Review
Pharmacology & Pharmacy
Bryan Newman, Andrew Babiskin, Elizabeth Bielski, Susan Boc, Sneha Dhapare, Lanyan Fang, Katharine Feibus, Anubhav Kaviratna, Bing V. Li, Markham C. Luke, Tian Ma, Michael Spagnola, Ross L. Walenga, Zhong Wang, Liang Zhao, Nashwa El-Gendy, Craig M. Bertha, Mohammed Abd El-Shafy, Dhaval K. Gaglani
Summary: Regulatory science for generic dry powder inhalers (DPIs) in the United States has developed over the past decade, with the FDA publishing guidelines in 2013 to establish bioequivalence. These guidelines utilized various research activities and led to the approval of the first generic DPI in 2019.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Editorial Material
Chemistry, Medicinal
Melissa Metry, Yan Shu, Bertil Abrahamsson, Rodrigo Cristofoletti, Jennifer B. Dressman, D. W. Groot, Alan Parr, Peter Langguth, Vinod P. Shah, Tomokazu Tajiri, Mehul U. Mehta, James E. Polli
Summary: The study evaluates the possibility of waiving in vivo bioequivalence testing for metformin based on its BCS classification and dissolution rate. Despite being a transporter-mediated drug, common excipients have little impact on metformin absorption.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Shigenori Wada, Seiya Kagatani, Hiroaki Nakagami
Summary: This study used multiple regression analysis to predict the extent of CVintra of pharmacokinetic parameters based on major factors, revealing that multiple regression equations can estimate the %CVintra values of Cmax and AUC with high correlation coefficients.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Takato Masada, Toshihide Takagi, Keiko Minami, Makoto Kataoka, Ken-ichi Izutsu, Kazuki Matsui, Shinji Yamashita
Summary: A new in vitro system BE checker was developed to assess and predict the bioequivalence of oral drug products by reproducing the environmental changes in the gastrointestinal tract. The experiment revealed that factors such as paddle speed, gastric emptying time, and GI agitation strength influence the dissolution and permeation of drugs, potentially leading to bioinequivalence in different patient populations. The BE checker proved to be a valuable tool for evaluating the BE of oral drug products in various populations.
Article
Pharmacology & Pharmacy
Joyce S. Macwan, Grace Fraczkiewicz, Mauro Bertolino, Phillip Kruger, Sheila-Annie Peters
Summary: This study evaluated the impact of in vitro dissolution on the clinical performance of bisoprolol using a physiologically based pharmacokinetics model and demonstrated that in vitro dissolution was not critical for the clinical performance of bisoprolol over a wide range of tested values. Safe space expansion was explored using hypothetical dissolution data, showing that a formulation with specific dissolution rates could be considered bioequivalent to the classical fast dissolution of bisoprolol based on virtual bioequivalence trials.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Timothy R. Lex, Jason D. Rodriguez, Lei Zhang, Wenlei Jiang, Zongming Gao
Summary: This literature review assesses the current methodologies of in vitro dissolution and absorption PBPK modeling in simulating and predicting the dissolution and absorption of oral drug products. The findings help identify the gaps in knowledge and guide further development of in vitro dissolution methods that consider fasted and fed states. The research in in vitro dissolution and modeling contributes to improving quality control and clinical efficacy prediction of oral drug products.
Article
Chemistry, Multidisciplinary
Jiahuan You, Changwei Yang, Jinpeng Han, Hao Wang, Wentao Zhang, Ying Zhang, Ziyi Lu, Shiqi Wang, Ruisi Cai, Hongjun Li, Jicheng Yu, Jianqing Gao, Yuqi Zhang, Zhen Gu
Summary: An ultrarapid-acting microneedle (URA-MN) patch is proposed for minimally invasive transdermal delivery of biotherapeutics. By incorporating effervescent agents into the needle tip, accelerated drug release is achieved. Rapid release, easy administration, and excellent biocompatibility of URA-MN are demonstrated in three different mouse models.
ADVANCED MATERIALS
(2023)
Article
Pharmacology & Pharmacy
Pieter J. J. Glerum, Walter M. M. Yamada, Michael N. N. Neely, David M. M. Burger, Marc Maliepaard, Cees Neef
Summary: Patients often switch between different brand formulations of the same drug, but there are concerns about generic interchangeability. This study aims to identify subpopulations with altered pharmacokinetics that have a difference in comparative bioavailability compared to healthy individuals. The results indicate that patients with lower absorption rates or reduced renal function have increased pharmacokinetic variability, leading to a reduced likelihood of demonstrating bioequivalence. Therefore, these results support generic interchangeability and current approval requirements for generics.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Kelen Carine Costa Soares, Chang Chiann, Silvia Storpirtis
Summary: The requirements for multiple-dose bioequivalence studies for generic prolonged-release formulations are inconsistent between EMA and FDA. The assessment of partial AUC is suggested as an additional metric and has gained increasing regulatory recognition. However, a study found that 33.9% of evaluated prolonged-release products failed to demonstrate bioequivalence based on partial AUC, while for the majority of studies, there was no significant increase in intrasubject variability compared to usual metrics.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Avery Belenos, Erin Leigh Wood, Meng Hu, Darby Kozak, Xiaoming Xu, Adam C. Fisher
Summary: The approval of the first generic 0.05% cyclosporine ophthalmic emulsion (COE) in the U.S. is a significant achievement for the science and research program of the U.S. Food and Drug Administration's Center for Drug Evaluation and Research (CDER). This approval required overcoming scientific challenges to determine the therapeutic equivalence of COE to the reference listed drug. CDER researchers developed a quality by design approach to understand the effects of process and formulation variables on the product's critical quality attributes. This research is important as it may support the development and assessment of other complex generics. Rating: 8/10
Article
Information Science & Library Science
Xiang (Shawn) Wan, Anuj Kumar, Xitong Li
Summary: This study examines the impact of retargeted and generic recommendations on product sales at different stages of users' purchase funnel. The results show that generic recommendations increase conversion rates in the early stage, while retargeted recommendations do not affect conversion rates. Both recommendations result in a higher number of product impressions. In the late stage, retargeted recommendations lead to higher recommended and total product sales.
INFORMATION SYSTEMS RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Abhinav Ram Mohan, Qiang Wang, Sneha Dhapare, Elizabeth Bielski, Anubhav Kaviratna, Liangfeng Han, Susan Boc, Bryan Newman
Summary: This review provides a comprehensive understanding of the complexity of dry powder inhalers and explores the implications of advancements in formulation and device design for generic drug development.
Article
Clinical Neurology
Lanyan Fang, Zhichuan Li, Minori Kinjo, Sara Lomonaco, Nan Zheng, Wenlei Jiang, Liang Zhao
Summary: This study assessed the bioequivalence of generic and brand lamotrigine ER products in healthy subjects using a fully replicated study design. The results showed that the two products had similar pharmacokinetic profiles, supporting the substitution of the generic product.
Review
Behavioral Sciences
Roberta Roberti, Alessandro Casarella, Alfonso Iudice, Angela La Neve, Ettore Beghi, Giuseppe Capovilla, Carlo Di Bonaventura, Filippo S. Giorgi, Salvatore Grosso, Luigi F. Iannone, Andrea Romigi, Luigi M. Specchio, Gaetano Zaccara, Oriano Mecarelli, Emilio Russo
Summary: The article reviews the use of generic drugs in the treatment of epilepsy, finding that generic ASMs have similar efficacy and safety as branded drugs, with cost advantages. The study suggests avoiding switching between branded and generic (or vice versa) or between different generics during seizure remission.
EPILEPSY & BEHAVIOR
(2021)
Article
Chemistry, Medicinal
Paul Harmon
Summary: Nitrosamine impurities can be formed during drug substance manufacturing processes. This article focuses on the growth of nitrosamine impurity levels in oral drug products during long-term stability studies. The mechanisms of nitrosamine growth in oral dosage forms are typically attributed to nitrosating agents formed in nitrous acid solutions with a pH value of approximately pH 5 or below. The authors aim to raise awareness among pharmaceutical scientists about the catalytic effect of formaldehyde, commonly found in excipients of oral dosage forms, on the reaction between secondary amines and nitrite ions, leading to the formation of nitrosamine products. This mechanism occurs at higher pH values (>6) and is relevant to pharmaceutical solid dosage forms. Recent recalls of solid dosage form products are discussed as examples to demonstrate the formaldehyde-catalyzed nitrosation pathway in the solid state. (c) 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Brandy Garzel, Lei Zhang, Shiew-Mei Huang, Hongbing Wang
CURRENT DRUG METABOLISM
(2019)
Article
Pharmacology & Pharmacy
Maciej J. Zamek-Gliszczynski, Vishal Sangha, Hong Shen, Bo Feng, Matthias B. Wittwer, Manthena V. S. Varma, Xiaomin Liang, Yuichi Sugiyama, Lei Zhang, Reina Bendayan
Summary: The International Transporter Consortium (ITC) provided updates on emerging clinically relevant transporters for drug development during its fourth workshop in 2021. The transporters previously highlighted and newly examined include folate transport pathways, intestinal OATP2B1 inhibition, and hepatic, renal, and intestinal MRPs. The prediction of folate deficiency toxicities from in vitro folate metabolism and transport inhibition is not well-established enough for drug development, while the evaluation of OATP2B1 transport can be considered to assess the absorption of new molecular entities. The importance of hepatic, renal, and intestinal MRPs, particularly MRP2 inhibition, in drug disposition, including drug-induced hyperbilirubinemia, remains justified.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Pharmacology & Pharmacy
Lei Zhang, Qi Liu, Shiew-Mei Huang, Robert Lionberger
Summary: Transporters play a crucial role in drug distribution and can affect the pharmacokinetics and pharmacodynamics of a drug. Dr. Giacomini's contributions to transporter science have been significant and have had a major impact on drug development and research.
DRUG METABOLISM AND DISPOSITION
(2022)
Article
Pharmacology & Pharmacy
Daniel Scotcher, Vikram Arya, Yang Xinning, Zhao Ping, Zhang Lei, Huang Shiew-Mei, Amin Rostami-Hodjegan, Aleksandra Galetin
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2020)
Article
Pharmacology & Pharmacy
Daniel Scotcher, Vikram Arya, Xinning Yang, Ping Zhao, Lei Zhang, Shiew-Mei Huang, Amin Rostami-Hodjegan, Aleksandra Galetin
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2020)