Development of a pediatric oral solution of ONC201 using nicotinamide to enhance solubility and stability.

Diffuse intrinsic pontine glioma (DIPG) poses a significant treatment challenge in pediatric patients due to its aggressive nature and difficulty in crossing the blood-brain barrier with effective therapies. ONC201 (dordaviprone) shows promises in inducing apoptosis in cancer cells but suffers from poor water solubility and stability issues. Moreover, conventional solubilizing agents acceptable in formulations intended for adult patients are not suitable for pediatric use.

Preformulation evaluation of selumetinib for topical application: skin distribution and photodegradation analysis using MALDI imaging and LC-MS/MS.

Understanding drug behavior within the skin, especially for photosensitive compounds, is crucial for developing effective and safe topical therapies. This study employs Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) and Liquid Chromatography-Mass Spectrometry (LC-MS/MS) to investigate the skin permeation and photostability of selumetinib, a MEK inhibitor used in treating type 1 neurofibromatosis (NF1). The highest amounts of selumetinib in the skin sections were obtained when using the gel formulation, suggesting that it is to be preferred to cream formulations to achieve higher permeation of the drug.

Physicochemical Stability of Doravirine (Pifeltro): Characterization of Main Degradation Products and Assessment of Stability of Tablets Repackaged in Single-Dose Unit Containers.

Doravarine (DOR) is an antiviral drug with a marketed authorization for the management of occupational blood and body fluid exposure. The currently existing packaging, consisting of multiple unit bottles comprising 30 tablets, is not fully appropriate for daily nominative dispensing at the hospital. This study aims at assessing the impact of the change in packaging on the key attributes of the drug: assay, impurity profile, and dissolution.

Molecular Mechanisms Involved in the Chemical Instability of ONC201 and Methods to Counter Its Degradation in Solution.

Glioblastoma is one of the most common and aggressive forms of brain tumor, a rare disease for which there is a great need for innovative therapies. ONC201, a new drug substance, has been used in a compassionate treatment program where the choice of dosage form and regimen have yet to be justified. The prior knowledge needed to anticipate ONC201 stability problems has recently been partially addressed, by (i) showing that ONC201 is sensitive to light and oxidation and (ii) identifying the molecular structures of the main degradation products formed.

Evolution of the Chronic Venous Leg Ulcer Microenvironment and Its Impact on Medical Devices and Wound Care Therapies.

Studies have reported that the constituents of the wound microenvironment are likely to have critical roles in the degradation and fate of the polymeric matrix and the compounds dissolved in the wound dressing matrix. Thus, chronic wound assessment and the design of effective medical devices and drug products for wound care partly rely on an in-depth understanding of the wound microenvironment. The main aim of this review is to identify and discuss the different stages of chronic wound progression, focusing on the changes in the biochemical composition of the wound microenvironment, with particular attention given to venous leg ulcers (VLUs), as they are one of the most prevalent chronic wound aetiologies.

3D-Printed, Liquid-Filled Capsules of Concentrated and Stabilized Polyphenol Epigallocatechin Gallate, Developed in a Clinical Trial.

In vitro studies have shown that epigallocatechin gallate (EGCG), the most potent antioxidant of the green tea polyphenol catechins, is able to effectively prevent the formation of amyloid plaques and induce their clearance. However, its high chemical reactivity promotes high chemical instability, which represents a major obstacle for the development of pharmaceutical forms containing solubilized EGCG, an essential condition for a better systemic passage via the oral route. After discovering that EGCG forms a deep eutectic with choline chloride, we exploited this property to formulate and patent liquid-filled capsules containing 200-800 mg of soluble EGCG in easy-to-administer sizes.

Identification of the Major Degradation Pathways of Selumetinib.

Selumetinib is administered orally in capsule form and is indicated for the treatment of neurofibromatosis. To facilitate dosage adjustments, liquid preparations, such as solutions or suspensions, are to be developed. This led, first, to determine the stability profile of soluble or dispersed selumetinib and, secondly, to look for ways to stabilize the active substance.

Unequal Behaviour between Hydrolysable Functions of Nirmatrelvir under Stress Conditions: Structural and Theoretical Approaches in Support of Preformulation Studies.

Nirmatrelvir is an antiviral drug approved for the treatment of COVID-19. The available dosage form consists of tablets marketed under the brand name PAXLOVID. Although knowledge of nirmatrelvir's intrinsic stability may be useful for any potential development of other pharmaceutical forms, no data regarding this matter is available to date.

Mixed Polymeric Micelles for Rapamycin Skin Delivery.

Facial angiofibromas (FA) are one of the most obvious cutaneous manifestations of tuberous sclerosis complex. Topical rapamycin for angiofibromas has been reported as a promising treatment. Several types of vehicles have been used hitherto, but polymeric micelles and especially those made of d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) seem to have shown better skin bioavailability of rapamycin than the so far commonly used ointments.

Therapeutic Treatment Plan Optimization during the COVID-19 Pandemic: A Comprehensive Physicochemical Compatibility Study of Intensive Care Units Selected Drugs.

Background: The SARS-CoV-2 pandemic has resulted in a dramatic rise of the demand for medical devices and drugs. In this context, an important shortage of programmable syringe pumps, used to administrate different drugs in intensive care units, was seen. The opportunity of administrating combinations of five intensive care units selected drugs (Sufentanil, Clonidine, Loxapine, Midazolam, and Ketamine) was considered.

Stability and Formulation of Erlotinib in Skin Creams.

Recent studies have highlighted the benefit of repurposing oral erlotinib (ERL) treatment in some rare skin diseases such as Olmsted syndrome. The use of a topical ERL skin treatment instead of the currently available ERL tablets may be appealing to treat skin disorders while reducing adverse systemic effects and exposure. A method to prepare 0.

Simple Approach to Enhance Green Tea Epigallocatechin Gallate Stability in Aqueous Solutions and Bioavailability: Experimental and Theoretical Characterizations.

Because of its antioxidant, antimutagenic, and anti-infectious properties, epigallocatechin gallate (EGCG) is the most interesting compound among the green tea catechins polyphenols. However, its health effects are inconclusive due to its very low bioavailability, largely due to a particular instability that does not allow EGCG to reach the potency required for clinical developments. Over the last decade, many efforts have been made to improve the stability and bioavailability of EGCG using complex delivery systems such as nanotechnology, but these efforts have not been successful and easy to translate to industrial use.

Hospital compounding to face shortage: A case study of the development of a lopinavir-ritonavir oral suspension during the first wave of SARS-COV-2 in France.

The potential usefulness of lopinavir-ritonavir on Covid 19 infection during the first wave of contamination in France had boosted Kaletra® syrup prescription to the point of causing its national shortage. In the intensive care units of Parisian hospitals in charge of patients with life-threatening viral contamination, caregivers had to resort to lopinavir-ritonavir-based tablets, crushing them and then dispersing the powder in milk to facilitate administration by nasogastric tube. The difficulties and poor control of this degraded mode, which does not always ensure control of the amount of the drug in the prepared dose and may induce insufficient antiviral exposure, led us to develop in a very short time, while ensuring quality control proportional to the risk, a liquid form as an alternative to Kaletra® oral solution shortage.

Stability of Pentobarbital Hydrogel for Rectal Administration in Pediatric Procedural Sedation.

Pentobarbital is a sedative agent to limit children motion during computed tomography or magnetic resonance imaging (MRI) and ensures the successful completion of the imaging procedure. However, data on rectal drug formulation and its stability in practice are not available. The aim of this study was to formulate and evaluate the stability of a ready-to-use rectal pentobarbital gel.

Intrinsic stability of the antiviral drug umifenovir by stress testing and DFT studies.

Umifenovir is an antiviral drug approved in China and Russia for the treatment of influenza. The available dosage form consists of capsules marketed under the brand name Arbidol®. Due to its broad spectrum, umifenovir may also be used in other viral contexts, alone or combined with other antiviral drugs.

Formulation and stability study of hydroxychloroquine sulfate oral suspensions.

Hydroxychloroquine is an antimalarial drug indicated in the treatment of acute attacks of malaria due to , , , and susceptible strains of . It is also used for the treatment of rheumatoid arthritis, discoid and systemic lupus erythematosus, and more recently proposed in COVID-19 therapy. Hydroxychloroquine is only available in tablets which are not easy to administer for pediatric and geriatric patients, and patients unable to swallow such as patients found in intensive care units.

Formulation and Stability of Ataluren Eye Drop Oily Solution for Aniridia.

Congenital aniridia is a rare and severe panocular disease characterized by a complete or partial iris defect clinically detectable at birth. The most common form of aniridia occurring in around 90% of cases is caused by PAX6 haploinsufficiency. The phenotype includes ptosis, nystagmus, corneal limbal insufficiency, glaucoma, cataract, optic nerve, and foveal hypoplasia.

Assessment of practices for suspended oral drugs by tablet crushing in pediatric units.

The aim of this study was to assess the impact of suspended drug by tablet crushing in our pediatric hospital in term of targeted dose and to identify parameters involved in the potential variability. Four usually crushed pediatric drug substances were selected: amiodarone, warfarin, hydrocortisone and captopril. Each tablet was crushed in a bag using a crusher device.

External contamination of antineoplastic drug vials: an occupational risk to consider.

Risk management for workers involved in the handling and preparation of cytotoxic drugs is challenging. This study aims to investigate drug contamination of the exterior surfaces of cytotoxic drug vials. Two batches of commercially available cytotoxic drugs in unprotected vials (ifosfamide, etoposide phosphate and cyclophosphamide) and plastic shrink wrap vials (doxorubicin, cytarabine and busulfan) were tested without removing the flip-off cap or the plastic wrap, and without prewashing.

Voriconazole topical cream formulation: evidence for stability and antifungal activity.

Systemic use of voriconazole (VCZ) might be restricted by adverse events, such as hepatotoxicity and neurotoxicity, or drug-drug interactions. Topical VCZ application to skin may help to treat local infection more effectively and limit unwanted whole-body exposure. Topical VCZ cream was stable for 90 days when refrigerated.

Are we correctly treating invasive candidiasis under continuous renal replacement therapy with echinocandins? Preliminary in vitro assessment.

There is major concern regarding the pharmacokinetics of drugs under continuous renal replacement therapy (CRRT), including anti-infectious agents and more especially antifungal agents. From a regulatory viewpoint, only dialysis and filtration are considered meanwhile there is growing evidence that adsorption may also significantly alter the pharmacokinetics of anti-infectious agents. Adsorption results from a complex drug-filter interaction and might be considered an unexpected adverse effect induced by CRRT.

Administration of gamma-hydroxybutyrate instead of beta-hydroxybutyrate to a liver transplant recipient suffering from propionic acidemia and cardiomyopathy: A case report on a medication prescribing error.

Beta-hydroxybutyrate (BHB) is a synthetic ketone body used as an adjuvant energy substrate in the treatment of patients with metabolic cardiomyopathy. A medication prescribing error led to the administration of the general anesthetic sodium gamma-hydroxybutyrate (GHB) instead of sodium BHB in a liver transplant recipient with propionic acidemia and cardiomyopathy, causing acute coma. A 15-year-old boy suffering from neonatal propionic acidemia underwent liver transplantation (LT) for metabolic decompensation and cardiomyopathy (treated with cardiotropic drugs and BHB) diagnosed a year previously.