Pharmaceutical Salts of Carvedilol: Polymorphism and Physicochemical Properties.
We report novel pharmaceutical salts of an anti-hypertensive drug carvedilol (CVD) with pharmaceutically acceptable salt formers, including oxalic acid (OXA), fumaric acid (FUMA), benzoic acid (BZA), and mandelic acid (MDA) via conventional solvent evaporation technique. The pKa difference between CVD and selected acids was greater than 3, thus suggesting salt formation. Two polymorphic forms of CVD/MDA salts and one p-Dioxane solvate of CVD/FUMA salt were also reported in this paper. The salts were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Stability of the salts was assessed by storage at 40°C/75% RH for 1 month. All CVD salts exhibited higher solubility in phosphate buffer solution pH 6.8 compared to the parent drug CVD and showed good stability in accelerated ICH conditions at 40°C/75% RH for 1 month. CVD/FUMA salt showed the highest solubility (1.78 times). Based on thermal analysis and slurry experiment, it was found that CVD/MDA polymorphs were related monotropically with Form 1 as the stable form. The results suggested that salt formation could be an alternative method to improve CVD solubility.
Dexa Laboratories of Biomolecular Sciences (DLBS), PT Dexa Medica, Industri Selatan V, Block PP No. 7, Jababeka Industrial Estate II, Cikarang, 17550, West Java, Indonesia.
Stevanus
S
Hiendrawan
Dexa Laboratories of Biomolecular Sciences (DLBS), PT Dexa Medica, Industri Selatan V, Block PP No. 7, Jababeka Industrial Estate II, Cikarang, 17550, West Java, Indonesia.
Edward
E
Widjojokusumo
Dexa Laboratories of Biomolecular Sciences (DLBS), PT Dexa Medica, Industri Selatan V, Block PP No. 7, Jababeka Industrial Estate II, Cikarang, 17550, West Java, Indonesia.
Bambang
B
Veriansyah
Dexa Laboratories of Biomolecular Sciences (DLBS), PT Dexa Medica, Industri Selatan V, Block PP No. 7, Jababeka Industrial Estate II, Cikarang, 17550, West Java, Indonesia. raymond@dexa-medica.com.
Raymond R
RR
Tjandrawinata
D000959:Antihypertensive Agents / Q000737:chemistry*; D002227:Carbazoles / Q000737:chemistry*; D000077261:Carvedilol; D005650:Fumarates / Q000737:chemistry; D008333:Mandelic Acids / Q000737:chemistry; D019815:Oxalic Acid / Q000737:chemistry; D011412:Propanolamines / Q000737:chemistry*; D012492:Salts / Q000737:chemistry; D012995:Solubility
D000959:Antihypertensive Agents; D002227:Carbazoles; D005650:Fumarates; D008333:Mandelic Acids; D011412:Propanolamines; D012492:Salts; D000077261:Carvedilol; C032005:fumaric acid; D019815:Oxalic Acid; C037938:mandelic acid
carvedilol; polymorph; salt; solubility; solvate