Thalluri Chandrashekar, Vasam Mallikarjun, Jampala Rajkumar, Alagarsamy Shanmugarathinam, Dubey Anubhav, Lather Amit, Hooda Tanuj
Department of Pharmaceutics, Faculty of Pharmaceutical Science, Assam Downtown University, Gandhinagar, Panikhaiti, Guwahati-781026, Assam, India.
Annasaheb Dange college of B Pharmacy, Ashta, Taluka-Walwa, Sangli- 416301, Maharashtra.
Pharm Nanotechnol. 2024 Dec 23. doi: 10.2174/0122117385350217241122151638.
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).
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).
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).
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.
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.
盐酸曲马多是一种强效镇痛药，常用于治疗中度至重度疼痛。盐酸曲马多速溶片通过快速缓解疼痛，在提高患者依从性方面具有显著优势。快速溶解片（FDT）的研发需要仔细考虑制剂参数，以实现最佳的崩解和溶出曲线。在本研究中，目的是通过选择合适的超级崩解剂如交联羧甲基纤维素钠和交联聚维酮来制备盐酸曲马多FDT，这两种超级崩解剂作为两个自变量。采用直接压片法制备了九种不同的盐酸曲马多制剂（TH1至TH9）。
本研究利用Design-Expert®软件版本13.0和响应面法（RSM）对盐酸曲马多FDT进行优化。采用直接压片法制备制剂，使用不同浓度的超级崩解剂交联羧甲基纤维素钠和交联聚维酮。本优化研究中考虑的主要响应变量包括崩解时间（Y1）、15分钟时的药物释放百分比（Q15，Y2）和30分钟时的药物释放百分比（Q30，Y3）。对每种制剂的所有压片前和压片后参数进行评估，并进行体外溶出研究。此外，使用统计工具DD Solver根据回归系数值（r²）、赤池信息准则（AIC）和模型选择标准（MSC）来确定药物释放动力学和释放顺序机制。
评估研究表明，TH5制剂在规定时间内表现出最快的崩解时间和最高的药物释放百分比。所使用的超级崩解剂对响应变量有显著影响，特别是提高了盐酸曲马多的溶解度和溶出速率。根据指数释放（n）值，该研究得出结论，TH5制剂遵循一级释放动力学和菲克扩散机制进行药物释放。按照国际协调理事会（ICH）指南进行稳定性研究，以评估优化制剂 的保质期。方差分析数据显示p值大于0.05，表明在储存期内无显著差异。此外，进行了相似性因子（f2）分析，以将优化制剂与市售制剂（Tydol 100 mg）进行比较。
研究结果突出了超级崩解剂在快速溶解片制剂中的关键作用，对崩解时间和溶出曲线有显著影响。TH5制剂在快速崩解和药物释放方面表现出色，通过RSM和Design-Expert软件进行优化，统计分析证实了药物释放遵循菲克扩散机制。
本研究使用直接压片法和响应面法成功开发并优化了盐酸曲马多速溶片。TH5制剂显示出快速崩解和最佳药物释放，在ICH条件下稳定性得到证实。这突出了超级崩解剂在FDT制剂中对快速起效和患者依从性的重要性。
