Journal of Pharmaceutical Innovation

, Volume 3, Issue 4, pp 249–257 | Cite as

Reduction in Moisture Sensitivity/Uptake of Moisture Sensitive Drugs Through Adduction in Urea

Research Article


In the present study, use of hexagonal urea as a means for the reduction in moisture sensitivity/uptake has been investigated using nicorandil as a model endocytic drug. Urea, a well-known adductor for linear compounds, was successfully employed for adduction of nicorandil—a substituted cyclic organic compound through recently reported technique. Formation of urea inclusion compounds was confirmed by Fourier transform infrared, differential scanning calorimetry (DSC) and X-ray diffraction. Modified Zimmerschied calorimetric method was employed for estimation of the minimum amount of rapidly adductible endocyte (RAE) required per unit weight of nicorandil for adduction in urea. Urea–nicorandil–RAE inclusion compounds containing varying proportions of guests were prepared and their thermal behavior studied by DSC. However, coinclusion of nicorandil—a normally non-adductible endocytic compound in urea—naturally resulted in distortion of narrow channels of hexagonal lattice leading to the formation of distorted hexagonal urea. Both the normal and distorted hexagonal urea revealed appreciable reduction in moisture uptake when compared to that of tetragonal urea. The distorted urea framework exhibited increased moisture uptake as compared to the non-distorted one. Study also revealed improved stability of included nicorandil upon exposure to atmosphere at higher humidity levels. The coinclusion compounds of nicorandil were found to exhibit good content uniformity. Urea inclusion compounds of nicorandil in the presence of suitable RAE can be a promising alternative for the development of stable formulations of the drug.


Adduction Complexation Content uniformity Moisture sensitivity Nicorandil Solid state stability Urea inclusion compounds 


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Copyright information

© International Society for Pharmaceutical Engineering 2008

Authors and Affiliations

  1. 1.PDM College of PharmacyBahadurgarhIndia
  2. 2.Faculty of Pharmaceutical SciencesM.D. UniversityRohtakIndia

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