The formulation and stability of dispersible or chewable tablets containing anti retroviral drugs

Abstract

Lamivudine (3TC), Nevirapine (NVP) and Zidovudine (AZT) is indicated as part of antiretroviral combination therapy for the treatment of Human Immunodeficiency Virus (HIV) infected adults and children who present clinical or immunological evidence of progression of the disease. Current dosage forms of these drugs in single or dual-therapy include tablets, coated tablets and oral solutions. Three problem areas are currently experienced with the above mentioned dosage forms. Firstly tablets and coated tablets, although they provide good stability and therefore shelf life, cannot be easily administered to children and geriatrics due to the fact that they cannot swallow tablets. Oral solutions on the other hand can be easily administered to children and geriatrics but provides poor stability and shelf life especially in harsh African conditions. Thirdly, according to UNICEF, extemporaneous preparation of pediatric suspensions from solid adult dosage forms can reduce the stability of the drugs as well as the bioavailability. The aim of this study was to formulate a novel dosage form that will provide a solution for the above-mentioned problems. Combinations of the three drugs were formulated in a dispersible or chewable tablet. Preformulation studies were carried out to determine the compatibility of the drugs and the excipients used in the formulae. Four batches of tablets were manufactured, each containing a different amount of the three drugs mentioned above, in accordance with WHO requirements. Accelerated stability tests were carried out at different temperatures and degrees of humidity to determine the stability of the drugs in the dosage form. Physical tests that were carried out on the tablets include assay, hardness, friability, loss on drying, disintegration time, dissolution and uniformity of mass, diameter and thickness. Initial studies revealed that 3TC were the least stable of the three drugs in watery solutions. 3TC was least stable in a solution at a high pH (NaOH in water), it was more stable at a lower pH (HCI in water) and most stable at neutral conditions (Water). NVP was also less stable at lower pH conditions in solution. The dosage form complied with requirements for rapid disintegration and palatability in solution. The dosage form can be classified as a dispersible as well as a chewable tablet.