EVALUATION OF TOPICAL BIOAVAILABILITY OF

ERYTHROMYCIN USING
DERMATOPHARMACOKINETIC METHOD
 Definition of Bioequivalence

Pharmaceutical equivalents whose rate and

extent of absorption are not statistically
different when administered to patients or
subjects at the same molar dose under
similar experimental/clinical conditions
 DermatoPharmacoKinetic (DPK)
Theory
Pharmacokinetic approach applied to drug
concentrations in stratum corneum (SC)
Method
Tape stripping is used to remove successive
layers of SC after topical drug administration
Uptake and elimination from SC are determined
Differences in formulation performance (BE) are
determined at the same time in the same
individual
 Model of Oral Dosage Form
Performance

Pharmacokinetic Clinical/PD
Dosage Form Measurement Measurement
Performance

Dosage Drug in Site of Therapeutic

Gut Wall Blood
Form Solution Activity Effect

Dose ln Dose
 Model of Topical (Skin) Dosage
Form Performance

Clinical/PD Pharmacokinetic
Dosage Form Measurement Measurement
DPK
Performance

Dosage Drug Site of Therapeutic Systemic

Blood
Form In Tissue Activity Effects Effects

ln Dose Dose
 Research Concern
Is the DPK method an appropriate approach for
establishing bioequivalence of topical drug
products?
Are results and conclusions derived from the DPK
method consistent within and between
laboratories?
Can DPK methodology be established in any
laboratory or CRO with a reasonable amount of
time, effort and expense?
 Objective
 To develop and validate simple, specific and sensitive analytical
method in vitro for the estimation of Erythromycin in human
Stratum corneum.
 To assess the in vivo pharmacokinetics of two Erythromycin
Marketed formulations by Dermatopharmacokinetic methods
using Indian male subjects to meet the following sub-objectives:
 Efficacy: To assess the pharmacokinetic profile of Erythromycin
Marketed formulations by Dermatopharmacokinetic methods.
 Safety: To monitor the safety of the study formulations in subjects.
 To investigate the in vitro penetration characteristics of the two
Erythromycin formulations and to check if any in vitro-in vivo
correlation could be established.
Study Design
 Analytical Method for Sample
Analysis
For better sensitivity and accuracy, HPLC method
for analysis of Erythromycin from SC samples was
developed and validated.
Both the methods were developed using working
standard of Erythromycin and validated for
accuracy for Erythromycin estimation for the
formulations used in the study.
Comparative DPK Results
 Comparative DPK Results

Dependent Test FormRef RefGeoLSM TestGeoLSM Ratio[%Ref] CI_90_Lower CI_90_Upper

Ln(AUCINF_o
bs) A B

Ln(AUClast) A B

Ln(Cmax) A B
In vitro findings
IVIVC