Advantages of drug delivery via the nasal route Essay

In the past years, drug delivery via the nasal route has established itself as a competitor alternative over other routes of administration. It provides a higher degree of patient compliance and drugs can be painlessly self-administered by the patient (Illum, 2003). Drugs administered through nasal route are absorbed rapidly and can reach therapeutically effective plasma levels quickly due to highly permeable membranes and rich vasculature of the nasal cavity (Majithiya et al., 2006). In addition, the nasal route offers further advantages over the oral route, especially for those drugs that have poor oral bioavailability due to high hepatic first-pass metabolism, pH instability and enzyme degradation in GIT (Ugwoke et al., 2001).
Nowadays, the intranasal route has gained more interest to target drugs to the brain and cerebrospinal fluid by passing bloodbrain barrier. Intranasal formulation of drugs for the treatment of Parkinson's disease (Khan et al., 2010),Alzheimer's disease (Zhang et al., 2004) and psychosis(Kumar et al., 2008) have been elaborated and their therapeutic efficiency over conventional oral dosage form has been verified.
Rivastigmine tartrate (RV) is the drug of choice for the treatment of Alzheimer's disease that is characterized by progressive memory dysfunction due to significant insufficient levels of acetylcholine in the brain (Williams et al., 2003). RV is categorized in the class of reversible cholinesterase inhibitor which inhibits both acetylcholinesterase and butyrylcholinesterase selectively in the central nervous system, resulting in an increase in acetylcholine concentration in the brain (Mller, 2007, Thomas et al., 2012). RV is available in the market as an oral capsule, solution, and transdermal patches. It is shown to undergo extensive first-pass metabolism in the liver, resulting in a short elimination half-life of 90 min, imposing frequent administration, which may result in accumulation of the cholinergic side effects of the drug (Bastiat et al., 2010Wilson et al., 2008).
Nasal in situ gelation can be achieved by different techniques, one of them is using thermosensitive polymers which form a gel upon the administration by sensing nasal temperature. Pluronic F-127 is a polymer characterized by good thermosensitive gelling properties, low irritation and toxicity, high water solubility, good drug release characteristics and adequate compatibility with other polymers (Anderson et al., 2001 Jeong et al., 2002 Li and Guan, 2011, Escobar-Chavez et al., 2006).
However, intranasally administered drugs have low residence time at the site of the administration taking into consideration the anatomical and physiological environment of the nasal cavity. This is owed to nasal rapid mucociliary clearance (MC) which in turn limits the time necessary for drug absorption (Ugwoke et al., 2000, 2001). Consequently, in the design of intranasal formulations, one must improve nasal residence time. This may be achieved using polymers with higher viscosity, and preferably, with mucoadhesive properties that are particularly helpful in providing intimate contact between dosage form and nasal mucosa thus maximizing the likelihoods of drug absorption.
Therefore, the objective of this study is to formulate RV in situ gel to overcome its low bioavailability and low concentration in the brain tissue after oral administration.