Buprenorphine Transdermal Delivery System: Bioequivalence Assessment and Adhesion Performance of Two Patch Formulations

Abstract

Background and Objective: Buprenorphine is an opioid drug indicated for the management of severe and persistent pain. The buprenorphine transdermal patch provides a non-invasive method of rate-controlled drug release, ensuring constant and predictable drug plasma levels over an extended period. This study aimed to assess the bioequivalence, skin adhesion non-inferiority, and tolerability of two buprenorphine transdermal patches to meet the regulatory requirements for the registration of a generic product in Brazil. Methods: A randomized, single-dose, two-period, two-sequence crossover trial was performed involving healthy subjects of both genders. The subjects received a single dose of either the test formulation or the reference formulation (Restiva^®), separated by a 29-day washout period. For pharmacokinetic analysis, blood samples were collected up to 12 days post-dose and quantified using a validated bioanalytical method. Skin adhesion was assessed over a 7-day period (dosing interval) following patch application. Seventy-six subjects were enrolled and fifty-two completed the study. Results and Conclusion: The 90% confidence intervals for Cmax, AUC_0-t, and partial AUCs were within the acceptable bioequivalence limits of 80 to 125%. Adhesion comparison showed the non-inferiority of the test formulation. Based on ANVISA's regulatory requirements, the test and reference formulations were considered bioequivalent and could be interchangeable in clinical practice.

Keywords: adhesion; bioequivalence; buprenorphine; opioid; patch; pharmacokinetics; transdermal delivery system.

Figure 1

Photograph of the test (left) and reference (right) formulations used in the study.

Figure 2

Mean plasma concentration vs. time (± SD) curves after the administration of the test (buprenorphine transdermal patch 20 µg/h) and the reference (Restiva^® 20 µg/h) formulations in healthy male and non-pregnant female subjects (n = 52). The patches were removed 168 h (7 days) after the application, and the blood samples were collected up to 288 h.

Figure 3

Adhesion assessment within the dosing interval (7 days) for the test (squares) and reference (empty circles) patch formulations. Data are expressed as mean ± SD (n = 52).