Introducing a passively targeted formulation of diclofenac potassium for application in endodontics to minimize renal and gastrointestinal side effects

Abstract

This research aims to formulate, evaluate, and conduct a clinical investigation of mucoadhesive buccal discs of diclofenac potassium (DP) for application in endodontics to minimize side effects, mainly renal and gastrointestinal. The discs were compressed directly utilizing bioadhesive polymers like hydroxypropyl methylcellulose K4M (HPMC K4M), sodium carboxymethyl cellulose (NaCMC), Carbopol 934 (Cp934), methylcellulose (MC) and combinations of these polymers. In-vitro, release studies and ex-vivo and in-vivo determination of bioadhesion time were conducted. The selected formula was sealed on one surface with ethyl cellulose to allow unidirectional drug release. It was evaluated for permeation through the chicken pouch membrane in the absence and presence of permeation enhancers. The formula of choice (F3) containing methyl cellulose was further assessed for the swelling index, bioadhesion strength, hardness, friability, surface pH, in-vivo bioadhesion performance, and storage effect under ambient and accelerated conditions. It showed drug release of 99 % ± 1 in 2 h, permeation flux (Jss) of 3.5 ± 1.6 mg cm-2 h-1, and bioadhesion time of 4 ± 0.5 h without bitterness, irritation, or fragmentation. The introduced 25 mg DP bioadhesive disc formulation F3 was then clinically compared with the marketed 50 mg oral Cataflam® tablets regarding the effect of single-dose pretreatment in endodontic procedures of subjects with symptomatic irreversible pulpitis (SIP) through a randomized clinical trial. No significant difference was detected in all evaluated clinical criteria. This proves clinical efficiency with the advantage of half-dose administration and targeted localized effect leading to minimized renal and gastrointestinal side effects.