Sundani Nurono Soewandhi

Physicochemical and mechanical properties of paracetamol cocrystal with 5-nitroisophthalic acid

We report novel pharmaceutical cocrystal of a popular antipyretic drug paracetamol (PCA) with coformer 5-nitroisophhthalic acid (5NIP) to improve its tabletability. The cocrystal (PCA-5NIP at molar ratio of 1:1) was synthesized by solvent evaporation technique using methanol as solvent. The physicochemical properties of cocrystal were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), fourier transform infrared spectroscopy (FTIR), hot stage polarized microscopy (HSPM) and scanning electron microscopy (SEM). Stability of the cocrystal was assessed by storing them at 40°C/75% RH for one month. Compared to PCA, the cocrystal displayed superior tableting performance. PCA-5NIP cocrystal showed a similar dissolution profile as compared to PCA and exhibited good stability. This study showed the utility of PCA-5NIP cocrystal for improving mechanical properties of PCA.

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.

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.

Influence of mechanical and thermal energy on rifampicin

The same raw material has opportunity to show different physical properties if it is produced by different industries. For such reason, rifampicin was chosen as a raw materials model, thats obtaining from five resource countries and were obtained from five different suppliers, each coded A, B, C, D and E. Each raw material was handled under tribomechanic and thermal treatment. Mechanical treatment was carried out by using grinding mill at 100 rpm for 30 minutes. Thermal treatment was carried out by oven at 105oC for 2 hours. Transformation occured, was identified by differential scanning calorymetry (DSC), X-ray powder diffraction and dissolution rate. The intrinsic dissolution rate was determined in 900 mL HCl 0,1N oxygen free, using basket and calculated through simultaneously determination method using uv spectrophotometry at λabs.maks. 475 nm. Thermograms of five milled raw material showed endothermic curve at 58oC without obviously melting curve. Thermogram of heated raw material did not show endothermic curve except its melting at 188oC-192oC. Crystallinity indices of the raw materials decreased from C, E, B, A to D. The milled raw materials were mixture of rifampicin II (2%) and amorphous (98%). A and D were mixture of rifampicin form II and fines (amorph). The other samples were only rifampicin form II. All of the raw materials showed different dissolution rates. Rifampicin B,C and D had sameness dissolution rate, whether milled or heated. Key words : Rifampicin II, rifampicin amorphous, DSC, powder X-ray diffraction, dissolution rate