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

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Abstract

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.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India

    Jivan Jyoti, Sachin Kumar Singh, Bimlesh Kumar, Monica Gulati, Rajesh Kumar, Ankit Kumar Yadav, Bhupinder Kapoor, Narendra Kumar Pandey, Sananda Som, Souvik Mohanta, Indu Melkani & Rubiya Khursheed

  2. Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (Deemed to be University), Ootacamund, Tamilnadu, India

    Nandha Kumar Anandhakrishnan & K. Gowthamarajan

  3. Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, India

    Rakesh Narang

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  1. Jivan Jyoti
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  2. Nandha Kumar Anandhakrishnan
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  3. Sachin Kumar Singh
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  4. Bimlesh Kumar
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  11. Sananda Som
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  15. Rakesh Narang
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Correspondence to Sachin Kumar Singh.

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Jyoti, J., Anandhakrishnan, N.K., Singh, S.K. et al. A three-pronged formulation approach to improve oral bioavailability and therapeutic efficacy of two lipophilic drugs with gastric lability. Drug Deliv. and Transl. Res. 9, 848–865 (2019). https://doi.org/10.1007/s13346-019-00635-0

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  • DOI: https://doi.org/10.1007/s13346-019-00635-0

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