Release characteristics of some bronchodilators from compressed hydrophilic polymeric matrices and their correlation with molecular geometry

Abstract For a series of structurally related water-soluble bronchodilators namely ephedrine hydrochloride, phenylpropanolamine hydrochloride, salbutamol sulphate, terbutaline sulphate, reproterol hydrochloride and anunophylline, the release rates from compressed matrices of hydroxypropylmethylcellulose (HPMC) were investigated. On varying the drug tracer it was observed that despite almost identical aqueous solubilities different drug molecules show different release rates from matrix tablets. The release rates through HPMC matrices of different viscosity grades were found to be highly correlated ( r > 0.95) with the accessible surface area (ASA) of the drugs; indicating the importance of geometrical features like shape and size of the solute molecules in release rates through HPMC matrices. The predictive capability of the correlations was tested for orciprenaline sulphate, outside the training sample. The agreement between the experimental and the predicted release rates was found to be within experimental uncertainty (±5%). The internal consistency of the quantitative relationship was established by the ‘hold-one-out’ procedure.