Diky Mudhakir

Improving mechanical properties of desloratadine via multicomponent crystal formation

ABSTRACT We report the first multicomponent crystal of desloratadine, an important anti‐histamine drug, with a pharmaceutically acceptable coformer of benzoic acid. The single crystal structure analysis revealed that this novel multicomponent crystal is categorized as salt due to the proton transfer from benzoic acid to the desloratadine molecule. By forming the salt multicomponent crystal, we demonstrated that the tabletability and plasticity of the multicomponent crystal was improved from the parent drug. In addition, neither capping nor lamination tendency was observed in the desloratadine‐benzoic acid multicomponent crystal. The existence of a layered structure and slip planes are proposed to be associated with this improvement. The desloratadine‐benzoate in this case shows an improved solubility in water and HCl 0.1N media and a better dissolution profile in water. However, the dissolution rate in HCl 0.1N media was found to be essentially indifference. Graphical abstract Figure. No Caption available.

Synthesis, characterization, and stability study of desloratadine multicomponent crystal formation

This study describes the formation of multicomponent crystal (MCC) of desloratadine (DES). The objective of this study was to discover the new pharmaceutical MCC of DES using several coformers. The MCC synthesis was performed between DES and 26 coformers using an equimolar ratio with a solvent evaporation technique. The selection of the appropriate solvent was carried out using 12 solvents. The preview of the MCC of DES was performed using polarized light microscopy (PLM). The formation of MCC was confirmed using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The accelerated stability of MCC at 40 °C and relative humidity of 75% was investigated using PXRD and FTIR. Depending on the prior evaluation, DES and benzoic acid (BA) formed the MCC. PLM and SEM results showed that crystal habit of combination between DES and BA differed from the constituent components. Moreover, the diffractogram pattern of DES-BA was distinct from the constituent components. The DSC thermogram showed a new peak which was distinct from both constituent components. The FTIR study proved a new spectrum. All characterizations indicated that a new solid crystal was formed, ensuring the MCC formation. In addition, DES-BA MCC had both chemical and physical stabilities for a period of 4 months.

Phytosome Containing Silymarin for Oral Administration: Formulation and Physical Evaluation

Silymarin is a unique flavonoid complex isolated from milk thistle (Silybum marianum). It has been widely used as a hepatoprotective agent. Orally administered silymarin can be absorbed rapidly but only 20-50% of silymarin will be absorbed through gastrointestinal tract, resulting in low bioavailability. Those limitations are due to its low solubility, either in water and oil, and its low intestinal permeability. This study was aimed to develop silymarin-containing phytosome in order to improve the bioavailability of silymarin with sufficient safety and stability. This system consisted of silymarin-phospholipid complex prepared by solvent evaporation method, which was incorporated to form phytosome vesicles using thin layer method with various concentrations and molar ratios of silymarin and phospholipid. The vesicle size of phytosome was reduced with sonication. The results demonstrated that formula with 2% silymarin-phospholipid complex and molar ratio of silymarin to phospholipid of 1:5 showed the best phytosomal characteristics, with mean vesicle diameter of 133.534 ± 8.76 nm, polidispersity index of 0.339 ± 0.078, entrapment efficiency of 97.169 ± 2.412 %, and loading capacity of 12.18 ± 0.30 %. The preparation remained stable after freeze-thaw stability test. Analysis of Infrared spectroscopy and Differential Scanning Calorimetry confirmed the presence of physical and chemical interactions between silymarin and phospholipid within complex formation. Well formed and discrete vesicles were revealed by Transmission Electron Microscopy analysis, drug content measurement, and freeze-thaw stability test.

A Novel Desloratadine-Benzoic Acid Co-Amorphous Solid: Preparation, Characterization, and Stability Evaluation

Low physical stability is the limitation of the widespread use of amorphous drugs. The co-amorphous drug system is a new and emerging method for preparing a stable amorphous form. Co-amorphous is a single-phase amorphous multicomponent system consisting of two or more small molecules that are a combination of drugs or drugs and excipients. The co-amorphous system that uses benzoic acid (BA) as an excipient was studied to improve the physical stability, dissolution, and solubility of desloratadine (DES). In this study, the co-amorphous formation of DES and BA (DES–BA) was prepared by melt-quenching method and characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and polarized light microscopy (PLM). Dissolution, solubility, and physical stability profiles of DES–BA were determined. The DES crystals were converted into DES–BA co-amorphous form to reveal the molecular interactions between DES and BA. Solid-state analysis proved that the co-amorphous DES–BA system (1:1) is amorphous and homogeneous. The DSC experiment showed that the glass transition temperature (Tg) of tested DES–BA co-amorphous had a higher single Tg compared to the amorphous DES. FTIR revealed strong interactions, especially salt formation. The dissolution rate and solubility of co-amorphous DES–BA (1:1) obtained were larger than the DES in crystalline form. The PXRD technique was used to assess physical stability for three months at 40 °C with 75% RH. The DES–BA co-amorphous system demonstrated better physical stability than a single form of amorphous DES. Co-amorphous DES–BA has demonstrated the potential for improving solid-state stability, as the formation of DES–BA co-amorphous salt increased solubility and dissolution when compared to pure crystalline DES. This study also demonstrated the possibility for developing a DES–BA co-amorphous system toward oral formulations to improve DES solubility and bioavailability.

An Improvement Delivery of siRNA by IRQ Ligand‐Modified Double Membranous Nano‐Carrier

In the present study, the enhancement of siRNA delivery into cytosol from the IRQ‐modified multi‐envelope type nano‐device (IRQ‐MEND) was investigated. It is known that IRQ‐MEND efficiently enters cells by clathrin‐mediated endocytosis and caveolar endocytosis pathways, resulting in gene silencing. In the present study, we controlled the number of layers of IRQ‐MEND encapsulating siRNA by using double membranous nano‐device strategy. This vector design overcomes intracellular barriers such as endosomal membrane, resulting drastically enhance transgene expression. In addition, the contribution of uptake mechanism of IRQ‐modified nano‐carrier to transgene expression was studied. The use of hypertonic treatment inhibited gene silencing, but it was not suppressed by the addition of filipin. These results indicate that low pH is important to induce the transgene expression. In conclusion, delivery of cytosolic siRNA can be enhanced by the use of double‐membranous nano‐carrier system which utilizes a clathrin‐m...