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Sensitivity of Different In Vitro Performance Tests and Their In Vivo Relevance for Calcipotriol/Betamethasone Ointment

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Abstract

Purpose

We compared results of in vitro performance testing with results of therapeutic equivalence study for calcipotriol/betamethasone ointment, to evaluate their sensitivity and in vivo relevance.

Methods

Different in vitro methods were used to evaluate drug release and permeation from the test and reference ointment. Moreover, 444 psoriasis patients were randomized in the therapeutic equivalence study and the parameters of efficacy and safety were compared with in vitro results.

Results

In vitro release and permeation rate of calcipotriol and betamethasone from the test formulation was higher than from the reference product for all methods used (p ≤ 0.05 for calcipotriol and p < 0.01 for betamethasone). Observed batch-to-batch variability of reference product confirmed high sensitivity and discriminatory power of in vitro methods. Higher release and permeation rate of calcipotriol and betamethasone from test product was reflected in the efficacy assessment (mean response difference 4.78 mPASI percentage points), but the observed difference was within the equivalence margins. Systemic exposure to calcipotriol and betamethasone was similar in both treatment groups.

Conclusion

The results of in vitro experiments rank orderly correlated with the results of clinical study. In vitro methods are more sensitive and highly discriminatory when compared to in vivo performance.

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Abbreviations

BSA:

Body surface area

CI:

Confidence interval

CN:

Cellulose-nitrate

IPGA:

Investigators Psoriasis Global Assessment

MFA, MFB:

Mobile phase A/B

mPASI:

Modified Psoriasis Area and Severity Index

PPGA:

Patients Psoriasis Global Assessment

Q1:

Qualitative

Q2:

Quantitative

Q3:

Microstructure

SD:

Standard deviation

TCS:

Topical Drug Classification System

USA:

United States of America

UPLC:

Ultra Performance Liquid Chromatography

USP:

United States Pharmacopeia

UV:

Ultraviolet

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Funding

The study was funded by Lek Pharmaceuticals d.d., a Sandoz company.

Author information

Correspondence to Katja Kristan.

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Habjanič, N., Kerec Kos, M. & Kristan, K. Sensitivity of Different In Vitro Performance Tests and Their In Vivo Relevance for Calcipotriol/Betamethasone Ointment. Pharm Res 37, 52 (2020). https://doi.org/10.1007/s11095-020-2766-5

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Key Words

  • betamethasone
  • calcipotriol
  • permeation
  • release
  • therapeutic equivalence