Formulation and assessment of monolithic beta blocker sustained release tablets prepared by direct compression

Kieser, Leith Faye (2003) Formulation and assessment of monolithic beta blocker sustained release tablets prepared by direct compression. Masters thesis, Rhodes University.

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Beta blockers are commonly prescribed for the chronic treatment of hypertension, one of the most prolific disease states worldwide. The beta blockers selected for this study include acebutolol hydrochloride, labetalol hydrochloride, metoprolol tartrate oxprenolol hydrochloride and propranolol hydrochloride. All of these compounds have a short elimination half-life, necessitating multiple dose per day regimens and therefore the development of sustained release dosage forms incorporating these agents was considered beneficial in terms of extending the dosing interval, with the aim of improving patient compliance and subsequent therapeutic outcomes. Preformulation studies that were conducted included moisture content analysis by Karl Fischer titration, and DSC, a method used to predict potential interactions between the drugs and tablet excipients. Tablets were manufactured by both wet granulation and direct compression techniques, and the resultant drug release characteristics were evaluated using the USP Apparatus 3(BIO.DIS). A validated isocratic HPLC method, capable of separating the five drug candidates simultaneously, was developed and used for the analysis of drug samples. Tablet quality was assessed using analyses that included the physical assessment of weight, diameter, thickness, hardness and friability, as well as content uniformity of tablets, before and after dissolution testing. Direct compression tablet formulations containing each of the five beta blockers were successfully adapted from a prototype wet granulation matrix tablet containing metoprolol tartrate, and various formulation variables were investigated to establish,their effect on the rate and extent of drug release from these tablets. The grade and quantity of ethylcellulose used in the wet granulation and direct compression formulae influenced the release rate of some drug candidates. In addition, an alternative formulation method, involving freeze-drying of the drug with an ethylcellulose dispersion, was shown to have potential for altering release rates further. Anti-frictional agents, talc and colloidal silicon dioxide, did not affect drug release from these matrices,however, they affected the physical character:istics such as tablet weight and thickness, of the resultant tablets. All of the matrix tablets formulated were shown to release drug according to square root of time kinetics, in a sustained manner over a 22 hour period.

Item Type:Thesis (Masters)
Uncontrolled Keywords:Beta blockers, Hypertension, Acebutolol hydrochloride, Labetalol hydrochloride, Metoprolol tartrate oxprenolol hydrochloride, Propranolol hydrochloride, Sustained release dosage, Therapeutic outcomes, Tablets, Drug release, Quality, Ethylcellulose, Time kinetics
Subjects:R Medicine > RS Pharmacy and materia medica
Divisions:Faculty > Faculty of Pharmacy
Supervisors:Walker, Roderick B.
ID Code:3750
Deposited By: Philip Clarke
Deposited On:23 Oct 2012 12:18
Last Modified:23 Oct 2012 12:18
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