ZIPRASIDONE HYDROCHLORIDE LOADED NANOSTRUCTURED LIPID CARRIERS (NLCS) FOR INTRANASAL DELIVERY: OPTIMIZATION AND IN VIVO STUDIES Original Article PRAVEEN SIVADASU 1 , GOWDA D. V. 1* , SIDDARAMAIAH H. 2 , HEMALATHA S. 3 1 Department of Pharmaceutics, JSS College of Pharmacy, JSSAHER, Mysuru 570015, India, 2 Department of Polymer Science and Technology, Sri Jayachamarajendra College of Engineering, Mysuru 570006, India, 3 Received: 13 Sep 2019, Revised and Accepted: 01 Nov 2019 Department of Anaesthesiology, JSS Medical College, JSSAHER, Mysuru 570015, India Email: dvgowda@jssuni.edu.in ABSTRACT Objective: The present study was an attempt to systemically deliver the most desirable schizophrenia drug, ziprasidone hydrochloride (ZRS) via the intranasal route using nanostructured lipid carrier (NLC) approach. Methods: The desired ZRS loaded NLCs were developed using central composite statistical design and the developed formulation was monitored for improving ZRS bioavailability and their brain targeting efficacy. Results: Pharmacokinetic studies revealed a 10 fold increase (ZRS blood-brain ratio) for NLCs administered through nasal route (in comparison to intravenous route). Similarly, the concentration of ZRS (in the brain) delivered via nasal route exhibits 4 fold increment at all-time points. Conclusion: Therefore, the obtained results suggest a potential nose to brain transport of loaded ZRS by effective bypassing of the Blood-Brain Barrier (BBB). Keywords: Ziprasidone hydrochloride, Nanostructured lipid carriers, Blood/Brain barrier, Intranasal delivery © 2020 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open-access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) DOI: http://dx.doi.org/10.22159/ijap.2020v12i1.35683 Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Schizophrenia is considered a chronic health disorder pertaining to mental issues, which can be diagnosed by a range of symptoms like hallucinations, disorientation in both behavior and speech, cognitive impairment and delusive behavior. Further, due to its chronic nature and early-onset schizophrenia is considered as disabling disorder (due to negative and cognitive symptoms) both for patients and their people [1, 2]. Additionally, due to positive symptoms (hallucinations, delusional behavior and suspiciousness), there is a chance of relapse even after receiving treatment. Finally, due to its characteristic heterogeneousness, there is a lack of understanding regarding various aspects of this disorder [3]. Nevertheless, systemic drug delivery to treat schizophrenia is a potential challenge, owing to Blood-Brain Barrier (BBB) effects, which often obstruct the efficient transport of a rational drug (to the brain) [4]. Techniques employed to deliver drugs to the brain by by-passing blood- brain-barrier are categorized as invasive and non-invasive methods. Wherein, delivering drugs through invasive route was not always welcomed by the patient since it causes irreversible damage to barrier integrity which leads to severe adverse effects like changes in neuropathological functioning and enhanced contact to toxic molecules. Further, non-invasive delivery of drugs aids direct transport of drugs into the brain by evading surgical intrusions [5, 6]. In the modern era nose has been considered as a route of delivery for both local and systemic effects. In the last two decades, there are more advances in large scale production of drugs especially proteins and peptides [6]. Nasal cavity possesses a great expanse which affords potential alternative for brain delivery by avoiding first-pass metabolism and invasiveness and swift oncoming, simultaneously increasing the patient ease and compliance. Additionally, the nasal cavity acts as a barrier to transport moieties with high molecular weights like peptides. Further, this hurdle can be overcome by employing permeation enhancers in the formulations which in turn opens up the tight joints of the barrier for paracellular transport of the selected moieties. Nasal delivery also owns other advantages like trouble-free administration and self-medication is possible during critical conditions [7]. Since the beginning of the 20 th In the current study, a second-generation, atypical antipsychotic drug Ziprasidone hydrochloride (ZRS) is selected. Further, it has a half-life of 7 h and requires repeated dosage (i.e. 20-100 mg per day) with poor oral bioavailability. Additionally, the said drug also suffers from extensive first-pass metabolism, low absorption and very low drug concentration reach the brain, especially during oral administration [12]. Thus, herein, we intend to establish the ZRS delivery efficacy (to the brain) via NLC based nasal route, which may aid in enhancing permeation and bioavailability and thereby act as an effective approach towards systemic drug delivery. century, nanotechnology growing interested in pharmaceutical technology research groups worldwide. Further, excipients used in this nanoformulations are generally biocompatible and degradable, so that drugs can be delivered at the required site of action with the controlled release by reducing the toxicity [8]. The method of complete crystallization or recrystallization of fat present in the formulation reduces the solubility of the loaded drug, thereby leading to expulsion of the drug from the formulation especially in lipid nanoparticles. Additionally, most of the lipophilic drugs are highly soluble in a liquid lipid when compared with a solid lipid. Thus, NLC is an updated version for solid lipid nanoparticles (SLN), where both solid and liquid lipids were present in the oil phase are increasingly preferred over SLN, as it overcomes major disadvantages of SLN, such as low drug loading and drug expulsion related issues [9-11]. MATERIALS AND METHODS Materials Ziprasidone hydrochloride was obtained as a gift sample from Jubilant Generics Ltd (Mysuru, India). While, Gelucire 43/01 and 44/14, was gifted by Gattefosse (France). Further, Capmul MCM, Captex 200, Cremophor EL, Sterotex FL were also obtained as a gift sample from Abitec Group, (USA). However, Span 80, PEG 400 and Oleic acid were purchased from Merck (Mumbai, India). While, Tween 80, Tween 20 and polyvinyl alcohol (PVA) were purchased from Loba Chemie Pvt. Ltd., (Mumbai, India). International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 12, Issue 1, 2020