9 research outputs found
New biomimetic barrier Permeapad™ for efficient investigation of passive permeability of drugs
No full textIn this work the suitability of a newly invented physical patch comprising a biomimetic barrier (named Permeapad™) for drug permeability tests has been investigated. Exemplars of Permeapad™ were adapted to Franz diffusion cells and apparent permeability (Papp) of a series of drugs were measured and compared with calculated partition coefficients (log Pcal) of the investigated drugs as well as literature reference values obtained from Parallel Artificial Membrane Permeation Assay (PAMPA) and the cellular based method Caco-2. Moreover, tightness of the barrier to hydrophilic marker's permeation, resistance of these barriers to proton permeation (pH changes) and shelf-life functionality were also investigated. Comparison with the published data indicated a good correlation between the permeability values measured and partition coefficients (log Pcal). Moreover, a good correlation between the permeabilities measured with the new barrier and well-established in vitro permeability methods (PAMPA and Caco-2 respectively) was found for both highly absorbed and poorly permeable compounds. Permeapad™ also proved to maintain high integrity over time and in different pH environments. In conclusion, Permeapad™ as an innovative barrier appears to be a promising tool for fast, cost effective and reliable screening of drugs and chemical entities' passive permeability.</p
Permeapad™ for investigation of passive drug permeability:The effect of surfactants, co-solvents and simulated intestinal fluids (FaSSIF and FeSSIF)
No full textAbstract The aim of the present work was to investigate the potential of the new and innovative artificial barrier, Permeapad™, when exposed to surfactants and co-solvents, often employed for poorly water soluble compounds. The barrier was in addition also exposed to fasted and fed state simulated intestinal fluids versions 1 and 2 (FaSSIF and FeSSIF), all of which the Permeapad™ barrier was compatible with based upon relative comparison of the permeability of the hydrophilic marker calcein in phosphate buffer. The new barrier therefore holds a huge potential due to its functional stability and robustness. It can be used as a standard tool to investigate permeability of drugs in the presence of different surfactants and co-solvents, from DMSO stock solutions at even high concentrations and for the evaluation of permeability in the presence of biomimetic media (BMM). 1 </p
New biomimetic assay for the prediction of biopharmaceutical properties of drug formulations
No full textMange nye lægemiddelstoffer er lipofile og tungopløselige i vandige opløsninger, hvilket kan føre til begrænsninger ved oral indtagelse. Udfordringen med tungopløselige stoffer kan løses ved at designe en god lægemiddelformulering. En god lægemiddelformulering, vil kunne resultere i højere biotilgængelighed for tungopløselige lægemiddelstoffer ved oral indtagelse. Lipid baseret formuleringer (LBF) har vist sig at være en god formulering til at øge opløseligheden af tungopløselige stoffer in vitro. Dette har dog ikke været observeret i in vivo studier. Derfor er det vigtigt at forstå LBF i forhold til lipid nedbrydning, lægemiddelfrigørelse og lægemiddeloptagelse in vitro for bedre at kunne efterligne situationen som forekommer in vivo.Formålet med denne afhandling var at undersøge, og validere, Permeapad®, en ny biomimetisk barriere, som et in vitro redskab til at studere lægemiddelstoffers permeabilitet, både som formulering og uden formulering. Formålet var også at opstille en in vitro lipolyse/permeation model til at studere LBF i forhold til lipid nedbrydning, lægemiddelfrigivelse og den efterfølgende lægemiddeloptagelse.Den biomimetiske barrieres egenskaber og dens modstandsdygtighed mod relevante surfaktanter og solventer, som ofte anvendes i lægemiddelformuleringer blev undersøgt og valideret. Data viste, at barrieren var modstandsdygtig overfor de anvendte surfaktanter og mod biomimetisk media, som simuleret tarmvæsker (FaSSIF/FeSSIF). Dette gør barrieren til en god in vitro permeabilitets model til at undersøge effekten af lægemiddelformuleringer for tungopløselige lægemiddelstoffer. Den pH- og koncentrationsafhængige permeabilitet af forskellige lægemiddelstoffer blev også undersøgt ved hjælp af den biomimetiske barriere og caco-2 celler. Data viste, at apparent permeabilitets koefficienten (Papp), formentlig ikke er koncentrationsuafhængig som hidtil antaget.En in vitro model som kombinere lipid nedbrydning og lægemiddeloptagelse i en og samme model blev udviklet og etableret. Barrieren blev valideret ift. relevante enzymer og forskellige LBF, og var i alle tilfælde fundet modstandsdygtig. Data viste, at permeabiliteten af et lægemiddelstof var 50 gange højere når lipid nedbrydning blev kombineret med lægemiddeloptagelse, sammenlignet med permeabiliteten af et lægemiddelstof inkorporeret i en LBF, hvor nedbrydning ikke fandt sted. Disse resultater viste vigtigheden af et absorptions trin in lipolyse studier for LBF. Udviklingen af denne in vitro lipolyse/permeation model er et yderst relevant og vigtigt skridt hen mod at kunne forudsige biotilgængeligheden af LBF.In the drug development field, many of the new chemical entities (NCE) exhibit high lipophilicity and poor aqueous solubility, which result in difficulties for oral administration. Low aqueous solubility can be overcome by a good formulation design. An appropriate design could potentially result in a drug formulation which is suitable for oral administration. Lipid based formulations (LBF) is a promising approach to formulate poorly water soluble drugs (PWSD). LBF have shown to increase drug solubility, in vitro. However, a corresponding increase in oral bioavailability was not always found in vivo. Therefore, it is of great importance to understand LBF in terms of lipid digestion, drug release and drug absorption in vitro.The aim of this thesis was to study and validate Permeapad®, a new biomimetic barrier, as an in vitro tool to study permeability of drug compounds and enabling formulations, e.g. LBF. This would include the setup of an in vitro lipolysis/permeation model, which comprises of lipid digestion and a drug absorption step.The properties of the biomimetic barrier and its resistance against relevant surfactants and solvents, commonly used in enabling formulations, was studied and validated. Results showed the barrier to be resistant towards the studied surfactants, even in the highest concentration. The barrier was also shown to be resistant to biomimetic media, such as fasted/fed simulated intestinal fluids (FaSSIF/FeSSIF), which makes the barrier a good in vitro permeability model to study the effect of enabling formulations of PWSD.The effect of pH and different concentrations, on permeation of different drugs was also studied in both the biomimetic barrier and caco-2 cells, and results showed that the apparent permeability coefficient (Papp) may not be concentration independent, as previously suggested.An in vitro model which combines lipid digestion and drug permeation in a simultaneous way was proposed and developed in this thesis. The barrier was validated in relation to pancreatic enzymes and different LBF. Results showed that drug permeability of LBF may be increased up to 50x when combining lipid digestion with a permeation step, compared to drug permeability of the nondigested formulations. These findings indicate the importance of adding an absorptive step in lipolysis studies of LBF. The development of an in vitro model combing lipolysis and drug permeation is of high relevance and an important step towards the predictability of LBF bioavailability
Use of Permeapad® for prediction of buccal absorption:A comparison to in vitro, ex vivo and in vivo method
No full textThe present work explores the usefulness of Permeapad® for prediction of buccal absorption. Permeability studies with the model drug metoprolol were carried out using the Permeapad® barrier at pH values 7.4; 8.5; 9.0, and 9.5. It was confirmed that Permeapad® can withstand these conditions, and as expected, a clear increase in permeability was found with increasing pH. The permeation results across Permeapad® were compared to published in vitro, ex vivo and in vivo studies for the same formulations. Results showed that the permeability of metoprolol using the Permeapad® barrier correlated very well to both in vitro and ex vivo studies, (r 2 = 0.98 and 0.97), respectively. Furthermore, excellent in vitro in vivo correlation IVIVC (r 2 = 0.98) was obtained when comparing apparent permeability coefficient to the absolute bioavailability of metoprolol administered buccally to mini-pigs. Results indicate that Permeapad® can be used to mimic the buccal absorption of metoprolol as a faster and less laborious method as compared to any of the other mentioned methods. </p
Using object-z to formalize testing c++ classes
No full textThis thesis was scanned from the print manuscript for digital preservation and is copyright the author.
Researchers can access this thesis by asking their local university, institution or public library to
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Simultaneous lipolysis/permeation in vitro model, for the estimation of bioavailability of lipid based drug delivery systems
No full textThe simultaneous processes of lipid digestion and absorption together determine the oral bioavailability of drugs incorporated into lipid based drug delivery systems (LBDDS). A number of slightly different protocols for in vitro lipolysis are widely accepted; however, the permeation process has so far not been included into the models due to the harsh conditions of lipid digestion compromising permeation barriers. The present study for the first time combines biomimetic permeation and lipolysis of LBDDS. The focus of the current work was on the functional stability of the barrier - Permeapad® during lipid digestion. Using calcein as a marker molecule the investigations demonstrated that the barrier was able to maintain its permeation properties in the presence of the SNEDDS (self-emulsifying drug delivery system) formulation, the lipolysis medium, and the lipolysis medium while digesting the SNEDDS. Furthermore, the permeation of cinnarizine (CINN) from SNEDDS was demonstrated to be lower, if the formulation as such was applied as compared to the digested formulation. This support the general perception that meaningful in vitro evaluation of lipid based formulations requires consideration of both, the digestion and absorption, i.e. lipolysis and permeation.</p
Successes and challenges of Arabic sentiment analysis research: a literature review
No full textThe analysis of sentiment in text has mainly been focused on the English language. The complexity of the Arabic language and its linguistic features that oppose those found in English resulted in the inability to adapt extant research to Arabic contexts limiting advancement in Arabic sentiment analysis. The need for Arabic sentiment analysis research is accentuated by the driving changes in different Arab regions like heavy political movements in some areas and fast growth in others. These changes help shape not just policies and implications of this region but affect the entire world on a global scale. Therefore, it is essential to utilise effective methods of sentiment analysis to analyse Arabic tweets to understand regional and global implications in microblogging mediums such as Twitter. In this paper, we conduct a comprehensive review of Arabic sentiment analysis, present the pros and cons of the different approaches used and highlight the challenges of it. Finally, we outline the relevant gaps in the literature and suggest recommendations for future Arabic sentiment analysis research. - 2017, Springer-Verlag GmbH Austria.This publication was made possible by the NPRP award [NPRP 7-1334-6-039 PR3] from the Qatar National Research Fund (a member of The Qatar Foundation). The statements made herein are solely the responsibility of the author[s].Scopu
Homocysteine levels and cardiovascular disease risk factors in chronic kidney disease (CKD), hypertensive and healthy Nigerian adults: A comparative retrospective study
No full text© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. http://creativecommons.org/licenses/by-nc/4.0/OBJECTIVES: To investigate homocysteine (Hcy) levels in individuals with chronic kidney disease (CKD), hypertension and a healthy Nigerian population, and to assess their association with cardiovascular disease (CVD) risk. SETTING: The study was conducted using data from the Ibadan CRECKID (Cardiovascular and Renal Event in People with Chronic Kidney Disease) study in Nigeria. Participants: A total of 420 adults (aged 18+) categorised into three groups: individuals with stage 2 CKD or higher, hypertensive non-CKD individuals and normotensive individuals. OUTCOMES: The primary outcome was the difference in serum Hcy levels across the groups; secondary outcomes included the prevalence of hyperhomocysteinaemia (HHcy) and correlation with fibroblast growth factor (FGF). RESULTS: No significant difference in mean serum Hcy levels among the CKD, hypertensive and healthy groups (p=0.39) was observed. However, HHcy (≥15 µmol/L) prevalence was significantly higher in the hypertensive group (p<0.05). A strong positive correlation between Hcy levels and FGF was identified across all groups (p<0.001). CONCLUSIONS: The present study indicates that Hcy levels may not serve as a reliable predictor of CVD outcomes across populations with varying kidney function and CVD risk profiles.Unfunde
Exploring different stroke populations’ information needs: a cross-sectional study in England
No full textBackground: While tailored information might have the potential to motivate stroke survivors to make essential lifestyle changes and improve long-term outcomes, how this varies among different stroke populations is not yet fully understood. Method: From November 2022 to May 2023, stroke survivors in the UK, who were clinically stable, participated in a community-based, descriptive cross-sectional study. Participants rated several information themes on a Likert scale from one to five, indicating the relevance of each information group to them. Data were analysed using Wilcoxon and chi-squared tests on SPSS. Descriptive statistics were employed for examining the preferred information delivery method, timing, personnel, and frequency. Results: Seventy survivors, with an average age of 67 ± 19 (61% males), were recruited. Survivors emphasised the importance of symptoms, risk factors, and recovery information during hospital stay, while medication and lifestyle change information were more significant in the community. Subgroup analysis revealed distinct patterns: First-time stroke survivors highlighted the importance of social and financial support (acute phase median Likert score 3, chronic phase median Likert score 4; p < 0.01), while those with prior strokes emphasised information on driving and working after stroke (acute phase median Likert score 4, chronic phase median Likert score 3; p < 0.05). Survivors recruited after six months of stroke prioritised knowledge of carer support in the community (acute phase median Likert score 3.5, chronic phase median Likert score 4; p < 0.01). Conclusion: Survivors’ information needs differ depending on factors such as the recovery phase, type of stroke, time since diagnosis, and the presence of a previous stroke. Considering these factors is essential when developing or providing information to stroke survivors.Acknowledgements: The corresponding author (Allam Harfoush) gratefully acknowledges the support and efforts of the Council for At-Risk Academics (Cara
