Transdermal delivery of an antipsychotic drug using Nano-carriers

Abstract

Schizophrenia is a complicated life disabling psychotic disease. Pathophysiology of schizophrenia has been related to structural brain changes and neurotransmittence disturbances. Symptoms of schizophrenia are manifested as three main groups; positive, negative and cognitive symptoms. Effective treatment of schizophrenia is a challenging goal itself; it requires implementation of pharmacological, psychological and environmental tools. Many obstacles are encountered by medical team making successful treatment is much more difficult such as medication non adherence, remission achievement and resistance of certain symptoms. Pharmacological treatment of schizophrenia primarily depends on antipsychotics; first and second generations. Second generation antipsychotics outweighs first one on level of clinical outcomes achieved. Asenapine maleate (ASPM) is a new second generation antipsychotic drug. It received FDA approval on 13 August, 2009 for sublingual administration. Asenapine is indicated for the acute treatment of schizophrenia in adults. The start and target doses were 5 mg twice daily and 10 mg twice daily for manic episodes. The pharmacological effect of asenapine is due to antagonistic activity on dopamine, serotonin receptors, adrenergic (α1 and α2) and histamine (H1) receptors along with moderate antagonistic affinity for the H2 receptor. The oral bioavailability of asenapine is extremely low (~2%) since it is extensively metabolized by liver to give inactive metabolites. Therefore, asenapine is available in the market as sublingual tablets with bioavailability about 35%. Unfortunately, the sublingual bioavailability of asenapine is also greatly affected by food and water intake prior and post administration leading to up to 20% decrease in bioavailability. On the level of physicochemical properties of the drug, asenapine is a small poorly soluble lipophilic molecule as manifested by its molecular weight, Log P and pKa values; 401g/mol, 4.72 and 7.29 respectively. One of the critical problems associated with poorly soluble drugs is their low oral bioavailability and erratic absorption.