Formulation, Development, and Optimization of Fast Dissolving Tablets Containing Tapentadol Hydrochloride.

Abstract

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.