Article
Medicine, Research & Experimental
Kai Wang, Yangbing Li, Bing Chen, Hao Chen, David E. Smith, Duxin Sun, Meihua R. Feng, Gordon L. Amidon
Summary: This study focused on exploring the variability of the MMF absorption process through population PK models in the context of the wide applicability and significant plasma concentration variability of the prodrug mycophenolate mofetil. The results showed that intra-individual variability played a more significant role in explaining the variability of MMF systemic appearance.
MOLECULAR PHARMACEUTICS
(2022)
Review
Chemistry, Medicinal
Mauricio A. Garcia, Rodrigo Cristofoletti, Bertil Abrahamsson, Dirk W. Groot, Alan Parr, James E. Polli, Mehul Mehta, Vinod P. Shah, Tajiri Tomakazu, Jennifer B. Dressman, Peter Langguth
Summary: Carbamazepine is a BCS Class 2 drug with high permeability but a narrow therapeutic index, not recommended for a BCS-based biowaiver; USP dissolution conditions effectively differentiate between bioinequivalent products, potentially aiding in predicting bioequivalence of formulations.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Chemistry, Medicinal
Naseem A. Charoo, Daud B. Abdallah, Daoud T. Ahmed, Bertil Abrahamsson, Rodrigo Cristofoletti, Peter Langguth, Mehul Mehta, Alan Parr, James E. Polli, Vinod P. Shah, Atsushi Kambayashi, Jennifer Dressman
Summary: This study investigated the feasibility of using the Biopharmaceutics Classification System (BCS) as a substitute for pharmacokinetic studies in human volunteers to evaluate the bioequivalence of immediate-release (IR) oral, solid dosage forms containing levocetirizine dihydrochloride. The properties of levocetirizine, such as solubility, permeability, dissolution profile, therapeutic uses, pharmacokinetics, and pharmacodynamics, were reviewed according to the BCS. The data unequivocally classified levocetirizine as BCS Class 1. Based on the wide therapeutic index and low risk of severe adverse effects, it was concluded that a BCS-based biowaiver can be implemented for products containing levocetirizine dihydrochloride, with specific requirements for excipients, data gathering methods, and in vitro dissolution.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Milica Markovic, Moran Zur, Sapir Garsiani, Daniel Porat, Sandra Cvijic, Gordon L. Amidon, Arik Dahan
Summary: The study aimed to evaluate the intestinal permeability mechanisms of minoxidil, with a focus on paracellular transport, and determine its suitability as a reference drug for the Biopharmaceutics Classification System (BCS). The results indicated that paracellular transport plays a significant role in the intestinal permeability of minoxidil following oral administration.
Article
Chemistry, Medicinal
Debora Priscila de Campos, Neila Marcia Silva-Barcellosa, Tamires Guedes Caldeira, Wagner da Nova Mussel, Virginia Silveira, Jacqueline de Souza
Summary: The study aimed to clarify the Biopharmaceutics Classification System (BCS) classification of donepezil hydrochloride (DH) and discuss the possibility of biowaiver for new medicines containing it. Results showed that DH has high permeability and solubility, classifying it as BCS class 1. Based on the literature review, new immediate-release drug products containing DH should be eligible for BCS-based biowaiver.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Medicinal
Dhanusha Dhananjani Thambavita, Priyadarshani Galappatthy, Raveendra Laal Jayakody
Summary: The study aimed to compare the bioequivalence of two formulations of amoxicillin 500 mg capsules in healthy volunteers, with results showing bioequivalence of the test and reference products under both fasted and fed conditions. Although Cmax was significantly lower and Tmax delayed under fed conditions, it did not affect the AUC.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Editorial Material
Pharmacology & Pharmacy
Arik Dahan, Isabel Gonzalez-Alvarez
Summary: The environment and conditions of different regions in the gastrointestinal tract have a significant impact on drug absorption, leading to the importance of studying regional-dependent intestinal drug absorption and delivery. Factors such as pH, fluid composition, and transporter expression can alter drug solubility, intestinal permeability, and overall absorption.
Editorial Material
Chemistry, Medicinal
Naseem A. Charoo, Daud B. Abdallah, Ahmed Abdalla Bakheit, Kashif Ul Haque, Hassan Ali Hassan, Bertil Abrahamsson, Rodrigo Cristofoletti, Peter Langguth, Mehul Mehta, Alan Parr, James E. Polli, Vinod P. Shah, Tomokazu Tajiri, Jennifer Dressman
Summary: This study assessed the bioequivalence of solid immediate-release oral dosage forms containing sitagliptin phosphate monohydrate using methods based on the Biopharmaceutics Classification System (BCS). The results supported the classification of sitagliptin as a BCS Class 1 drug and concluded that the BCS-based biowaiver can be implemented for solid IR oral drug products containing sitagliptin phosphate monohydrate.
JOURNAL OF PHARMACEUTICAL SCIENCES
(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
Chemistry, Medicinal
James Butler, Patrick Augustijns
Summary: Despite adequate solubility properties, immediate release formulations containing BCS1/3 drugs occasionally fail in bioequivalence (BE) studies. A comprehensive assessment of risk factors leading to BE failure was conducted by evaluating a set of 17 soluble drugs that have reported unexpected BE failures and comparing them to a set of 29 drugs with no such failures. The study found that BE failures for BCS1/3 drugs were mainly associated with changes in C-max, rather than AUC. Drugs with a sharp plasma peak were identified as a key factor in BE failure risk.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Zichen Zhang, Yi Lu, Jianping Qi, Wei Wu
Summary: Orally administered drugs must survive the gastrointestinal environment, penetrate the enteric epithelia, and avoid hepatic metabolism before reaching the systemic circulation. Hepatic metabolism is a significant barrier, and alternative pathways like intestinal lymphatic transport are being explored. Main pathways for peroral lymphatic transport include the chylomicron and microfold cell pathways, with increasing research input and applications.
ACTA PHARMACEUTICA SINICA B
(2021)
Editorial Material
Chemistry, Medicinal
M. Mehta, J. E. Polli, P. Seo, S. Bhoopathy, K. Berginc, K. Kristan, J. Cook, J. B. Dressman, H. Mandula, U. Munshi, R. Shanker, D. A. Volpe, J. Gordon, S. Veerasingham, J. Welink, S. Almeida, P. Gonzalez, D. Painter, Y. C. Tsang, J. Vaidyanathan, R. Velagapudi
Summary: This workshop, organized by the University of Maryland Center of Excellence in Regulatory Science and Innovation and the FDA, focused on generating and evaluating drug permeability data and facilitating the development of high-quality drug products globally. It included lectures, panel discussions, and breakout sessions covering various topics, such as permeability assessment, influencing factors, and future directions.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Raul Edison Luna Lazo, Lilian Klein Teleginski, Aline Biggi Maciel, Marcos Antonio Segatto Silva, Cassiana Mendes, Larissa Sakis Bernardi, Fabio Seigi Murakami, Fabio Sonvico, Paulo Renato Oliveira
Summary: The aim of this study was to assess whether commercially available Fluconazole drug products meet the biowaiver criteria set by FDA and ANVISA. The results showed that some formulations, including the comparator, did not meet the required dissolution percentage in certain media, indicating inconsistent dissolution profiles. Therefore, it is necessary to revise regulatory norms to allow for the switching of comparator products.
BRAZILIAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Rong Lu, Yun Zhou, Jinqian Ma, Yuchen Wang, Xiaoqing Miao
Summary: This review focuses on intestinal efflux transporters that actively transport drugs from the enterocytes to the intestinal lumen, leading to poor absorption of orally-administered drugs. Various functional amphiphilic excipients and inhibitors that can suppress efflux transporter activity are discussed with the aim of reversing intestinal drug efflux and improving oral drug absorption. Different strategies of reducing intestinal drug efflux and various nano-formulations for improving oral drug absorption by inhibiting intestinal drug efflux are explored.
Article
Chemistry, Multidisciplinary
Nikolaos Alimpertis, Athanasios A. Tsekouras, Panos Macheras
Summary: This article reconsiders the application of the Wagner-Nelson and Loo-Riegelman methods in the construction of percent of drug absorbed as a function of time and in in vitro-in vivo correlations, in light of the physiologically sound Finite Absorption Time (F.A.T.) concept. The classical equations for drug absorption percentage were modified to take into account the termination of drug absorption at F.A.T. A computer-based methodology for estimating F.A.T. from experimental data is described. The findings indicate the importance of using the F.A.T. concept in drug absorption research and regulatory guidelines.
PHARMACEUTICAL RESEARCH
(2023)