Original Article SOLUBILITY ENHANCEMENT OF LURASIDONE HYDROCHLORIDE BY PREPARING SMEDDS FORAM JANGIPURIA*, VAISHALI LONDHE Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, NMIMS, Vile Parle-W, Mumbai 400056, Maharashtra, India Email: fmforam@gmail.com Received: 29 Sep 2015 Revised and Accepted: 03 Oct 2015 ABSTRACT Objective: The objective of the study was to enhance solubility of Lurasidone HCl, an atypical antipsychotic drug, by formulating self-micro emulsifying drug delivery system (SMEDDS) and its characterization. Methods: Solubility study of Lurasidone hydrochloride (LH) was carried out in various surfactants, co surfactants and oils. Pseudo ternary phase diagrams were constructed to identify the self-micro emulsification region. Screening was done so as to determine the proper combination of components. Based on this, LH SMEDDS were prepared using Cremophor RH40 (surfactant), Soluphor P (co-surfactant) and Capmul MCM (oil). The preconcentrate SMEDDS were evaluated for clarity(visual), precipitation, % transmittance, robustness to dilution, freeze thawing, particle size distribution and zeta potential and adsorbed SMEDDS were evaluated for drug content, flow properties, in-vitro dissolution and ex-vivo diffusion studies. Results: The optimized LH SMEDDS composed of 14% Cremophor RH40, 68% Soluphor P, 18% Capmul MCM with a particle size of 3.95 µm and zeta potential of more than 50 mV showing 80% dissolution in 60 min. Conclusion: The results of this study prove that SMEDDS help in improving the solubility, dissolution and bioavailability of lurasidone hydrochloride. Keywords: Lurasidone Hydrochloride, Solubility enhancement, SMEDDS, In-vitro dissolution, Ex-vivo diffusion. INTRODUCTION Lurasidone Hydrochloride (Brand name: Latuda) was approved in 2010 by USFDA as the tenth atypical antipsychotic for the treatment of schizophrenia. It belongs to a class of drugs known as benzoisothiazol or azapirone derivatives, and is most similar to ziprasidone (Geodon) among the available atypical antipsychotics. It is a second generation antipsychotic, which may be better tolerated than the older antipsychotics. Atypical antipsychotics quickly replaced the older antipsychotics, such as chlorpromazine and haloperidol, as first-line treatment for schizophrenia and other psychotic disorders, because of their lower risks of extra pyramidal symptoms as well as better effectiveness in treating negative symptoms in schizophrenia [1]. LH has a poor bioavailability (<12% in all species tested) [2]. This is because of its poor solubility. It is found to be soluble in methanol and insoluble in acetone, ethanol and water. Till date solubility enhancement of LH has been tried by forming solid dispersions [3]. As compared to other enhancement techniques, SMEDDS help in increasing the absorption of lipophilic drugs taken orally. They spread readily in the GI tract, and the digestive motility of the stomach and the intestine provides the agitation necessary for self- emulsification. Also they can be encapsulated in hard or soft gelatin capsules or can be converted to solid state (Solid SEDDS/SMEDDS). Moreover they help in improving the efficacy of the drug allowing dose reduction and side effect minimization [4]. The potential of microemulsions or self-microemulsifying drug delivery systems (SMEDDS) in the improvement of the bioavailability and therapeutic performance of the hydrophobic agents has been very well- established for drugs like tacrolimus, glibenclamide, fenofibrate & furosemide [5-9]. The rationale of this project was to develop SMEDDS of Lurasidone HCl which will help in enhancing its solubility and thereby increase its bioavailability. Hence the present study was aimed to develop and evaluate an optimal SMEDDS formulation containing LH. MATERIALS AND METHODS LH was obtained as a gift sample from Glenmark Generics Limited (Gujarat, India). Capmul MCM, Captex 355 and Captex 200P were obtained as gift samples from Abitec (USA). Maisine, Peceol, Labrasol and Transcutol HP were obtained as gift samples from Gattefosse India Pvt. Ltd. (Mumbai, India). Kolliphor RH40(Cremophor RH40), Kolliphor EL(Cremophor EL) and Kollisolv P(Soluphor P) were obtained as gift samples from BASF South East Asia Pvt Ltd (India). Span 20, Span 80, Tween 20, Tween 80 and Propylene Glycol (all AR grade) were obtained from SDFCL (Mumbai, India). Microcrystalline cellulose (MCC) was obtained from Research Lab-Fine Chemical Industries Pvt Ltd (Mumbai, India). Aeroperl 300 Pharma was purchased from Evonik (India). All other chemicals and reagents used were of AR grade. Characterization of liquid SMEDDS Solubility studies The saturation solubility of LH was evaluated in various oils, surfactants, and cosurfactants as given in fig. 1. In this study, an excess amount of LHwas added to 2 ml of each of the vehicle in eppendorf tubes and the mixture was mixed on a cyclomixer till it remained undissolved. Then they were put in an orbital shaker for 24 h under ambient temperature to attain equilibrium. Aliquots of supernatant were diluted with methanol and analyzed for dissolved drug by the UV spectrophotometry (Lambda 25 UV/Visible spectrometer with UV Win lab software, Perkin Elmer, MA, USA) at λmax 315 nm. Water uptake studies Using different combinations of surfactant: cosurfactant: oil, the amount of water uptake in each mixture was determined. The mixtures showing maximum water uptake were chosen and carried forward for drug loading. Drug loading Since LH has a poor solubility hence the mixtures showing maximum water uptake were loaded with 20 mg (dose) drug. From these batches, the mixture containing Cremophor RH40, Soluphor P and Capmul MCM was found to solubilize 20 mg drug. Hence this was selected and ternary phase diagrams were constructed for further optimization. International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 7, Issue 11, 2015 Innovare Academic Sciences