Investigating the structure and properties of hydrated hydroxypropyl methylcellulose and egg albumin matrices containing carbamazepine: EPR and NMR study.
OBJECTIVE
The present study was conducted in order to investigate the correlation between the hydration properties of HPMC and EA matrices, gel microstructure and mobility, crystalline changes occurring in the gel and CBZ release kinetics. The influence of HPMC and EA erosion modes on CBZ release kinetics was interpreted in terms of gel microstructures.


METHODS
NMR technique was used to determine the T1 and T2 relaxation rates of water in hydrated matrices. PFGSE NMR technique was employed to determine the SDC of water in the gels. EPR technique was used to determine the rotational correlation time of PCA in the hydrated matrices, gel microviscosity, mobile compartment, alpha, beta, gamma parameters and lorentzian/ gaussian ratio. These parameters are indicative of matrix microstructure.


RESULTS
CBZ release mechanism from HPMC and EA matrices was markedly different. This behavior was related to the different structures of the polymer and protein. T2 relaxation studies and SDC measurements by NMR revealed higher chain hydration for HPMC compared to EA. Using the EPR technique it has been shown that the microviscosity and mobile compartment of matrices containing HPMC are lower than matrices containing EA. The microviscosity, mobile compartment and S-parameter values of hydrated matrices containing different EA/CBZ ratios were in correlation with the crystallization properties of CBZ in the gels, matrix erosion properties and CBZ release kinetics from the matrices.


CONCLUSIONS
Characterization of matrix structures using EPR and NMR techniques supported our hypothesis concerning the mechanism involved in HPMC-CBZ interaction. EA/CBZ matrix microstructure features, analyzed by NMR and EPR techniques, were in correlation with the crystalline changes occurring in the gel and drug release kinetics.
Katzhendler
I
I
Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Israel.
Mäder
K
K
Azoury
R
R
Friedman
M
M
D002220:Carbamazepine / Q000737:chemistry*; D003460:Crystallization; D003497:Cyclic N-Oxides / Q000737:chemistry; D004337:Drug Carriers; D004578:Electron Spin Resonance Spectroscopy; D005782:Gels; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010047:Ovalbumin / Q000737:chemistry*; D013113:Spin Labels; D013329:Structure-Activity Relationship; D013499:Surface Properties; D013607:Tablets; D014783:Viscosity; D014867:Water / Q000737:chemistry
D003497:Cyclic N-Oxides; D004337:Drug Carriers; D005782:Gels; D013113:Spin Labels; D013607:Tablets; D014867:Water; C032289:2,2,5,5-tetramethyl-1-pyrrolidinyloxy-3-carboxylic acid; D002220:Carbamazepine; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D010047:Ovalbumin