A Solid Ultra Fine Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) of Deferasirox for Improved Solubility: Optimization, Characterization, and In Vitro Cytotoxicity Studies

The research work was designed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of deferasirox (DFX). According to the solubility studies of DFX in different components, Peceol, Kolliphor EL, and Transcutol were selected as excipients. Pseudo-ternary phase diagrams were constructed, and then SNEDDS formation assessment studies and solubility of DFX in selected SNEDDSs formulations were performed. DFX loaded SNEDDS were prepared and characterized. The optimum DFX-SNEDDS formulations were developed. The relative safety of the optimized SNEDDS formulation was examined in a human immortalized myelogenous leukemia cell line, K562 cells, using the MTT cell viability test. Cytotoxicity studies revealed more cell viability (71.44%) of DFX loaded SNEDDS compared to pure DFX (3.99%) at 40 μM. The selected DFX-SNEDDS formulation was converted into S-SNEDDS by adsorbing into porous carriers, in order to study its dissolution behavior. The in vitro drug release studies indicated that DFX release (Q5%) from S-SNEDDS solidified with Neusilin UFL2 was significantly higher (93.6 ± 0.7% within 5 min) compared with the marketed product (81.65 ± 2.10%). The overall results indicated that the S-SNEDDS formulation of DFX could have the potential to enhance the solubility of DFX, which would in turn have the potential to improve its oral bioavailability as a safe novel delivery system.

[1]  T. G. Singh,et al.  Impact of solidification on micromeritic properties and dissolution rate of self-nanoemulsifying delivery system loaded with docosahexaenoic acid , 2020, Drug development and industrial pharmacy.

[2]  Ameeduzzafar,et al.  Development of novel dapagliflozin loaded solid self-nanoemulsifying oral delivery system: Physiochemical characterization and in vivo antidiabetic activity , 2019 .

[3]  N. Khurana,et al.  Self-nanoemulsifying drug delivery system of fisetin: Formulation, optimization, characterization and cytotoxicity assessment , 2019 .

[4]  S. Sahin,et al.  Effect of particle size and surfactant on the solubility, permeability and dissolution characteristics of deferasirox , 2019, Journal of Research in Pharmacy.

[5]  A. Mishra,et al.  Development and evaluation of doxorubicin self nanoemulsifying drug delivery system with Nigella Sativa oil against human hepatocellular carcinoma , 2019, Artificial cells, nanomedicine, and biotechnology.

[6]  I. Antal,et al.  Optimization of Quality Attributes and Atomic Force Microscopy Imaging of Reconstituted Nanodroplets in Baicalin Loaded Self-Nanoemulsifying Formulations , 2018, Pharmaceutics.

[7]  A. Nugroho,et al.  Novel Self-Nano Emulsifying Drug Delivery System (SNEDDS) of andrographolide isolated from Andrographis paniculata Nees: Characterization, in-vitro and in-vivo assessment , 2018, Journal of Drug Delivery Science and Technology.

[8]  E. A. Mohamed,et al.  Self-nanoemulsifying drug-delivery systems for potentiated anti-inflammatory activity of diacerein , 2018, International journal of nanomedicine.

[9]  M. Mujahid,et al.  Development of self-nanoemulsifying tablet (SNET) for bioavailability enhancement of sertraline , 2018, Brazilian Journal of Pharmaceutical Sciences.

[10]  Han‐Gon Choi,et al.  Comparison of a revaprazan-loaded solid dispersion, solid SNEDDS and inclusion compound: Physicochemical characterisation and pharmacokinetics. , 2018, Colloids and surfaces. B, Biointerfaces.

[11]  F. Vrečer,et al.  Overview of solidification techniques for self-emulsifying drug delivery systems from industrial perspective. , 2017, International journal of pharmaceutics.

[12]  N. Nasongkla,et al.  Imidazole-modified deferasirox encapsulated polymeric micelles as pH-responsive iron-chelating nanocarrier for cancer chemotherapy , 2017 .

[13]  P. Sengupta,et al.  Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view , 2016, Drug delivery.

[14]  A. Nasr,et al.  Novel Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) for Oral Delivery of Olmesartan Medoxomil: Design, Formulation, Pharmacokinetic and Bioavailability Evaluation , 2016, Pharmaceutics.

[15]  T. Essam,et al.  Self-nanoemulsifying drug delivery system (SNEDDS) with enhanced solubilization of nystatin for treatment of oral candidiasis: Design, optimization, in vitro and in vivo evaluation , 2016 .

[16]  M. Al-Ghazawi,et al.  Development of a biphasic dissolution test for Deferasirox dispersible tablets and its application in establishing an in vitro-in vivo correlation. , 2016, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[17]  Payghan Santosh,et al.  Potential Investigation of Peceol for formulation of Ezetimibe self nano emulsifyingDrug Delivery Systems , 2016 .

[18]  K. Winnicka,et al.  Development and Evaluation of Liquid and Solid Self-Emulsifying Drug Delivery Systems for Atorvastatin , 2015, Molecules.

[19]  J. Patel,et al.  Self nano-emulsifying drug delivery system for Embelin: Design, characterization and in-vitro studies , 2015 .

[20]  Jun-Bom Park,et al.  Effects of absorbent materials on a self-emulsifying drug delivery system for a poorly water soluble drug , 2015, Journal of Pharmaceutical Investigation.

[21]  Raju Jukanti,et al.  Solid self-nanoemulsifying drug delivery system (S-SNEDDS) of darunavir for improved dissolution and oral bioavailability: In vitro and in vivo evaluation. , 2015, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[22]  J. Ali,et al.  Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design, characterization, in vitro and in vivo evaluation , 2015, Drug delivery.

[23]  Krishna Sanka,et al.  Solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of glimepiride: development and antidiabetic activity in albino rabbits , 2015, Drug delivery.

[24]  N. Babu,et al.  FORMULATION OF DEFERASIROX INTO DISPERSIBLE TABLET FOR THE TREATMENT OF CHRONIC IRON OVERLOAD , 2015 .

[25]  Parul Jaiswal,et al.  Development of self-microemulsifying drug delivery system and solid-self-microemulsifying drug delivery system of telmisartan , 2014, International journal of pharmaceutical investigation.

[26]  F. Shakeel,et al.  Thermodynamic modeling for solubility prediction of indomethacin in self-nanoemulsifying drug delivery system (SNEDDS) and its individual components , 2014, Drug development and industrial pharmacy.

[27]  C. Tanaka Clinical Pharmacology of Deferasirox , 2014, Clinical Pharmacokinetics.

[28]  S. Arora,et al.  Lipid-Based Drug Delivery Systems , 2014, Journal of pharmaceutics.

[29]  F. Shakeel,et al.  Thermodynamics and solubility prediction of talinolol in self-nanoemulsifying drug delivery system (SNEDDS) and its oil phase components using mathematical modeling , 2014 .

[30]  C. V. Raghavan,et al.  Self nanoemulsifying drug delivery system (SNEDDS) of rosuvastatin calcium: design, formulation, bioavailability and pharmacokinetic evaluation. , 2013, Colloids and surfaces. B, Biointerfaces.

[31]  M. Dixit,et al.  Preparation and Evaluation of Self-nanoemulsifying Formulation of Efavirenz , 2013 .

[32]  S. Beg,et al.  Development, Optimization, and Characterization of Solid Self-Nanoemulsifying Drug Delivery Systems of Valsartan Using Porous Carriers , 2012, AAPS PharmSciTech.

[33]  Rakesh K. Sharma,et al.  Potentials and challenges in self-nanoemulsifying drug delivery systems , 2012, Expert opinion on drug delivery.

[34]  D. Vir,et al.  Identification, characterization and quantification of a new impurity in deferasirox active pharmaceutical ingredient by LC-ESI-QT/MS/MS. , 2012, Journal of pharmaceutical and biomedical analysis.

[35]  Raju Jukanti,et al.  Paliperidone-Loaded Self-Emulsifying Drug Delivery Systems (SEDDS) for Improved Oral Delivery , 2012 .

[36]  K. V. R. Murthy,et al.  Development and characterization of self-nanoemulsifying drug delivery systems (SNEDDS) of atorvastatin calcium. , 2012, Current drug delivery.

[37]  Sandip S Chavhan,et al.  Self-nanoemulsifying drug delivery system for adefovir dipivoxil: Design, characterization, in vitro and ex vivo evaluation , 2011 .

[38]  K. Kohli,et al.  Study of cosurfactant effect on nanoemulsifying area and development of lercanidipine loaded (SNEDDS) self nanoemulsifying drug delivery system. , 2011, Colloids and surfaces. B, Biointerfaces.

[39]  Han‐Gon Choi,et al.  Enhanced oral bioavailability of curcumin via a solid lipid-based self-emulsifying drug delivery system using a spray-drying technique. , 2011, Biological & pharmaceutical bulletin.

[40]  B. K. Reddy,et al.  Biopharmaceutics Classification System: A Regulatory Approach , 2011 .

[41]  A. Date,et al.  Self-nanoemulsifying drug delivery systems: formulation insights, applications and advances. , 2010, Nanomedicine.

[42]  G. Bruin,et al.  Pharmacokinetics, Metabolism, and Disposition of Deferasirox in β-Thalassemic Patients with Transfusion-Dependent Iron Overload Who Are at Pharmacokinetic Steady State , 2010, Drug Metabolism and Disposition.

[43]  Gang Cheng,et al.  Development of solid self-emulsifying drug delivery systems: preparation techniques and dosage forms. , 2008, Drug discovery today.

[44]  Christopher J H Porter,et al.  Formulation of lipid-based delivery systems for oral administration: materials, methods and strategies. , 2008, Advanced drug delivery reviews.

[45]  K. Wasan,et al.  Lipid excipients Peceol and Gelucire 44/14 decrease P-glycoprotein mediated efflux of rhodamine 123 partially due to modifying P-glycoprotein protein expression within Caco-2 cells. , 2007, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.

[46]  S. Yuk,et al.  Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. , 2004, International journal of pharmaceutics.

[47]  Ronald T Borchardt,et al.  A comparison of commonly used polyethoxylated pharmaceutical excipients on their ability to inhibit P-glycoprotein activity in vitro. , 2002, Journal of pharmaceutical sciences.

[48]  P. Costa,et al.  Modeling and comparison of dissolution profiles. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[49]  C. Pouton,et al.  Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and 'self-microemulsifying' drug delivery systems. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[50]  S. Yalkowsky,et al.  Data base of aqueous solubility for organic non-electrolytes , 1991 .