Design and evaluation of fast dispersible tablets of lamivudine using selected natural superdisintegrants

Abstract

Fast dispersible tablets (FDTs) are solid single-unit dosage forms that are placed in the mouth and allowed to disperse or dissolve in the saliva without the need of water. The basic approach to formulating FDTs consists of adding a superdisintegrant to a tablet formulation. These tablets offer both the advantages of conventional tablets and liquid dosage forms along with distinctive properties which include accurate dosing, ease of administration, quick onset of action, enhanced bioavailability, and increased patient adherence.

FDTs have been found to be effective in remedying therapeutic in-adherence caused by dysphagia (swallowing difficulties) particularly in paediatric and geriatric subjects. There is a strong correlation between therapeutic success and patient adherence especially with HIV/AIDS treatment regimens, consequently the dosage form should be patient friendly and devoid of unappealing characteristics. This study aimed at developing a cost effective fast dispersible tablet of lamivudine using alternative excipients and conventional techniques. Only conventional tablets and oral liquid dosage forms of lamivudine are available on the South African market.

Two natural polymers reported to have superdisintegrating properties were selected to serve as multipurpose excipients in this study. The polymers were identified, characterised and compared using thermal, spectroscopic and micromeritic analytical tools. The polymer that displayed the best characteristics in terms of micromeritic, tableting and disintegrating properties was retained and used for the optimum formulation.

The optimum formulation was composed of 150 mg of lamivudine, 23% w/w unripe banana powder and 2% w/w magnesium stearate. FDTs of lamivudine were obtained using the compression technique with and without wet granulation. The tablets were assessed as per the United States Pharmacopoeia (USP) guidelines and other evaluation procedures pertaining to FDTs. The wet granulated tablets were found to be less friable and thus more resilient than the directly compressed tablets. In-vitro disintegration of the wet granulated tablets occurred within 50±3 sec in deionised water (pH 7) and 35±2 sec in a phosphate buffer solution (pH 6.8). Consequently, the innovative tablets fulfilled the core requirement of FDTs i.e. rapid disintegration.

Drug release studies were carried out by analysing dissolution aliquots of the innovative tablets using a validated High Performance Liquid Chromatography (HPLC) method, and comparing them to Aspen Lamivudine®, a conventional tablet of lamivudine presently on the South African market. Complete dissolution in deionised water (pH 7) was attained within 10 minutes and 30 minutes for the innovative tablets and Aspen Lamivudine® respectively.