Enthalpy relaxation studies of two structurally related amorphous drugs and their binary dispersions.
OBJECTIVE
The purpose of the current study was to evaluate the enthalpy relaxation behavior of valdecoxib (VLB) and etoricoxib (ETB) and their binary dispersions to derive relaxation constants and to understand their molecular mobilities.


METHODS
Solid dispersions of VLB and ETB were prepared with 1%, 2%, 5%, 10%, 15%, and 20% (w/w) concentrations of polyvinylpyrrolidone (PVP) in situ using differential scanning calorimetry (DSC). Enthalpy relaxation studies were carried out with isothermal storage periods of 1, 2, 4, 6, 16, and 24 hours at 40°C and 0% relative humidity (RH).


RESULTS
PVP increased the glass transition temperature (T(g)) and decreased the enthalpy relaxation. Significant differences between two drugs were observed with respect to their relaxation behavior which may be due to differences in intermolecular interactions as predicted by Couchman-Karasz equation and molecular mobility. Kohlrausch-Williams-Watts equation was found to be inadequate in describing complex molecular relaxations in binary dispersions. The enthalpy relaxation behavior of VLB and ETB was found to be significantly different. PVP stabilized VLB significantly; however, its effect on ETB was negligible. The extent of enthalpy relaxation was found to correlate with hydrogen bonding tendency of the drug molecules.


CONCLUSIONS
The outcome can help in rational designing of amorphous systems with optimal performance.
Bansal
Shyam Sunder
SS
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Mohali, Punjab, India.
Kaushal
Aditya Mohan
AM
Bansal
Arvind Kumar
AK
D002152:Calorimetry, Differential Scanning; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D000077613:Etoricoxib; D005079:Excipients / Q000737:chemistry; D006813:Humidity; D006860:Hydrogen Bonding; D007555:Isoxazoles / Q000008:administration & dosage / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D011725:Pyridines / Q000008:administration & dosage / Q000737:chemistry*; D013449:Sulfonamides / Q000008:administration & dosage / Q000737:chemistry*; D013450:Sulfones / Q000008:administration & dosage / Q000737:chemistry*; D013816:Thermodynamics; D044366:Transition Temperature; D000096926:Benzenesulfonamides
D052246:Cyclooxygenase 2 Inhibitors; D000077613:Etoricoxib; D005079:Excipients; D007555:Isoxazoles; D011205:Povidone; D011725:Pyridines; D013449:Sulfonamides; D013450:Sulfones; C406224:valdecoxib; D000096926:Benzenesulfonamides