FORMULATION AND EVALUATION OF MOUTH DISSOLVING FILM OF TADALAFIL

This research work was aimed to enhance the oral bioavailability and provide faster onset of action of Tadalafil (used for the treatment of the erectile dysfunction (ED) and pulmonary arterial hypertension) by formulating its mouth dissolving film (MDF). Tadalafil belongs to BCS class II and the oral bioavailability of it’s about 28%. The MDF of Tadalafil was prepared by solvent casting method using HPMC-E5 (film forming agent), Methyl cellulose (thickening agent), Propylene glycol (plasticizer), Tween-80 (solubilizing agent), Microcrystalline cellulose (disintegrating agent), Citric acid (saliva stimulating agent), Sucrose (sweetening agent), Vanillin (flavoring agent), EDTA disodium (preservative). The formulation was optimized by two factors, three level (23) full factorial design using concentration of Plasticizer (X1) and concentration of film forming agent (X2) as independent variables and formulation was evaluated for uniformity of mass, thickness, folding endurance, drug content uniformity, in-vitro disintegration, in-vitro drug dissolution study and stability study. Based on results it was concluded that MDF (F5) showed enhanced bioavailability and faster onset of action as compared to available tablet dosage form

Repurposing Thioridazine (TDZ) as an anti-inflammatory agent

Nuclear factor-kB (NF-kB) is a crucial transcription factor in the signal transduction cascade of the inflammatory signaling. Activation of NF-κB depends on the phosphorylation of IκBα by IκB kinase (IKKβ) followed by subsequent ubiquitination and degradation. This leads to the nuclear translocation of the p50- p65 subunits of NF-κB, and further triggers pro-inflammatory cytokine gene expression. Thus, in the need of a more effective therapy for the treatment of inflammatory diseases, specific inhibition of IKKβ represents a rational alternative strategy to the current therapies. A computer-aided drug identification protocol was followed to identify novel IKKβ inhibitors from a database of over 1500 Food and Drug Administration (FDA) drugs. The best scoring compounds were compared with the already known high-potency IKKβ inhibitors for their ability to bind and inhibit IKKβ by evaluating their docking energy. Finally, Thioridazinehydrochloride (TDZ), a potent antipsychotic drug against Schizophrenia was selected and its efficiency in inhibiting IκBα protein degradation and NF-κB activation was experimentally validated. Our study has demonstrated that TDZ blocks IκBα protein degradation and subsequent NF-κB activation to inhibit inflammation. Thus, it is a potential repurposed drug against inflammation