Pharmacokinetic and pharmacodynamic evaluation of Solid self-nanoemulsifying delivery system (SSNEDDS) loaded with curcumin and duloxetine in attenuation of neuropathic pain in rats.

The present investigation is focused on improving oral bioavailability of poorly soluble and lipophilic drugs, curcumin (CRM) and duloxetine (DXH), through the solid self-nanoemulsifying drug delivery system (S-SNEDDS) and identifying their potential against attenuation of NP in chronic constriction injury (CCI)-induced rats through the solid self-nanoemulsifying drug delivery system (S-SNEDDS). The optimized batch of S-SNEDDS reported was containing CRM and DXH (30 mg each), castor oil (20% w/w), tween-80 (40% w/w), transcutol-P (40% w/w), and syloid 244 FP (1 g). The high dose of each of naïve CRM (NCH), naïve DXH (NDH), physical mixture of DXH and CRM (C-NCM-DXH), S-SNEDDS-CRM (SCH), S-SNEDDS-DXH (SDH), and S-SNEDDS-CRM-DXH (C-SCH-SDH) was subjected for MTT assay. The developed formulations were subjected to pharmacokinetic studies and results showed about 8 to 11.06 and 2-fold improvement in oral bioavailability of CRM and DXH through S-SNEDDS. Furthermore, CCI-induced male Wistar rats were treated with SSNEDDS containing CRM and DXH, S-SNEDDS containing individual drug, individual naïve forms, and their combination from the day of surgery for 14 days and evaluated for behavioral at pre-determined time intervals. On the terminal day, animals were sacrificed to assess tissue myeloperoxidase, superoxide anion, protein, tumor necrosis factor-α, total calcium levels, and histopathological changes. Pronounced effect was observed in rats treated with S-SNEDDS containing both drugs with respect to rats receiving any of other treatments owing to enhanced oral bioavailability through S-SNEDDS. Therefore, it can be concluded that S-SNEDDS of both drugs and their coadministration can accelerate the prevention of NP.

A three-pronged formulation approach to improve oral bioavailability and therapeutic efficacy of two lipophilic drugs with gastric lability.

The aim of present study was to co-administer curcumin (CRM) liquisolid pellets and coated duloxetine hydrochloride (DXH) pellets in rats to treat neuropathic pain (NP) associated with chronic constriction injury (CCI). To formulate liquisolid pellets of CRM, it was first dissolved in Tween-80 and then adsorbed on the porous surface of MCC PH102 and Syloid XDP that were used as carrier and coating materials, respectively. Central composite design was used to optimize the liquisolid formulation. The results of powder X-ray diffraction studies, differential scanning calorimetry, and scanning electron microscopy showed complete solubility of drug in Tween-80 followed by its complete adsorption on the porous surface of Syloid XDP and MCC PH102. Both DXH and liquisolid CRM powders were converted into pellets using extrusion-spheronization. DXH pellets were further coated with Eudragit S100 to bypass the gastric pH. About 32.31-fold increase in dissolution rate of CRM present in liquisolid formulation was observed as compared to its unprocessed form. Similarly, the dissolution profile in 0.1 N HCl for Eudragit S100-coated DXH showed complete protection of drug for 2 h and complete release after its introduction in buffer medium (0.2 M phosphate buffer pH 6.8). he pharmacokinetic studies carried out on rats revealed 7.3-fold increase in bioavailability of CRM present in liquisolid pellets and 4.1-fold increase in bioavailability of DXH present in coated pellets was observed as compared to their unprocessed pellets. This increase in bioavailability of drugs caused significant amelioration of CCI-induced pain in rats as compared to their unprocessed forms. The histological sections showed better improvement in regeneration of nerve fibers in rats.