Enantioselective retardation of rac-propranolol from matrices containing cellulose derivatives

✍ Scribed by Roongnapa Suedee; Keith R. Brain; Charles M. Heard

• Book ID: 101294589
• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 172 KB
• Volume: 9
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/(sici)1520-636x(1997)9:3<307::aid-chir18>3.0.co;2-r

✦ Synopsis

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

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 mgcm 2 min -1 for R-propranolol and 0.30 ± 0.02 mgcm 2 min -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.