| Abstract: | The dissolution characteristics of propranolol enantiomers from tablet formulations containing cellulose, or one of eight cellulose derivatives, were determined under a range of conditions. The derivatives examined were: cellulose tris(phenylcarbamate) (1), cellulose tris(2,3-dichlorophenylcarbamate) (2), cellulose tris 2,4-dichlorophenylcarbamate (3), cellulose tris(2,6-dichlorophenylcarbamate) (4), cellulose tris(2,3-dimethylphenylcarbamate) (5), cellulose tris(3,4-dichlorophenylcarbamate) (6), cellulose tris (3,5-dichlorophenylcarbamate) (7), cellulose tris(3,5-dimethylphenylcarbamate) (8). In water at 25°C, the release rates of (-)R-propranolol were generally greater than those of (-)-S-propranolol, although these differences were not always statistically significant; only compounds 5 and 8 demonstrated significant enantioselectivity. Using compound 8 in further experiments, statistically significant stereoselective dissolution of propranolol HCl was observed in buffer pH 7.4 at 25°C (intrinsic dissolution rates: 0.41 ± 0.01 mgcm2min−1 for R-propranolol and 0.30 ± 0.02 mgcm2min−1 for S-propranolol; P = 0.003). The cumulative amounts of enantiomers released at every time point were also found to be statistically significant (mean ratio R:S 1.25 ± 0.05). The observed low stereoselectivity of 8 with propranolol base was probably attributable to low solubility in pH 7.4 buffer, although stereoselective release did increase with time. This suggested that there is a relationship between stereoselectivity and contact time in an aqueous environment. Results also suggested that increased temperature may affect the release process as well as stereoselective interactions of 8 with individual enantiomers. To conclude, differential release of rac-propranolol from cellulose derivative matrices has been demonstrated, which supports the principle of stereoselective retardation as a potential means of stereoselective drug delivery for solid dosage forms. Chirality 9:307–312, 1997. © 1997 Wiley-Liss, Inc. |
