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

The present study aimed to develop fast melting tablets (FMTs) using silymarin (SM) owing to FMTs rapid disintegration and dissolution. FMTs represent a pathway to help patients to increase their compliance level of treatment via facile administration without water or chewing beside reduction cost. One of the methods for FMTs formulation is lyophilization. Optimization of SM-FMTs was developed via a 32 factorial design. All prepared SM-FMTs were evaluated for weight variation, thickness, breaking force, friability, content uniformity, disintegration time (DT), and % SM released. The optimized FMT formula was selected based on the criteria of scoring the fastest DT and highest % SM released after 10 min (Q10). Optimized FMT was subjected to Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) besides investigating its lung-protective efficacy. All SM-FMT tablets showed acceptable properties within the pharmacopeial standards. Optimized FMT (F7) scored a DT of 12.5 ± 0.64 Sec and % SM released at Q10 of 82.69 ± 2.88%. No incompatibilities were found between SM and excipients, it showed a porous structure under SEM. The optimized formula decreased cytokines, up-regulated miRNA133a, and down-regulated miRNA-155 and COX-2 involved in the protection against lung toxicity prompted by HgCl2 in a manner comparable to free SM at the same dosage.

A Promising Single Oral Disintegrating Tablet for Co-Delivery of Pitavastatin Calcium and Lornoxicam Using Co-Processed Excipients: Formulation, Characterization and Pharmacokinetic Study.

SIGNIFICANCE: Statins are an important class of drugs that help to control hyperlipidemia, and one of these statins recently used is pitavastatin calcium (PITA). Nevertheless, the most reported adverse effect of statins is myopathy. Therefore, combining statins with non-steroidal anti-inflammatory drugs (NSAIDs) as Lornoxicam (LORNO) can help in the management of statin-induced myopathy. PURPOSE: This study aimed to formulate and evaluate different oral disintegrating tablets (ODTs) containing PITA using different co-processed excipients. The best PITA-ODT was selected and reformulated with the addition of LORNO, forming a single ODT comprising both drugs. The pharmacokinetic parameters of PITA and LORNO in a single ODT were compared to those of the marketed products (Lipidalon® and Lornoxicam®). METHODS: Eight PITA-ODTs were prepared via direct compression. The prepared PITA-ODTs were evaluated for their weight variation, thickness, breaking force, friability, drug content, and wetting time (WT). In-vitro disintegration time (DT) and dissolution were also evaluated and taken as parameters for selection of the best formula based on the criteria of scoring the fastest DT and highest Q10 min. LORNO was added to the selected PITA-ODT, forming a single ODT (M1) comprising both drugs, which was subjected to an in-vivo pharmacokinetic study using rats as an animal model and liquid chromatography-mass spectrometry (LC-MS/MS) for analysis of both drugs in rat plasma. RESULTS: Results showed that all PITA-ODTs had acceptable physical properties in accordance with pharmacospecial standards. PITA-ODT prepared with Pharmaburst® (F2) had significantly (p<0.05) the fastest DT (6.66±1.52 s) and highest Q10 min (79.07±2.02%) and was chosen as the best formula. The in-vivo pharmacokinetic study of M1 formula showed higher percent relative bioavailability (%RB) of 286.7% and 169.73% for PITA and LORNO, respectively, compared with the marketed products. CONCLUSION: The single ODT comprising PITA and LORNO was promising for instant co-delivery of both drugs with higher %RB when compared with the marketed products.

Core in Cup Ethylmorphine Hydrochloride Tablet for Dual Fast and Sustained Pain Relief: Formulation, Characterization, and Pharmacokinetic Study.

Ethylmorphine hydrochloride (EtM) is a derivative of morphine used as analgesic to treat severe pain in case of cancer and bone injury. This study aimed to formulate and evaluate core in cup tablets containing 2 doses of EtM, the cup was formulated as lyophilized oro-dispersible tablet (ODT) for immediate release (IR), and the core was formulated as directly compressed tablet for sustained release (SR). Factorial design was adopted for the optimization of tablets prepared via lyophilized form and direct compression techniques: a 41.22 design was used for the former, while a 32 one was used for the latter. All prepared tablets showed acceptable physical properties which were in accordance with pharmacopeial standards. Two lyophilized ODTs (F9 and F10) formulae were selected as the cup for instant release. While one directly compressed tablet formula (S6) was selected based on the in vitro release profile to represent the sustained core, the outcome was 2 core in cup tablets, namely B1 and B2 which were evaluated for their in vivo absorption and showed a maximum plasma concentration (Cpmax) of 354.12 ± 17.55 ng/mL and 350.82 ± 12.15 ng/mL respectively attained after 3.0 h which were twofolds significantly higher in comparison to the market tablet with Cpmax of only 172.05 ± 12.53 ng/mL attained after 2.20 ± 0.24 h.