scholarly journals Development of an Age-Appropriate Mini Orally Disintegrating Carvedilol Tablet with Paediatric Biopharmaceutical Considerations

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 831
Author(s):  
Dilawar Khan ◽  
Daniel Kirby ◽  
Simon Bryson ◽  
Maryam Shah ◽  
Afzal Rahman Mohammed
Keyword(s):  
Paediatric Population ◽  
European Medicines Agency ◽  
Gi Tract ◽  
Anatomy And Physiology ◽  
Conventional Tablet ◽  
Adequate Dose ◽  
Fasted State ◽  
Swallowing Difficulties ◽  
Age Appropriate ◽  
And Performance

Owing to considerable differences observed in anatomy and physiology between paediatric subsets, it has been well established that children respond to drugs differently compared to adults. Furthermore, from a formulation perspective, there is a distinct challenge to develop a dosage form that is capable of safely, accurately, and reliably delivering the dose across the whole paediatric population. Orally disintegrating mini-tablets (ODMT) have widely been considered as an age-appropriate formulation option that possess the ability for adequate dose flexibility, avoids swallowing difficulties, and exhibits superior stability due to its solid state. Within this study, two strengths (0.5 mg and 2 mg) of carvedilol ODMT formulations were developed using an excipient composition and load that is appropriate for paediatric use. The formulations demonstrated adequate mechanical strength (>20 N) and fast disintegration times (<30 s). Dissolution profiles observed were robust and comparable to the marketed conventional tablet formulation across various parts of the gastrointestinal (GI) tract in both the fed and fasted state, signifying appropriate efficacy, quality, and performance. As such, the formulations developed in this study show potential to address the need of an ‘age-appropriate’ formulation of carvedilol, as highlighted by the European Medicines Agency (EMA) Inventory of the Needs for Paediatric Medicine.

scholarly journals P23 Accelerating and de-risking the production of paediatric oral formulations

2020 ◽  
Vol 105 (9) ◽  
pp. e18.1-e18
Author(s):  
Dilawar Khan ◽  
Daniel Kirby ◽  
Simon Bryson ◽  
Maryam Shah ◽  
Mohammed Afzal
Keyword(s):  
Paediatric Population ◽  
European Medicines Agency ◽  
List Type ◽  
Scanning Calorimetry ◽  
Glycopyrronium Bromide ◽  
Paediatric Regulation ◽  
Age Appropriate ◽  
Screening Platform ◽  
The Eu ◽  
Paediatric Medicines

Background & AimAs part of the EU paediatric regulation, the paediatric use marketing authorisation (PUMA) was introduced, with an aim to stimulate research in existing compounds that are off-patent and/or to help transform known off-label use into authorised use.1 However, success has been limited, with only a few products gaining a PUMA, such as Sialanar 320 micrograms/mL glycopyrronium (equivalent to 400 micrograms/mL glycopyrronium bromide). A distinct challenge to overcome in this area is the development of more ‘age appropriate formulations’, particularly with an excipient composition and load that is suitable for paediatric patients. This project aims to establish an excipient screening platform, supplemented with analytical characterisation of materials, which will act as a decision making tool to accelerate and de-risk the production of age appropriate paediatric medicines.MethodTo develop this excipient screening platform, a list of drugs that require an age appropriate formulation was produced using the ‘needs for paediatric medicines’ documents provided by the European medicines agency (EMA),2whilst common problematic excipients in paediatrics were identified using an EMA reflection paper.3 Literature and prescribing data were also reviewed to ensure drugs selected would benefit from an age appropriate formulation. Differential scanning calorimetry (DSC) to determine compatibility of selected drugs with widely used excipients was carried out using a TA DSCQ200 instrument (TA Instruments, New Castle, DE) with TA Instruments Universal Analysis 2000 software. Data was collected under nitrogen atmosphere (50 mL min−1) using pierced flat-bottomed TZero aluminium pans (sample mass about 2 mg) and heating rate of 10 °C min−1 in the range from 50 to 400°C. For samples containing both the drug and an excipient, 1 mg of each was measured out and gently mixed with a spatula for one minute.ResultsThe most common class of drugs identified as requiring age appropriate formulations were related to cardiovascular disorders and neurology, whilst the majority of drugs identified also exhibit poor aqueous solubilities. Some identified problematic excipients include ethanol, sodium benzoate and sorbitol; however, these excipients may still be used in paediatric formulations, as long as they are below certain concentrations (for example, ethanol concentration should not exceed 0.5% w/v for under 6 years old). Two drugs identified through the initial screening, carvedilol and nifedipine, were analysed by DSC, alone and then alongside starch from corn and starch 1500; the resulting DSC curves showed no changes in peak size, position (peak onset temperatures for nifedipine and carvedilol were observed at 173.2°C and 117.3°C, respectively) and shape, as well as no additional peaks, therefore suggesting compatibility between the tested samples.ConclusionThis first phase of the development of an excipient screening platform will continue to scan several different excipients with selected active pharmaceutical ingredients (APIs) in order to create compatibility profiles. The excipient screening platform generated will accelerate and de-risk the production of age appropriate formulations, as it would allow screening for potential incompatibilities and acceptability, alongside informing formulation of appropriate oral paediatric dosage forms.ReferencesEuropean Commission. State of Paediatric Medicines in the EU. 10 years of the EU Paediatric Regulation. COM (2017) 626. Available at: https://ec.europa.eu/health/sites/health/files/files/paediatrics/docs/2017_childrensmedicines_report_en.pdfNeeds for paediatric medicines - European Medicines Agency [Internet]. 2019 [cited 28 June 2019]. Available from: https://www.ema.europa.eu/en/human-regulatory/research-development/paediatric-medicines/needs-paediatric-medicinesReflection paper: formulations of choice for the paediatric population [Internet]. European Medicines Agency. 2019 [cited 28 June 2019]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-formulations-choice-paediatric-population_en.pdf

scholarly journals Light-degradable hydrogels as dynamic triggers for gastrointestinal applications

2020 ◽  
Vol 6 (3) ◽  
pp. eaay0065 ◽  
Author(s):  
Ritu Raman ◽  
Tiffany Hua ◽  
Declan Gwynne ◽  
Joy Collins ◽  
Siddartha Tamang ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Implantable Devices ◽  
Large Animal Model ◽  
Large Animal ◽  
Gi Tract ◽  
Biomedical Device ◽  
Precise Tool ◽  
And Performance

Triggerable materials capable of being degraded by selective stimuli stand to transform our capacity to precisely control biomedical device activity and performance while reducing the need for invasive interventions. Here, we describe the development of a modular and tunable light-triggerable hydrogel system capable of interfacing with implantable devices. We apply these materials to two applications in the gastrointestinal (GI) tract: a bariatric balloon and an esophageal stent. We demonstrate biocompatibility and on-demand triggering of the material in vitro, ex vivo, and in vivo. Moreover, we characterize performance of the system in a porcine large animal model with an accompanying ingestible LED. Light-triggerable hydrogels have the potential to be applied broadly throughout the GI tract and other anatomic areas. By demonstrating the first use of light-degradable hydrogels in vivo, we provide biomedical engineers and clinicians with a previously unavailable, safe, dynamically deliverable, and precise tool to design dynamically actuated implantable devices.

Article Commentary: The Management of Pediatric Polytrauma: Review

2014 ◽  
Vol 5 ◽  
pp. CMTIM.S12260
Author(s):  
H. Mevius ◽  
M. van Dijk ◽  
A. Numanoglu ◽  
A.B. van As
Keyword(s):  
Developing Countries ◽  
Emergency Room ◽  
Web Of Science ◽  
Current Knowledge ◽  
Paediatric Population ◽  
Crucial Point ◽  
Comprehensive Overview ◽  
Mortality And Morbidity ◽  
Age Appropriate ◽  
Polytrauma Patients

Polytrauma is a major cause of mortality and morbidity in both developed and developing countries. The primary goal of this review is to provide a comprehensive overview on current knowledge in the management of pediatric polytrauma patients (PPPs). A database review was conducted based on a search in the Embase, Medline OVID-SP, Web of Science, Cochrane central, and Pubmed databases. Only studies with “paediatric population” and “polytrauma” as criteria were included. A total of 3310 citations were retrieved. Of these, 3271 were excluded after screening, based on title and abstract. The full texts of 39 articles were assessed; further selection left 25 articles to be included in this review. The most crucial point in the management of PPPs is preparedness of the staff and an emergency room furnished with age-appropriate drugs and equipment combined with a systemic approach.

Fed and fasted state gastro-intestinal in vitro lipolysis: In vitro in vivo relations of a conventional tablet, a SNEDDS and a solidified SNEDDS

2014 ◽  
Vol 57 ◽  
pp. 232-239 ◽  
Author(s):  
Philip Carsten Christophersen ◽  
Martin Lau Christiansen ◽  
Rene Holm ◽  
Jakob Kristensen ◽  
Jette Jacobsen ◽  
...  
Keyword(s):  
In Vitro Lipolysis ◽  
Conventional Tablet ◽  
Fasted State

scholarly journals Survival of vaccine-induced human milk SARS-CoV-2 IgG and IgA immunoglobulins across simulated human infant gastrointestinal digestion

2021 ◽  
Author(s):  
Myrtani Pieri ◽  
Vicky Nicolaidou ◽  
Irene Paphiti ◽  
Spyros Pipis ◽  
Kyriacos Felekkis ◽  
...  
Keyword(s):  
Human Milk ◽  
Enzymatic Degradation ◽  
Natural Infection ◽  
In Vitro Digestion ◽  
Human Infant ◽  
European Medicines Agency ◽  
Igg Antibodies ◽  
Gi Tract ◽  
Lactating Mothers

Four vaccines have been approved to date by the European Medicines Agency for the management of the COVID-19 pandemic in Europe, with all four being targeted to adults over 18 years of age. One way to protect the younger population such as infants or younger children until pediatric vaccines are licensed is through passive immunity via breastfeeding. Recent evidence points to the fact that human milk contains immunoglobulins (Ig) against the SARS-CoV-2 virus, both after natural infection or vaccination, but it is not known whether these antibodies can resist enzymatic degradation during digestion in the infant gastrointestinal (GI) tract or indeed protect the consumers. Here, we describe our preliminary experiments where we validated commercially available ELISA kits to detect IgA and IgG antibodies in human milk from two lactating mothers vaccinated with either the Pfizer/BioNTech or the Astra Zeneca vaccine, and the effect of a static in vitro digestion protocol on the IgA and IgG concentrations. Our data, even preliminary, provide an indication that the IgA antibodies produced after vaccination with the Pfizer/BioNTech vaccine resist the gastric phase but are degraded during the intestinal phase of infant digestion, whereas the IgGs are more prone to degradation in both phases of digestion. We are in the process of recruiting more individuals to further evaluate the vaccine-induced immunoglobulin profile of breastmilk, and the extent to which these antibodies can resist digestion in the infant GI tract.

scholarly journals An Overview of Robotic Capsules for Drug Delivery to the Gastrointestinal Tract

2021 ◽  
Vol 10 (24) ◽  
pp. 5791
Author(s):  
Pablo Cortegoso Valdivia ◽  
Alexander R. Robertson ◽  
Nanne K. H. De Boer ◽  
Wojciech Marlicz ◽  
Anastasios Koulaouzidis
Keyword(s):  
Drug Delivery ◽  
Targeted Therapy ◽  
Gastrointestinal Tract ◽  
Small Bowel ◽  
Drug Delivery Systems ◽  
Rapid Evolution ◽  
Gi Tract ◽  
Standard Drug ◽  
Anatomy And Physiology ◽  
Complex Anatomy

The introduction of capsule endoscopy two decades ago marked the beginning of the “small bowel revolution”. Since then, the rapid evolution of microtechnology has allowed the development of drug delivery systems (DDS) designed to address some of the needs that are not met by standard drug delivery. To overcome the complex anatomy and physiology of the gastrointestinal (GI) tract, several DDS have been developed, including many prototypes being designed, built and eventually produced with ingenious drug-release mechanisms and anchoring systems allowing targeted therapy. This review highlights the currently available systems for drug delivery in the GI tract and discusses the needs, limitations, and future considerations of these technologies.

Establishing Healthy Chest Register in Child Singers

2014 ◽  
Vol 24 (2) ◽  
pp. 87-93
Author(s):  
Barbara M. Wilson Arboleda
Keyword(s):  
Functional Activity ◽  
Relevant Information ◽  
Voice Training ◽  
Motor Patterns ◽  
General Lack ◽  
Anatomy And Physiology ◽  
Age Appropriate ◽  
Physiological Differences ◽  
The Impact ◽  
Chest Voice

Historically, teaching children to utilize their chest voice in singing has been actively discouraged. These admonitions arise from assumed rather than scientifically based conclusions regarding the anatomical and physiological differences between children and adults. Chest voice singing is both an enjoyable and functional activity for children. The general lack of distinction children have between speaking and singing and their readiness to incorporate new motor patterns—for better or worse—make them ideally suited for age-appropriate training. In this article, the controversy regarding children's use of chest register will be reviewed along with relevant information about anatomy and physiology. Updated information regarding the impact of training on children will be illuminated and a framework for implementing chest voice training will be presented.

Anatomy and physiology of the gastrointestinal tract

2021 ◽  
pp. 1-16
Author(s):  
Jennie Burch ◽  
Brigitte Collins
Keyword(s):  
Gastrointestinal Tract ◽  
Gall Bladder ◽  
Abdominal Cavity ◽  
Structure And Function ◽  
Pelvic Cavity ◽  
Gi Tract ◽  
Waste Products ◽  
Anatomy And Physiology ◽  
And Function

The anatomy and physiology of the gastrointestinal (GI) tract chapter provides information on the parts, structure, and function of the gut. The hollow tube of the gastrointestinal tract begins at the mouth and ends at the anus. The GI tract in part lies within the abdominal cavity and the pelvic cavity. There are also the accessory organs of the liver, pancreas, and gall bladder. The nerves, hormones, secretions, and blood supply to the gut are also explored. The role of the GI tract is to ingest food and fluids. These are digested through mechanical and chemical means such as chewing. The nutrients are then absorbed, predominantly in the ileum. Waste products are finally eliminated via the anus.

Response of Patients with Aggressive Non Hodgkin's Gastro Intestinal Tract Lymphoma to Upfront Rituximab Based Chemotherapy: A Single Institution Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4791-4791
Author(s):  
Bety Ciobanu ◽  
Shylendra B Sreenivasappa ◽  
Mousami Shah ◽  
Barbara Yim ◽  
Rosalind Catchatourian
Keyword(s):  
High Risk ◽  
Surgical Complications ◽  
Cell Lymphoma ◽  
Risk Group ◽  
Performance Status ◽  
Gastric Lymphoma ◽  
B Cell Lymphoma ◽  
High Risk Group ◽  
Gi Tract ◽  
And Performance

Abstract Abstract 4791 Background Response and factors affecting response in patients with aggressive Non Hodgkin's Gastro Intestinal (GI) tract lymphoma to upfront Rituximab based chemotherapy is not well characterized. Methods 41 consecutive pts diagnosed and treated with GI tract lymphoma in 2002 to 2009 were studied as a retrospective cohort for clinical presentation, prognostic characteristics and long term survival. Prognostic characteristics and survival was analyzed using logistic regression and Cox Proportional Hazards model. Multiple imputation methods were used for missing data. Results 41 pts, median age at presentation was 58 yr (28-80). 10 (24.4%) were African Americans, 22 (51.2%) were Hispanics and 10 (24.4%) were Caucasians. 35 (85.4%) had gastric lymphoma and 6 (14.6%) had intestinal lymphoma. 33 pts had aggressive NHL. 31 had Diffuse large B cell lymphoma, 2 Mantel cell lymphoma and 1 Burkitt's lymphoma. 6 (17.6%) presented with stage IE, 4 (11.8) stage II1, 6(17.6%) Stage II2, 7(20.6%) Stage IIE, and 10 (29.4%) Stage IV. 28(82.3%) pts were diagnosed by endoscope. 5 (14.7%) pts underwent surgery as they presented with obstruction or bleeding, none underwent curative resection. All pts received Rituximab based chemotherapy upfront. 29 received CHOPR, 2 CVPR and 2 Hyper CVAD R. Mean follow up was 23.7 months. 22 (64.8%) pts had a complete response, 6 (17.6%) partial response and 6 (17.6%) had progressive disease. 11 pts relapsed. The median disease free survival (DFS) was 13 months (1-105). Age was the sole significant prognostic factor that influenced DFS OR 1.047 CI 1.003-1.094). Age (OR 1.164 CI 1.045-1.296), stage (OR 1.743 CI 1.053-2.888) and performance status (OR 2.703 CI 1.030-7.097) were factors which significantly affect survival. Survival function was 100%, 55.6% and 58.3% for low, intermediate and high risk group of stage modified IPI for gastric lymphoma. 100%, 70% 58.3% for low intermediate and high risk group as per the revised IPI but survival functions are not significant. 12 (35.3%) of pts tolerated chemotherapy with no grade 3 or 4 adverse events. 13 (38%) had g 3or 4 hematological toxicity. 5 (15%) had surgery post chemotherapy. 2 (6%) has GI perforation and 3 (9%) developed GI bleeding post chemotherapy. Surgical complications occurred after the 1st cycle of chemotherapy. Conclusion Aggressive Non Hodgkins GI lymphoma can be effectively treated with Rituximab based chemotherapy as upfront therapy with a response rate of 83%. Age, stage and performance status significantly effect survival. R IPI may need to be revised to predict survival in gastric lymphoma. 15% treated with chemotherapy upfront may need surgery for complications. Perforation rate was about 3% and most surgical complications occur after 1st cycle of chemotherapy. Disclosures: No relevant conflicts of interest to declare.

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