Application of NMR and Chemometric Analyses to Better Understand the Quality Attributes in pH and Thermally Degraded Monoclonal Antibodies
ConclusionThe chemometric analyses support the lack of statistical differences in the structure of pH-thermal stressed adalimumab, however, it reveals conformational changes or chemical modifications in trastuzumab after forced degradation. Application of chemometrics in comparative NMR studies enables HOS characterization and showcases the sensitivity and specificity in detecting differences in the spectra of mAbs after pH-thermal forced degradation with respect to local and global protein structure. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 5, 2023 Category: Drugs & Pharmacology Source Type: research
Preclinical Pharmacokinetics and Translational Pharmacokinetic/Pharmacodynamic Modeling of M8891, a Potent and Reversible Inhibitor of Methionine Aminopeptidase 2
ConclusionThe defined target PK and PD levels supported the design of the clinical Phase Ia dose escalation study of M8891 (NCT03138538) and selection of the recommended Phase II dose. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 5, 2023 Category: Drugs & Pharmacology Source Type: research
Application of NMR and Chemometric Analyses to Better Understand the Quality Attributes in pH and Thermally Degraded Monoclonal Antibodies
ConclusionThe chemometric analyses support the lack of statistical differences in the structure of pH-thermal stressed adalimumab, however, it reveals conformational changes or chemical modifications in trastuzumab after forced degradation. Application of chemometrics in comparative NMR studies enables HOS characterization and showcases the sensitivity and specificity in detecting differences in the spectra of mAbs after pH-thermal forced degradation with respect to local and global protein structure. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 5, 2023 Category: Drugs & Pharmacology Source Type: research
Preclinical Pharmacokinetics and Translational Pharmacokinetic/Pharmacodynamic Modeling of M8891, a Potent and Reversible Inhibitor of Methionine Aminopeptidase 2
ConclusionThe defined target PK and PD levels supported the design of the clinical Phase Ia dose escalation study of M8891 (NCT03138538) and selection of the recommended Phase II dose. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 5, 2023 Category: Drugs & Pharmacology Source Type: research
Development and Validation of Discriminatory In-vitro Release Method for Intramammary Drug Product
ConclusionThe developedin-vitro release methods can be used as a potential tool forin-vitro comparability evaluations for IMM formulations. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 3, 2023 Category: Drugs & Pharmacology Source Type: research
Physiological Dynamics in the Upper Gastrointestinal Tract and the Development of Gastrointestinal Absorption Models for the Immediate-Release Oral Dosage Forms in Healthy Adult Human
AbstractThis review is a revisit of various oral drug absorption models developed in the past decades, focusing on how to incorporate the physiological dynamics in the upper gastrointestinal (GI) tract. For immediate-release oral drugs, GI absorption is a critical input of drug exposure and subsequent human body response, yet difficult to model largely due to the complex GI environment. One of the biggest hurdles lies at capturing the high within-subject variability (WSV) of bioavailability measures, which can be mechanistically explained by the GI physiological dynamics. A thorough summary of how GI dynamics is handled in...
Source: Pharmaceutical Research - October 3, 2023 Category: Drugs & Pharmacology Source Type: research
Development and Validation of Discriminatory In-vitro Release Method for Intramammary Drug Product
ConclusionThe developedin-vitro release methods can be used as a potential tool forin-vitro comparability evaluations for IMM formulations. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 3, 2023 Category: Drugs & Pharmacology Source Type: research
Physiological Dynamics in the Upper Gastrointestinal Tract and the Development of Gastrointestinal Absorption Models for the Immediate-Release Oral Dosage Forms in Healthy Adult Human
AbstractThis review is a revisit of various oral drug absorption models developed in the past decades, focusing on how to incorporate the physiological dynamics in the upper gastrointestinal (GI) tract. For immediate-release oral drugs, GI absorption is a critical input of drug exposure and subsequent human body response, yet difficult to model largely due to the complex GI environment. One of the biggest hurdles lies at capturing the high within-subject variability (WSV) of bioavailability measures, which can be mechanistically explained by the GI physiological dynamics. A thorough summary of how GI dynamics is handled in...
Source: Pharmaceutical Research - October 3, 2023 Category: Drugs & Pharmacology Source Type: research
Practical Advice on Scientific Design of Freeze-Drying Process: 2023 Update
ConclusionsThe authors revisited advice from a seminal paper by Tang and Pikal (Pharm Res. 21(2):191-200, 2004) on selecting freeze-drying process conditions and found that the majority of recommendations are still applicable today. There have been a number of advancements, including methods to promote ice nucleation and computer modeling for all steps of freeze-drying process. The authors created a database for primary drying and provided examples of complete freeze-drying cycles design. The paper may supplement the knowledge of scientists and formulators and serve as a user-friendly tool for quickly estimating the design...
Source: Pharmaceutical Research - October 2, 2023 Category: Drugs & Pharmacology Source Type: research
Modeling Gasotransmitter Availability to Brain Capillary Endothelial Cells with Ultrasound-sensitive Microbubbles
ConclusionsThis computational study demonstrates feasibility of the CO / MB strategy, and that controlled delivery is important for viability of this strategy. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 2, 2023 Category: Drugs & Pharmacology Source Type: research
In vivo Pharmacokinetic/Pharmacodynamic Analysis of the Efficacy of the Cefepime/Nacubactam Combination Against β-Lactamase-Producing Enterobacterales based on the Instantaneous MIC Concept
ConclusionsOur results indicate thatfT > MICi is a PK/PD parameter is suitable for monitoring the CFPM/NAC combination. The minimum target value for achieving a static effect against β-lactamase-producing Enterobacterales is 30%. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 2, 2023 Category: Drugs & Pharmacology Source Type: research
Practical Advice on Scientific Design of Freeze-Drying Process: 2023 Update
ConclusionsThe authors revisited advice from a seminal paper by Tang and Pikal (Pharm Res. 21(2):191-200, 2004) on selecting freeze-drying process conditions and found that the majority of recommendations are still applicable today. There have been a number of advancements, including methods to promote ice nucleation and computer modeling for all steps of freeze-drying process. The authors created a database for primary drying and provided examples of complete freeze-drying cycles design. The paper may supplement the knowledge of scientists and formulators and serve as a user-friendly tool for quickly estimating the design...
Source: Pharmaceutical Research - October 2, 2023 Category: Drugs & Pharmacology Source Type: research
Modeling Gasotransmitter Availability to Brain Capillary Endothelial Cells with Ultrasound-sensitive Microbubbles
ConclusionsThis computational study demonstrates feasibility of the CO / MB strategy, and that controlled delivery is important for viability of this strategy. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 2, 2023 Category: Drugs & Pharmacology Source Type: research
In vivo Pharmacokinetic/Pharmacodynamic Analysis of the Efficacy of the Cefepime/Nacubactam Combination Against β-Lactamase-Producing Enterobacterales based on the Instantaneous MIC Concept
ConclusionsOur results indicate thatfT > MICi is a PK/PD parameter is suitable for monitoring the CFPM/NAC combination. The minimum target value for achieving a static effect against β-lactamase-producing Enterobacterales is 30%. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - October 2, 2023 Category: Drugs & Pharmacology Source Type: research
Investigation of Dispersion Kinetics of Particulate Lubricants and their Effect on the Mechanical Strength of MCC Tablets
ConclusionsThe lubricant particle size controls the tensile strength reduction if short mixing times are applied. For extended mixing times, the investigated lubricants can be divided into two groups in terms of dispersion kinetics. Possible underlying reasons are discussed in detail in order to enhance the general understanding of lubricant dispersions in tablet formulations. (Source: Pharmaceutical Research)
Source: Pharmaceutical Research - September 26, 2023 Category: Drugs & Pharmacology Source Type: research
