No abstract

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 nonsteroidal 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 Q 10 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 Q 10 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 codelivery of both drugs with higher %RB when compared with the marketed products.

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 3 2 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 (Q 10 ). 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 Q 10 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 HgCl 2 in a manner comparable to free SM at the same dosage.

Objective: Pitavastatin calcium (PT) is an innovative drug of statins that enhances HDL-C and lowers LDL-C. However, myalgia has been reported in hyperlipidemic patients receiving statins. Therefore, co-administration of statins with NSAIDs such as Lornoxicam (LN) could be a solution to the former problem. Accordingly, this study aimed to formulate a bi-laminated oral disintegrating film (ODF) comprising PT in one layer and LN in the second one. Methods: For the formulation and optimization of PT-ODFs, a 31.21 full factorial design was carried out, where the impact of polymer type and concentration on disintegration time (DT) and % PT released after 10 min (Q10) was studied. PT-ODFs were prepared via the solvent casting method and then evaluated. One PT-ODF was chosen to represent the optimum formula according to the criteria of scoring the fastest DT and the highest Q10. The optimized PT-ODF was merged with the second film layer containing LN, forming a bi-laminated ODF named S1 that underwent an in vivo pharmacokinetic study compared to the commercially available tablets for PT (Lipidalon®) and LN (Lornoxicam®) using rats as an animal model. LC-MS/MS was used to analyze plasma drug concentrations. Results: All PT-ODFs showed acceptable outcomes. F1 scored the fastest DT (18.6±1.5 s) and the highest Q10 (91.3±3.0 %). S1 successfully recorded a maximum plasma concentration (Cmax) of 2.04 and 2.24 folds increase for PT and LN, correspondingly, compared to commercially available tablets. Conclusion: Merging PT and LN into bi-laminated ODF was promising for the fast delivery of both drugs with enhanced bioavailability.

Objective: Transethosomes (TEs) have introduced an emerging avenue of interest in vesicular research for transdermal delivery of drugs and can be a proper delivery system for painkillers like NSAIDS. This study aimed to formulate and characterize the potential of TE to enhance the transdermal transport of Dexketoprofen trometamol (DKT) to achieve controlled pain management compared to DKT solution. Methods: Factorial design (23) was adopted to appraise the influence of independent variables, namely, Lipoid S100 and surfactant concentrations and surfactant type (X3) on the % solubilization efficiency (% SE), vesicle size (VS), and % release efficiency (% RE). Thin film hydration was the preferred approach for preparing TEs where vesicle size, zeta potential, polydispersity index, %SE and %RE were investigated. The optimized formula was nominated and subjected to several studies. For the permeation study, optimum TE was incorporated into carbapol gel base for comparison with DKT solution. Also, an accelerated stability study was assessed for optimized formula. Results: All the prepared DKT-loaded TEs revealed acceptable VS, PDI, and ZP. The highest %SE (86.08±1.05 %) and lowest %RE (44.62±1.36 %) were observed in case of F1. The optimized formula (F1) displayed VS of 133.2±1.62 nm, PDI of 0.342±0.03 and ZP of-21.6±2.45 mV. F1 revealed enhanced skin permeation of a 2.6-fold increase compared with DKT solution. Moreover, F1 was stable upon storage and a non-significant change (P>0.05) was observed. Conclusion: DKT was successfully incorporated into vesicle carrier and can signify an alternative option for providing this therapy, bypassing the poor bioavailability and considerable adverse consequences of using the oral route besides improved patient compliance.