Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein01:20

Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein

258
Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
258
Drugs for Treatment of Constipation-Predominant IBS01:21

Drugs for Treatment of Constipation-Predominant IBS

139
Pharmacological therapies for IBS-C are designed to alleviate abdominal discomfort and enhance bowel function. In patients with IBS-C, fiber supplements may help soften stools and decrease straining, but may also lead to increased gas production and bloating. Osmotic laxatives like milk of magnesia are frequently used to soften stools and increase stool frequency in IBS-C patients. In addition, two drugs approved for use in severe IBS-C adult cases are linaclotide (Linzess) and lubiprostone...
139
Nondepolarizing (Competitive) Neuromuscular Blockers: Pharmacokinetics01:11

Nondepolarizing (Competitive) Neuromuscular Blockers: Pharmacokinetics

431
All neuromuscular blocking agents are injected intravenously because they are poorly absorbed from the GI tract. Rapid onset is achieved with intravenous administration, although absorption is also adequate from an intramuscular injection. Since these agents are highly ionized, they do not readily penetrate cell membranes or cross the blood-brain barrier.
Instead, they are transported by the blood to different tissues. Muscles with a greater blood supply (arteries) and blood flow receive more...
431
Antiepileptic Drugs: Potassium Channel Activators01:20

Antiepileptic Drugs: Potassium Channel Activators

147
Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
147
Depolarizing Blockers: Pharmocokinetics01:19

Depolarizing Blockers: Pharmocokinetics

311
Depolarizing blockers are administered through intravenous injection. Succinylcholine is the most common choice of depolarizing blockers in emergency clinical practices. Although they have a rapid onset, they readily diffuse away from the motor end plate into the extracellular fluid. They are metabolized by enzymes such as liver butyrylcholinesterase and plasma pseudocholinesterases. This produces a short duration of action, typically 5-10 minutes long, unlike nondepolarizing blockers, which...
311
Drug Delivery: Parenteral Route01:29

Drug Delivery: Parenteral Route

434
The parenteral route is a critical method of drug administration. It delivers compounds directly into the systemic circulation and bypasses the gastrointestinal tract. This approach is particularly advantageous for drugs that exhibit poor absorption or instability when administered orally.
There are three primary parenteral routes: intravenous (IV), intramuscular (IM), and subcutaneous (SC). The IV route introduces the drug directly into the bloodstream, ensuring immediate action. The IM route...
434

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Ritonavir release from spherical amorphous solid dispersions: prediction and observation.

International journal of pharmaceutics·2026
Same author

Impact of gastric mixing and water intake on postprandial pharmacokinetics of orally disintegrating tablets: A PBBM-based study.

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V·2026
Same author

Predicting surfactant effects on drug permeation across hollow fiber membrane.

Journal of pharmaceutical sciences·2026
Same author

Mastering particle size analysis: lessons, challenges, and future directions from the FDA-CRCG workshop.

AAPS open·2026
Same author

Transient pH film model for in vitro powder dissolution of weakly basic drugs into buffer and comparison to conventional film model.

Journal of pharmaceutical sciences·2026
Same author

Reduced-Resistances Model for Enhanced Drug Permeation via a Solubilizing Receiver Medium: A Mechanistic Study with Hollow Fiber Membranes.

Molecular pharmaceutics·2026

Related Experiment Video

Updated: Jun 9, 2025

Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
08:49

Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention

Published on: October 16, 2013

13.6K

Biowaiver monographs for immediate-release solid oral dosage forms: Lemborexant.

Kristian Beran1, Bertil Abrahamsson2, Naseem Charoo3

  • 1Fraunhofer Institute for Translational Medicine and Pharmacology, Frankfurt am Main, Germany.

Journal of Pharmaceutical Sciences
|October 25, 2024
PubMed
Summary

Lemborexant, a dual orexin receptor antagonist, faces challenges with immediate-release dosage forms due to Biopharmaceutics Classification System (BCS) class II limitations. The refined Developability Classification System (rDCS) offers a path to virtual bioequivalence assessment by focusing on dissolution risks.

Keywords:
AbsorptionBiopharmaceutics classification system (BCS)LemborexantPermeabilityRefined developability classification system (rDCS)SolubilityVirtual bioequivalence

More Related Videos

Urethral Stricture Induction Followed by Buccal Mucosa Graft Urethroplasty in a Rat Model
05:09

Urethral Stricture Induction Followed by Buccal Mucosa Graft Urethroplasty in a Rat Model

Published on: April 28, 2023

892
Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients
06:14

Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients

Published on: October 15, 2017

8.3K

Related Experiment Videos

Last Updated: Jun 9, 2025

Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
08:49

Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention

Published on: October 16, 2013

13.6K
Urethral Stricture Induction Followed by Buccal Mucosa Graft Urethroplasty in a Rat Model
05:09

Urethral Stricture Induction Followed by Buccal Mucosa Graft Urethroplasty in a Rat Model

Published on: April 28, 2023

892
Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients
06:14

Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients

Published on: October 15, 2017

8.3K

Area of Science:

  • Pharmaceutical Sciences
  • Biopharmaceutics
  • Drug Development

Background:

  • Lemborexant, a dual orexin receptor antagonist, is classified as Biopharmaceutics Classification System (BCS) class II.
  • This classification prevents immediate-release (IR) solid oral dosage forms from BCS-based biowaivers per ICH M9 Guideline.
  • The refined Developability Classification System (rDCS) classifies lemborexant as class I, indicating minimal biopharmaceutics risks.

Purpose of the Study:

  • To explore alternative strategies for establishing bioequivalence (BE) for lemborexant formulations.
  • To address the limitations of the BCS-based approach for lemborexant IR solid oral dosage forms.
  • To propose a virtual BE assessment pathway for lemborexant and similar compounds.

Main Methods:

  • Utilized the refined Developability Classification System (rDCS) for lemborexant classification.
  • Conducted customized rDCS investigations to identify critical bioavailability attributes.
  • Employed biorelevant dissolution testing to assess dissolution behavior.
  • Proposed a four-step pathway involving rDCS, biorelevant dissolution, Physiologically Based Biopharmaceutics Modeling (PBBM), and virtual BE assessment.

Main Results:

  • rDCS analysis identified dissolution as the primary risk factor for lemborexant, not solubility or permeability.
  • Clinical data in humans supports that lemborexant absorption is not limited by solubility or permeability.
  • The proposed four-step pathway offers a method to mitigate risks associated with formulation changes or generic introductions.
  • This approach facilitates virtual bioequivalence assessment when BCS-based justification is not feasible.

Conclusions:

  • The refined Developability Classification System (rDCS) provides a more nuanced risk assessment for lemborexant than BCS.
  • Dissolution is the critical attribute to monitor for lemborexant formulation development and generic substitution.
  • A virtual bioequivalence assessment pathway combining rDCS, biorelevant dissolution, and PBBM is a viable strategy for lemborexant and similar drugs.
  • This strategy can streamline drug development and generic approval processes by reducing reliance on clinical bioequivalence studies.