein/casein-stabilized nanoparticles. Milk and infant formula were used as the lipid vehicles, and time-resolved synchrotron X-ray scattering was used to monitor the presence of crystalline clofazimine in suspension during in vitro lipolysis under intestinal conditions. The study confirmed faster dissolution of clofazimine from all the FNP formulations after the digestion of infant formula was initiated, and a reduced quantity of fat was required to achieve similar levels of drug solubilization compared to the reference drug material and the commercial formulation. These attributes highlight not only the potential benefits of the FNP approach to prepare drug particles but also the fact that enhanced dissolution rates can be complemented by considering the amount of co-administered fat in lipid-based formulations to drive the solubilization of poorly soluble drugs.

Interactions of Artefenomel (OZ439) with Milk during Digestion: Insights into Digestion-Driven Solubilization and Polymorphic Transformations.

Milk has been used as a vehicle for the delivery of antimalarial drugs during clinical trials to test for a food effect and artefenomel (OZ439) showed enhanced oral bioavailability with milk. However, the nature of the interaction between milk and OZ439 in the gastrointestinal tract remains poorly understood. To understand the role of milk digestion on the solubilization of OZ439 and polymorphism, we conducted real-time monitoring of crystalline drug in suspension during in vitro intestinal lipolysis of milk containing OZ439 using synchrotron X-ray scattering. OZ439 formed an unstable solid-state intermediate free base form (OZ439-FB form 1) at intestinal pH and was partially solubilized by milk fat globules prior to lipolysis. Dissolution of the free base form 1 and recrystallization of OZ439 in a more stable polymorphic form (OZ439-FB form 2) occurred during in vitro lipolysis in milk. Simply stirring the milk/drug suspension in the absence of lipase or addition of lipase to OZ439 in a lipid-free buffer did not induce this polymorphic transformation. The formation of OZ439-FB form 2 was therefore accelerated by the solubilization of OZ439-FB form 1 during the digestion of milk. Our findings confirmed that although crystalline precipitates of OZ439-FB form 2 could still be detected after in vitro digestion, milk-based lipid formulations provided a significant reduction in crystalline OZ439 compared to lipid-free formulations, which we attribute to the formation of colloidal structures by the digested milk lipids. Milk may therefore be particularly suited as a form of lipid-based formulation (LBF) for coadministration with OZ439, from which both an enhancement in OZ439 oral bioavailability and the delivery of essential nutrients should result.

Infant formula as a solid lipid dose form for enhancement of the oral bioavailability of cannabidiol for paediatric patients.

Cannabinoids can save paediatric patients from harmful psychological conditions caused by epilepsy. However, the limited aqueous solubility of the drug presents a limitation to oral absorption and bioavailability. Previous studies have shown the enhancement of oral bioavailability for poorly water-soluble drugs using milk or milk-based products like infant formula as a novel lipid-based formulation, due to digestion of the lipids to enhance drug solubility that is particularly well suited to infants and in low economy settings. Therefore, this study has investigated the in vitro solubilisation enhancement of cannabidiol (CBD) in milk-based products during digestion using synchrotron small angle X-ray scattering, followed by pharmacokinetic studies to determine the relative oral bioavailability. The in vitro results, coupled with in vivo data, demonstrate a two-fold increase in the oral bioavailability of CBD in bovine milk as well as infant formula. The results of this study indicate the potential for infant formula to be considered as a novel formulation approach for CBD. Further study is encouraged for more drugs with infant formula to strengthen the correlation between the solubilisation of drug and their oral bioavailability.

Modeling digestion, absorption, and ketogenesis after administration of tricaprilin formulations to humans.

At present, tricaprilin is used as a ketogenic source for the management of mild to moderate Alzheimer's disease. After administration of the medium-chain triglyceride, tricaprilin is hydrolyzed to octanoic acid and further metabolized to ketones, acting as an alternative energy substrate for the brain. In this investigation, we developed a physiologically-based biopharmaceutics model simulating in vivo processes following the peroral administration of tricaprilin. The model includes multiple data sources to establish a partially verified framework for the simulation of plasma profiles. The input parameters were identified based on existing literature data and in vitro digestion studies. Model validation was conducted using the data from a phase I clinical trial. A partial parameter sensitivity analysis elucidated various influences on the plasma ketone levels that are mainly responsible for the therapeutic effects of tricaprilin. Based on our findings, we concluded that dispersibility and lipolysis of tricaprilin together with the gastric emptying patterns are limiting ketogenesis, while other steps such as the conversion of octanoic acid to ketone bodies play a minor role only.

Revisiting the Dissolution of Praziquantel in Biorelevant Media and the Impact of Digestion of Milk on Drug Dissolution.

Praziquantel is a poorly water-soluble drug used to treat parasitic infections. Previous studies have suggested that its rate and extent of dissolution in milk and biorelevant media are slow and limited compared to dissolution in the pharmacopoeial-recommended medium, despite being reported as displaying a positive food effect upon administration. This study aimed to revisit the dissolution of praziquantel in biorelevant media and milk to better understand this apparent dichotomy. The context of digestion was introduced to better understand drug solubilisation under more relevant gastrointestinal conditions. The amount of praziquantel solubilised in the various media during digestion was quantified using high performance liquid chromatography (HPLC) and the kinetics of dissolution were confirmed by tracking the disappearance of solid crystalline drug using in situ small angle X-ray scattering (SAXS). For the dissolution media, where sodium lauryl sulfate (SLS) is typically included as a wetting agent, a prominent effect of SLS on drug dissolution was also apparent where >2.5 fold more drug was solubilised in SLS-containing dissolution medium compared to that without (0.1 M HCl only). In milk, significant dissolution of praziquantel was observed only during digestion and not during dispersion, hence suggesting that (1) milk can be potentially administered with praziquantel to improve oral bioavailability and (2) incorporating a digestion step into existing in vitro dissolution testing can better reflect the potential for a positive food effect when lipids are present.

Towards mesoporous silica as a pharmaceutical treatment for obesity - impact on lipid digestion and absorption.

Mesoporous silica particles (MSPs) are emerging as an interesting option to reduce calorific uptake as a treatment for obesity and other metabolic conditions. However, their further development under the pharmaceutical regulatory framework is hindered by poor understanding of the mechanisms by which they exert their effects. In the current study the interaction of MSPs with the lipid digestion process is investigated, specifically interactions with lipase enzymes and lipid digestion products as a key contributing factor to lipid absorption and calorific intake. The impact of exposing lipase to MSPs on the enzyme activity was assessed directly using the tributyrin digestion test. The extent of interaction of digestion products with MSPs was studied using selectively radiolabeled bile components and lipids, while the impact on in vivo absorption of lipids was studied by incorporation of radiolabelled lipid (triolein) into milk and administration with and without particles. The studies showed that particles that inhibited lipase activity also tended to interact more extensively with lipid digestion products. In vitro X-ray scattering studies revealed the interaction of some MSPs with lipid digestion products through changes in lipid self-assembly during digestion. The MSPs led to reduced lipid absorption in vivo compared to the control particles and MSP-free milk. While the specific properties of the MSPs that drive the differences between the behavior of MSPs during lipid digestion remain elusive, the studies highlight that interactions with the lipid digestion and absorption pathways are a likely mechanism for reducing calorific uptake.

Sustained absorption of delamanid from lipid-based formulations as a path to reduced frequency of administration.

Delamanid is a poorly water-soluble drug currently being used for the treatment of tuberculosis. The high frequency of dosing leads to poor adherence for patients who live in lower economic and nomadic populations. Non-digestible self-assembling lipids as a formulation approach for poorly water-soluble drugs have previously been shown to extend the window of absorption through gastric retention. We hypothesise that this approach could lead to the reduction of dosing frequency for delamanid and thereby has potential to improve adherence. Formulations of delamanid were prepared in selachyl alcohol and phytantriol as non-digestible self-assembling lipid vehicles, and their behaviour was compared with reconstituted milk powder, as a digestible lipid-based formulation, and an aqueous suspension. The self-assembly of selachyl alcohol and phytantriol in aqueous media in the presence of delamanid was studied using small angle X-ray scattering and produced the inverse hexagonal (H2) and inverse bicontinuous cubic (V2) liquid crystal structures, respectively. The times at which maximum delamanid levels in plasma were observed (Tmax) after oral administration of the phytantriol, selachyl alcohol and reconstituted milk powder formulations of delamanid to rats were 27 ± 3, 20 ± 4 and 6.5 ± 1.0 h, respectively, compared with the aqueous suspension formulation with a Tmax of 3.4 ± 1 h, which confirms the hypothesis of an extended duration of absorption after administration in non-digestible self-assembling lipids. The digestion products of the triglycerides in the milk formulation increased the solubilisation of delamanid in the gastrointestinal tract, leading to an increase in exposure compared with the aqueous suspension formulation but did not significantly extend Tmax. Overall, the non-digestible nanostructured lipid formulations extended the duration of absorption of delamanid well beyond that from milk or suspension formulations. Graphical abstract.

Correlating Digestion-Driven Self-Assembly in Milk and Infant Formulas with Changes in Lipid Composition.

Lipids in mammalian milks such as bovine milk and human breast milk have been shown to self-assemble into various liquid crystalline materials during digestion. In this study, the direct correlation between the composition of the lipids from three types of mammalian milk, three brands of infant formulas (IFs), and soy milk and the liquid crystalline structures that form during their digestion was investigated to link the material properties to the composition. The self-assembly behavior was assessed using in vitro digestion coupled with in situ small-angle X-ray scattering (SAXS). Lipid composition was determined during in vitro digestion using ex situ liquid chromatography-mass spectrometry. All tested milks self-assembled into ordered structures during digestion, with the majority of milks displaying nonlamellar phases. Milks that released mostly long-chain fatty acids (>95 mol % of the top 10 fatty acids released) with more than 47 mol % unsaturation predominantly formed a micellar cubic phase during digestion. Other milks released relatively more medium-chain fatty acids and medium-chain monoglycerides and produced a range of ordered liquid crystalline structures including the micellar cubic phase, the hexagonal phase, and the bicontinuous cubic phase. One infant formula did not form liquid crystalline structures at all as a consequence of differences in fatty acid distributions. The self-assembly phenomenon provides a powerful discriminator between different classes of nutrition and a roadmap for the design of human milklike systems and is anticipated to have important implications for nutrient transport and the delivery of bioactives.

Differential Effects of TPM, A Phosphorylated Tocopherol Mixture, and Other Tocopherol Derivatives as Excipients for Enhancing the Solubilization of Co-Enzyme Q10 as a Lipophilic Drug During Digestion of Lipid- Based Formulations.

BACKGROUND: The tocopherol-based excipient, TPM, when incorporated into a medium-chain triglyceride (MCT)-based lipid formulation, has been previously shown to improve the solubilization of Coenzyme Q10 (CoQ10) during in vitro digestion which is strongly correlated with enhanced exposure in vivo. METHODS: The current study aimed to gain further understanding of the MCT + TPM co-formulation, by assessing the formulation performance under fasted and fed in vitro digestion conditions, with different drug and excipient loading levels. Natural and synthetic-derived TPM were equivalent, and with d-α- tocopherol polyethylene glycol 1000 succinate (TPGS) outperformed other derivatives in enhancing the solubilisation of CoQ10 during digestion. RESULT: Fed conditions significantly improved the solubility of CoQ10 during in vitro digestion of the formulation in comparison with fasted conditions. The addition of TPM at 10% (w/w) of the total MCT + TPM provided optimal performance in terms of CoQ10 solubilization during digestion. CONCLUSION: The results further highlights the potential of TPM as an additive in lipid formulations to improve the solubilization and oral bioavailability of poorly water-soluble compounds.

The impact of digestion is essential to the understanding of milk as a drug delivery system for poorly water soluble drugs.

Milk has previously been considered as a potential lipid-based drug delivery system for poorly water soluble drugs but it has never gained significant attention. This is in part because relying on solubility in lipid-based formulations (in this case milk) does not provide a complete picture of the behavior of such systems upon digestion. Herein, we demonstrate using time resolved X-ray scattering that the digestion of milk is actually crucial to the solubilisation of a poorly water-soluble drug, halofantrine. Halofantrine was chosen because its behaviour in lipid-based formulations has been widely investigated and because of its close structural relationship to lumefantrine, an antimalarial drug of current interest for the treatment of paediatric malaria. The transformation of the drug from a crystalline solid form in suspension in milk, to a solubilised form as a direct consequence of lipolysis highlights that consideration of digestion of the milk lipids as a critical process that influences drug solubilisation and availability for absorption is vital.

Conocimientos de lactancia materna en embarazadas antes y después de una intervención educativa / Knowledge of breastfeeding in pregnant women before and after an educational intervention

Introducción: la lactancia materna es el mejor alimento para el recién nacido y hasta los 6 meses de edad, proporciona nutrientes y anticuerpos para el correcto desarrollo, por lo que se debe dar educación sobre lactancia materna a la mujer desde el embarazo para que pueda llevar a cabo adecuadamente este proceso. Objetivo: evaluar el nivel de conocimiento de lactancia materna en embarazadas antes y después de una intervención educativa. Material y métodos: estudio cuasiexperimental, longitudinal, en 150 embarazadas primigestas y multigestas mayores de 18 años. Se aplicó el instrumento validado en 2019 por Palomino et al. denominado Conocimientos sobre lactancia materna, con un coeficiente alfa de Cronbach de 0.7058. Posteriormente se realizó una intervención educativa y se les pidió que contestaran nuevamente el cuestionario. Se analizaron los datos con estadística descriptiva y medidas de tendencia central, así como proporciones, para evaluar las medianas de nivel de conocimiento antes y después de la intervención educativa se utilizó la prueba estadística Wilcoxon. Resultados: el promedio de edad fue 27.06 + 5.956 años. La escolaridad fue preparatoria 42.7%, en unión libre 48.7%, amas de casa 45.3%, el nivel de conocimiento alto postintervención en concepto general fue de 98.7%, respecto a posición y técnica 96.7% y para beneficios 96%. Con la prueba de Wilcoxon para conocimiento general se reportó z = -10.598, p = 0.000. Conclusiones: existe diferencia estadísticamente significativa entre la mediana de conocimiento al inicio y al final del estudio, con un 95% de confianza.

Introduction: Breastfeeding is the best food for the neonate and up to 6 months of age, it provides nutrients and antibodies for proper development, so the woman must be educated about breastfeeding from pregnancy so that she can properly carry out this process. Objective: To evaluate the level of breastfeeding knowledge in pregnant women before and after an educational intervention. Material and methods: Quasi experimental, longitudinal study in 150 primigravida and multigravida women between 20 and 35 years old. The validated instrument in 2019 by Palomino et al. called Breastfeeding Knowledge with a Cronbach's Alpha coefficient of 0.7058 was used. Educational intervention was given, and the questionnaire was reapplied. The data was analyzed with descriptive statistics and measures of central tendency and proportions. The Wilcoxon statistical test was used to evaluate the median levels of knowledge before and after the educational intervention. Results: The average age was 27.06 + 5.956 years. In total, 42.7% in High school, 48.7% in common law, 45.3% were housewives. The post-intervention high level of knowledge in general concept was 98.7%, respect position and technique 96.7% and for benefits 96%. Wilcoxon test for general knowledge reported z = -10.598 p = 0.000. Conclusions: There is a statistically significant difference between the median knowledge at baseline and at the end of the study with 95% confidence.

A new lipid excipient, phosphorylated tocopherol mixture, TPM enhances the solubilisation and oral bioavailability of poorly water soluble CoQ10 in a lipid formulation.

Phosphorylated tocopherols are a new class of lipid excipients that have demonstrated potential in pharmaceutical applications. Their ability to solubilise poorly water soluble drugs indicates their potential utility in improving bioavailability of drugs where solubility limits their bioavailability. In this study a commercial mixture of phosphorylated tocopherols, TPM was combined with medium chain triglyceride (MCT) as a formulation for CoQ10, and in vitro and in vivo performance compared to the effect of addition of alternative tocopherol-based excipients. In in vitro digestion experiments, CoQ10 was poorly solubilised in the digesting MCT as anticipated. Addition of TPM facilitated the enhanced solubilisation of CoQ10 as did vitamin E TPGS (TPGS). Other tocopherol derivatives (tocopherol acetate, tocopherol) were less effective at solubilising the active during the digestion process. The trends in in vitro solubilisation were conserved in the in vivo bioavailability of CoQ10 after oral administration to rats, with TPM and TPGS formulations providing approximately double the exposure of MCT alone, while the addition of the other tocopherol derivatives reduced the overall exposure. Collectively, the results indicate potential of TPM as a new solubilising excipient for use in oral drug delivery for poorly water soluble drugs.

Competencias de dirección para la gestión del proceso docente en escenarios docente-asistenciales / Managerial skills for the management of the teaching process in teaching-care institutions

RESUMEN Fundamento: la gestión del proceso docente requiere el desarrollo de competencias de dirección en sus ejecutores. Objetivo: caracterizar el estado actual de las competencias de dirección para la gestión del proceso docente en los escenarios docente-asistenciales de la Universidad de Ciencias Médicas de Holguín. Métodos: se realizó un estudio descriptivo en la Universidad de Ciencias Médicas de Holguín, hospitales provinciales, hospitales municipales de Moa, Mayarí y Sagua de Tánamo y en escenarios de la Atención Primaria de Salud en el municipio cabecera, en el periodo septiembre 2017-2020. Se aplicaron métodos teóricos para la fundamentación de la investigación y métodos empíricos: cuestionarios a estudiantes, profesores y directivos, revisión documental, entrevista a expertos y entrevista grupal. Resultados: se plantearon competencias necesarias para la gestión del proceso docente: liderazgo, toma de decisiones, creatividad, comunicación, sentido de pertenencia, preparación didáctica, desarrollo profesional, trabajo en equipo, dominio de las etapas de dirección, trabajo político-ideológico y enfoque estratégico. Conclusiones: la valoración que los directivos y profesores hacen de las competencias para la gestión docente presenta un nivel medio (bueno) en los escenarios de atención de salud, lo que coincide con la opinión de los estudiantes. Los valores más bajos se relacionan con las competencias: comunicación, creatividad, preparación docente, dominio de las etapas de dirección, toma de decisiones, trabajo en equipo y dominio de los documentos rectores del proceso docente.

ABSTRACT Background: the management of the teaching process requires the development of managerial skills in its executors. Objective: to characterize the current state of managerial competencies for the management of the teaching process in the teaching-care settings of Holguín University of Medical Sciences. Methods: a descriptive study was carried out in Holguín University of Medical Sciences, provincial hospitals, municipal hospitals of Moa, Mayarí and Sagua de Tánamo and in settings of Primary Health Care in Holguin city, from September 2017 to 2020 . Theoretical methods were applied for the foundation of the research and empirical methods: questionnaires for students, teachers and executives, documentary review, interview with experts and group interview. Results: necessary competencies for the management of the teaching process were proposed: leadership, decision-making, creativity, communication, sense of belonging, didactic preparation, professional development, teamwork, mastery of the management stages, political-ideological work and strategic approach. Conclusions: the assessment that managers and teachers make of the competences for teaching management presents an average level in the health care settings, which coincides with the opinion of the students. The lowest values ​​are related to the competences: communication, creativity, teaching preparation, mastery of the management stages, decision-making, teamwork and mastery of the governing documents of the teaching process.

Intervención educativa sobre el Ébola para estudiantes de Medicina de. 5to año. Septiembre - noviembre 2018 / Educational intervention about Ébola for 5th year medicine students. September- november 2018

RESUMEN Introducción: el virus del Ébola es el causante de la enfermedad vírica febril hemorrágica del Ébola: infecciosa, altamente contagiosa, muy severa, afecta tanto a animales como a seres humanos, presenta alta mortalidad y constituye un problema de salud que, sin un control adecuado, puede llegar a convertirse en epidemia de alcance mundial. Objetivo: evaluar el nivel de conocimientos acerca de la enfermedad del Ébola en los estudiantes de 5to año de Medicina, de la Universidad de Ciencias Médicas de Holguín, Cuba. Métodos: se realizó un estudio de intervención educativa sobre la enfermedad del Ébola, mediante un programa educativo a partir de la identificación de las necesidades de aprendizaje de los estudiantes de 5to año de Medicina, a través de un cuestionario para medir el nivel de conocimientos sobre aspectos de esta dolencia Resultados: el grupo de edades con mayores conocimientos sobre el tema fue el de 21 a 24 años (60,52%). El sexo femenino predominó sobre el masculino en cuanto a conocimientos de la enfermedad (82,85%). Al presenciar un largometraje como parte del programa educativo confeccionado, los estudiantes de 21 a 24 años mostraron mayor dominio (65,51%). Conclusiones: previo a nuestra intervención, el nivel de conocimiento de los estudiantes sobre la enfermedad del Ébola eran incorrectos. Se aplicó el método de intervención educativa de forma satisfactoria. Al culminar, se modificó el nivel de conocimientos incorrectos y los suficientes y correctos se incrementaron.

ABSTRACT Introduction: Èbola virus causes hemorrhagic febrile viral disease of Èbola, a severe infectious disease, highly contagious, with a high mortality level, which affects animals and humans; a health problem which may become epidemic worldwide without a suitable control. Objective: evaluate knowledge about Èbola disease of 5th year medicine students from September to November 2018. Methods: an educational intervention study about Èbola disease for 5th year medicine students, through an educational program from the identification of their needs, with one summary to measure their knowledge level about fundamental aspects of this disease, was carried out. Results: the age group with suitable knowledge about the subject was between 21 and 24 (60, 52%). Females predominated with (82, 85%). When they all watch the film included in the educational program, the same age group predominated (65, 51%). Conclusions: before the intervention, 5th year medicine student's knowledge level about Èbola disease was inadequate. Educational intervention method was successfully applied. As the conclusion of the educational intervention, adequate and sufficient knowledge increased and those incorrect were modified.

Mortalidad por accidentes cerebrovasculares en el Hospital Clínico Quirúrgico Lucía Íñiguez Landín, Holguín, Cuba, 2012-2017 / Cerebrovascular Accidents Mortality at the Clinical Surgical Hospital "Lucía Íñiguez Landín", Holguín, Cuba, 2012-2017

RESUMEN Introducción: actualmente, el Accidente Cerebrovascular (ACV) produce importantes limitaciones, discapacidades y constituye una de las primeras causas de muerte a nivel mundial. La mortalidad hospitalaria es uno de los indicadores más utilizados para medir la calidad de la atención en los servicios de salud. Objetivo: determinar la tendencia de la mortalidad por ACV. Métodos: se realizó una investigación descriptiva de una serie de casos. El universo fueron 382 pacientes; el total de fallecidos con el diagnóstico clínico, tomográfico y/o necrológico de ACV, del 2012 hasta el 2017, en el Hospital Clínico-Quirúrgico Lucía Íñiguez Landín. Los datos recogidos fueron procesados estadísticamente. Resultados: en los años estudiados fallecieron por ACV, un promedio anual de 63 pacientes. El grupo etario de 71 a 80 años sobresalió con un promedio de 17,5 fallecidos. Llamó la atención la tendencia al aumento del grupo de 51 a 60 años. Predominó el sexo masculino con un promedio de 35,6 fallecidos; aunque la tendencia fue a igualarse. Prevalecieron las hemorragias intracerebrales con 34 fallecidos como promedio, y la hipertensión arterial acompañó a más del 50% de los fallecidos, en la mayoría de los años estudiados. Las causas directas de los fallecimientos fueron: el edema cerebral y la hipertensión endocraneana refractaria, principalmente durante las estadías hospitalarias cortas o intermedias. Conclusiones: la mortalidad por ACV tuvo un comportamiento similar en los diferentes años; pero con una tendencia a elevarse con el tiempo y aparecer en edades más tempranas.

ABSTRACT Introduction: nowadays, Cerebrovascular Accident (CVA) invalidantes patients and is one of the main mortality causes around the world. Hospital mortality is one of the most adequate indicators to measure the attention quality, in health services. Objective: to determine mortality tendency of CVA. Methods: a descriptive series of cases research, with the universe of the 382 deceased patients, diagnosed with tomographic and/or obituary of CVA, from 2012 to 2017, at the Clinical Surgical Hospital "Lucía Íñiguez Landín". Data were processed statistically. Results: during the years of study, an average of 62 patients perished for CVA. Age bracket from 71 to 80 stood out with 17.5 average. Tendency raised in the group from 51 to 60. Males prevailed with a mortality of 35.6 average; though it tend to become equal. Intracerebral Hemorrhages prevailed with a 34 average mortality, and arterial hypertension accompanied the 50% of dead patients, in most of the studied years. Mortality direct causes were the cerebral edema and intracraneal hypertension with refration, mainly when hospital stays were short or intermediates. Conclusions: CVA mortality behaved differently through the studied years; though it increased and appeared, more frequently, in premature ages.