Development of orally disintegrating tablets containing solid dispersion of a poorly soluble drug for enhanced dissolution: In-vitro optimization/in-vivo evaluation

Abstract

Diacerein (DCN), a potent anti-inflammatory API used to treat osteoarthritis yet, it suffers from poor water solubility which affects its oral absorption. Unabsorbed colonic DCN is converted into rhein, which is responsible for laxation as a main side effect of DCN treatment. Therefore, in this study orally disintegrating tablets (ODTs) loaded with optimized DCN solid dispersion system were prepared using different co-processed excipients (Prosolv® ODT, Pharmaburst® 500 and F-melt®), aiming to achieve improved solubility, rapid absorption and consequently limited amount of rhein reaching the colon. Prepared ODTs were evaluated for physical characteristics, in-vitro drug release, disintegration and wetting times. Dissolution parameters; dissolution efficiency percent at 10 (DE (10 min)%) and 30 (DE (30 min)%) min and mean dissolution time (MDT) were determined. The optimized ODT showed 1.50 and 1.12 fold increase in DE (10 min)% and DE (30 min)%, respectively and 2 fold decrease in MDT, compared to Diacerein® capsules. In-vivo anti-inflammatory effect of optimized ODT, using rat paw edema revealed significant increase in edema inhibition (p < 0.0465) and promoted onset of action compared to Diacerein® capsules at 0.5 hr. It could be concluded that optimized ODT could be promising for enhanced dissolution and rapid absorption of DCN from the oral cavity.

Formulation and Evaluation of Baclofen-Meloxicam Orally Disintegrating Tablets (ODTs) Using Co-Processed Excipients and Improvement of ODTs Performance Using Six Sigma Method

“…48 F-melt showed longer DT than Pharmaburst; this may be due to the lower specific surface area of F-melt than Pharmaburst 500, which was the reason for the delay of DT in F-melt based formula (F2) than Pharamaburst formula (F1). 49 On the other hand, ODTs containing Prosolv had prolonged DT; as mentioned before, Prosolv consists of crospovidone, MCC, and mannitol, which was likely to cause DT delay. These results agree with Jacob et al 50 Using of First Derivative Spectrophotometric Analysis in the Simultaneous Determination of Baclofen and Meloxicam in Phosphate Buffer pH = 6.8…”

Design and optimization of silymarin loaded in lyophilized fast melt tablets to attenuate lung toxicity induced via HgCl2 in rats

“…SM FMTs dissolution was proceeded via the USP dissolution system, Distek (Model 2500i Type II, TCS-0500 Scheduler, New Jersey, USA) at 37 ± 0.5oC and at 50 rpm using 900 mL of SSF as the dissolution medium (Moqbel et al., 2016 ; Shohin et al., 2016 ; Fouad et al., 2020 ; AlAli et al., 2021 ; Ali et al., 2021 . Samples were taken at (2, 4, 6, 8, 10, 20 and 30 min), 5 mL aliquots samples were withdrawn and instantaneously replaced with 5 mL SSF kept at the same temperature (Cirri et al., 2005 ; Sheta & Boshra, 2021 ).…”

“…This can be achieved via developing an oral delivery system that allows pre-gastric absorption in addition to applying solubility improvement, hence enhancing the oral bioavailability of SM (Wen et al., 2008 ; Zhu et al., 2013 ; Tawfeek et al., 2018 ). FMTs have been developed as an appealing alternative to overcome the drawbacks of conventional SM oral tablets, such as the difficulty of swallowing in geriatrics by rapid disintegration in the mouth (30 Sec) and the faster onset of action, which leads to improved patient compliance, as well as bypassing first-pass metabolism (ElMeshad et al., 2020 ; Fouad et al., 2020 ). Several techniques are currently used to formulate FMT, including lyophilization, solid dispersion, direct compression, and molding (Bhowmik et al., 2009 ).…”

Stereomicroscope with Imaging Analysis: A Versatile Tool for Wetting, Gel Formation and Erosion Rate Determinations of Eutectic Effervescent Tablet

“…All formulations showed the same trends of DT in both media but slightly lesser in distilled water. As a result, solubility should be regarded as the important factor influencing the disintegration behavior of the formulation and resulting in higher dissolution of the formulation [51,52]. The carbonation reaction from effervescent agents caused the surface erosion, resulting in a deeper penetration distance of the medium and accelerated disintegration of the eutectic effervescent tablet [48][49][50].…”