1. ABSTRACT
©Kishor Vasantrao Kande, Institute of Chemical Technology (ICT), Mumbai.
Abstract
A major critical and challenging task in the development of orally disintegrating tablets (ODTs)
is to achieve equilibrium between disintegration time (DT) and hardness. Various approaches to
achieve these characteristics have been evaluated till date which includes lyophilisation,
orosolv,etc. In this research work we have applied the principle of microwave technology to
achieve increased tablet porosity along with acceptable hardness. The principle of microwave
technology is based on vibration of polar molecules leading to heat generation. This approach is
explored by evaporating polar solvent from tablets after relative humidity exposure leading to the
porous tablet formation. For this work we choose lamotrigine (BCS II) as a model drug and
complexed it with beta-cyclodextrin to enhance its solubility. The complexation ratio (1:1) was
decided by phase solubility and molecular modeling studies. Complexation also had the added
advantage of being able to mask the bitter taste of the drug along with the addition of suitable
flavour. The in vitro taste masking was studied using an Electronic tongue device. The ODTs
were prepared by conventional method and subsequently exposed to relative humidity followed
by microwave irradiation. This led to formation of pores in the tablets which resulted in its rapid
disintegration. Sodium starch glycolate, Ac-Di-Sol and crosspovidone were evaluated to be used
as a superdisintegrant. Crosspovidone was found to provide the required disintegration and
hardness. In addition DC lactose, pregelatinized starch and mannitol (Perlitol-200) were screened
as diluents out of which mannitol could offer desirable hardness to tablet. The placebo
formulations were prepared to screen the above exciepients. 23 factorial analysis was then
applied to the drug tablet batches to optimize the critical quality attributes (CQA) (Disintegration
time and hardness), critical material attribute (CMA) (Concentration of Crosspovidone) critical
process parameters (CPP) (relative humidty exposure time and microwave heating time) for final
formulation. The results indicate that concentration of superdisintegrant (5.40%), relative
humidity exposure of 34.85 min. (35 min) and microwave exposure time of 3.5 min resulted in
decreased DT of 23 sec and hardness of 5.05kg/cm.
Final formulation was kept for accelerated stability study according to ICH guidlines at
conditions of 400C ± 20C/ 75 ± 5 % RH and 300C ± 20C/ 65 ± 5 %, and evaluated for DT,
hardness and release profile. The results show that formulation was stable.