Investigations of a novel self-emulsifying osmotic pump tablet containing carvedilol.
Carvedilol has been made into a novel osmotic pump tablet which includes Gelucire 44/14, Lutrol F68, Transcutol P, silicon dioxide, mannitol, citric acid, and sodium hydrogen carbonate. The Self-emulsifying osmotic pump tablet (SEOPT) has two outstanding features. It could improve the bioavailability of carvedilol by self-emulsifying drug delivery system (SEDDS), control the release rate and make the plasma concentrations more stable by elementary osmotic pump tablet. The results of transmission electron microscope (TEM) and particle size assessment showed that the shape of the resultant emulsion was round and regular, the average diameter of the particles was 246 nm. Since the solubility of carvedilol was improved by the emulsion, the elementary SEOPT could guarantee a complete release of carvedilol under the osmotic pressure of mannitol. The cumulative release at 12 hr was 85.18%. Therefore the disadvantage that lipophilic drugs can not be released completely when prepared into elementary osmotic pump tablet was resolved. The results of Differential scanning calorimetry (DSC), Infrared spectroscopy (IR) and X-ray diffraction diffraction (XRD) proved that carvedilol was amorphous in the preparation. The relative bioavailability of carvedilol in beagle dogs was 156.78%. The plasma concentrations were more stable compared with that of commercially available tablet (Luode). And the in vitro and in vivo correlation was good (r = 0.9725). Therefore, the elementary SEOPT developed in this paper might provide a new idea for preparing lipophilic drugs into osmotic pump tablet conveniently.
Wei
Lanlan
L
Department of Pharmaceutics, Shen Yang Pharmaceutical University, Shen Yang, PR China.
Li
Jie
J
Guo
Liangran
L
Nie
Shufang
S
Pan
Weisan
W
Sun
Peinan
P
Liu
Hui
H
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002227:Carbazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004285:Dogs; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D008353:Mannitol / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D009995:Osmosis; D009997:Osmotic Pressure; D010316:Particle Size; D011412:Propanolamines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011897:Random Allocation; D012995:Solubility; D013607:Tablets
D000959:Antihypertensive Agents; D002227:Carbazoles; D003692:Delayed-Action Preparations; D004655:Emulsions; D005079:Excipients; D011412:Propanolamines; D013607:Tablets; D000077261:Carvedilol; D008353:Mannitol