Stability and Release Kinetics of an Advanced Gliclazide-Cholic Acid Formulation: The Use of Artificial-Cell Microencapsulation in Slow Release Targeted Oral Delivery of Antidiabetics.
BACKGROUND
In previous studies carried out in our laboratory, a bile acid (BA) formulation exerted a hypoglycaemic effect in a rat model of type-1 diabetes (T1D). When the antidiabetic drug gliclazide (G) was added to the bile acid, it augmented the hypoglycaemic effect. In a recent study, we designed a new formulation of gliclazide-cholic acid (G-CA), with good structural properties, excipient compatibility and exhibits pseudoplastic-thixotropic characteristics. The aim of this study is to test the slow release and pH-controlled properties of this new formulation. The aim is also to examine the effect of CA on G release kinetics at various pH values and different temperatures.


METHODS
Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) and G-CA-SA (test) at a constant ratio (1:3:30), respectively. Microcapsules were examined for efficiency, size, release kinetics, stability and swelling studies at pH 1.5, pH 3, pH 7.4 and pH 7.8 and temperatures of 20 and 30 °C.


RESULTS
The new formulation is further optimised by the addition of CA. CA reduced microcapsule swelling of the microcapsules at pH 7.8 and pH 3 at 30 °C and pH 3 at 20 °C, and, even though microcapsule size remains similar after CA addition, percent G release was enhanced at high pH values (pH 7.4 and pH 7.8,p< 0.01).


CONCLUSIONS
The new formulation exhibits colon-targeted delivery and the addition of CA prolonged G release suggesting its suitability for the sustained and targeted delivery of G and CA to the lower intestine.
Biotechnology and Drug Development Research Laboratory, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, WA Australia.
Armin
A
Mooranian
Biotechnology and Drug Development Research Laboratory, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, WA Australia.
Rebecca
R
Negrulj
Biotechnology and Drug Development Research Laboratory, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, WA Australia.
Sangeetha
S
Mathavan
Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Science, Curtin University, Perth, WA Australia.
Jorge
J
Martinez
Biotechnology and Drug Development Research Laboratory, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, WA Australia.
Jessica
J
Sciarretta
Faculty of Science & Engineering, Curtin University, Perth, WA Australia.
Nigel
N
Chen-Tan
Curtin Health Innovation Research Institute, Biosciences Research Precinct, School of Biomedical Science, Curtin University, Perth, WA Australia.
Tk
T
Mukkur
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia ; Faculty of Pharmacy, University of Montenegro Podgorica, 8100 Podgorica, Montenegro.
Momir
M
Mikov
Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Mladena
M
Lalic-Popovic
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Maja
M
Stojančević
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia ; Faculty of Pharmacy, University of Montenegro Podgorica, 8100 Podgorica, Montenegro.
Svetlana
S
Golocorbin-Kon
Biotechnology and Drug Development Research Laboratory, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, WA Australia.
Hani
H
Al-Salami
Artificial-cell microencapsulation; Bile acid; Diabetes; Gliclazide