Solubility and stability of melatonin in propylene glycol and 2-hydroxypropyl-β-cyclodextrin vehicles

Abstract

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.

Transmucosal, Oral Controlled-Release, and Transdermal Drug Administration in Human Subjects: A Crossover Study with Melatonin

“…16 No significant local skin irritation was observed. The possibility of a lagtime for absorption of MT across human skin and deposition of MT in the skin with this route of administration is suggested by previously reported work.…”

“…[14][15][16][17][18] Transdermal administration of MT may be feasible, resulting in sustained plasma MT levels that can be tailored to the normal physiological range and avoid the first-pass effect. [14][15][16][17][18] Transdermal administration of MT may be feasible, resulting in sustained plasma MT levels that can be tailored to the normal physiological range and avoid the first-pass effect.…”

A Phase II, Randomized, Double-Blind, Placebo Controlled, Dose-Response Trial of the Melatonin Effect on the Pain Threshold of Healthy Subjects

“…The preparation of the melatonin solution was performed using propylene glycol (PG) (40%) plus cyclodextrins (30%) [20]. The dose-adjustment was performed by changing the concentration of melatonin in the vehicle.…”

Correlation of Drug Solubility with Trapping Efficiency and Release Characteristics of Alginate Beads

“…As the drug solubility (0Á2±383 mg mL À1 ) increased in gastric¯uid, the trapping ef®ciency (10±89%) of the model drugs in alginate beads after gelation in CaCl 2 solution had a tendency to decrease. The trapping ef®ciency of ibuprofen, Lee et al (1997).…”