Formulation, Development, and Optimization of Fast Dissolving Tablets Containing Tapentadol Hydrochloride
Authors: Thalluri Chandrashekar , vasam mallikarjun , Jampala Rajkumar , Alagarsamy Shanmugarathinam , Dubey Anubhav , Lather Amit , HOODA TANUJ 
Published: December 2024

Background:

Tapentadol hydrochloride is a potent analgesic commonly used to manage
moderate to severe pain. Rapidly dissolving tablets of Tapentadol offer a significant advantage in
enhancing patient compliance by providing quick pain relief. The development of fast-dissolving
tablets (FDTs) requires careful consideration of formulation parameters to achieve optimal disintegration
and dissolution profiles. In this study, the aim was to fabricate Tapentadol FDTs by selecting
suitable super disintegrating agents such as croscarmellose sodium and crospovidone, which
serve as two independent variables. The direct compression method was employed to formulate nine
different Tapentadol hydrochloride formulations (TH1 to TH9).

Materials and Methods:

The study utilized Design-Expert® software version 13.0 and the Response
Surface Methodology (RSM) for the optimization of Tapentadol FDTs. The formulations
were prepared using the direct compression method with varying concentrations of the super disintegrants,
croscarmellose sodium, and crospovidone. The primary response variables considered in
this optimization study included disintegration time (Y1), percentage drug release at 15 minutes
(Q15, Y2), and percentage drug release at 30 minutes (Q30, Y3). All pre-compressional and postcompressional
parameters were evaluated for each formulation, along with in vitro dissolution studies.
Furthermore, DD Solver, a statistical tool, was employed to determine the kinetics of drug release
and the release order mechanism based on regression coefficient value (r²), Akaike Information
Criterion (AIC), and Model Selection Criteria (MSC).

Results:

The evaluation studies indicated that the TH5 formulation exhibited the most rapid disintegration
time and the highest drug release percentage within the specified time frame. The super disintegrants
used demonstrated a significant impact on the response variables, notably enhancing the
solubility and dissolution rate of Tapentadol hydrochloride. Based on the exponent release (n) value,
the study concluded that the TH5 formulation followed a first-order release kinetics and Fickian
diffusion mechanism for drug release. Stability studies were performed following the International
Council for Harmonization (ICH) guidelines to assess the shelf-life of the optimized formulation.
The ANOVA data revealed that the p-value was greater than 0.05, indicating no significant differences
during the storage period. Additionally, a similarity factor (f2) analysis was conducted to
compare the optimized formulation with the marketed formulation (Tydol 100 mg).

Discussion:

The findings highlight the crucial role of super disintegrants in fast-dissolving tablet
formulation, significantly impacting disintegration time and dissolution profile. The TH5 formulation
excelled in rapid disintegration and drug release, optimized using RSM and Design-Expert
software, with statistical analysis confirming the Fickian diffusion mechanism for drug release.

Conclusion:

The study successfully developed and optimized Tapentadol fast-dissolving tablets using
direct compression and response surface methodology. The TH5 formulation showed rapid disintegration
and optimal drug release, with stability confirmed under ICH conditions. This highlights
the importance of super disintegrants in FDT formulation for rapid action and patient compliance.