Solubility and stability of melatonin in propylene glycol and 2-hydroxypropyl-beta-cyclodextrin vehicles.
The physicochemical properties of melatonin (MT) in propylene glycol (PG) and 2-hydroxypropyl-beta-cyclodextrin (2-HPbetaCD) vehicles were characterized. MT was endothermally decomposed as determined by differential scanning calorimetry (DSC). Melting point and heat of fusion obtained were 116.9+/-0.24 degrees C and 7249+/-217 cal/mol, respectively. MT as received from a manufacture was very pure, at least 99.9%. The solubility of MT in PG solution increased slowly until reaching 40% PG and then steeply increased. Solubility of MT increased linearly as concentration of 2-HPbetaCD without PG increased (R(2)=0.993). MT solubility in the mixtures of PG and 2-HPbetaCD also increased linearly but was less than the sum of its solubility in 2-HPbetaCD and PG individually. The MT solubility was low in water, simulated gastric or intestinal fluid but the highest in the mixture of PG (40 v/v%) and 2-HPbetaCD (30 w/v%) although efficiency of MT solubilization in 2-HPbetaCD decreased as the concentration of PG increased. MT was degraded in a fashion of the first order kinetics (r(2)>0.90). MT was unstable in strong acidic solution (HCl-NaCl buffer, pH 1.4) but relatively stable in other pH values of 4 approximately 10 at 70 degrees C. In HCl-NaCl buffer, MT in 10% PG was more quickly degraded and then slowed down at a higher concentration. However, the degradation rate constant of MT in 2-HPbetaCD was not changed significantly when compared to the water. The current studies can be applied to the dosage formulations for the purpose of enhancing percutaneous absorption or bioavailability of MT.
Lee
B J
BJ
Biological Rhythm and Controlled Release Lab., College of Pharmacy, Kangwon National University, 200-701, Chuncheon, Korea.
Choi
H G
HG
Kim
C K
CK
Parrott
K A
KA
Ayres
J W
JW
Sack
R L
RL