When the fast absorption of diazepam is needed in order to suppress febrile convulsions and epileptic seizures, the most suitable is intravenous application diazepam. To avoid inappropriate self administration of such diazepam dosage form, orodispersible tablets of diazepam would be the dosage form of choice. Poor solubility of diazepam in water is directly related to its dissolution rate after release from a solid dosage form. Inadequate dissolution rate of diazepam can be the limiting factor for its absorption rate. Inclusion complexation of diazepam with 2-hydroxypropyl-β-cyclodextrin was carried out to increase the solubility of diazepam at pH 6.8. Determination of the intrinsic dissolution rate of diazepam as well as complexated diazepam was carried out to predict the absorption rate of diazepam at given pH value. The solubility of micronized diazepam (particle size 5.4 µm) at pH 6.8, was 0.043 mg mL-1, while the solubility of non-micronized diazepam (particle size 414.8 µm) at the same pH was 0.036 mg mL-1. Inclusion complexation of diazepam with 2-hydroxypropyl-β-cyclodextrin resulted in increased solubility of diazepam. One mole of 2-hydroxypropyl-β-cyclodextrin increased the solubility of micronized diazepam 6.82 fold, while two moles of 2-hydroxypropyl-β-cyclodextrin increased the solubility of diazepam 12.55 fold. Given that the values of intrinsic dissolution rates (IDR) of micronized diazepam, non-micronized diazepam and inclusion complex D: 2-HP-β-CD 1:1 were less than 0.1 mg min-1 cm-2, the absorption of diazepam dissolution would be the rate limiting step to absorption, while the inclusion complex D: 2-HP-β-CD 1:2 where an IDR value was greater than 0.1 mg min-1 cm-2 at pH 6.8, suggested that its dissolution might be the rate-limiting step to absorption. Hydroxypropyl-β-cyclodextrin increased the solubility of diazepam at pH 6.8, thus increasing the dissolution rate and causing faster absorption of diazepam at pH 6.8.
| Published in | International Journal of Science, Technology and Society (Volume 1, Issue 1) |
| DOI | 10.11648/j.ijsts.20130101.14 |
| Page(s) | 24-35 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
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Copyright © The Author(s), 2013. Published by Science Publishing Group |
Diazepam, 2-Hydroxypropyl-β-Cyclodextrin, Solubility, Intrinsic Dissolution Rate
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APA Style
Hadžiabdić J., Elezović A., Hadžović S., Vehabović M. (2013). The Solubility - Intrinsic Dissolution Rate of Diazepam and Inclusion Complexes Diazepam with 2-Hydroxypropyl-β-Cyclodextrin. International Journal of Science, Technology and Society, 1(1), 24-35. https://doi.org/10.11648/j.ijsts.20130101.14
ACS Style
Hadžiabdić J.; Elezović A.; Hadžović S.; Vehabović M. The Solubility - Intrinsic Dissolution Rate of Diazepam and Inclusion Complexes Diazepam with 2-Hydroxypropyl-β-Cyclodextrin. Int. J. Sci. Technol. Soc. 2013, 1(1), 24-35. doi: 10.11648/j.ijsts.20130101.14
AMA Style
Hadžiabdić J., Elezović A., Hadžović S., Vehabović M. The Solubility - Intrinsic Dissolution Rate of Diazepam and Inclusion Complexes Diazepam with 2-Hydroxypropyl-β-Cyclodextrin. Int J Sci Technol Soc. 2013;1(1):24-35. doi: 10.11648/j.ijsts.20130101.14
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Download@article{10.11648/j.ijsts.20130101.14,
author = {Hadžiabdić J. and Elezović A. and Hadžović S. and Vehabović M.},
title = {The Solubility - Intrinsic Dissolution Rate of Diazepam and Inclusion Complexes Diazepam with 2-Hydroxypropyl-β-Cyclodextrin},
journal = {International Journal of Science, Technology and Society},
volume = {1},
number = {1},
pages = {24-35},
doi = {10.11648/j.ijsts.20130101.14},
url = {https://doi.org/10.11648/j.ijsts.20130101.14},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijsts.20130101.14},
abstract = {When the fast absorption of diazepam is needed in order to suppress febrile convulsions and epileptic seizures, the most suitable is intravenous application diazepam. To avoid inappropriate self administration of such diazepam dosage form, orodispersible tablets of diazepam would be the dosage form of choice. Poor solubility of diazepam in water is directly related to its dissolution rate after release from a solid dosage form. Inadequate dissolution rate of diazepam can be the limiting factor for its absorption rate. Inclusion complexation of diazepam with 2-hydroxypropyl-β-cyclodextrin was carried out to increase the solubility of diazepam at pH 6.8. Determination of the intrinsic dissolution rate of diazepam as well as complexated diazepam was carried out to predict the absorption rate of diazepam at given pH value. The solubility of micronized diazepam (particle size 5.4 µm) at pH 6.8, was 0.043 mg mL-1, while the solubility of non-micronized diazepam (particle size 414.8 µm) at the same pH was 0.036 mg mL-1. Inclusion complexation of diazepam with 2-hydroxypropyl-β-cyclodextrin resulted in increased solubility of diazepam. One mole of 2-hydroxypropyl-β-cyclodextrin increased the solubility of micronized diazepam 6.82 fold, while two moles of 2-hydroxypropyl-β-cyclodextrin increased the solubility of diazepam 12.55 fold. Given that the values of intrinsic dissolution rates (IDR) of micronized diazepam, non-micronized diazepam and inclusion complex D: 2-HP-β-CD 1:1 were less than 0.1 mg min-1 cm-2, the absorption of diazepam dissolution would be the rate limiting step to absorption, while the inclusion complex D: 2-HP-β-CD 1:2 where an IDR value was greater than 0.1 mg min-1 cm-2 at pH 6.8, suggested that its dissolution might be the rate-limiting step to absorption. Hydroxypropyl-β-cyclodextrin increased the solubility of diazepam at pH 6.8, thus increasing the dissolution rate and causing faster absorption of diazepam at pH 6.8.},
year = {2013}
}
TY - JOUR T1 - The Solubility - Intrinsic Dissolution Rate of Diazepam and Inclusion Complexes Diazepam with 2-Hydroxypropyl-β-Cyclodextrin AU - Hadžiabdić J. AU - Elezović A. AU - Hadžović S. AU - Vehabović M. Y1 - 2013/06/10 PY - 2013 N1 - https://doi.org/10.11648/j.ijsts.20130101.14 DO - 10.11648/j.ijsts.20130101.14 T2 - International Journal of Science, Technology and Society JF - International Journal of Science, Technology and Society JO - International Journal of Science, Technology and Society SP - 24 EP - 35 PB - Science Publishing Group SN - 2330-7420 UR - https://doi.org/10.11648/j.ijsts.20130101.14 AB - When the fast absorption of diazepam is needed in order to suppress febrile convulsions and epileptic seizures, the most suitable is intravenous application diazepam. To avoid inappropriate self administration of such diazepam dosage form, orodispersible tablets of diazepam would be the dosage form of choice. Poor solubility of diazepam in water is directly related to its dissolution rate after release from a solid dosage form. Inadequate dissolution rate of diazepam can be the limiting factor for its absorption rate. Inclusion complexation of diazepam with 2-hydroxypropyl-β-cyclodextrin was carried out to increase the solubility of diazepam at pH 6.8. Determination of the intrinsic dissolution rate of diazepam as well as complexated diazepam was carried out to predict the absorption rate of diazepam at given pH value. The solubility of micronized diazepam (particle size 5.4 µm) at pH 6.8, was 0.043 mg mL-1, while the solubility of non-micronized diazepam (particle size 414.8 µm) at the same pH was 0.036 mg mL-1. Inclusion complexation of diazepam with 2-hydroxypropyl-β-cyclodextrin resulted in increased solubility of diazepam. One mole of 2-hydroxypropyl-β-cyclodextrin increased the solubility of micronized diazepam 6.82 fold, while two moles of 2-hydroxypropyl-β-cyclodextrin increased the solubility of diazepam 12.55 fold. Given that the values of intrinsic dissolution rates (IDR) of micronized diazepam, non-micronized diazepam and inclusion complex D: 2-HP-β-CD 1:1 were less than 0.1 mg min-1 cm-2, the absorption of diazepam dissolution would be the rate limiting step to absorption, while the inclusion complex D: 2-HP-β-CD 1:2 where an IDR value was greater than 0.1 mg min-1 cm-2 at pH 6.8, suggested that its dissolution might be the rate-limiting step to absorption. Hydroxypropyl-β-cyclodextrin increased the solubility of diazepam at pH 6.8, thus increasing the dissolution rate and causing faster absorption of diazepam at pH 6.8. VL - 1 IS - 1 ER -
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