scholarly journals Performance Evaluation of Montelukast Pediatric Formulations: Part I—Age-Related In Vitro Conditions

2022 ◽  
Vol 24 (1) ◽  
Author(s):  
Mariana Guimarães ◽  
Pascal Somville ◽  
Maria Vertzoni ◽  
Nikoletta Fotaki
Keyword(s):  
Pediatric Population ◽  
Water Soluble ◽  
Dissolution Studies ◽  
Biorelevant Dissolution ◽  
Age Related ◽  
Negative Effect ◽  
Age Appropriate ◽  
The Impact ◽  
Positive Effect

AbstractThis study aimed to explore the potential of biopharmaceutics in vitro tools to predict drug product performance in the pediatric population. Biorelevant dissolution set-ups were used to predict how age and medicine administration practices affect the in vitro dissolution of oral formulations of a poorly water-soluble compound, montelukast. Biorelevant age-appropriate dissolution studies of Singulair® (granules and chewable tablets) were conducted with the µDISS profiler™, USP 4 apparatus, USP 2 apparatus, and mini-paddle apparatus. Biorelevant simulating fluids representative of adult and pediatric conditions were used in the dissolution studies. The biorelevant dissolution conditions were appropriately selected (i.e. volumes, transit times, etc.) to mimic the gastrointestinal conditions of each of the subpopulations tested. Partial least squares regression (PLS-R) was performed to understand the impact of in vitro variables on the dissolution of montelukast. Montelukast dissolution was significantly affected by the in vitro hydrodynamics used to perform the dissolution tests (µDISS profiler™: positive effect); choice of simulation of gastric (negative effect) and/or intestinal conditions (positive effect) of the gastrointestinal tract; and simulation of prandial state (fasted state: negative effect, fed state: positive effect). Age-related biorelevant dissolution of Singulair® granules predicted the in vivo effect of the co-administration of the formulation with applesauce and formula in infants. This study demonstrates that age-appropriate biorelevant dissolution testing can be a valuable tool for the assessment of drug performance in the pediatric population. Graphical Abstract

The depressing (negative) effect of oestradiol benzoate on the in vitro secretion of LH and FSH by the pituitary gland of the LRH-pretreated long-term ovariectomized rat changes into the augmentative (positive) effect after discontinuation of the LRH-pretreatment

1985 ◽  
Vol 110 (3) ◽  
pp. 329-337 ◽  
Author(s):  
G. A. Schuiling ◽  
H. Moes ◽  
T. R. Koiter
Keyword(s):  
Depressing Effect ◽  
Ovx Rats ◽  
Gonadotrophin Secretion ◽  
Oestradiol Benzoate ◽  
Negative Effect ◽  
Positive Effect ◽  
Perifusion System

Abstract. The effect of pretreatment in vivo with oestradiol benzoate on in vitro secretion of LH and FSH was studied in long-term ovariectomized (OVX) rats both at the end of a 5-day continuous in vivo pretreatment with LRH and 4-days after cessation of such LRH pretreatment. Rats were on day 0 sc implanted with osmotic minipumps which released LRH at the rate of 250 ng/h. Control rats were implanted with a piece of silicone elastomer with the dimensions of a minipump. On days 2 and 4 the rats were injected with either 3 μg EB or with oil. On day 5 part of the rats were decapitated and the in vitro autonomous (i.e. non-LRH-stimulated) and 'supra-maximally' LRHstimulated release of LH and FSH was studied using a perifusion system. From other rats the minipumps were removed on day 5 and perifusion was performed on day 9. On the 5th day of the in vivo LRH pretreatment the pituitary LH/FSH stores were partially depleted; the pituitaries of the EB-treated rats more so than those of the oil-injected rats. EB alone had no significant effect on the content of the pituitary LH- and FSH stores. On day 9, i.e. 4 days after removal of the minipumps, the pituitary LH and FSH contents had increased in both the oil- and the EB injected rats, but had not yet recovered to control values. In rats not subjected to the 5-days pretreatment with LRH EB had a positive effect on the supra-maximally LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. EB had no effect on the non-stimulated secretion of FSH. After 5 days of in vivo pretreatment with LRH only, the in vitro non-stimulated and supra-maximally LRH-stimulated secretion of both LH and FSH were strongly impaired, the effect correlating well with the LRH-induced depletion of the pituitary LH/FSH stores. In such LRH-pretreated rats EB had on day 5 a negative effect on the (already depressed) LRH-stimulated secretion of LH (not on that of FSH). EB had no effect on the non-stimulated LH/FSH secretion. It could be demonstrated that the negative effect of the combined LRH/EB pretreatment was mainly due to the depressing effect of this treatment on the pituitary LH and FSH stores: the effect of oestradiol on the pituitary LRH-responsiveness (release as related to pituitary gonadotrophin content) remained positive. In LRH-pretreated rats, however, this positive effect of EB was smaller than in rats not pretreated with LRH. Four days after removal of the minipumps there was again a positive effect of EB on the LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. The positive effect of EB on the pituitary LRH-responsiveness was as strong as in rats which had not been exposed to exogenous LRH. The non-stimulated secretion of FSH was again not affected by EB. The results demonstrate that the effect of EB on the oestrogen-sensitive components of gonadotrophin secretion consists of two components: an effect on the pituitary LRH-responsiveness proper, and an effect on the pituitary LH/FSH stores. The magnitude of the effect of EB on the LRH-responsiveness is LRH dependent: it is very weak (almost zero) in LRH-pretreated rats, but strong in rats not exposed to LRH as well as in rats of which the LRH-pretreatment was stopped 4 days previously. Similarly, the effect of EB on the pituitary LH and FSH stores is LRH-dependent: in the absence of LRH, EB has no influence on the contents of these stores, but EB can potentiate the depleting effect of LRH on the LH/FSH-stores. Also this effect disappear after cessation of the LRH-pretreatment.

scholarly journals An In Vivo Predictive Dissolution Methodology (iPD Methodology) with a BCS Class IIb Drug Can Predict the In Vivo Bioequivalence Results: Etoricoxib Products

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 507
Author(s):  
Isabel Gonzalez-Alvarez ◽  
Marival Bermejo ◽  
Yasuhiro Tsume ◽  
Alejandro Ruiz-Picazo ◽  
Marta Gonzalez-Alvarez ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
In Vitro Dissolution ◽  
Case Examples ◽  
Dissolution Studies ◽  
Weak Bases ◽  
Transit Times ◽  
Class Iib ◽  
The Impact

The purpose of this study was to predict in vivo performance of three oral products of Etoricoxib (Arcoxia® as reference and two generic formulations in development) by conducting in vivo predictive dissolution with GIS (Gastro Intestinal Simulator) and computational analysis. Those predictions were compared with the results from previous bioequivalence (BE) human studies. Product dissolution studies were performed using a computer-controlled multicompartmental dissolution device (GIS) equipped with three dissolution chambers, representing stomach, duodenum, and jejunum, with integrated transit times and secretion rates. The measured dissolved amounts were modelled in each compartment with a set of differential equations representing transit, dissolution, and precipitation processes. The observed drug concentration by in vitro dissolution studies were directly convoluted with permeability and disposition parameters from literature to generate the predicted plasma concentrations. The GIS was able to detect the dissolution differences among reference and generic formulations in the gastric chamber where the drug solubility is high (pH 2) while the USP 2 standard dissolution test at pH 2 did not show any difference. Therefore, the current study confirms the importance of multicompartmental dissolution testing for weak bases as observed for other case examples but also the impact of excipients on duodenal and jejunal in vivo behavior.

scholarly journals In Vitro Drug Release, Permeability, and Structural Test of Ciprofloxacin-Loaded Nanofibers

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 556
Author(s):  
Luca Éva Uhljar ◽  
Sheng Yuan Kan ◽  
Norbert Radacsi ◽  
Vasileios Koutsos ◽  
Piroska Szabó-Révész ◽  
...  
Keyword(s):  
Amorphous State ◽  
Physical Mixture ◽  
Water Soluble ◽  
Vinyl Pyrrolidone ◽  
Amorphous Solid Dispersion ◽  
Release Mechanism ◽  
Dissolution Studies ◽  
In Vitro Diffusion ◽  
Poly Vinyl Pyrrolidone

Nanofibers of the poorly water-soluble antibiotic ciprofloxacin (CIP) were fabricated in the form of an amorphous solid dispersion by using poly(vinyl pyrrolidone) as a polymer matrix, by the low-cost electrospinning method. The solubility of the nanofibers as well as their in vitro diffusion were remarkably higher than those of the CIP powder or the physical mixture of the two components. The fiber size and morphology were optimized, and it was found that the addition of the CIP to the electrospinning solution decreased the nanofiber diameter, leading to an increased specific surface area. Structural characterization confirmed the interactions between the drug and the polymer and the amorphous state of CIP inside the nanofibers. Since the solubility of CIP is pH-dependent, the in vitro solubility and dissolution studies were executed at different pH levels. The nanofiber sample with the finest morphology demonstrated a significant increase in solubility both in water and pH 7.4 buffer. Single medium and two-stage biorelevant dissolution studies were performed, and the release mechanism was described by mathematical models. Besides, in vitro diffusion from pH 6.8 to pH 7.4 notably increased when compared with the pure drug and physical mixture. Ciprofloxacin-loaded poly(vinyl pyrrolidone) (PVP) nanofibers can be considered as fast-dissolving formulations with improved physicochemical properties.

scholarly journals PENGARUH RELATIONSHIP MARKETING DAN RELATIONSHIP QUALITY TERHADAP LOYALITAS PELANGGAN DENGAN KEPUASAN PELANGGAN SEBAGAI VARIABEL INTERVENING PADA PRODUK PARFUM MULEGH DI PURWOKERTO

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Ilham Akbar
Keyword(s):  
Customer Satisfaction ◽  
Relationship Quality ◽  
Relationship Marketing ◽  
Customer Loyalty ◽  
Structural Equation ◽  
Marketing Relationship ◽  
Negative Effect ◽  
The Impact ◽  
The Relationship ◽  
Positive Effect

The research entitled �The Influence of Relationship Marketing and Relationship Quality Towards Customer Loyalty with Customer Satisfaction as The Intervening Variable on Mulleg Perfume Product in Purwokerto� aims to determine the impact of relationship marketing and relationship quality towards customer satisfaction and customer loyalty and to determine whether customer satisfaction could become the intervening variable. The hypothesis of this research is the relationship marketing has negative effect towards customer satisfaction, the relationship marketing has positive effect towards customer loyalty, the relationship quality has positively effect towards customer satisfaction, the relationship quality has positively effect towards the customer loyalty, and the customer loyalty could be able to mediate the influence of relationship marketing and relationship quality toward customer loyalty.� The analysis method that used on this research is the structural equation modeling.The results show that the relationship marketing has positive and significant effect towards customer satisfaction. It will increase the customer satisfaction of Mulleg Aromatic perfume product in Purwokerto. The relationship quality has positive and significant effect towards customer satisfaction, so it will increase the customer satisfaction of Mulleg Aromatic perfume product in Purwokerto. The relationship marketing has positive and significant effect towards customer loyalt. It will increase the customer loyalty of Mulleg Aromatic perfume product in Purwokerto. The relationship quality has positive and significant effect towards the customer loyalty. The Customer Satisfaction has positive and significant effect towards customer loyalty. The customer satisfaction could mediate the influence of relationship marketing towards the customer loyalty on Mulleg Aromatic perfume product in Purwokerto. The customer satisfaction could mediate the influence of relationship quality towards the customer loyalty of Mulleg Aromatic perfume product in Purwokerto.�Keywords : Relationship Marketing , Relationship Quality , Customer Satisfaction and Customer Loyalty�

scholarly journals Age Differences in the Required Coefficient of Friction During Level Walking Do Not Exist When Experimentally-Controlling Speed and Step Length

2014 ◽  
Vol 30 (4) ◽  
pp. 542-546 ◽  
Author(s):  
Dennis E. Anderson ◽  
Christopher T. Franck ◽  
Michael L. Madigan
Keyword(s):  
Older Adults ◽  
Age Differences ◽  
Coefficient Of Friction ◽  
Age Groups ◽  
Step Length ◽  
Age Difference ◽  
Age Related ◽  
Negative Effect ◽  
Independent Effects ◽  
Positive Effect

The effects of gait speed and step length on the required coefficient of friction (COF) confound the investigation of age-related differences in required COF. The goals of this study were to investigate whether age differences in required COF during self-selected gait persist when experimentally-controlling speed and step length, and to determine the independent effects of speed and step length on required COF. Ten young and 10 older healthy adults performed gait trials under five gait conditions: self-selected, slow and fast speeds without controlling step length, and slow and fast speeds while controlling step length. During self-selected gait, older adults walked with shorter step lengths and exhibited a lower required COF. Older adults also exhibited a lower required COF when walking at a controlled speed without controlling step length. When both age groups walked with the same speed and step length, no age difference in required COF was found. Thus, speed and step length can have a large influence on studies investigating age-related differences in required COF. It was also found that speed and step length have independent and opposite effects on required COF, with step length having a strong positive effect on required COF, and speed having a weaker negative effect.

An Analysis of the Effect of selected Factors on microsurgical Performance

2021 ◽  
Author(s):  
Andrzej Zyluk ◽  
Konrad Czernikiewicz ◽  
Joanna Antoniak ◽  
Urszula Abramczyk
Keyword(s):  
Physical Exercise ◽  
Medical Studies ◽  
Latex Glove ◽  
Physical Exercises ◽  
Surgical Expertise ◽  
Negative Effect ◽  
The Times ◽  
The Impact ◽  
Positive Effect

Abstract Background Microsurgery is a specific surgical expertise that involves operating on very small structures, and requires the assistance of a magnifying device: a microscope or loupes. Several factors have been identified that could affect the quality of microsurgical performance in training or surgical procedures. Objective The objective of this study was to assess the impact of the selected factors – caffeine, alcohol and physical exercise – on a microsurgical task prior its performance. Methods Ten students from the 5th and 6th years of medical studies who had completed the advanced microsurgical course performed a “6-stitches test” on a latex glove spanned over a cup prior to and after consumption of caffeine, alcohol and performing physical exercises. The times taken to complete the task at baseline and post-exposure were recorded. Results The results of the study show a statistically significant positive effect of caffeine and a statistically significant negative effect of physical exercise on microsurgical performance when performed shortly before the task. Small dose of alcohol taken before the task showed had little effect on performance.

Household finances and social comparison: Determinants of financial well-being in Indonesia

2021 ◽  
Vol 4 (1) ◽  
pp. 81
Author(s):  
Aisyah Amatul Ghina ◽  
Subiakto Sukarno
Keyword(s):  
Social Comparison ◽  
Financial Education ◽  
Well Being ◽  
Standard Of Living ◽  
Current Standard ◽  
Financial Position ◽  
Negative Effect ◽  
Socioeconomic And Demographic Factors ◽  
The Impact ◽  
Positive Effect

To achieve a vision of sustainable financial well-being (FWB) in Indonesia, generating more knowledge in household behavior and FWB is pivotal. This study assesses the impact of household financial position and social comparison on individual FWB in Indonesia. Using the latest wave of Indonesia Family Life Survey (IFLS) dataset, subjective FWB assessed by questions on subjective prosperity, perceived current standard of living adequacy and perceived future standard of living. The empirical analysis shows that net wealth and total assets are also essential determinants and positively related to FWB along with income. On the contrary, though it is only found significant on the perceived current standard of living adequacy, the total debt level has a negative effect on FWB. The findings also confirm that socioeconomic and demographic factors also significantly affect FWB (e.g., being female and more educated has a positive effect on FWB). Furthermore, it also found that relative financial position (i.e., social comparison) has important roles in determining individuals' FWB level. Being above the reference group's average for a particular financial measure (i.e., income and total assets) has a positive effect on an individual's FWB. The findings of this study suggest for promoting financial education in the national school system starting senior high school to increase the level of financial well-being among young adult and people with lower educational attainment.JEL Classification C31; D14; I31

METAPHYLAXIS OF APPLICATION OF VETERINARY PREPARATIONS «MULTIOMYCIN 1%» AND «YUBERIN ORAL»

2021 ◽  
pp. 41-47
Author(s):  
E. V. Romanova
Keyword(s):  
Microbial Contamination ◽  
Veterinary Drug ◽  
Production Test ◽  
Combined Use ◽  
Negative Effect ◽  
The Impact ◽  
Daily Gain ◽  
Positive Effect ◽  
Experimental Group

We studied the effect of the antimicrobial drug «Multiomycin 1 %» on the hematological and biochemical pa-rameters of blood, the activity of digestive enzymes (amylase, alkaline phosphatase, protease), the structure of the mi-crobiocenosis of the small and large intestines, and the quality of the products. Based on the results of preclinical stud-ies, a production test was carried out in conjunction with the veterinary drug «Yuberin oral», as well as an assessment of the impact on the productivity of poultry was given. «Multiomycin 1 %» did not adversely affect the chickens. The drug had a positive effect on the activity of the digestive processes, increased their activity. Contributed to a decrease in the total microbial contamination in the contents of the small and large intestines and an increase in the content of bifidobacteria and lactobacilli. Combined use with yuberin contributed to an increase in safety, an increase in the aver-age daily gain, as well as a decrease in the incidence of gastroenteritis. The weight gain at the end of the experiment in the chickens of the experimental group was 3,74 % higher than in the control. The use of the veterinary drug «Multiomycin 1 %» did not have a negative effect on the quality of the products.

scholarly journals Neuroinflammation in Aged Brain: Impact of the Oral Administration of Ellagic Acid Microdispersion

2020 ◽  
Vol 21 (10) ◽  
pp. 3631 ◽  
Author(s):  
Raffaella Boggia ◽  
Federica Turrini ◽  
Alessandra Roggeri ◽  
Guendalina Olivero ◽  
Francesca Cisani ◽  
...  
Keyword(s):  
Oral Administration ◽  
Ellagic Acid ◽  
Ex Vivo ◽  
Behavioral Skills ◽  
Aged Mice ◽  
Age Related ◽  
The Central Nervous System ◽  
The Impact ◽  
Old Mice

The immune system and the central nervous system message each other to preserving central homeostasis. Both systems undergo changes during aging that determine central age-related defects. Ellagic acid (EA) is a natural product which is beneficial in both peripheral and central diseases, including aging. We analyzed the impact of the oral administration of a new oral ellagic acid micro-dispersion (EAm), that largely increased the EA solubility, in young and old mice. Oral EAm did not modify animal weight and behavioral skills in young and old mice, but significantly recovered changes in “ex-vivo, in vitro” parameters in old animals. Cortical noradrenaline exocytosis decreased in aged mice. EAm administration did not modify noradrenaline overflow in young animals, but recovered it in old mice. Furthermore, GFAP staining was increased in the cortex of aged mice, while IBA-1 and CD45 immunopositivities were unchanged when compared to young ones. EAm treatment significantly reduced CD45 signal in both young and old cortical lysates; it diminished GFAP immunopositivity in young mice, but failed to affect IBA-1 expression in both young and old animals. Finally, EAm treatment significantly reduced IL1beta expression in old mice. These results suggest that EAm is beneficial to aging and represents a nutraceutical ingredient for elders.

scholarly journals Examining the Impact of Innovation Forms on Sustainable Economic Performance: The Influence of Family Management

2019 ◽  
Vol 11 (21) ◽  
pp. 6132 ◽  
Author(s):  
Rubén Martínez-Alonso ◽  
María J. Martínez-Romero ◽  
Alfonso A. Rojo-Ramírez
Keyword(s):  
Family Involvement ◽  
Economic Performance ◽  
Firm Growth ◽  
Process Innovation ◽  
Family Management ◽  
Sustained Competitive Advantage ◽  
Negative Effect ◽  
Family Involvement In Management ◽  
The Impact ◽  
Positive Effect

The aim of this research is to explore the effect that innovation, as a potential source of sustained competitive advantage and firm growth, has on the achievement of sustainable economic performance. In particular, this paper empirically examines the influence of four innovation forms (intramural R&D, extramural R&D, product innovation, and process innovation) on firms’ sustainable economic performance, considering the moderating effect of family involvement in management. To test the hypotheses, random-effects regression analyses are applied to a longitudinal sample of 598 Spanish private manufacturing firms throughout the 2006–2015 period. The results show a negative effect of intramural and extramural R&D on sustainable economic performance and a positive effect of process innovation on sustainable economic performance. Moreover, a reinforced relationship between process innovation and sustainable economic performance is also revealed when family involvement in management acts as a moderator. The findings make several contributions to research and practice.

Sign in / Sign up

Export Citation Format

Share Document