Tracking of crystalline-amorphous transition of carvedilol in rotary spun microfibers and their formulation to orodispersible tablets for in vitro dissolution enhancement.
Physicochemical characterization of microfibers including powder X-ray diffraction, differential scanning calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, and positron annihilation spectroscopy were used to track the crystalline-amorphous transition of carvedilol during formulation and stability testing. The applied methods unanimously indicated the amorphous transition of carvedilol in the course of rotary spinning, furthermore a supramolecular ordering of chains of polymer matrix was revealed out by positron annihilation spectroscopy. The accelerated stability study (40±2°C/75±5% RH, for 4 weeks) indicated a large stress tolerance capacity of fibers, since only a partial crystallization of the active compound was observable at the last sampling point. To demonstrate possible utilization of microfibers, orodispersible tablets containing 10mg of carvedilol were successfully prepared by direct compression applying common tableting excipients. All of the investigated tablet parameters (hardness, friability, in vitro disintegration time) complied with the pharmacopoeial requirements. The performed dissolution (pH 1.0 and 6.8) study indicated that the drug dissolution from the microfiber based formula was rapid, complete and independent from the pH of the applied media, while the dissolution from the control tablets, containing crystalline carvedilol was incomplete and was strongly influenced by the pH of the applied media.
Gedeon Richter Plc., Formulation R&D, Gyömrői Str. 19-21, H-1103 Budapest, Hungary; University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre Str. 7-9, H-1092 Budapest, Hungary.
Péter
P
Szabó
University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre Str. 7-9, H-1092 Budapest, Hungary.
István
I
Sebe
Gedeon Richter Plc., Formulation R&D, Gyömrői Str. 19-21, H-1103 Budapest, Hungary.
Bernadett
B
Stiedl
Department of Pharmaceutics, Semmelweis University, Hőgyes Endre Str. 7, H-1092 Budapest, Hungary.
Barnabás
B
Kállai-Szabó
University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre Str. 7-9, H-1092 Budapest, Hungary. Electronic address: zelko.romana@pharma.semmelweis-univ.hu.
Romána
R
Zelkó
D000284:Administration, Oral; D002152:Calorimetry, Differential Scanning; D002227:Carbazoles / Q000008:administration & dosage / Q000737:chemistry* / Q000145:classification; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D006244:Hardness; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D033362:Powder Diffraction; D011412:Propanolamines / Q000008:administration & dosage / Q000737:chemistry* / Q000145:classification; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*
D002227:Carbazoles; D005079:Excipients; D011412:Propanolamines; D013607:Tablets; D000077261:Carvedilol
Differential scanning calorimetry (DSC); Dissolution enhancement; FTIR; Positron annihilation spectroscopy (PALS); Rotary-spun microfiber; X-ray diffractometry (XRD)