Related Experiment Video
Updated: Jun 3, 2026
09:24
Application and Methodology of the Non-destructive 19F Time-domain NMR Technique to Measure the Content in Fluorine-containing Drug Products
Published on: August 22, 2017
Biowaiver monographs for immediate release solid oral dosage forms: levofloxacin
Marcelle O Koeppe1, Rodrigo Cristofoletti, Eduardo F Fernandes
1Brazilian Health Surveillance Agency (Anvisa), Division of Bioequivalence, Brazil.
Journal of Pharmaceutical Sciences
|March 5, 2011
Summary
A biowaiver for levofloxacin immediate-release (IR) solid oral dosage forms is recommended. This applies if the drug, classified under Class I, meets specific dissolution and excipient criteria, simplifying bioequivalence (BE) testing.
Area of Science:
- Pharmaceutical Sciences
- Drug Development
- Regulatory Science
Background:
- Levofloxacin is an active pharmaceutical ingredient (API) often formulated as immediate-release (IR) solid oral dosage forms.
- The Biopharmaceutics Classification System (BCS) categorizes drugs based on solubility and permeability, influencing regulatory requirements.
- Bioequivalence (BE) testing ensures that generic drugs perform comparably to reference drugs.
Purpose of the Study:
- To review literature data supporting a waiver of in vivo bioequivalence (BE) testing for levofloxacin IR solid oral dosage forms.
- To assess the feasibility of biowaiver for levofloxacin based on its physicochemical properties and formulation characteristics.
- To establish criteria for granting a biowaiver for levofloxacin formulations.
Main Methods:
- Literature review of existing data on levofloxacin formulations and bioequivalence.
- Classification of levofloxacin within the Biopharmaceutics Classification System (BCS).
- Analysis of reported issues with levofloxacin formulations regarding bioequivalence and dissolution.
Main Results:
- Levofloxacin is classified as BCS Class I, indicating high solubility and permeability.
- No significant issues with bioequivalence for IR levofloxacin formulations using various excipients and manufacturing methods have been reported.
- Levofloxacin possesses a wide therapeutic index, suggesting a low risk of clinical issues due to minor formulation variations.
Conclusions:
- A biowaiver is recommended for IR solid oral dosage forms of levofloxacin as the sole API.
- Conditions for the biowaiver include specific excipient profiles, rapid dissolution rates, and demonstrated dissolution profile similarity across relevant pH levels.
- Quantitative and qualitative similarity of polysorbate content is required if present in the formulation.
Related Concept Videos
01:13Bioequivalence studies: Biowaivers
In certain scenarios, in vitro dissolution tests can replace in vivo bioequivalence studies. This is particularly true when a drug product, though available in varying strengths, maintains proportional similarity in its active and inactive ingredients. In such cases, the need for in vivo bioequivalence studies for lower strength variants may be waived, provided dissolution tests and in vivo studies on the highest strength yield satisfactory results.Bioequivalence can be indicated through...
01:28Inhibitors of Bacterial DNA Synthesis
Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
01:28IV Infusion to Oral Dosing: Conversion Methods
The development of extended-release formulations has facilitated the transition from intravenous to oral medication, offering a more convenient and patient-friendly approach to drug administration. This transition, however, requires careful management to ensure that therapeutic drug levels are maintained, preserving efficacy and avoiding adverse effects. Understanding pharmacokinetic principles and dosage calculations is critical during this process.Pharmacokinetics of the...
01:26Oral Drug Delivery Systems: Continuous-Release Systems
Continuous-release drug delivery systems offer a strategic approach to maintaining therapeutic drug levels over extended periods following oral administration. By modulating the release rate of active pharmaceutical ingredients, these systems minimize fluctuations in plasma concentrations, which enhances clinical efficacy and reduces the need for frequent dosing. Such characteristics make them particularly advantageous in managing chronic diseases where patient adherence and stable drug...
01:27Drug Delivery Systems: Different Types
Conventional oral drug products, termed immediate-release (IR) formulations, are engineered to promptly release their active pharmaceutical ingredient (API) upon ingestion, typically in tablets or capsules. This rapid release often results in swift drug absorption and consequent pharmacodynamic effects, although the timing and intensity can vary depending on the drug's properties. Prodrugs within these formulations require metabolic conversion to activate their pharmacodynamic effects,...
01:11Oral Drug Delivery Systems: Delayed-Release Systems
Delayed-release drug delivery systems are specialized pharmaceutical formulations designed to postpone the release of active compounds until the drug reaches a specific region of the gastrointestinal (GI) tract, typically the intestine. These systems are essential for drugs that may cause gastric irritation, are unstable in acidic environments, or need to exert therapeutic effects locally in the intestinal or colonic regions.The core feature of delayed-release systems is the use of enteric...