Design of an In Situ Cross-Linked Eutectic Tablet for Enhanced Delivery of Gastro-Sensitive Proteins and Peptides.
In the present study, a eutectic platform was designed as an in situ cross-linked eutectic tablet for structural protection, enhanced intestinal permeation, and controlled release of proteins after oral administration. Physicochemical and physicomechanical analyses of the eutectic tablets were undertaken to elucidate the in situ cross-linking mechanism, thermal transitions, crystallinity, ex vivo permeation, and in vitro release of the protein. Following thermal characterization, results revealed successful eutectic formation with a melting point to 37°C. Protein release from the formulation was controlled over 24 h with a maximum fractional release of ±0.8 for all formulations. The release pattern alternated between phases of burst and slow release which was attributed to the combined effects of swelling, surface erosion, and in situ cross-linking. Mathematical modeling of the protein release kinetics corresponded best with the Higuichi model with near zero-order (R(2) ≈ 0.9787) release. The permeation-enhancing effect of menthol contained within the eutectic powder blend was investigated and results showed an enhanced protein flux (0.0576-0.0720 mg·cm(-2) h(-1)) across the intestinal tissue model compared with a control formulation. Extensive in vitro characterization highlighted the successful design of the eutectic tablets as a potential oral delivery system for proteins with structural protection, enhanced intestinal permeation, and controlled release.
Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
Bibi F
BF
Choonara
Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
Yahya E
YE
Choonara
Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
Pradeep
P
Kumar
Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
Lisa C
LC
du Toit
Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa. Electronic address: viness.pillay@wits.ac.za.
Viness
V
Pillay
D000818:Animals; D003432:Cross-Linking Reagents; D003460:Crystallization; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D005753:Gastric Mucosa / Q000378:metabolism*; D007408:Intestinal Absorption; D007700:Kinetics; D008962:Models, Theoretical; D010455:Peptides / Q000008:administration & dosage* / Q000378:metabolism; D010539:Permeability; D011506:Proteins / Q000008:administration & dosage* / Q000378:metabolism; D013552:Swine; D013607:Tablets / Q000737:chemistry*; D013816:Thermodynamics
D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D010455:Peptides; D011506:Proteins; D013607:Tablets
bovine serum albumin; controlled release; eutectic mixture; intestinal absorption; oral protein delivery; solid dispersion