Pak. J. Pharm. Sci., Vol.21, No.4, October 2008, pp.455-459 455 EFFECT OF STARCH 1500 AS A BINDER AND DISINTEGRANT IN LAMIVUDINE TABLETS PREPARED BY HIGH SHEAR WET GRANULATION BYTUL M. RAHMAN, MIR IMAM IBNE WAHED, PROMA KHONDKAR, MARUF AHMED, ROBIUL ISLAM, RANJAN K BARMAN* AND M. ANWAR UL ISLAM Department of Pharmacy, University of Rajshahi, Rajshahi-6205, Bangladesh *Quality Compliances Department, Square Pharmaceuticals Ltd. Bangladesh ABSTRACT High shear wet granulation is a preferred manufacturing method of tablets. It allowed for rapid production of compressible granulations. The resultant granulation characteristics depend on a combination of formulation properties and processing parameters. Fully pregelatinized starches are currently being used as binders in wet granulated formulations. But due to the gelatinization, much of the disintegration properties are lost. Partially pregelatinized starches (Starch 1500) have a mixture of properties of both native and fully gelatinized starches; made them useful as both a binder and a disintegrant in wet granulated formulations. Starch 1500 performed as an excellent binder producing a granulation that was compressible and produced Lamivudine tablets of improved hardness and friability compared with those prepared with povidone. The formulation of Lamivudine tablets with Starch 1500 exceeded the disintegration and dissolution performance of the povidone formulation that utilized a super disintegrant. High shear wet granulation is also well suited for the use of partially pregelatinized starches. Keywords: Starch 1500, binder, disintegrant, lamivudine tablets, wet granulation. INTRODUCTION The majority of formulations in the development of new drug products contained maize starch that was used as a both binder and disintegrant (Herbert et al., 1989). But now present days, its use was limited because the starch lost much of its disintegration properties when it gelatinized in the preparation of the starch paste (Colorcon, 2005). As a dry addition to the granulation, the maize starch did not flow well and was not very compressible. Today, polymers such as povidone are preferred as binders for wet granulated products. When hydrated these binders produce viscous, tacky solutions. The tackiness holds the individual granules together. Added dry to a granulation polymers aid in the agglomeration of fine powders upon addition of an appropriate solvent to the granulator. However, polymer binders can also lead to processing difficulties such as rapid over granulation. Over time they occasionally lead to tablet hardening and a decrease in dissolution performance (Colorcon, 2005; Moore and Flanner, 1996). A balance must be maintained between the binding and the disintegration properties of a formulation. When polymer binders are chosen, the addition of strong disintegtants such as super disintegrants is typically required but these are considerably expensive and have a negative effect on product stability as well as film coating appearance of the finished products (Levina and Cunningham, 2005). An alternative to maize starch and polymers for wet granulations is pregelatinized starch that is a starch that has been previously gelatinized and dried to powder form (Cunningham et al., 1999; Anastasiades et al., 2002). Lamivudine (2’,3’-dideoxy-3’-thiacytidine, commonly called 3TC) is a potent oral nucleoside analog reverse transcriptase inhibitor (nRTI) has demonstrated efficacy against the hepatitis B virus (HBV) in both HBeAg- positive and HBeAg-negative patients with chronic hepatitis B. Treatment with lamivudine is safe and well tolerated and induces a virological and biochemical response in most patients within a short time. In 1998, lamivudine became the first commercially available oral agent for the treatment of chronic hepatitis B. Lamivudine is a synthetic nucleoside analogue that undergoes intracellular phosphorylation to its active metabolite, lamivudine triphosphate. Unlike interferon, lamivudine has direct antiviral activity and is a powerful inhibitor of HBV reverse transcriptase (Doong et al., 1991). Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV. Long term use of lamivudine unfortunately leads to emergence of a resistant hepatitis B virus (YMDD) mutant. Despite this, lamivudine is still used widely as it is well tolerated. Wet granulation is a commonly used method used in the manufacture of tablets, which improves the tabletting process via the production of a product (granulate) that has Corresponding author: Tel: +88(0721) 750041/4110, Fax: (+880721) 750064, e-mail: bmokaddes3@yahoo.com