Solid state stabilisation of the orally delivered drugs atenolol, glibenclamide, memantine and paracetamol through their complexation with cucurbit[7]uril.
The inclusion of the cardiovascular beta-blocker drug atenolol, the antidiabetic drug glibenclamide, the Alzheimer's NMDA glutamate receptor drug memantine and the analgesic/antipyretic drug paracetamol by cucurbit[7]uril (CB[7]) has been studied by (1)H nuclear magnetic resonance spectroscopy, electrospray ionisation mass spectrometry, molecular modelling, fluorescence displacement assays and differential scanning calorimetry. All four drugs form 1 : 1 host-guest complexes with CB[7], but the exchange kinetics and location of the binding is different for each drug. Atenolol is bound over the central phenyl ring with a binding constant of 4.2 x 10(4) M(-1), whereas glibenclamide is bound over the terminal cyclohexyl group with a binding constant of 1.7 x 10(5) M(-1), and memantine is totally bound within the CB[7] cavity. Paracetamol is bound in two locations, over the central phenyl ring and over the methyl group, with the CB[7] molecule shuttling quickly between the two sites. Inclusion by CB[7] was shown by differential scanning calorimetry to physically stabilise all four drugs, which has applications preventing drug degradation and improving drug processing and formulation.
McInnes
Fiona J
FJ
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, John Arbuthnott Building, 27 Taylor Street, Glasgow, United KingdomG4 0NR.
Anthony
Nahoum G
NG
Kennedy
Alan R
AR
Wheate
Nial J
NJ
D000082:Acetaminophen / Q000008:administration & dosage*; D000284:Administration, Oral; D001262:Atenolol / Q000008:administration & dosage*; D004355:Drug Stability; D005905:Glyburide / Q000008:administration & dosage*; D047028:Macrocyclic Compounds / Q000737:chemistry*; D008559:Memantine / Q000008:administration & dosage*; D008958:Models, Molecular; D015394:Molecular Structure; D000099246:Cucurbit(n)urils
D000082:Acetaminophen; D001262:Atenolol; D005905:Glyburide; D047028:Macrocyclic Compounds; D008559:Memantine; D000099246:Cucurbit(n)urils