Bioavailability of sustained release propranolol formulations

✍ Scribed by James McAinsh; Nigel S. Baber; Brian F. Holmes; Jean Young; Stuart H. Ellis

• Publisher: John Wiley and Sons
• Year: 1981
• Tongue: English
• Weight: 377 KB
• Volume: 2
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510020105

✦ Synopsis

Abstract

In this comparative bioavailability study two sustained release capsule formulations of propranolol, one a clinical trial formulation and the other the U.K. sales formulation (‘Inderal’ LA), were compared with a conventional ‘Inderal’ tablet. Twelve healthy adult male volunteers received, on a cross‐over basis, on three separate occasions, 160 mg oral doses of three formulations of ‘Inderal’. Bioavailability was based on concentration of propranolol in whole blood. The peak blood level and area under the propranolol blood level curve fell as the dissolution time increased. The half‐lives of the three formulations were inversely proportional to their dissolution rates, those of the sustained release formulations being considerably longer than that of the conventional tablet.

The 160 mg ‘Inderal’ tablet produced a rapid 90‐fold decline over 24 h in propranolol blood levels following a high initial peak. By comparison both sustained release formulations showed a less rapid fall in systemic levels and gave higher blood levels at the end of 24 h and plateau values between 8 and 14 ng ml ^−1^.

The ‘Inderal’ LA sustained release formulation gave consistently higher propranolol blood levels than the clinical trial sustained release formulation. This result is in good agreement with their dissolution profiles. The lowering of the systemic bioavailability as the dissolution time increases is thought to be due to an increased metabolism of propranolol.