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Novel Approach for the Bioequivalence Assessment of Topical Cream Formulations: Model-Based Analysis of Tape Stripping Data Correctly Concludes BE and BIE.
Pharm Res. 2020 Jan 02; 37(2):20.PR

Abstract

PURPOSE

The purpose of this study was (a) to suggest a novel dermatopharmacokinetic (DPK) approach from which pharmacokinetic parameters relevant to the bioequivalence (BE) assessment of a topical formulation can be deduced while circumventing the need for numerous measurements and assumptions, and (b) to investigate whether this approach enables the correct conclusion of BE and bioinequivalence (BIE).

METHODS

Bioequivalent and bioinequivalent formulations of acyclovir were compared versus a reference product (Zovirax®). Tape Stripping was conducted at only one dose duration during the uptake phase to generate drug content in stratum corneum versus time profiles, each time point corresponding to one stripped layer. Nonlinear mixed effect modeling (ADAPT5®) (MLEM algorithm) was used to fit the DPK data and to estimate the rate (Kin) and extent (FS) of drug absorption/input into the skin. Results were evaluated using the average BE approach.

RESULTS

Estimated exposure metrics were within the usual BE limits for the bioequivalent formulation (FS: 102.4 [90%CI: 97.5-107.7]; Kin: 94.2 [90%CI: 83.7-106.0]), but outside those limits for the bioinequivalent formulation (FS: 43.4 [90%CI: 27.9-67.6]; Kin: 54.5 [90%CI: 36.6-81.1]).

CONCLUSIONS

The proposed novel DPK approach was shown to be successful, robust and applicable to assess BE and BIE correctly between topical formulations.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Ozdin D
Faculté de pharmacie, Université de Montréal, Pavillon Jean Coutu, 2940 Chemin de la polytechnique, Montréal, Quebec, Canada. Learn and Confirm Inc., 750 Marcel-Laurin Suite 235, St-Laurent, Quebec, Canada.
Kanfer I
Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St, Toronto, Ontario, Canada. Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa.
Ducharme MP
Faculté de pharmacie, Université de Montréal, Pavillon Jean Coutu, 2940 Chemin de la polytechnique, Montréal, Quebec, Canada. murray.ducharme@learnandconfirm.ca. Learn and Confirm Inc., 750 Marcel-Laurin Suite 235, St-Laurent, Quebec, Canada. murray.ducharme@learnandconfirm.ca.

MeSH

Administration, CutaneousBiological AvailabilityChemistry, PharmaceuticalEpidermisFemaleHumansMaleOintmentsSkinSkin AbsorptionTherapeutic Equivalency

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31897770

Citation

Ozdin, Deniz, et al. "Novel Approach for the Bioequivalence Assessment of Topical Cream Formulations: Model-Based Analysis of Tape Stripping Data Correctly Concludes BE and BIE." Pharmaceutical Research, vol. 37, no. 2, 2020, p. 20.
Ozdin D, Kanfer I, Ducharme MP. Novel Approach for the Bioequivalence Assessment of Topical Cream Formulations: Model-Based Analysis of Tape Stripping Data Correctly Concludes BE and BIE. Pharm Res. 2020;37(2):20.
Ozdin, D., Kanfer, I., & Ducharme, M. P. (2020). Novel Approach for the Bioequivalence Assessment of Topical Cream Formulations: Model-Based Analysis of Tape Stripping Data Correctly Concludes BE and BIE. Pharmaceutical Research, 37(2), 20. https://doi.org/10.1007/s11095-019-2724-2
Ozdin D, Kanfer I, Ducharme MP. Novel Approach for the Bioequivalence Assessment of Topical Cream Formulations: Model-Based Analysis of Tape Stripping Data Correctly Concludes BE and BIE. Pharm Res. 2020 Jan 2;37(2):20. PubMed PMID: 31897770.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel Approach for the Bioequivalence Assessment of Topical Cream Formulations: Model-Based Analysis of Tape Stripping Data Correctly Concludes BE and BIE. AU - Ozdin,Deniz, AU - Kanfer,Isadore, AU - Ducharme,Murray P, Y1 - 2020/01/02/ PY - 2019/08/06/received PY - 2019/10/17/accepted PY - 2020/1/4/entrez PY - 2020/1/4/pubmed PY - 2020/6/2/medline KW - bioequivalence and bioinequivalence KW - population PK modeling KW - regulatory sciences KW - tape stripping KW - topical dermatological formulations SP - 20 EP - 20 JF - Pharmaceutical research JO - Pharm Res VL - 37 IS - 2 N2 - PURPOSE: The purpose of this study was (a) to suggest a novel dermatopharmacokinetic (DPK) approach from which pharmacokinetic parameters relevant to the bioequivalence (BE) assessment of a topical formulation can be deduced while circumventing the need for numerous measurements and assumptions, and (b) to investigate whether this approach enables the correct conclusion of BE and bioinequivalence (BIE). METHODS: Bioequivalent and bioinequivalent formulations of acyclovir were compared versus a reference product (Zovirax®). Tape Stripping was conducted at only one dose duration during the uptake phase to generate drug content in stratum corneum versus time profiles, each time point corresponding to one stripped layer. Nonlinear mixed effect modeling (ADAPT5®) (MLEM algorithm) was used to fit the DPK data and to estimate the rate (Kin) and extent (FS) of drug absorption/input into the skin. Results were evaluated using the average BE approach. RESULTS: Estimated exposure metrics were within the usual BE limits for the bioequivalent formulation (FS: 102.4 [90%CI: 97.5-107.7]; Kin: 94.2 [90%CI: 83.7-106.0]), but outside those limits for the bioinequivalent formulation (FS: 43.4 [90%CI: 27.9-67.6]; Kin: 54.5 [90%CI: 36.6-81.1]). CONCLUSIONS: The proposed novel DPK approach was shown to be successful, robust and applicable to assess BE and BIE correctly between topical formulations. SN - 1573-904X UR - https://www.unboundmedicine.com/medline/citation/31897770/Novel_Approach_for_the_Bioequivalence_Assessment_of_Topical_Cream_Formulations:_Model_Based_Analysis_of_Tape_Stripping_Data_Correctly_Concludes_BE_and_BIE_ DB - PRIME DP - Unbound Medicine ER -