Solubility and stability of melatonin in propylene glycol and 2-hydroxypropyl-β-cyclodextrin vehicles
Beom Jin Lee, Han Gon Choi, Chong Kook Kim, Keith A. Parrott, James W. Ayres, Robert L. Sack
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.
Archives of Pharmacal Research
2-Hydroxypropyl-β-cyclodextrin
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Cyclodextrins Medicine & Life Sciences 100%
Propylene Glycol Medicine & Life Sciences 97%
Melatonin Chemical Compounds 95%
Solubility Medicine & Life Sciences 73%
Glycol Chemical Compounds 67%
Propene Chemical Compounds 59%
Buffers Medicine & Life Sciences 10%
Percutaneous Chemical Compounds 7%
Lee, B. J., Choi, H. G., Kim, C. K., Parrott, K. A., Ayres, J. W., & Sack, R. L. (1997). Solubility and stability of melatonin in propylene glycol and 2-hydroxypropyl-β-cyclodextrin vehicles. Archives of Pharmacal Research, 20(6), 560-565. https://doi.org/10.1007/BF02975212
Solubility and stability of melatonin in propylene glycol and 2-hydroxypropyl-β-cyclodextrin vehicles. / Lee, Beom Jin; Choi, Han Gon; Kim, Chong Kook et al.
In: Archives of Pharmacal Research, Vol. 20, No. 6, 12.1997, p. 560-565.
Lee, BJ, Choi, HG, Kim, CK, Parrott, KA, Ayres, JW & Sack, RL 1997, 'Solubility and stability of melatonin in propylene glycol and 2-hydroxypropyl-β-cyclodextrin vehicles', Archives of Pharmacal Research, vol. 20, no. 6, pp. 560-565. https://doi.org/10.1007/BF02975212
Lee BJ, Choi HG, Kim CK, Parrott KA, Ayres JW, Sack RL. Solubility and stability of melatonin in propylene glycol and 2-hydroxypropyl-β-cyclodextrin vehicles. Archives of Pharmacal Research. 1997 Dec;20(6):560-565. doi: 10.1007/BF02975212
Lee, Beom Jin ; Choi, Han Gon ; Kim, Chong Kook et al. / Solubility and stability of melatonin in propylene glycol and 2-hydroxypropyl-β-cyclodextrin vehicles. In: Archives of Pharmacal Research. 1997 ; Vol. 20, No. 6. pp. 560-565.
@article{5dbf1160643746f19e2b635eeb1e7464,
title = "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-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.",
keywords = "2-Hydroxypropyl-β-cyclodextrin, Melatonin, Propylene glycol, Solubility, Stability",
author = "Lee, {Beom Jin} and Choi, {Han Gon} and Kim, {Chong Kook} and Parrott, {Keith A.} and Ayres, {James W.} and Sack, {Robert L.}",
note = "Funding Information: This work was in part supported by the Ministry of Health and Welfare (#HMP: 96-D-7-0049) and by the Gustavus and Louise Pfeiffer Research Foundation. The part of this work was presented as a podium at the American Association Pharmaceutical Scientists annual meeting held in Washington D.C., USA.",
journal = "Archives of Pharmacal Research",
publisher = "Pharmaceutical Society of Korea",
T1 - Solubility and stability of melatonin in propylene glycol and 2-hydroxypropyl-β-cyclodextrin vehicles
AU - Lee, Beom Jin
AU - Choi, Han Gon
AU - Kim, Chong Kook
AU - Parrott, Keith A.
AU - Ayres, James W.
AU - Sack, Robert L.
N1 - Funding Information: This work was in part supported by the Ministry of Health and Welfare (#HMP: 96-D-7-0049) and by the Gustavus and Louise Pfeiffer Research Foundation. The part of this work was presented as a podium at the American Association Pharmaceutical Scientists annual meeting held in Washington D.C., USA.
N2 - 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.
AB - 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.
KW - 2-Hydroxypropyl-β-cyclodextrin
KW - Melatonin
KW - Propylene glycol
KW - Solubility
KW - Stability
JO - Archives of Pharmacal Research
JF - Archives of Pharmacal Research