Please cite this article in press as: N. Jawahar, et al., Int. J. Biol. Macromol. (2018), https://doi.org/10.1016/j.ijbiomac.2018.01.121 ARTICLE IN PRESS G Model BIOMAC-8953; No. of Pages 7 International Journal of Biological Macromolecules xxx (2018) xxx–xxx Contents lists available at ScienceDirect International Journal of Biological Macromolecules j ourna l h o mepa ge: www.elsevier.com/locate/ijbiomac Enhanced oral bioavailability of an antipsychotic drug through nanostructured lipid carriers Natarajan Jawahar a,∗ , Prashant Kumar Hingarh a , Radhakrishnan Arun a , Jubie Selvaraj d , Arigo Anbarasan a , Sathianarayanan S b , Nagaraju G c a Department of Pharmaceutics, JSS College of Pharmacy, Ootacamund, JSS Academy of Higher Education & Research, Mysuru, India b Department of Pharmaceutical Analysis, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, India c Department of Chemistry, Siddaganga Institute of Technology, Tumkur, India d Department of Pharmaceutical chemistry, JSS College of Pharmacy, Ootacamund, JSS Academy of Higher Education & Research, Mysuru a r t i c l e i n f o Article history: Received 22 October 2017 Received in revised form 4 January 2018 Accepted 17 January 2018 Available online xxx Keywords: Olanzapine Poor bioavailability Nanostructured lipid carrier Solvent diffusion method Lymphatic transport schizophrenia a b s t r a c t Olanzapine is an atypical antipsychotic, undergoes extensive first pass metabolism, also has poor aqueous solubility and belongs to BCS (Biopharmaceutical Classification System) Class II drug) exhibit low oral bioavailability. To overcome this and to enhance the bioavailability, intestinal lymphatic transport of drugs can be exploited through Nano structured lipid carriers (NLCs). The NLCs were formulated by solvent diffusion method using solid lipid (glyceryl tripalmitate), liquid lipid (castor oil) and surfactants (Pluronic F-68, Soylecithin). The formulated NLCs were characterized for physico-chemical properties, in- vitro release studies and in-vivo oral bioavailability. F6 has shown average particle size of 158.5 nm with PI of 0.115 indicating narrow particle size distribution and follows uni modal distribution. It was found that the batch with stearyl amine has a zeta potential of 28.39 mV which confers stability to the dispersion. Bioavailability studies indicate that there was more than 5½-fold increase in oral bioavailability in case of NLCs (F6) compared to olanzapine suspension which indicates that NLCs provided sustained release of the drugs, and these systems can be the preferred as drug carriers for lipophilic drugs in long term disease conditions such as schizophrenia for enhanced bioavailability. © 2018 Elsevier B.V. All rights reserved. 1. Introduction Oral route is the most accepted and preferable way of drug administration, due to low cost and easy administration which in turn high patient compliance. Now a day, lipophilic drugs show low oral bioavailability due to various reasons like poor aqueous solubility, high first pass metabolism [1]. Lipids have been used for a long time as a carrier for lipophilic drugs to improve their oral bioavailability. Lipid emulsions are biphasic systems composed of oil phase dispersed as fine droplets in the aqueous phase and stabilized by phospholipids resulting in oil in water (O/W) emulsions [2]. The first safe intravenous lipid emulsion introduced as Intralipid ® in the 1960 ′ s consisted of an O/W emulsion of 10 or 20% soybean oil droplets (70–400 nm in size) stabilized by a monolayer of 1.2% egg yolk mixed phospholipids and 2.25% glycerol [3]. Lipid emulsion systems are more potential as drug carriers for highly lipophilic ∗ Corresponding author. E-mail address: jawahar.n@jssuni.edu.in (N. Jawahar). molecules solubilized in the core oil. Drug delivery and targeting research using lipid emulsions as carriers of poorly water soluble drugs have been explored [4]. However, due to the liquid state of the oil droplets, a prolonged drug release cannot be achieved. The use of solid lipid, which remains in solid state at room temperature and body temperature, instead of liquid oils is very attractive to achieve controlled drug release, leading to the formation of solid lipid nanoparticles (SLN) at the beginning of the1990 ′ s. The SLN combined the advantages of solid particles, emulsions and liposomes. The advantages of liposomes and emulsions are that they are composed of well tolerated excipients and they can eas- ily be produced on a large scale, the pre- requisite for a carrier to be introduced to the market. SLN had different advantages, Mader and Mehnert showed various limitations of SLN such as poor drug loading, high water content, drug expulsion during storage due to the formation of more stable lipid structure [5]. To overcome the above problems, a third generation of lipid matrix was designed as Nanostructured Lipid Carrier – NLC [6]. Olanzapine is an atypical antipsychotic that belongs to thioenobenzodiazepine class used orally in treatment of Schizophrenia undergoes extensive first pass metabolism with https://doi.org/10.1016/j.ijbiomac.2018.01.121 0141-8130/© 2018 Elsevier B.V. All rights reserved.