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

• Published in: Archives of pharmacal research Vol. 20; no. 6; pp. 560 - 565
• Main Authors: Lee, Beom-Jin, Choi, Han-Gon, Kim, Chong-Kook, Parrott, Keith A, Ayres, James W, Sack, Robert L
• Format: Journal Article
• Language: English
• Published: Korea (South) Pharmaceutical Society of Korea 01.12.1997
• Subjects: absorption; bioavailability; differential scanning calorimetry; heat; manufacturing; melatonin; melting point; propylene glycol; solubility; solubilization
• DOI: 10.1007/BF02975212
• ISSN: 0253-6269

The physicochemical properties of melatonin (MT) in propylene glycol (PG) and 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) 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°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-HPβCD without PG increased (R²=0.993). MT solubility in the mixtures of PG and 2-HPβCD also increased linearly but was less than the sum of its solubility in 2-HPβCD 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-HPβCD (30 w/v%) although efficiency of MT solubilization in 2-HPβCD decreased as the concentration of PG increased. MT was degraded in a fashion of the first order kinetics (r²>0.90). MT was unstable in strong acidic solution (HCl−NaCl buffer, pH 1.4) but relatively stable in other pH values of 4∼10 at 70°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-HPβCD 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.