Development of nanocarriers of mirtazapine for depression and pruritus

Abstract

Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) drug used to treat major depression. Although primarily mirtazapine is prescribed to treat depression, its antipruritic effect has also been reported in the literature upon oral administration. The oral therapy of mirtazapine in both conditions causes some common side effects and, the oral bioavailability of the drug is only 50% mainly due to gut wall and hepatic first-pass metabolism. Thus, the present research work was an attempt to overcome these systemic side effects associated with oral therapy and to avoid first pass metabolism by delivering the drug through skin in both conditions. Thus, the present research work was aimed at developing transdermal formulation based on microemulsions which would deliver mirtazapine in the systemic circulation to treat depression and; also to develop topical formulations based on SLNs and NLCs which would deliver mirtazapine in therapeutically effective concentration for the management of pruritus. For the treatment of depression, microemulsions based gel formulation was successfully developed and found appreciable in skin penetration as demonstrated by ex vivo and CLSM studies. The pharmacodynamics studies performed in mice further confirmed the clinical efficacy of the microemulsions based gel in treating depression. For the purpose of targeting pruritus, SLNs and NLCs based gels were successfully developed and found appreciable in skin penetration. The ex vivo and dermatokinetic study indicate that these nanocarriers based developed gels were able to localize drug in the vicinity of the target receptors in pruritic conditions. These findings are further supported by pharmacodynamic studies which showed significant therapeutic efficacy of SLNs based gel and NLCs based gel in managing pruritus. newline