Characterization of nifedipine solid dispersions.
The sublingual administration of nifedipine (NIF) is currently used in clinical practice. The sublingual administration of NIF solid dispersions (SD), by using a suitable dispenser, appears an interesting approach in the treatment of moderate and severe hypertensive emergencies. With this aim nine SD made of NIF and a low viscosity hydroxypropylmethylcellulose (HPMC) in different ratio were prepared by means of spray-drying technique and their structure was studied. Moreover, the drug dissolution properties from SD were verified. The characteristic peaks of crystalline NIF were not detectable by using the X-ray analysis when the NIF/HPMC ratios were lower than 50/50 w/w. In thermograms obtained from SD, the NIF melting endothermic peak disappeared when NIF/HPMC ratios were lower than 30/70 w/w; the experimental Tg values of SD were lower than the Tg values predicted by Gordon Taylor equation suggesting some type of non-ideality of mixing. In the SD FTIR spectra the NH stretching vibrations and the C=O stretch in esteric groups of NIF shift to free NH and C=O regions indicating the rupture of intermolecular hydrogen bond in the crystalline structure of NIF. The prepared SD improved the NIF dissolution rate in comparison with that of commercial NIF or NIF/HPMC physical mixtures. Moreover, the concentration of NIF in the dissolution medium increased decreasing the NIF content.
Cilurzo
F
F
Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Milano, Viale Abruzzi 42, 20131, Milan, Italy. francesco.cilurzo@unimi.it
Minghetti
P
P
Casiraghi
A
A
Montanari
L
L
D000286:Administration, Sublingual; D002121:Calcium Channel Blockers / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004055:Differential Thermal Analysis; D005079:Excipients; D007785:Lactose / Q000031:analogs & derivatives*; D008747:Methylcellulose / Q000031:analogs & derivatives*; D009543:Nifedipine / Q000737:chemistry*; D010078:Oxazines; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared
D002121:Calcium Channel Blockers; D005079:Excipients; D010078:Oxazines; D008747:Methylcellulose; C071191:MK 458; D009543:Nifedipine; D007785:Lactose