The effect of inorganic cations Ca2+ and Al3+ on the release rate of propranolol hydrochloride from sodium carboxymethylcellulose matrices

Abstract

Background and purpose of the study: Several methods are available for control release of propranolol hydrochloride (PLH). The aim of the present study was to develop a novel technique to sustain PLH release from matrices. Materials and methods: Matrices of PLH containing sodium carboxymethylcellulose (Na CMC) and various amounts of the inorganic cations Ca2+ and Al3+ were prepared. Dissolution of the matrices was carried out using the USP apparatus I. Analysis of release data was performed by some model independent and dependent approaches. Results: The release of PLH was affected by incorporation of different amounts (milliequivalents, meq) of Ca2+ and Al3+. When the Ca2+ amount increased from 0- 0.375 meq, the fraction of PLH which released within 480 min was augmented from 0.74 to 1 apparently via disintegrating effect of the cation. Al3+ in the range 0- 0.125 meq, decreased the fractional release from 0.74 to 0.37 presumably by in situ cross- linking with polymer. Al3+ between 0.125 and 0.5 meq enhanced the release from 0.37 to 1 possibly due to the disintegrating effect. Among model independent metrics, the mean release time (MRT) failed to represent the effect of the cations on the release but the release efficiency (R-E) as well as a suggested mean release rate (MRR) correlated well with the experimental release rate. Due to the complexity of the release, the only suitable kinetic model was the Weibull distribution. The minimum and maximum Weibull release rate constants for matrices containing Al3+ were 0.0007-0.017 l/min. The corresponding values for the matrices with Ca2+ were 0.0029-0.0082 l/min. Conclusion: Through careful choice of the amount of Al3+ in NaCMC matrices the release of PLH can be controlled at a desired rate. The best model independent approach is MRR and the most accurate model dependent method is Weibull distribution to describe the release data.