Design and Assessment of Chlorpheniramine Maleate Sublingual Tablets Using Novel Ternary Phase Superdisintegrants

Abstract

Sublingual tablets are gaining popularity over conventional tablets due to their convenience in administration and suitability for elderly and children who have swallowing difficulties. The aim of this study was to formulate Chlorpheniramine Maleate (CPM) sublingual tablets to achieve rapid onset of action. CPM is a first generation antihistamines, undergoes first pass metabolism in liver. Sublingual dosage forms bypass the metabolism of CPM in liver and so improve the drug bioavailability. The novel ternary phase developed by co-processed superdisintegrants via solvent evaporation method using crospovidone, croscarmellose and sodium starch glycolate in different ratios (1:1:1, 3:1:1, 1:3:1and 1:1:3) were prepared. The pre-compression parameters (angle of repose, Hausner ratio and Carr’s index) of the prepared co-processed superdisintegrants were evaluated in comparison to physical mixture of superdisintegrants. The developed co-processed formulae were compared with those the corresponding physical mixtures and individual superdisintegrant sublingual tablets. The tablets were evaluated for its disintegration time, wetting time, in-vitro dispersion time as well as hardness, weight variation, friability, drug content and in-vitro dissolution study. Among all the designed formulations, the formulations CP1 and PM1 containing 4% w/w co-processed and physical mixture of superdisintegrant respectively (1:1:1 mixture of crospovidone, croscarmellose and sodium starch glycolate) were considered to be best formulations, which showed the shortest disintegration time (6.29 and 6.31 sec), in-vitro dispersion time (18.67 and 18.83 sec) and wetting time (12.47 and 12.58 sec) respectively. As well as these promising formulae showed highest drug release (100 and 97.52 %) within two min. Finally, the promising formulae were compared with CPM sublingual tablet prepared using commercially available co-processed mixture of excipients containing superdisintegrant (PharmaburstTM500). There were significance differences in disintegration time, in-vitro dispersion time, wetting time and in vitro drug release (p<0.001) using ANOVA-one way test.