Influence of a common pharmaceutical excipient on BCS-based biowaivers for oral drug products

Terrmin

HT23

Beskrivning

Background

The Biopharmaceutical Classification System (BCS), based on the solubility and intestinal permeability of drugs, has been used by pharmaceutical and regulatory scientists to identify candidates from immediate release oral solid drug products for biowaivers of in vivo bioequivalence studies for more than 15 years (Amidon et al. 1995). In the regulatory guideline ICH M9 it is stated that BCS class I and III drug products are eligible for BCS based biowaivers, i.e., to show bioequivalence with the reference product based only on in vitro dissolution data, without doing an in vivo bioequivalence study. This option is not possible if the two products differ in the amounts of certain excipients that could affect the rate and extent of absorption in vivo. Examples of such excipients are mannitol, sorbitol and magnesium stearate. However, these excipient thresholds stated in the guideline (ICH M9) may be too conservative, resulting in unnecessary in vivo bioequivalence studies.

Knowledge of the “excipients effect” threshold for common pharmaceutical excipients, in relation to the BCS class of the drug product, is expected to significantly reduce the number of clinical bioequivalence studies during the development of new oral solid drug products.

Overall Aim

To investigate the influence of one commonly used pharmaceutical excipient on the rate and extent of absorption in vivo, to find an excipient effect threshold for that excipient. These results are believed to be applicable in future revision of the current ICH M9 guideline and would also reduce the number of clinical bioequivalence studies during the development of new oral solid drug products.

Suggested work plan

Literature study, chose one excipient for further investigation, identify oral drug products containing this excipient (internal Medical Product Agency, MPA, data base), find bioequivalence studies performed with these products (internal MPA data base), extract the pharmacokinetic parameters Cmax and AUC, summarize the findings, define the excipient effect threshold if possible, blind the drug products involved and, finally, write a scientific manuscript.

References
Amidon et al. A theoretical basis for a biopharmaceutics drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 12. 413-420. 1995.

ICH M9, Biopharmaceutics classification system-based biowaivers. Adopted on 20 November 2019. https://www.ich.org/page/multidisciplinary-guidelines

Huvudområde

Läkemedelsutveckling

Ämne

Läkemedelsformulering och Molekylär galenisk farmaci

Typ

Litteraturstudie

Företag

Läkemedelsverket

Ort/Plats

Uppsala

Handledarens namn

Anders Lindahl

Handledarens e-post

anders.lindahl@lakemedelsverket.se

Institution

Institutionen för farmaci

Program

Apotekarprogrammet

Kurs

Fördjupningsprojekt i molekylär galenisk farmaci och läkemedelsformulering - 3FG090

Omfattning/hp

30hp

Hur många studenter kan antagas för detta projekt?

1

© 2022 Uppsala universitet | Teknisk support