TY - JOUR
T1 - Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems
AU - Aroso, Ivo M
AU - Silva, João C
AU - Mano, Francisca
AU - Ferreira, Ana Sofia Diogo
AU - Dionísio, Madalena
AU - Sá-Nogueira, Isabel
AU - Barreiros, Susana
AU - Reis, Rui L
AU - Paiva, Alexandre
AU - Duarte, Ana Rita C
N1 - Sem pdf conforme despacho.
European Union's Seventh Framework Programme (FP7) - REGPOT-CT2012-316331-POLARIS
Project "Novel smart and biomimetic materials for innovative regenerative medicine approaches" (RL1 - ABMR - NORTE-01-0124-FEDER-000016 )
Fundacao para a Ciencia e a Tecnologia (UID/QUI/50006/2013 ; UID/Multi/04378/2013)
PY - 2016/1
Y1 - 2016/1
N2 - A therapeutic deep eutectic system (THEDES) is here defined as a deep eutectic solvent (DES) having an active pharmaceutical ingredient (API) as one of the components. In this work, THEDESs are proposed as enhanced transporters and delivery vehicles for bioactive molecules. THEDESs based on choline chloride (ChCl) or menthol conjugated with three different APIs, namely acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA), were synthesized and characterized for thermal behaviour, structural features, dissolution rate and antibacterial activity. Differential scanning calorimetry and polarized optical microscopy showed that ChCl:PA (1:1), ChCl:AA (1:1), menthol:AA (3:1), menthol:BA (3:1), menthol:PA (2:1) and menthol:PA (3:1) were liquid at room temperature. Dissolution studies in PBS led to increased dissolution rates for the APIs when in the form of THEDES, compared to the API alone. The increase in dissolution rate was particularly noticeable for menthol-based THEDES. Antibacterial activity was assessed using both Gram-positive and Gram-negative model organisms. The results show that all the THEDESs retain the antibacterial activity of the API. Overall, our results highlight the great potential of THEDES as dissolution enhancers in the development of novel and more effective drug delivery systems.
AB - A therapeutic deep eutectic system (THEDES) is here defined as a deep eutectic solvent (DES) having an active pharmaceutical ingredient (API) as one of the components. In this work, THEDESs are proposed as enhanced transporters and delivery vehicles for bioactive molecules. THEDESs based on choline chloride (ChCl) or menthol conjugated with three different APIs, namely acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA), were synthesized and characterized for thermal behaviour, structural features, dissolution rate and antibacterial activity. Differential scanning calorimetry and polarized optical microscopy showed that ChCl:PA (1:1), ChCl:AA (1:1), menthol:AA (3:1), menthol:BA (3:1), menthol:PA (2:1) and menthol:PA (3:1) were liquid at room temperature. Dissolution studies in PBS led to increased dissolution rates for the APIs when in the form of THEDES, compared to the API alone. The increase in dissolution rate was particularly noticeable for menthol-based THEDES. Antibacterial activity was assessed using both Gram-positive and Gram-negative model organisms. The results show that all the THEDESs retain the antibacterial activity of the API. Overall, our results highlight the great potential of THEDES as dissolution enhancers in the development of novel and more effective drug delivery systems.
KW - Pharmacology & Pharmacy
KW - Research Support, Non-U.S. Gov't
KW - Therapeutic deep eutectic systems
KW - Drug solubility
KW - Green technologies
KW - Pharmaceutical and biomedical applications
U2 - 10.1016/j.ejpb.2015.11.002
DO - 10.1016/j.ejpb.2015.11.002
M3 - Article
C2 - 26586342
VL - 98
SP - 57
EP - 66
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
SN - 0939-6411
ER -