Effect of hydroxypropyl methylcellulose on beta cyclodextrin
complexation of praziquantel in solution and in solid state
JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY, 85 (1-2):
151-160 (2016)DOI: 10.1007/s10847-016-0614-3
Abstract
The effect of hydroxypropyl methylcellulose (HPMC) on complexation of
praziquantel with beta cyclodextrin (PRZ-beta CD) in solution and in the
solid state was investigated. Phase solubility studies of beta CD (0, 3,
6, 9 and 12 mmol L-1) were carried out by adding an excess amount of PRZ
(8 mmol L-1) in the absence and presence of the polymer (with and
without heating at 120 A degrees C). Equimolar binary and ternary
complexes were prepared by kneading and freeze-drying and characterized
by DSC, DTA TGA, FTIR, XRPD and SEM patterns. A stoichiometry ratio of
1:1 was indicated by phase-solubility studies both in the presence and
absence of 0.5 % HPMC. The molecular modeling confirms the 1:1
stoichiometry rate with Higuchi's A(l) type. The presence of HPMC
improved the complexation between PRZ and beta CD by increases in both
the intrinsic solubility of the drug as well as in values of the
stability constant, complexation efficiency and Gibb's free energy of
the complex, principally in the presence of heating (up to ninefold
relative to aqueous solubility of the drug). The synergic effect of HPMC
was also observed in thermal analysis, with lower dehydration enthalpy
for ternary complexes. The results of melting enthalpy were according to
XRPD results, indicating that the preparation technique and presence of
HPMC influenced thermal and crystallographic characteristics of
inclusion complexes. The FTIR patterns suggest the complexation
mechanism while SEM patterns showed the formation of inclusion
complexes. The use of the HPMC and freeze-drying technique suggest more
effective formation of PRZ:beta CD inclusion complexes.