Post-COVID Pediatric Budd-Chiari Syndrome

Introduction: Budd-Chiari syndrome (BCS) is rare in children. Underlying etiologies, natural history and management differ in children and adults. Treatment options like liver transplantation and transjugular intrahepatic portosystemic shunt have also been less well-studied in children. Presented here is the case of a male child with BCS after coronavirus disease 2019 (COVID-19) infection. Case presentation: A 3-year-old male child presented with complaints of gradually increasing abdominal distension, constipation, decreased urine output, visible veins over abdomen and swelling in lower limbs and periorbital edema since last 15 days. He was diagnosed as BCS after multiple imaging investigations, including triple phase contrast-enhanced computed tomography (CECT) abdomen. His COVID antibody tested positive. Conclusion: Practice guidelines for children with BCS should be formulated, expert group recommendations should be reviewed and a consensus statement should be issued. Underlying etiology remains obscure despite extensive work-up in most of the children. Association of COVID-19 with BCS may be incidental but should be studied further as COVID is known to cause thrombotic complications

An update on oral drug delivery

Orally administered drug entities have to survive the harsh gastrointestinal environment, penetrate the enteric epithelia and circumvent hepatic metabolism before reaching the systemic circulation. Whereas the gastrointestinal stability can be well maintained by taking proper measures, hepatic metabolism presents as a formidable barrier to drugs suffering from first-pass metabolism. The pharmaceutical academia and industries are seeking alternative pathways for drug transport to circumvent problems associated with the portal pathway. Intestinal lymphatic transport is emerging as a promising pathway to this end. In this review, we intend to provide an updated overview on the rationale, strategies, factors and applications involved in intestinal lymphatic transport. There are mainly two pathways for peroral lymphatic transport-the chylomicron and the microfold cell pathways. The underlying mechanisms are being unraveled gradually and nowadays witness increasing research input and applications.

Quality By Design Approach For Enhancement The Dissolution Rate Of Lafutidine Liquisolid Tablets

The aim of present work was to enhancing the solubility and dissolution rate of the aquaphobic drug Lafutidine by liquisolid technique. Lafutidine is a H2-receptor antagonist BCS class II drug. Lafutidine compatibility with excipients was evaluated by FT-IR and DSC spectrum. Preliminary trial taken to check the effect of carrier to coating material ratio (R) and non-volatile solvent (PEG- 600) on pre compression and post compression characteristic. Flowable liquid retention potential (Ø -value) and Liquid load factors (Lf) were calculated for required amount of excipients necessary to preparing Lafutidine liquisolid tablet. A 32 full factorial design was employed to check the effect of carrier to coating material ratio R (X1) and PEG- 600 (X2) on hardness (Y1), angle of repose (Y2), % of Cumulative drug release at 5 min Q5 (Y3), and disintegration time (Y4). Multiple linear regression analysis, ANOVA and graphical representation of the influence of factor by 3D plots were performing by using Design expert 7.0. In this study, the following constraints were arbitrarily used for the selection of an optimized batch: Hardness: 3 to 5.5, Angle of repose: 25 to 30, % of Cumulative Drug Release at 5 min (Q5) > 27.09 % and Disintegration time <1.3 min. The desirability value of various dependent variables calculated for determining the optimized batch of tablet and it was also found to be nearer to one. Performance of optimized batch had no shown any significant change at the end of stability study.

Identification of a novel mutation in the BCS1L gene causing Bj(o)rnstad syndrome / 中华皮肤科杂志

Objective To identify gene mutations in the BCS1L gene in a patient with Bj(o)rnstad syndrome mainly manifesting as congenital pili torti and sensorineural hearing loss.Methods Clinical data were collected and DNA was extracted from the peripheral blood of the patient and her parents.All the exons and their flanking sequences of the BCS1L gene were amplified by PCR followed by Sanger sequencing,and the sequencing results were compared with the normal sequences.A few hairs were collected from the patient,and examined by the scanning electron microscope.Results There were two mutations in BCS1L gene in the patient,i.e.,a heterozygous nonsense mutation in exon 4 and a heterozygous missense mutation in exon 8.The nonsense mutation in exon 4,which caused a change from CGA to TGA at position 144 and resulted in the substitution of arginine by termination codon (p.R144*),was a novel mutation in the BCS1L gene causing Bj(o)rnstad syndrome,and had never been repotted in the literature.The missense mutation in exon 8 led to a change from CGC to CAC at position 306 and resulted in the substitution of arginine by histidine (p.R306H).The patient's mother only carried a heterozygous mutation c.430 C＞T (p.R144*) in exon 4 of the BCS1L gene,and her father only carried a heterozygous mutation c.917 G＞A (p.R306H) in exon 8 of the BCS1L gene.Scanning electron microscopy showed that flats,grooves and longitudinal twisting irregu larly appeared at intervals on the surface of hair shafts.Conclusions A novel mutation in the BCS1L gene,which causes a change from CGA to TGA at position 144 in the BCS1L gene and results in a premature termination codon,is firstly reported in a patient with Bj(o)rnstad syndrome,and the compound heterozygous mutations c.430 C＞T and c.917 G＞A in the BCS1L gene are associated with the clinical manifestations of the patient.Genetic analvsis is helpful for the diagnosis of Bj(o)rnstad syndrome.

A systematic evaluation of biopharmaceutics classification system of main efficacy and toxic ingredients in Polygoni Multiflori Radix Praeparata / 中草药

Objective: Biopharmaceutics classification system (BCS) of five main pharmacological/toxic components (gallic acid, emodin, stilbene glycoside, physcion, and emodin-8-O-β-D-glucoside) of Polygoni Multiflori Radix Praeparata (PMRP) were carried out. Methods: The solubility and permeability of each representative component were studied by equilibrium solubility method and everted intestinal sac method, respectively. Using two softwares (Pipeline Pilot 7.5, ChemDraw 7.0) to predict the solubility and permeability parameters of each component. Classical BCS classification of measured and predicted values of representative components was conducted according to Food and Drug Administration (FDA) standards, and their correlation was evaluated. Results: The emodin, emodin-8-O-β-D-glucoside, and physcion in PMRP was preliminary determined as BCS IV drugs. THSG and gallic acid belong to BCS III drugs, and permeability was the main limiting factor in their absorption process. There was software which predicts false positives of anthraquinone in BCS classification studies. Conclusion: In this study, five main pharmacodynamic/toxic components of PMRP were classified by BCS method, which provided data support and technical reference for in vivo absorption prediction and in vitro safety evaluation of traditional Chinese medicine.

Basic procedure and technical requirements of equilibrium solubility experiments / 中国药学杂志

OBJECTIVE: To introduce the basic procedure and technical requirements of equilibrium solubility experiments and provide reference for design and conduct of equilibrium solubility experiments scheme. METHODS: The concept and influence factors of solubility, principle and determination method of solubility experiments, equilibrium solubility project of world health organization were analyzed. RESULTS: The influence factors of equilibrium solubility include composition of buffers, temperature, time of oscillation, time of sedimentation, techniques for separation of solid and liquid phases etc. CONCLUSION: To ascertain the BCS classification of drugs, the first step is to determine the equilibrium solubility of drugs under physiological pH conditions. To date, there is no accepted standard method for the determination of equilibrium solubility. This paper introduces the basic procedure and technical requirements of equilibrium solubility experiments recommended by WHO, which would provide instructive and practical assists to conduct of equilibrium solubility experiments and standardize its application in BCS classification and biowaiver.

Improving oral absorption of BCS Ⅱ drugs by increasing solubility: frequently overlooked permeability / 药学学报

BCS Ⅱ drugs are characterized by low solubility and high permeability. Improving their solubility is considered an important approach to improve its oral absorption. Recent strategies to increase the solubility of poorly-soluble drugs may unexpectedly result in greatly depressed permeability, ultimately leading to failure in improving oral absorption. Based on the mathematics of membrane permeability coefficient of a drug, the membrane/aqueous partition coefficient is dependent on the drug's solubility in the gastrointestinal milieu, suggesting a unique interplay between the solubility and permeability of the drug, and treating the one irrespectively of the other may be insufficient. When we focus on the increase of drug solubility and overlook the efficacy of drug permeability, the positive effect of increased solubility to drug oral absorption might be traded off by depressed permeability. To provide rational formulary designs, by optimizing excipients and evaluation, this review summarizes solubility- permeability interplay for different types of solubilizing techniques, such as cyclodextrin, surfactants-based vehicle, cosolvent, amorphous solid dispersions, other infectors such as P-gp transporters and new techniques for simultaneous evaluation of drug solubility and permeability.

Advances in coamorphous drug delivery systems

In recent years, the coamorphous drug delivery system has been established as a promising formulation approach for delivering poorly water-soluble drugs. The coamorphous solid is a single-phase system containing an active pharmaceutical ingredient (API) and other low molecular weight molecules that might be pharmacologically relevant APIs or excipients. These formulations exhibit considerable advantages over neat crystalline or amorphous material, including improved physical stability, dissolution profiles, and potentially enhanced therapeutic efficacy. This review provides a comprehensive overview of coamorphous drug delivery systems from the perspectives of preparation, physicochemical characteristics, physical stability, and performance. Furthermore, the challenges and strategies in developing robust coamorphous drug products of high quality and performance are briefly discussed.

Final Health and Environmental Risk Assessment of Genetically Modified Cotton GHB614

Genetically modified cotton GHB614 from Bayer Crop Science expresses a modified epsps gene (2mepsps) gene from maize encoding the enzyme 5-enolpyruvylshikimate 3-phosphate synthase (2 mEPSPS), which confers tolerance to the herbicide glyphosate. Updated bioinformatics analyses of the inserted DNA and flanking sequences in GHB614 have not indicated potential production of putatively harmful toxins or allergens caused by the genetic modification. Genomic stability of the functional insert and consistent expression of the 2mepsps gene has been shown over several generations of cotton GHB614. Field trials indicate that with the exception of the introduced trait, cotton GHB614 is compositionally, phenotypically and agronomically equivalent to its conventional counterpart Coker 312 and other cotton cultivars. A 42-day nutritional assessment trial with broilers did not reveal adverse effects of cottonseed meal from GHB614. The 2mEPSPS protein produced in GHB614 does not show amino acid sequence resemblance to known toxins or IgE-dependent allergens, nor has it been reported to cause IgE-mediated allergic reactions. It is therefore unlikely that the 2 mEPSPS protein will cause toxic or IgE-mediated allergic reactions to food or feed containing cotton GHB614 compared to conventional cotton cultivars. Cotton is not cultivated in Norway, and there are no cross-compatible wild or weedy relatives of cotton in Europe. Based on current knowledge and with the exception of the introduced trait, the VKM GMO Panel concludes that cotton GHB614 is nutritionally, compositionally, phenotypically and agronomically equivalent to and as safe as its conventional counterpart and other cotton cultivars. Considering the intended uses, which exclude cultivation, the VKM GMO Panel concludes that GHB614 does not represent an environmental risk in Norway.

Mesoporous silica nanoparticles for drug and gene delivery

Mesoporous silica nanoparticles (MSNs) are attracting increasing interest for potential biomedical applications. With tailored mesoporous structure, huge surface area and pore volume, selective surface functionality, as well as morphology control, MSNs exhibit high loading capacity for therapeutic agents and controlled release properties if modified with stimuli-responsive groups, polymers or proteins. In this review article, the applications of MSNs in pharmaceutics to improve drug bioavailability, reduce drug toxicity, and deliver with cellular targetability are summarized. Particularly, the exciting progress in the development of MSNs-based effective delivery systems for poorly soluble drugs, anticancer agents, and therapeutic genes are highlighted.

Parenteral nanosuspensions: a brief review from solubility enhancement to more novel and specific applications

Advancements in techniques of lead molecule selection have resulted in the failure of around 70% of new chemical entities (NCEs). Some of these molecules are getting rejected at final developmental stage resulting in wastage of money and resources. Unfavourable physicochemical properties affect ADME profile of any efficacious and potent molecule, which may ultimately lead to killing of NCE at final stage. Numerous techniques are being explored including nanocrystals for solubility enhancement purposes. Nanocrystals are the most successful and the ones which had a shorter gap between invention and subsequent commercialization of the first marketed product. Several nanocrystal-based products are commercially available and there is a paradigm shift in using approach from simply being solubility enhancement technique to more novel and specific applications. Some other aspects in relation to parenteral nanosuspensions are concentrations of surfactant to be used, scalability and fate. At present, there exists a wide gap due to poor understanding of these critical factors, which we have tried to address in this review. This review will focus on parenteral nanosuspensions, covering varied aspects especially stabilizers used, GRAS (Generally Recognized as Safe) status of stabilizers, scalability challenges, issues of physical and chemical stability, solidification techniques to combat stability problems and fate.

Productive and Reproductive Perfomance of Dairy Cows During Peripartum

ABSTRACT Dairy activity is of great importance for the national economy. It is also an important source of income for families in the south east region of Paraná that work in this area. There has been a notable expansion in the activities as well as in the quantity of production and the quality of the products. With this has come problems in the reproductive efficiency of the dairy cattle principally in relation to those with the greatest production. The objective of this study was to evaluate the productive profile and the reproductive efficiency of dairy cows. The evaluation covered 30 days before calving and 15, 30, 45, 60 and 90 days after the calving. The study covered cows from two properties in the Municipality of Realza-PR in Brazil. In order to do the aforementioned, we used the Body Condition Score (BCS). We evaluated the production of milk and through the use of gynecological exams and we looked at uterine involution (UI) and ovarian cyclicality. The results showed falls in the BCS in the prepartum period and in the first weeks of lactation (p<0.05) and the differences in the BCS were based on the season of the year in which the calving took place (p<0.05) with the highest BCS being noted to occur in the hot seasons. The UI correlates with the presence of corpus luteum where animals were late in their uterine involution and had delays in their first postpartum ovulation (p<0.05). The average service period and calving interval were similar to those described for dairy cattle, however, we observed variations based on the seasons of the year which was possibly related to the greater availability and quality of the forage in the hot seasons.

Principles of biowaiver about consistency evaluation of generic drug products and varieties of biowaiver in countries and international organizations / 药物评价研究

Objective For bioequivalence test of the consistency evaluation of generic drug products,providing a reference of varieties of biowaiver.Methods Based on Human bioequivalence test waiver guidelines (draft),on condition that first drug of the consistency evaluation,to introduce and conclude briefly the standards of biowaiver and varieties of biowaiver in FDA,WHO and EMA.Results Contrast to FDA,there are 59 varieties applied for the waiver and 19 varieties not applied for the waiver in the 289 varietie;compared to WHO,10 drugs are exempted and 1 grug is exempted in EMA.Conclusion At present,the specific list of drugs are not published of biowaiver in our country,the pharmaceutical companies should compare and consult revelant standards and specific drugs in China and abroad,to speed up the progress of the consistency evaluation.

Avaliação dos mecanismos envolvidos na permeabilidade de fármacos antirretrovirais por meio do modelo de perfusão in situ em ratos / Evaluation of mechanisms involved in the permeability of antiretroviral drugs using the intestinal in situ perfusion model in rats

Para medicamentos administrados oralmente, as etapas de liberação do fármaco a partir da forma farmacêutica e sua subsequente absorção constituem importantes processos para que a adequada biodisponibilidade oral ocorra. Deste modo, as características de solubilidade e de permeabilidade são de extrema importância para que mecanismos relacionados à absorção sejam compreendidos no âmbito das propriedades ADME (absorção, distribuição, metabolismo e excreção). Com base nisso, o Sistema de Classificação Biofarmacêutica (SCB) foi proposto como uma ferramenta que permite a classificação de fármacos em quatro classes distintas de acordo com a solubilidade e permeabilidade. De maneira complementar, o Sistema de Classificação Biofarmacêutica de Distribuição de Fármacos (SCBDF) foi proposto levando em consideração a solubilidade e o metabolismo das substâncias, além de considerar o impacto de transportadores presentes nos tecidos biológicas, inclusive no trato gastrintestinal (TGI). Assim, o presente trabalho teve como objetivo avaliar os mecanismos envolvidos na permeabilidade de fármacos antirretrovirais (estavudina, lamivudina e zidovudina) por meio do modelo de perfusão in situ com coleta de sangue mesentérico em ratos, considerando os aspectos relacionados ao efluxo e ao metabolismo pré-sistêmico que ocorrem nos enterócitos. Além disso, estudos in vitro em culturas celulares MDCK e MDCK-MDR1 foram realizados a fim de auxiliar na elucidação dos mecanismos de transporte dos referidos fármacos. Para a realização dos estudos de perfusão in situ, ratos Wistar foram anestesiados e a porção do jejuno foi canulada para permitir a entrada do fármaco solubilizado no interior do intestino, bem como a coleta das amostras de perfusato em intervalos regulares de tempo. A veia mesentérica também foi canulada para viabilizar a obtenção das amostras de sangue durante os experimentos. Para os estudos de efluxo, o verapamil foi adicionado à solução de perfusão como inibidor de Pgp (glicoproteína-P), enquanto que o cetoconazol foi empregado como inibidor de enzimas CYP3A. Em modelo in vitro MDCK e MDCK-MDR1, os experimentos foram conduzidos bidirecionalmente com o uso de GG918 como inibidor de P-gp. Em todos os experimentos realizados, o metoprolol e a ranitidina foram empregados como marcadores de alta e de baixa permeabilidade, respectivamente. Os resultados de permeabilidade mostraram que a estavudina e a zidovudina apresentam características de alta permeabilidade, enquanto a lamivudina apresentou o menor resultado dentre os três fármacos. Os ensaios bidirecionais em MDCK, no entanto, mostraram que os três antirretrovirais apresentam baixos valores de permeabilidade, uma vez que seus resultados foram significativamente menores que o valor encontrado para o metoprolol. Com relação à avaliação do mecanismo de efluxo, tanto a lamivudina quanto a zidovudina apresentaram interações significativas com a P-gp nos dois métodos empregados (perfusão in situ e MDCK-MDR1), uma vez que o aumento nos valores de permeabilidade foi constatado quando o inibidor de P-gp foi empregado. Os estudos de metabolismo intestinal realizados por meio do modelo de perfusão in situ mostraram que nenhum dos fármacos antirretrovirais apresentou interação significativa com as enzimas CYP3A quando o cetoconazol foi empregado como inibidor, uma vez que não foram constatadas mudanças significativas nos valores de permeabilidade. A comparação entre os resultados de permeabilidade efetiva (Pef) e de permeabilidade aparente (Pap), obtidos por meio da quantificação das amostras de perfusato e de plasma, respectivamente, permitiu verificar que as diferenças estatísticas entre estes dois parâmetros podem indicar variados mecanismos de transporte, uma vez que a Pap constata a quantidade da substância que realmente foi capaz de superar as barreiras físicas e bioquímicas presentes na parede do TGI. Logo, a Pap é considerada um parâmetro mais próximo das condições in vivo. Esta diferença foi constatada apenas para a zidovudina nos ensaios de transporte de efluxo, uma vez que o valor médio de Pef não representou a mesma conclusão fornecida pelo valor médio de Pap. Os resultados obtidos permitiram concluir que os fármacos antirretrovirais apresentam permeabilidade de moderada a alta em função do possível envolvimento de carreadores de influxo. Além disso, os três fármacos antirretrovirais interagiram de alguma forma com a P-gp, sendo os resultados referentes à lamivudina e à zidovudina mais significativos. Embora tenha sido constatada o envolvimento da P-gp na permeabilidade da zidovudina, sua elevada fração absorvida indica que a absorção desta substância não é limitada por este mecanismo e que a ação do carreador de efluxo não é clinicamente relevante neste caso. Com relação aos estudos de metabolismo, a presença de enzimas CYP3A nos enterócitos também não representou uma condição desfavorável para a absorção dos antirretrovirais. Assim, a avaliação dos mecanismos no presente trabalho contribuiu para a caracterização biofarmacêutica da estavudina, lamivudina e zidovudina e as metodologias descritas podem ser empregadas nas etapas iniciais de desenvolvimento farmacêutico com o objetivo de assegurar a segurança e a eficácia de medicamentos.

For orally administered pharmaceutical products, the drug release from the dosage form and its absorption are considered important processes for adequate oral bioavailability. Thus, the solubility and permeability characteristics are extremely important for understanding of mechanisms related to the absorption in the scope of the ADME properties (absorption, distribution, metabolism and excretion). Based on that, the Biopharmaceutics Classification System (BCS) was proposed as a tool for classifying drugs into four classes considering their solubility and permeability characteristics. In an additional way, the Biopharmaceutics Drug Disposition Classification System (BDDCS) was proposed considering the solubility and metabolism of compounds. Besides, the BDDCS also considers the impact of transporters in biological tissues, such as in the gastrointestinal tract (GIT). Thus, this study aimed to evaluate the mechanisms involved in the permeability of antiretroviral drugs (stavudine, lamivudine and zidovudine) using the intestinal in situ perfusion model with mesenteric blood sampling in rats, considering efflux and intestinal pre-systemic metabolism that occur in the enterocytes. Furthermore, in vitro studies in cell cultures MDCK and MDCK-MDR1 were performed in order to elucidate the transport mechanisms of the drugs. For intestinal in situ perfusion studies, Wistar rats were anesthetized and a portion of jejunum was cannulated to allow the drug entry into the intestine, as well as the perfusate sampling at regular time intervals. The mesenteric vein was also cannulated to allow blood sampling during the experiments. For efflux studies, verapamil was used as P-gp (P-glycoprotein) inhibitor while ketoconazole was used as CYP3A inhibitor. In in vitro model MDCK and MDCK-MDR1, the experiments were performed bidirectionally using GG918 as P-gp inhibitor. For all experiments, metoprolol and ranitidine were used as markers of high and low permeability, respectively. Permeability results showed that stavudine and zidovudine present high permeability characteristics while lamivudine showed the lowest value. However, bidirectional studies in MDCK showed that the antiretroviral drugs present low permeability since their results are far from metoprolol's results. Regarding efflux studies, both lamivudine and zidovudine presented relevant interaction with P-gp in in situ perfusion and MDCK-MDR1 models, since the increase in permeability values was observed when P-gp inhibitor was added. Metabolism studies performed through intestinal in situ perfusion showed that none of antiretroviral drugs interact significantly with CYP3A enzymes, since that no variation in permeability results were noticed. Comparison between effective permeability (Peff) and apparent permeability (Papp), obtained from prefusate and plasma, respectively, allowed to check that statistical differences between these two parameters can indicate different transport mechanisms, since Papp is related to the drug amount that really overcome the physical and biochemical barriers in the gut. Thus, Papp is considered the closest parameter to in vivo condition. This difference was observed for zidovudine in efflux studies, since Peff values does not match with the conclusion provided by the Papp. The results obtained allowed to conclude that the antiretroviral drugs presents moderate to high permeability due to the involvement of influx carriers. Furthermore, the antiretroviral drugs interacted with the P-gp, but lamivudine and zidovudine showed significant results. Although the involvement between zidovudine and P-gp is observed, its high fraction absorbed indicates that the absorption is not limited by efflux transporter, which is not relevant clinically. Regarding 32 metabolism studies, CYP3A enzymes is not considered as a limiting condition for absorption of the antiretroviral drugs. Thus, the evaluation of the mechanisms contributes for biopharmaceutical characterization of stavudine, lamivudine and zidovudine and the methodologies used in this study can be applied in early drug development to ensure adequate safety and efficacy of pharmaceutical products.

Solubility evaluation of didanosine: a comparison between the equilibrium method and intrinsic dissolution for biopharmaceutics classification purposes

ABSTRACT BCS (Biopharmaceutics Classification System) and BDDCS (Biopharmaceutics Drug Disposition Classification System) were proposed as tools for classifying drugs into four categories. Both systems consider the solubility as an important characteristic for the classification of compounds in drug development and in vivo disposition prediction. Although some results of drug solubility can be found in the literature, the aforementioned characteristic is not entirely clear when considering didanosine (ddI). Based on that, the solubility of ddI was evaluated using equilibrium and intrinsic dissolution methods. For the equilibrium method, excess amount of ddI was added to each media until obtaining a supersaturated solution and the mixture was submitted to agitation at 37 °C. For the intrinsic dissolution method, the drug was compressed into the Wood's apparatus matrix and subjected to dissolution in each media with agitation at 37 °C. The results obtained from the equilibrium method indicated that it was necessary 139.37 mL of pH 1.2 media, 87.72 mL of pH 4.5 media, 12.54 mL of pH 6.8 media, 5.03 mL of pH 7.5 media and 7.65 mL of purified water for drug solubilization. Furthermore, a very fast intrinsic dissolution rate (IDR) was obtained for each media: 0.1 mg/min/cm² (pH 1.2), 0.2 mg/min/cm² (pH 4.5), 0.2 mg/min/cm² (pH 6.8), 0.1 mg/min/cm² (pH 7.5) and 0.1 mg/min/cm² (purified water). Based on these results, ddI can be considered as a highly soluble drug for both equilibrium and intrinsic dissolution methods.

Biopharmaceutics classification and absorption mechanisms primary study on four kinds of flavonoids / 中国中药杂志

The solubility and permeability on four kinds of flavonoids (kaempferol, hesperidin, apigenin, genistein) were test according to the theory of biopharmaceutics classification system (BCS), and their absorption mechanism. The solubility was investigated by the method in determination of solubility of "Chinese Pharmacopoeia 2010". To detect appearance permeability of compounds mentioned above, the appropriate concentrations were selected by the MTT method in cell transfer experiments in Caco-2 cell model, which established by in vitro cell culture method. Therefore, these compounds were classified with BCS according to solubility and permeability. In addition, to explore absorption mechanisms, the experiments in three different concentrations of compounds in high, medium and low in bidirectional transformation methods in Caco-2 cell model contacted. The study indicated that all of kaempferol, hesperidin, apigenin, genistein have the characteristics in low solubility and high permeability, which belong to BCSⅡ, and the absorption mechanism of kaempferol was active transportation. Whereas, hesperidin, apigenin, genistein were passive transportation. In this study, it carried out initial explorations on establishment of determination for solubility and permeability in flavonoids, and provided theoretical reference for further research on BCS in traditional Chinese medicine.

Effects from right hepatic vein and inferior vena cava position on mechanism of Budd-Chiari syndrome / 医用生物力学

Objective To investigate the effects from various angles between inferior vein cava (IVC) and right hepatic vein (RHV) on pathogenesis of IVC membranous obstruction for patients with Budd-Chiari syndrome (BCS). Methods The normal 3D solid model of IVC and hepatic veins was reconstructed using MRI angiograms, and the angle between IVC and RHV was 56°. The two models with IVC-RHV angle of 30° and 120° were established, respectively, based on the reconstructed model. The distributions of wall shear stress, static pressure and blood velocity of the 3 models were calculated by numerical simulation. Results The wall shear stresses, static pressure and blood velocity of the 3 models displayed significantly differences. Compared with the normal 56° model, the 30° model showed a higher wall pressure and lower blood velocity, while the 120° model presented a lower wall pressure and blood velocity with turbulence of blood flowing, and such hemodynamic changes would increase the risk of thrombosis. The 56° model had the fastest blood velocity. Conclusions Numerical simulation of the flow in IVC and RHV can promote to discover the pathogenesis of BCS, and help to predict risk of IVC membranous obstruction, and provide theoretical references for BCS treatment.

Effect of dexmedetomidine on postoperative analgesia pump dose and effect / 中国生化药物杂志

Objective To investigate effect of dexmedetomidine on postoperative analgesia pump dose and effect.Methods 50 cases of patients with abdominal surgery under general anesthesia were selected.According to the postoperative analgesic drugs were divided into control group and experimental group, 25 cases in each group were given corresponding drug treatment.After treatment, the visual analogue scale, comfort score, adverse reaction rate and dosage of analgesic drugs were detected and compared.Results Compared with the control group,the VAS score were lower(P <0.05),the BCS score were higher(P<0.05),the adverse reaction rate were lower(P<0.05),the dosage of analgesic pump were lower(P<0.05). Conclusion Dexmedetomidine can significantly reduce postoperative pain degree of patients, reduce the incidence of adverse reaction, reduce analgesic dosage of the drug pump.

Síndrome de Budd Chiari: Reporte de tres casos y revisión de la literatura / Budd Chiari Syndrome: Three Case Reports and a Literature Review

Se describen los casos de tres pacientes de sexo femenino a quienes se les hizo diagnóstico de síndrome de Budd Chiari. En una paciente la presentación del síndrome fue subaguda, pudiendo ser manejada exitosamente con la colocación de TIPS. Otra con mutación del factor V Leyden asociada desarrolló disfunción hepática progresiva y requirió de trasplante hepático. En dos de los tres casos se identificó una enfermedad hematológica como trastorno de base, y en uno el uso de anticonceptivos orales como factor de riesgo. Las tres pacientes fueron sometidas a terapia anticoagulante y el manejo quirúrgico fue definido de acuerdo a su condición clínica. Sin embargo, en un caso la presentación fue aguda con falla hepática y muerte.

This article describes the cases of three female patients who were diagnosed with Budd-Chiari syndrome. One patient was subacute and could be successfully managed by placement of a transjugular intrahepatic portosystemic stent (TIPS). Another patient who had the Factor V Leiden mutation developed associated progressive liver dysfunction and required liver transplantation. A hematologic disease was identified as the underlying disorder in two of the three cases. For one patient, the use of oral contraceptives was a risk factor. Since all three patients were undergoing anticoagulant therapy, surgical management was determined according to each patient’s clinical condition. Nevertheless, the one patient who that presented acute hepatic failure did not survive.

Pharmacokinetic aspects and in vitro-in vivo correlation potential for lipid-based formulations

Lipid-based formulations have been an attractive choice among novel drug delivery systems for enhancing the solubility and bioavailability of poorly soluble drugs due to their ability to keep the drug in solubilized state in the gastrointestinal tract. These formulations offer multiple advantages such as reduction in food effect and inter-individual variability, ease of preparation, and the possibility of manufacturing using common excipients available in the market. Despite these advantages, very few products are available in the present market, perhaps due to limited knowledge in the in vitro tests (for prediction of in vivo fate) and lack of understanding of the mechanisms behind pharmacokinetic and biopharmaceutical aspects of lipid formulations after oral administration. The current review aims to provide a detailed understanding of the in vivo processing steps involved after oral administration of lipid formulations, their pharmacokinetic aspects and in vitro in vivo correlation (IVIVC) perspectives. Various pharmacokinetic and biopharmaceutical aspects such as formulation dispersion and lipid digestion, bioavailability enhancement mechanisms, impact of excipients on efflux transporters, and lymphatic transport are discussed with examples. In addition, various IVIVC approaches towards predicting in vivo data from in vitro dispersion/precipitation, in vitro lipolysis and ex vivo permeation studies are also discussed in detail with help of case studies.