Evaluation of USP 3 Apparatus to Develop Biopredictive Fasted and Fed Dissolution Methods for Extended-Release Desvenlafaxine Succinate Tablets

TL;DR

The study shows how the USP 3 apparatus can be used to create accurate dissolution methods for extended-release desvenlafaxine tablets in both fasted and fed states.

Contribution

The novel use of USP 3 apparatus for developing biopredictive dissolution methods for desvenlafaxine in fed states is demonstrated.

Findings

USP 3 apparatus successfully developed biopredictive fed state dissolution methods for desvenlafaxine.

USP 2 methods failed to predict fed state dissolution accurately.

No significant difference was found between pH-gradient and NaCl medium in USP 3 methods.

Abstract

The development of distinct biopredictive methods for
fasted and
fed states using a physiologically based biopharmaceutics modeling
(PBBM) approach is essential for accurately evaluating drug release
from solid oral dosage forms, especially extended-release products.
However, a fed state biopredictive method for desvenlafaxine tablets
is not currently available. Hence, the study aimed to investigate
the application of the USP 3 apparatus to develop biopredictive methods
for desvenlafaxine tablets. Initially, an existing fasted state biopredictive
USP 2 dissolution method was adapted to increase dissolution hydrodynamics
by scaling the rotation speed to 75 and 100 rotations per minute (rpm).
Subsequently, two dissolution methods were developed using the USP
3 apparatus to emulate fasted and fed conditions. The fed biopredictability
of the methods was assessed using a previously developed GastroPlus
model to simulate fed conditions under 800 kcal and 50% fat meal.
Statistical analysis of dissolution profiles obtained in the paddle
apparatus revealed no significant difference from the original 50
rpm method and lacked biopredictive for the fed state, indicating
the unfeasibility of developing such a method in this apparatus. In
contrast, USP 3 proved to be an important tool to develop a fed state
method, since it was biopredictable based on simulation analysis.
Additionally, no significant differences were observed between USP
3 methods employing pH-gradient media and those using 0.9% NaCl as
the sole medium. These findings highlight a hydrodynamic-driven approach
for applying USP 3 to develop distinct biopredictive dissolution methods
for fasted and fed states, particularly for high-solubility drugs
formulated in robust hypromellose matrices.

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