Background: Ischemic heart disorders and accumulation of lipids in blood vessels could contribute to angina pectoris. Therefore, the aim of this study was to formulate sublingual tablets containing a novel combination of Atorvastatin calcium (ATOR) and Trimetazidine HCl (TMZ) for efficient treatment of coronary heart disorders. Methods: The dissolution rate of water-insoluble ATOR was enhanced via complexation with sulfobutyl ether-b-cyclodextrin (SBE-b-CD) and addition of soluplus as a polymeric solubilizer excipient. The solubilized ATOR and TMZ were compressed into a sublingual tablets by direct compression technique and evaluated for their tableting characteristics. In addition, a new validated method based on High Performance Thin Layer Chromatography (HPTLC) was developed for simultaneous determination of both drugs in pure forms and sublingual tablets. Results: The developed HPTLC method showed LODs of 0.056 and 0.013 lg/band and LOQs of 0.17, 0.040 lg/band for TMZ and ATOR, respectively and proved to be linear, accurate, precise and robust. The optimum formulation containing mixture of superdisintegrants; Ac-Di-Sol and crospovidone (4.8% w/w, each) showed the shortest disintegration time (65 s) and enhanced release profiles of both drugs. Conclusions: The prepared sublingual tablets combining ATOR and TMZ will be a promising dosage form for coronary heart disease patients with an instant action and improved patient compliance.

Background: Ischemic heart disorders and accumulation of lipids in blood vessels could contribute to angina pectoris. Therefore, the aim of this study was to formulate sublingual tablets containing a novel combination of Atorvastatin calcium (ATOR) and Trimetazidine HCl (TMZ) for efficient treatment of coronary heart disorders. Methods: The dissolution rate of water-insoluble ATOR was enhanced via complexation with sulfobutyl ether-b-cyclodextrin (SBE-b-CD) and addition of soluplus as a polymeric solubilizer excipient. The solubilized ATOR and TMZ were compressed into a sublingual tablets by direct compression technique and evaluated for their tableting characteristics. In addition, a new validated method based on High Performance Thin Layer Chromatography (HPTLC) was developed for simultaneous determination of both drugs in pure forms and sublingual tablets. Results: The developed HPTLC method showed LODs of 0.056 and 0.013 lg/band and LOQs of 0.17, 0.040 lg/band for TMZ and ATOR, respectively and proved to be linear, accurate, precise and robust. The optimum formulation containing mixture of superdisintegrants; Ac-Di-Sol and crospovidone (4.8% w/w, each) showed the shortest disintegration time (65 s) and enhanced release profiles of both drugs. Conclusions: The prepared sublingual tablets combining ATOR and TMZ will be a promising dosage form for coronary heart disease patients with an instant action and improved patient compliance.

Background: Ischemic heart disorders and accumulation of lipids in blood vessels could contribute to angina pectoris. Therefore, the aim of this study was to formulate sublingual tablets containing a novel combination of Atorvastatin calcium (ATOR) and Trimetazidine HCl (TMZ) for efficient treatment of coronary heart disorders. Methods: The dissolution rate of water-insoluble ATOR was enhanced via complexation with sulfobutyl ether-b-cyclodextrin (SBE-b-CD) and addition of soluplus as a polymeric solubilizer excipient. The solubilized ATOR and TMZ were compressed into a sublingual tablets by direct compression technique and evaluated for their tableting characteristics. In addition, a new validated method based on High Performance Thin Layer Chromatography (HPTLC) was developed for simultaneous determination of both drugs in pure forms and sublingual tablets. Results: The developed HPTLC method showed LODs of 0.056 and 0.013 lg/band and LOQs of 0.17, 0.040 lg/band for TMZ and ATOR, respectively and proved to be linear, accurate, precise and robust. The optimum formulation containing mixture of superdisintegrants; Ac-Di-Sol and crospovidone (4.8% w/w, each) showed the shortest disintegration time (65 s) and enhanced release profiles of both drugs. Conclusions: The prepared sublingual tablets combining ATOR and TMZ will be a promising dosage form for coronary heart disease patients with an instant action and improved patient compliance.

Background: Ischemic heart disorders and accumulation of lipids in blood vessels could contribute to angina pectoris. Therefore, the aim of this study was to formulate sublingual tablets containing a novel combination of Atorvastatin calcium (ATOR) and Trimetazidine HCl (TMZ) for efficient treatment of coronary heart disorders. Methods: The dissolution rate of water-insoluble ATOR was enhanced via complexation with sulfobutyl ether-b-cyclodextrin (SBE-b-CD) and addition of soluplus as a polymeric solubilizer excipient. The solubilized ATOR and TMZ were compressed into a sublingual tablets by direct compression technique and evaluated for their tableting characteristics. In addition, a new validated method based on High Performance Thin Layer Chromatography (HPTLC) was developed for simultaneous determination of both drugs in pure forms and sublingual tablets. Results: The developed HPTLC method showed LODs of 0.056 and 0.013 lg/band and LOQs of 0.17, 0.040 lg/band for TMZ and ATOR, respectively and proved to be linear, accurate, precise and robust. The optimum formulation containing mixture of superdisintegrants; Ac-Di-Sol and crospovidone (4.8% w/w, each) showed the shortest disintegration time (65 s) and enhanced release profiles of both drugs. Conclusions: The prepared sublingual tablets combining ATOR and TMZ will be a promising dosage form for coronary heart disease patients with an instant action and improved patient compliance.

Background: Ischemic heart disorders and accumulation of lipids in blood vessels could contribute to angina pectoris. Therefore, the aim of this study was to formulate sublingual tablets containing a novel combination of Atorvastatin calcium (ATOR) and Trimetazidine HCl (TMZ) for efficient treatment of coronary heart disorders. Methods: The dissolution rate of water-insoluble ATOR was enhanced via complexation with sulfobutyl ether-b-cyclodextrin (SBE-b-CD) and addition of soluplus as a polymeric solubilizer excipient. The solubilized ATOR and TMZ were compressed into a sublingual tablets by direct compression technique and evaluated for their tableting characteristics. In addition, a new validated method based on High Performance Thin Layer Chromatography (HPTLC) was developed for simultaneous determination of both drugs in pure forms and sublingual tablets. Results: The developed HPTLC method showed LODs of 0.056 and 0.013 lg/band and LOQs of 0.17, 0.040 lg/band for TMZ and ATOR, respectively and proved to be linear, accurate, precise and robust. The optimum formulation containing mixture of superdisintegrants; Ac-Di-Sol and crospovidone (4.8% w/w, each) showed the shortest disintegration time (65 s) and enhanced release profiles of both drugs. Conclusions: The prepared sublingual tablets combining ATOR and TMZ will be a promising dosage form for coronary heart disease patients with an instant action and improved patient compliance.

Background: Ischemic heart disorders and accumulation of lipids in blood vessels could contribute to angina pectoris. Therefore, the aim of this study was to formulate sublingual tablets containing a novel combination of Atorvastatin calcium (ATOR) and Trimetazidine HCl (TMZ) for efficient treatment of coronary heart disorders. Methods: The dissolution rate of water-insoluble ATOR was enhanced via complexation with sulfobutyl ether-b-cyclodextrin (SBE-b-CD) and addition of soluplus as a polymeric solubilizer excipient. The solubilized ATOR and TMZ were compressed into a sublingual tablets by direct compression technique and evaluated for their tableting characteristics. In addition, a new validated method based on High Performance Thin Layer Chromatography (HPTLC) was developed for simultaneous determination of both drugs in pure forms and sublingual tablets. Results: The developed HPTLC method showed LODs of 0.056 and 0.013 lg/band and LOQs of 0.17, 0.040 lg/band for TMZ and ATOR, respectively and proved to be linear, accurate, precise and robust. The optimum formulation containing mixture of superdisintegrants; Ac-Di-Sol and crospovidone (4.8% w/w, each) showed the shortest disintegration time (65 s) and enhanced release profiles of both drugs. Conclusions: The prepared sublingual tablets combining ATOR and TMZ will be a promising dosage form for coronary heart disease patients with an instant action and improved patient compliance.

The last few years have witnessed a great advance in the development of nonviral systems for in vivo targeted delivery of nucleic acids. Lipid nanoparticles (LNPs) are the most promising carriers for producing clinically approved products in the future. Compared with other systems used for nonviral gene delivery, LNPs provide several advantages including higher stability, low toxicity, and greater efficiency. Additionally, systems based on LNPs can be modified with ligands and devices for controlled biodistribution and internalization into specific cells. Efforts are ongoing to improve the efficiency of lipid-based gene vectors. These efforts depend on the appropriate design of nanocarriers as well as the development of new lipids with improved gene delivery ability. Several ionizable lipids have recently been developed and have shown dramatically improved efficiency. However, enhancing the ability of nanocarriers to target specific cells in the body remains the most difficult challenge. Systemically administered LNPs can access organs in which the capillaries are characterized by the presence of fenestrations, such as the liver and spleen. The liver has received the most attention to date, although targeted delivery to the spleen has recently emerged as a promising tool for modulating the immune system. In this review, we discuss recent advances in the use of LNPs for cell-specific targeted delivery of nucleic acids. We focus mainly on targeting liver hepatocytes and spleen immune cells as excellent targets for gene therapy. We also discuss the potential of endothelial cells as an alternate approach for targeting organs with a continuous endothelium.

The last few years have witnessed a great advance in the development of nonviral systems for in vivo targeted delivery of nucleic acids. Lipid nanoparticles (LNPs) are the most promising carriers for producing clinically approved products in the future. Compared with other systems used for nonviral gene delivery, LNPs provide several advantages including higher stability, low toxicity, and greater efficiency. Additionally, systems based on LNPs can be modified with ligands and devices for controlled biodistribution and internalization into specific cells. Efforts are ongoing to improve the efficiency of lipid-based gene vectors. These efforts depend on the appropriate design of nanocarriers as well as the development of new lipids with improved gene delivery ability. Several ionizable lipids have recently been developed and have shown dramatically improved efficiency. However, enhancing the ability of nanocarriers to target specific cells in the body remains the most difficult challenge. Systemically administered LNPs can access organs in which the capillaries are characterized by the presence of fenestrations, such as the liver and spleen. The liver has received the most attention to date, although targeted delivery to the spleen has recently emerged as a promising tool for modulating the immune system. In this review, we discuss recent advances in the use of LNPs for cell-specific targeted delivery of nucleic acids. We focus mainly on targeting liver hepatocytes and spleen immune cells as excellent targets for gene therapy. We also discuss the potential of endothelial cells as an alternate approach for targeting organs with a continuous endothelium.

Rofecoxib (ROF), a potent selective COX-II inhibitor NSAID, has been withdrawn from the market due to its high risk on patients with cardiovascular disorders (CVD). In the current study, an attempted to re-introduce ROF into the market via co-formulation with the antiplatelet drug, Aspirin, to neutralize ROF effect on the platelet function has been investigated. Solubility and dissolution profiles of ROF were studied and improved through formulation into solid dispersions with Soluplus® before being mixed with a low dose of Aspirin. The novel drug combination was incorporated into oral tablets with various compositions to optimize the tablets physico-chemical performance. In addition, a new validated HPLC method was developed for simultaneous assessment of both drugs in the tablets. The optimized tablets demonstrated satisfactory physico-chemical performance. The developed HPLC method was accurate, precise, robust and sensitive with limits of detection (LODs) of 2.96 and 0.25 μg/mL and limits of quantitation (LOQs) of 8.77 and 0.77 μg/mL for Aspirin and ROF, respectively. The novel co-therapy showed normal platelet function in rabbits in opposite to ROF monothrapy. The data presented in this study can be promising to re-utilize ROF as an effective and selective NSAID, to satisfy the market's demand, while ensuring its safety in CVD patients.

Rofecoxib (ROF), a potent selective COX-II inhibitor NSAID, has been withdrawn from the market due to its high risk on patients with cardiovascular disorders (CVD). In the current study, an attempted to re-introduce ROF into the market via co-formulation with the antiplatelet drug, Aspirin, to neutralize ROF effect on the platelet function has been investigated. Solubility and dissolution profiles of ROF were studied and improved through formulation into solid dispersions with Soluplus® before being mixed with a low dose of Aspirin. The novel drug combination was incorporated into oral tablets with various compositions to optimize the tablets physico-chemical performance. In addition, a new validated HPLC method was developed for simultaneous assessment of both drugs in the tablets. The optimized tablets demonstrated satisfactory physico-chemical performance. The developed HPLC method was accurate, precise, robust and sensitive with limits of detection (LODs) of 2.96 and 0.25 μg/mL and limits of quantitation (LOQs) of 8.77 and 0.77 μg/mL for Aspirin and ROF, respectively. The novel co-therapy showed normal platelet function in rabbits in opposite to ROF monothrapy. The data presented in this study can be promising to re-utilize ROF as an effective and selective NSAID, to satisfy the market's demand, while ensuring its safety in CVD patients.