Dissolution Enhancement of BCS Class II Druges using Hybrid Technique of Solid Dispersion and adsorption Employing the concept of Quality by Design

Abstract

BCS Class II drug may behave as a BCS Class I drug if correct formulation strategy is newlineadopted. Solid dispersions have tremendous potential in increasing the dissolution rate but are newlinenot popular commercially because of problems like poor stability, poor compressibility and newlinedifficulty in process scale up. These can be overcome by converting the solid dispersion into a newlinefree flowing powder form by adsorbing it onto a porous adsorbent. So, with this hypothesis newlinethe aim of the present research work was to enhance the dissolution rate of selected BCS newlineClass-II drugs by employing the hybrid technology of melt adsorption and solid dispersion. newlineThree drugs were selected for the dissolution enhancement i.e. ritonavir, lamotrigine and newlinefebuxostat. Candesartan cilexetil was used as check-point API to validate the hypothesis. newlineSurfactant based carriers were used like Lutrol F127, Transcutol and Labrsol. Neusilin is used newlineas adsorbent due to its high porous structure, good adsorbing capacity, large surface area and newlineimproving stability. The target was set to achieve at least 85% drug release in 60 min of the newlineselected drugs as per the FDA guidelines except for Ritonavir where the dissolution criteria newlinewas set for gt70% drug release in 10 min. Following the development process according to the newlineQbD guidelines different design have been applied for each selected drug for the optimization newlineof the formula. The optimized formulations were then subjected to physical characterization newlinelike flow properties, FTIR, DSC and XRD analysis. Convolution modeling was done of the newlinethree drugs to predict in vivo plasma concentration profile. Stability studies were also carried newlineout for three months under accelerated conditions and all the developed formulations were newlinefound to be stable. newlineThe optimized SDA of ritonavir, lamotrigine and febuxostat showed around 2.5, 3.4 and 3.3 newlinefold increase in the dissolution rate respectively as compared to untreated API. This can be newlineattributed to hydrogen bonding between the drug and carrier and the drug and adsorbent