Formulation and evaluation of Duloxetine loaded bio-nano suspension for brain specificity via acoustic meatus

Abstract

Research article the deeper parts of the auricle are supplied by the vagus nerve [X] (the auricular branch) and the facial nerve [VII] (which sends a branch to the auricular branch of the vagus nerve [X]). (4) These unique features serve as a drug delivery platform for effective delivery of API molecules. The economic cost of depression and its treatment are estimated at $6 billion in Canada, US$ 83 billion and £118 billion. Depression is a chronic, recurring and potentially life-threatening illness that affects up to 20% of the population across the globe. The etiology of the disease is suboptimal concentrations of the monoamine neurotransmitters serotonin (5-HT) and norepinephrine (NE) in CNS. It is also due to consequence of dysfunctional endocrine, immune and neurotransmitter systems. Duloxetine is an antidepressant that blocks the reuptake of both serotonin (5-HT) and norepinephrine (NE) by presynaptic transporters and also has low affinity for muscarinic cholinergic, histamine H1, 1 adrenergic as well as serotonin and dopamine receptors (5). Duloxetine exhibits seven to nine-fold greater potency at blocking ligand binding to the serotonin transporter (SERT) than the norepinephrine transporter (NET) and is about 3.5 times more potent at blocking [3H] 5-HT uptake than that of [3H] NE. (6). Duloxetine shows a very different distribution pattern. Very low concentrations in the cerebrospinal fluid is seen may be due to the fact that the drug crosses the blood– cerebrospinal fluid barrier much worse than other antidepressants do, suggesting a low ability of duloxetine to enter the brain. Alternatively, low drug concentrations may be interpreted in a sense of a missing residence time in cerebrospinal fluid due to active transport mechanisms out of this environment either back into the bloodstream or into the brain. (7) Aim of the research was to design a suitable formulation loaded with Duloxetine using a novel biopolymer from kernels of Prunus amygdalus as a bio-retardent and stabilizer for delivering nanosized Duloxetine molecule through trans acoustic epithelial route for improved therapeutic efficacy of API. Abstract The aim of the current research work was to formulate drug loaded nano-suspension using novel bioexcepient isolated from kernels of Prunus amygdalus and to explore the capability of external acoustic meatus as novel acoustic drug delivery system. The biomaterial was extracted by simplified economical process and was further purified by hot dialysis method. The isolated biomaterial was subjected to various physicochemical evaluations along with spectral analysis including UV, IR, Mass, NMR, SEM. The bio-nano suspension formulated with the novel bioexcepient was tested for its functional properties, like retardability, stability and mucoadhesitivity using shear stress method. Different formulations of duloxetine were prepared by using biomaterial as a retardant cum stabilizer and glycerin as nanosizent. The formulations were subjected to various evaluations, including pH, dispersibility, Entrapment efficiency, Particle size, mucoadhesion, skin irritancy, in-vitro release, for over 36 hours Stability. Experimental result reveal that the biopolymer posses promising retardibility cum stability and mucoadhesivity. According to the in-vitro and pharmacodynamic results obtained it can be concluded that significant amount of drug reaches to the brain via external acoustic meatus and so it is feasible to deliver Duloxetine by acoustic meatus.