Influence of polymorphic form, morphology, and excipient interactions on the dissolution of carbamazepine compacts.
To gain a deeper understanding of the behavior of carbamazepine (CBZ) and CBZ dihydrate (DH) compacts during in vitro dissolution tests various factors were investigated: hydrate formation of CBZ, crystal morphology, surface area, and excipient influence. Dissolution tests were performed in three different dissolution media: distilled water, hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG) solutions. For the CBZ compacts, the dissolution rate of CBZ in water was fastest (0.338 mg L(-1) min(-1)). With increasing ability of the excipients to inhibit the hydration of CBZ (PEG < HPMC), surprisingly the dissolution rate of CBZ compacts decreased: PEG solution (0.314 mg L(-1) min(-1)) > HPMC solution (0.257 mg L(-1) min(-1)). This implies that DH formation resulted in an apparent increase in the dissolution rate rather than slowing it down. For the DH compacts, the dissolution rate in water (0.055 mg L(-1) min(-1)) was slower than that of PEG and HPMC solutions (0.174 and 0.178 mg L(-1) min(-1), respectively). The contact angle measurements showed a significantly higher value in water (61.0 degrees) than in PEG and HPMC solutions (44.8 degrees and 43.1 degrees, respectively). Although the dissolution of CBZ and DH compacts in various dissolution media are complex processes, the influence and relative importance of these factors were clearly detected providing better understanding of the dissolution behavior of the drug.
Tian
Fang
F
School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand.
Sandler
Niklas
N
Aaltonen
Jaakko
J
Lang
Carolin
C
Saville
Dorothy J
DJ
Gordon
Keith C
KC
Strachan
Clare J
CJ
Rantanen
Jukka
J
Rades
Thomas
T
D002220:Carbamazepine / Q000008:administration & dosage / Q000737:chemistry*; D005079:Excipients / Q000008:administration & dosage*; D008855:Microscopy, Electron, Scanning; D012995:Solubility
D005079:Excipients; D002220:Carbamazepine