Brain Targeted Nasal Microspheres of Gabapentin

Intranasal administration is an attractive option for local and systemic delivery of many therapeutic agents. The nasal mucosa is – compared to other mucous membranes – easily accessible and provides a practical entrance portal for small and large molecules. Intranasal administration offers a rapid onset of therapeutic effects, no firstpass effect ,no gastrointestinal degradation or lung toxicity ,non-invasiveness , essentially painless application For brain targeted nasal drug delivery .And to improve its bioavailability. Intranasal administration offers a variety of attractive options for local and systemic delivery of diverse therapeutic agents.[1] The nature of the nasal mucosa provides a series of unique attributes, all of which may help to maximize the patient’s safety, convenience and compliance. Over the recent decades the interest in intranasal delivery as a non-invasive route for drugs is increased. Since the nasal mucosa offers numerous benefits as a target tissue for drug delivery, a wide variety of therapeutic compounds may be administered intranasaly for topic, systemic and central nervous system action. The unique relationship between nasal cavity and cranial cavity tissues makes intranasal delivery to the brain feasible .An intranasal delivery provides some drugs with short channels to bypass the blood-brain barrier (BBB), especially for those with fairly low brain concentrations after a routine delivery, thus greatly enhancing the therapeutic effect on brain diseases .The nasal mucosa is nearby the brain, cerebrospinal fluid (CSF) and the drug concentrations can exceed plasma concentrations. Intranasal delivery provides a non-invasive method of bypassing the BBB to rapidly deliver therapeutic agents to the brain, spinal cord, lymphatic’s and to the vessel walls of the cerebrovasculature for treating CNS disorders. Intranasal delivery also offers the advantage of simple administration, cost effectiveness and convenient.[2] This novel delivery method allows drugs, therapeutic proteins, polynucleotides and viral vectors that do not normally cross the BBB to be delivered to the CNS. Additionally, intranasal targeting of drugs to the CNS avoids first pass elimination by the liver allowing a lower therapeutic drug dose and fewer systemic side effects. Delivery from the nose to the CNS occurs within minutes along both the olfactory and trigeminal nerves. Delivery occurs by an extracellular route and does not require that the drugs bind to any receptor or undergo axonal transport[3]. Criteria of selecting drug for nasal delivery It must pass through mucus layer and epithelial membrane before reaching CNS,Molecular size, complexity and lipophilicity of drug,pH of the solution and Pka of the drug[4],Properties of formulation vehicles used The drug must pass Blood flow,Enzymatic degradation,Should be Stable,Should have sufficient Viscosity,Should be of required pH All types of microspheres that have been used as nasal drug delivery systems are water-insoluble but absorb water into the sphere’s matrix, resulting in swelling of the spheres and the formation of a gel. The building materials in the microspheres have been starch, dextran, albumin and hyaluronic acid, and the bioavailability of several peptides and proteins has been improved in different animal models. Also, some low-molecular weight drugs have been successfully delivered in microsphere preparations.[5] The residence time in the cavity is considerably increased for microspheres compared to solutions. However, this is not the only factor to increase the absorption of large hydrophilic drugs..Microspheres also exert a direct effect on the mucosa, resulting in the opening of tight junctions between the epithelial cell.