Formulation and process optimization of multiparticulate pulsatile system delivered by osmotic pressure-activated rupturable membrane

Sheng Feng Hung, Chien Ming Hsieh, Ying Chen Chen, Cheng Mao Lin, Hsiu O. Ho, Ming Thau Sheu

研究成果: 雜誌貢獻文章

7 引文 (Scopus)

摘要

In this study, a multiparticulate pulsatile drug delivery system activated by a rupturable controlled-release membrane (Eudragit® RS) via osmotic pressure (with NaCl as the osmogent) was developed and characterized for omeprazole, omeprazole sodium, and propranolol HCl which have different water solubilities. Multiparticulates in pellet form for incorporation with or without the osmogent were manufactured by three methods and then used to coat a polymeric membrane. Results demonstrated that drug/osmogent-containing pellets manufactured by the extrusion/spheronization method with incorporation of the osmogent were optimal. The lag time (tL) to initiate pulsatile release is regulated by tL = l2/(6 × D), which is dependent on the coating levels (l2) and plasticizer content (D). The pulsatile release pattern was found to be dependent on the osmotic pressure (osmogent), drug solubility, and mechanical properties of the polymeric membrane (elasticity and toughness). Omeprazole with lower water solubility could not generate sufficient osmotic pressure to create a crack in the membrane to activate pulsatile release, whereas the two other model drugs with higher solubilities could. But adsorption of omeprazole sodium on Eudragit® RS via charge-charge interactions led the its incomplete release. Finally, with 4% osmogent of NaCl added, a lag time in a range from 0 to 12 h proportionally regulated by varying both the membrane thickness and plasticizer level initiated the complete pulsatile release of propranolol HCl. In conclusion, a multiparticulate pulsatile drug delivery system activated by a rupturable controlled-release membrane via osmotic pressure was successfully developed, and clinical applications of chronotherapy with drugs like propranolol HCl are expected.
原文英語
頁(從 - 到)15-26
頁數12
期刊International Journal of Pharmaceutics
480
發行號1-2
DOIs
出版狀態已發佈 - 三月 1 2015

指紋

Osmotic Pressure
Omeprazole
Solubility
Membranes
Propranolol
Plasticizers
Drug Delivery Systems
Drug Chronotherapy
Pharmaceutical Preparations
Water
Elasticity
Adsorption

ASJC Scopus subject areas

  • Pharmaceutical Science

引用此文

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title = "Formulation and process optimization of multiparticulate pulsatile system delivered by osmotic pressure-activated rupturable membrane",
abstract = "In this study, a multiparticulate pulsatile drug delivery system activated by a rupturable controlled-release membrane (Eudragit{\circledR} RS) via osmotic pressure (with NaCl as the osmogent) was developed and characterized for omeprazole, omeprazole sodium, and propranolol HCl which have different water solubilities. Multiparticulates in pellet form for incorporation with or without the osmogent were manufactured by three methods and then used to coat a polymeric membrane. Results demonstrated that drug/osmogent-containing pellets manufactured by the extrusion/spheronization method with incorporation of the osmogent were optimal. The lag time (tL) to initiate pulsatile release is regulated by tL = l2/(6 × D), which is dependent on the coating levels (l2) and plasticizer content (D). The pulsatile release pattern was found to be dependent on the osmotic pressure (osmogent), drug solubility, and mechanical properties of the polymeric membrane (elasticity and toughness). Omeprazole with lower water solubility could not generate sufficient osmotic pressure to create a crack in the membrane to activate pulsatile release, whereas the two other model drugs with higher solubilities could. But adsorption of omeprazole sodium on Eudragit{\circledR} RS via charge-charge interactions led the its incomplete release. Finally, with 4{\%} osmogent of NaCl added, a lag time in a range from 0 to 12 h proportionally regulated by varying both the membrane thickness and plasticizer level initiated the complete pulsatile release of propranolol HCl. In conclusion, a multiparticulate pulsatile drug delivery system activated by a rupturable controlled-release membrane via osmotic pressure was successfully developed, and clinical applications of chronotherapy with drugs like propranolol HCl are expected.",
keywords = "Eudragit{\circledR} RS, Lag time, Multiparticulate, Osmotic pressure, Pulsatile release",
author = "Hung, {Sheng Feng} and Hsieh, {Chien Ming} and Chen, {Ying Chen} and Lin, {Cheng Mao} and Ho, {Hsiu O.} and Sheu, {Ming Thau}",
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T1 - Formulation and process optimization of multiparticulate pulsatile system delivered by osmotic pressure-activated rupturable membrane

AU - Hung, Sheng Feng

AU - Hsieh, Chien Ming

AU - Chen, Ying Chen

AU - Lin, Cheng Mao

AU - Ho, Hsiu O.

AU - Sheu, Ming Thau

PY - 2015/3/1

Y1 - 2015/3/1

N2 - In this study, a multiparticulate pulsatile drug delivery system activated by a rupturable controlled-release membrane (Eudragit® RS) via osmotic pressure (with NaCl as the osmogent) was developed and characterized for omeprazole, omeprazole sodium, and propranolol HCl which have different water solubilities. Multiparticulates in pellet form for incorporation with or without the osmogent were manufactured by three methods and then used to coat a polymeric membrane. Results demonstrated that drug/osmogent-containing pellets manufactured by the extrusion/spheronization method with incorporation of the osmogent were optimal. The lag time (tL) to initiate pulsatile release is regulated by tL = l2/(6 × D), which is dependent on the coating levels (l2) and plasticizer content (D). The pulsatile release pattern was found to be dependent on the osmotic pressure (osmogent), drug solubility, and mechanical properties of the polymeric membrane (elasticity and toughness). Omeprazole with lower water solubility could not generate sufficient osmotic pressure to create a crack in the membrane to activate pulsatile release, whereas the two other model drugs with higher solubilities could. But adsorption of omeprazole sodium on Eudragit® RS via charge-charge interactions led the its incomplete release. Finally, with 4% osmogent of NaCl added, a lag time in a range from 0 to 12 h proportionally regulated by varying both the membrane thickness and plasticizer level initiated the complete pulsatile release of propranolol HCl. In conclusion, a multiparticulate pulsatile drug delivery system activated by a rupturable controlled-release membrane via osmotic pressure was successfully developed, and clinical applications of chronotherapy with drugs like propranolol HCl are expected.

AB - In this study, a multiparticulate pulsatile drug delivery system activated by a rupturable controlled-release membrane (Eudragit® RS) via osmotic pressure (with NaCl as the osmogent) was developed and characterized for omeprazole, omeprazole sodium, and propranolol HCl which have different water solubilities. Multiparticulates in pellet form for incorporation with or without the osmogent were manufactured by three methods and then used to coat a polymeric membrane. Results demonstrated that drug/osmogent-containing pellets manufactured by the extrusion/spheronization method with incorporation of the osmogent were optimal. The lag time (tL) to initiate pulsatile release is regulated by tL = l2/(6 × D), which is dependent on the coating levels (l2) and plasticizer content (D). The pulsatile release pattern was found to be dependent on the osmotic pressure (osmogent), drug solubility, and mechanical properties of the polymeric membrane (elasticity and toughness). Omeprazole with lower water solubility could not generate sufficient osmotic pressure to create a crack in the membrane to activate pulsatile release, whereas the two other model drugs with higher solubilities could. But adsorption of omeprazole sodium on Eudragit® RS via charge-charge interactions led the its incomplete release. Finally, with 4% osmogent of NaCl added, a lag time in a range from 0 to 12 h proportionally regulated by varying both the membrane thickness and plasticizer level initiated the complete pulsatile release of propranolol HCl. In conclusion, a multiparticulate pulsatile drug delivery system activated by a rupturable controlled-release membrane via osmotic pressure was successfully developed, and clinical applications of chronotherapy with drugs like propranolol HCl are expected.

KW - Eudragit® RS

KW - Lag time

KW - Multiparticulate

KW - Osmotic pressure

KW - Pulsatile release

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