Predicting Food Effects: Are We There Yet?
(Source: The AAPS Journal)
Source: The AAPS Journal - January 10, 2022 Category: Drugs & Pharmacology Source Type: research
Performance Evaluation of Montelukast Pediatric Formulations: Part II — a PBPK Modelling Approach
This study aimed to build a physiologically based pharmacokinetic (PBPK) model coupled with age-appropriatein vitro dissolution data to describe drug performance in adults and pediatric patients. Montelukast sodium was chosen as a model drug. Two case studies were investigated: case study 1 focused on the description of formulation performance from adults to children; case study 2 focused on the description of the impact of medicine co-administration with vehicles on drug exposure in infants. The PBPK model for adults and pediatric patients was developed in Simcyp® v18.2 informed by age-appropriatein vitro dissolution res...
Source: The AAPS Journal - January 10, 2022 Category: Drugs & Pharmacology Source Type: research
Performance Evaluation of Montelukast Pediatric Formulations: Part I —Age-Related In Vitro Conditions
This study aimed to explore the potential of biopharmaceuticsin 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 thein 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 us...
Source: The AAPS Journal - January 10, 2022 Category: Drugs & Pharmacology Source Type: research
Nano/microparticle Formulations for Universal Influenza Vaccines
AbstractInfluenza affects millions of people worldwide and can result in severe sickness and even death. The best method of prevention is vaccination; however, the seasonal influenza vaccine often suffers from low efficacy and requires yearly vaccination due to changes in strain and viral mutations. More conserved universal influenza antigens like M2 ectodomain (M2e) and the stalk region of hemagglutinin (HA stalk) have been used clinically but often suffer from low antigenicity. To increase antigenicity, universal antigens have been formulated using nano/microparticles as vaccine carriers against influenza. Utilizing poly...
Source: The AAPS Journal - January 7, 2022 Category: Drugs & Pharmacology Source Type: research
A Full Evaporation Static Headspace Gas Chromatography Method with Nitrogen Phosphorous Detection for Ultrasensitive Analysis of Semi-volatile Nitrosamines in Pharmaceutical Products
AbstractThe recent detection of potent carcinogenic nitrosamine impurities in several human medicines has triggered product recalls and interrupted the supply of critical medications for hundreds of millions of patients, illuminating the need for increased testing of nitrosamines in pharmaceutical products. However, the development of analytical methods for nitrosamine detection is challenging due to high sensitivity requirements, complex matrices, and the large number and variety of samples requiring testing. Herein, we report an analytical method for the analysis of a common nitrosamine, N-nitrosodimethylamine (NDMA), in...
Source: The AAPS Journal - January 6, 2022 Category: Drugs & Pharmacology Source Type: research
Proof of Concept in Assignment of Within-Subject Variability During Virtual Bioequivalence Studies: Propagation of Intra-Subject Variation in Gastrointestinal Physiology Using Physiologically Based Pharmacokinetic Modeling
AbstractWhile the concept of ‘Virtual Bioequivalence’ (VBE) using a combination of modelling,in vitro tests and integration of pre-existing data on systems and drugs is growing from its infancy, building confidence on VBE outcomes requires demonstration of its ability not only in predicting formulation-dependent systemic exposure but also the expected degree of population variability. The concept of variation influencing the outcome of BE, despite being hidden with the cross-over nature of common BE studies, becomes evident when dealing with the acceptance criteria that consider the 90% confidence interval (CI) around ...
Source: The AAPS Journal - January 5, 2022 Category: Drugs & Pharmacology Source Type: research
Flux-Based Formulation Development —A Proof of Concept Study
AbstractThe work aimed to develop the Absorption Driven Drug Formulation (ADDF) concept, which is a new approach in formulation development to ensure that the drug product meets the expected absorption rate. The concept is built on the solubility-permeability interplay and the rate of supersaturation as the driving force of absorption. This paper presents the first case study using the ADDF concept where not only dissolution and solubility but also permeation of the drug is considered in every step of the formulation development. For that reason, parallel artificial membrane permeability assay (PAMPA) was used for excipien...
Source: The AAPS Journal - January 5, 2022 Category: Drugs & Pharmacology Source Type: research
Evaluation of Excipient Risk in BCS Class I and III Biowaivers
The objective of this review article is to summarize literature data pertinent to potential excipient effects on intestinal drug permeability and transit. Despite the use of excipients in drug products for decades, considerable research efforts have been directed towards evaluating their potential effects on drug bioavailability. Potential excipient concerns stem from drug formulation changes (e.g., scale-up and post-approval changes, development of a new generic product). Regulatory agencies have establishedin vivo bioequivalence standards and, as a result, may waive thein vivo requirement, known as a biowaiver, for some ...
Source: The AAPS Journal - January 5, 2022 Category: Drugs & Pharmacology Source Type: research
Dissolution Challenges Associated with the Surface pH of Drug Particles: Integration into Mechanistic Oral Absorption Modeling
AbstractThe present work aimed to differentiate betweenin vitro dissolution profiles of ibuprofen as input for GastroPlus ™ and to see the impact on systemic exposure.In vitro dissolution profiles of ibuprofen obtained under low- and high-buffered dissolution media were used as input using the z-factor approach. In a second step, a customized surface pH calculator was applied to predict the surface pH of ibuprofen under these low- and high-buffered dissolution conditions. These surface pH values were adopted in GastroPlus ™ and simulations were performed to predict the systemic outcome. Simulated data were compared wit...
Source: The AAPS Journal - January 4, 2022 Category: Drugs & Pharmacology Source Type: research
Machine Learning and Artificial Intelligence in Pharmaceutical Research and Development: a Review
AbstractOver the past decade, artificial intelligence (AI) and machine learning (ML) have become the breakthrough technology most anticipated to have a transformative effect on pharmaceutical research and development (R&D). This is partially driven by revolutionary advances in computational technology and the parallel dissipation of previous constraints to the collection/processing of large volumes of data. Meanwhile, the cost of bringing new drugs to market and to patients has become prohibitively expensive. Recognizing these headwinds, AI/ML techniques are appealing to the pharmaceutical industry due to their automat...
Source: The AAPS Journal - January 4, 2022 Category: Drugs & Pharmacology Source Type: research
Zwitterionic Polymer Coatings Enhance Gold Nanoparticle Stability and Uptake in Various Biological Environments
AbstractZwitterionic polymers are a class of materials that have demonstrated utility as non-fouling surfaces for medical devices and drug delivery vehicles. Here, we develop a synthesis protocol to produce zwitterionic polymers as coatings for gold nanoparticles and evaluate nanoparticle stability and biological function after exposure to various biological fluids. Thiol-functionalized polymethacryloyloxyethyl phosphorylcholine polymers (pMPC) were synthesized in nontoxic solvents via photoinitiated free radical polymerization with a radical addition-fragmentation chain transfer (RAFT) agent and coated onto gold nanoparti...
Source: The AAPS Journal - January 4, 2022 Category: Drugs & Pharmacology Source Type: research
Exploring the Relationship of Drug BCS Classification, Food Effect, and Gastric pH-Dependent Drug Interactions
AbstractFood effect (FE) and gastric pH-dependent drug-drug interactions (DDIs) are both absorption-related. Here, we evaluated if Biopharmaceutics Classification System (BCS) classes may be correlated with FE or pH-dependent DDIs. Trends in FE data were investigated for 170 drugs with clinical FE studies from the literature and new drugs approved from 2013 to 2019 by US Food and Drug Administration. A subset of 38 drugs was also evaluated to determine whether FE results can inform the need for a gastric pH-dependent DDI study. The results of FE studies were defined as no effect (AUC ratio 0.80 –1.25), increased exposure...
Source: The AAPS Journal - December 27, 2021 Category: Drugs & Pharmacology Source Type: research
Assessment of Functional Characterization and Comparability of Biotherapeutics: a Review
AbstractAbstract. The development of monoclonal antibody (mAb) biosimilars is a complex process. The key to their successful development and commercialization is an in-depth understanding of the key product attributes that impact safety and efficacy and the strategies to control them. Functional assessment of mAb is a crucial part of the comparability of biopharmaceutical drugs. The development of a relevant and robust functional assay requires an interdisciplinary approach and sufficient flexibility to balance regulatory concerns as well as dynamics and variability during the manufacturing process. Although many advanced ...
Source: The AAPS Journal - December 20, 2021 Category: Drugs & Pharmacology Source Type: research
Reactive Oxygen Species –Responsive Celastrol-Loaded Bilirubin Nanoparticles for the Treatment of Rheumatoid Arthritis
AbstractCelastrol (CLT) has shown anti-rheumatic activity against rheumatoid arthritis, while its poor water solubility and high organ toxicity restrict its further therapeutic applications. To mitigate these challenges, a reactive oxygen species (ROS) –responsive nanoparticle was developed for celastrol delivery based on the excessive ROS at the pathologic sites, which was synthesized by conjugating bilirubin to a polyethylene glycol (PEG) chain. The PEGylated bilirubin self-assembled into nanoparticle (BRNP) in aqueous solution had a hydrodyna mic diameter of around 68.6 nm, and celastrol was loaded into BRNP (CLT/BRN...
Source: The AAPS Journal - December 14, 2021 Category: Drugs & Pharmacology Source Type: research
Reactive Oxygen Species –Responsive Celastrol-Loaded
AbstractCelastrol (CLT) has shown anti-rheumatic activity against rheumatoid arthritis, while its poor water solubility and high organ toxicity restrict its further therapeutic applications. To mitigate these challenges, a reactive oxygen species (ROS) –responsive nanoparticle was developed for celastrol delivery based on the excessive ROS at the pathologic sites, which was synthesized by conjugating bilirubin to a polyethylene glycol (PEG) chain. The PEGylated bilirubin self-assembled into nanoparticle (BRNP) in aqueous solution had a hydrodyna mic diameter of around 68.6 nm, and celastrol was loaded into BRNP (CLT/BRN...
Source: The AAPS Journal - December 14, 2021 Category: Drugs & Pharmacology Source Type: research
