FORMULATION OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM OF BOVINE SERUM ALBUMIN USING HLB (HYDROPHILIC-LYPOPHILIC BALANCE) APPROACH

Lina Winarti

Abstract


Self-Nanoemulsifying Drug Delivery System (SNEDDS) has potential to be developed for oral protein delivery because it is free from water, hence preserving the stability of protein, protecting protein from enzymatic degradation, and enhancing the protein permeability in the gastrointestinal tract (GIT). However, protein-based SNEDDS formulation is challenging due to low solubility property of protein in oil, which is towards zero. This present study aimed to obtain the most compatible SNEDDS system for protein using HLB approach. Bovine serum albumin (BSA) was used as a protein model in this study. A number of 78 formulae with HLB ranging between 11 and 15 were screened to acquire stable SNEDDS composition without the presence of phase separation. Of 13 stable formulae, two were selected (F30, F45) with HLB 15, and then loaded with BSA. Physical characteristics of both formulae were then evaluated and the results suggested that SNEDDS with single hydrophilic surfactant (F45) and HLB 15 was the best formula for protein template as the stability testing showed that phase separation and precipitation did not appear. It was robust to pH and dilution with percentage of transmittance of 96.40±1.05% and the droplet size of 180.9nm. F45 also had uniform distribution of droplets size since the polydispersity index was less than 0.1. The zeta potential of F45 was -0.12mv with loading efficiency 83.57±1.77%. The emulsifying time of F45 was > 2min due to the formation of crystalline gel that was difficult to disperse.

Keywords


SNEDDS; BSA; hydrophllic surfactant; lypophilic surfactant; protein delivery

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References


Bernkop-Schnürch A., Scerbe-Saiko A., 1998. Synthesis and in vitro evaluation of chitosan-EDTA-protease-inhibitor Cojugates Which Might Be Useful in Oral Delivery of Peptides and Proteins.Pharm.Res. 15(2):263-269

Chime SA., Kenechukwu FC., Attama AA., 2014. Nanoemulsions — Advances in Formulation, Characterization and Applications in Drug Delivery, in: Sezer AD., (Ed.), Application of Nanotechnology in Drug Delivery. InTech.

Chudasama A., Patel V., Nivsarkar M., Vasu K., Shishoo C., 2016. Investigation of Microemulsion System For Transdermal Delivery of Itraconazole. J.Adv.Phar.Tech.Res. March 12. IP.107.167.99.225

Croda, 2010. Tween and Span.Croda Europe Ltd Cowick Hall Snaith Goole East Yorkshire DN14 9AA England.www.Croda.com/Europe.Accessed 2 February 2016

Date AA., Nagarsenker MS., 2007. Design and Evaluation of Self Nanoemulsified Drug Delivery Systems (SNEDDS) for Cefpodoxime Proxetil. Int.J.Pharm.329:166-172

Fernandez P., Andre V., Rieger J., Kuhnle A., 2004. Nano-emulsion Formation By Emulsion Phase Inversion, Physiochem. Eng. Aspects., 251, 53-58

Fix JA., 1996. Oral Controlled Release Technology for Peptides: Status and Future Prospects.Pharm.Res. 13:1760-1764

Hauss DH., 2007. Oral lipid-based Formulations. Adv.Drug.Deliv.Rev. 59(7):667-76

Houen G., Svaerke C., Barkholt V., 1999. The Solubilities of Denatured Proteins in Different Organic Solvents. Acta.Chem.Scand. 53:1122-1126

Jain AK., Thanki K., Jain S., 2014. Solidified Self-Nanoemulsifying Formulation for Oral Delivery of Combinatorial Theurapeutic Regimen Part I. Formulation Development, Statistical Optimization, and In-vitro Characterization. Pharm.Res.31:923-945

Khedekar K., Mittal S., 2013. Self emulsifying Drug Delivery Systems: A Review. Int.J.Pharm.Sci.Res, IJPSR, 4(12):4494-4507

Kommuru TR., Gurley B., Khan MA., Reddy IK., Self-emulsifying Drug Delivery Systems (SEDDS) of coenzym Q10: Formulation development and Bioavailability Asessment.Int.J.Pharm. 212:233-246

Larsen AT., Ogbonna A., Abu-Rmaileh R., Abrahamsson B., Ostergaard J., Mullertz A., 2012. SNEDDS Containing Poorly Water Soluble Cinnarizine; Development and in vitro Characterization of Dispersion, Digestion and Solubilization. Pharmaceutics. 4, 641-665

Li P., Tan A., Prestidge CA., Nielsen HM., Müllertz A., 2014. Self-nanoemulsifying drug delivery systems for oral insulin delivery: In vitro and in vivo evaluations of enteric coating and drug loading. International Journal of Pharmaceutics. 477: 390–398.

Ma H., Liu Z., Zheng C., 2006. In vitro and in vivo evaluation of a novel oral insulin formulation1. Acta pharmacologica sinica. 27: 1382–1388.

Makadia HA., Bhatt AY., Parmar RB., Paun JS., Tank HM., 2013. Self-Nanoemulsifying Drug Delivery System (SNEDDS): Future Aspects, Asian.J.Pharm.Res.3(1):21-24

Mc Clements DJ., 2012. Nanoemulsions Versus Microemulsions: Terminology, Differences, and Similarities. Soft Matter. 8, 1719

Morais JM., Santos O., Delicato T., Rocha-Filho P., 2006. Characterization and Evaluation of Electrolyte Influence on Canola Oil/water Nano-emulsion. J.Disp.Sci.Tech. 27:1009-1014

Mueller EA., Kovarik JM., Van Bree JB., Tetzloff W., Grevel J., Kutz K., 1994. Improved Dose Linearity of Cyclosporine Pharmacokinetics from a Microemulsion Formulation. Pharm.Res.11(2):301-4

Noha NS., Natalie DE., Alessio F., 2006. Tight Junction Modulation and Its Relationship to Drug Delivery. Adv.Drug.Deliv.Rev. 58:15-28

Patel H., Santwani P., Patel P., Akshay K., Ranch K., Shah D., 2013. A Review on Solid Self Emulsification-Techniques, Dosage Forms Development and Pharmaceutical Applications .J.Biomed.Pharm.Res. 2(4);52-56

Patil P., Joshi P., Paradkar A., 2004. Effect of formulation variables on preparation and evaluation of gelled self-emulsifying drug delivery system (SEDDS) of ketoprofen. AAPS PharmSciTech. 5: 43–50.

Rachmawati H., Haryadi BM., 2014. The Influence of Polymer Structure on The physical Characteristic of Intraoral Film Containing BSA-loaded Nanoemulsion. J.Nanomed.Nanotechnol.5:187

Rachmawati, H., Rasaputri, D., Susilowidodo, R., Darijanto, S., Sumirtapura, Y., 2008. The Influence of Oils and Surfactants on The Formation of Self-nanoemulsifying Drug Delivery Systems (SNEDDS) Containing Therapeutic Protein.Materials Science and Technology.

Rao VR., Shao J., 2008. Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs: I. Formulation Development. Int.J.Pharm. 362(1-2): 2–9.

Ravi Kumar, Patil MB., Patil SR., Paschapur MS., 2009. Polysaccharides Based Colon Spesific Drug Delivery: A Review. Int.J.Pharm.Tech.Res. 1(2):334-346

Reddy S., Sowjanya N., 2015. Formulation and In-Vitro Characterization of Solid Self Nanoemulsifying Drug Delivery System (s-SNEDDS) of Simvastatin. J.Pharm.Sci.& Res. 7(1):40-48

Saffran M., Kumar GS., Savariar C., Burnham JC., Williams F., Neckers DC., 1986. A New Approach to the Oral Administration of Insulin and Other Peptide Drugs.Science. 233:1081-1084

Sakloetsakun D., Dünnhaupt S., Barthelmes J., Perera G., Bernkop-Schnürch, A., 2013. Combining two technologies: Multifunctional polymers and self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration. International Journal of Biological Macromolecules. 61: 363–372.

Shahba AAW., Mohsin K., Alanazi FK., 2012. Novel Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Oral Delivery of Cinnarizine: esign, Optimization, and In-Vitro Assesment. AAPS. 13(3):967-977

Sharma G., Wilson K., van der Walle CF., Sattar N., Petrie JR., Ravi Kumar, MNV., 2010. Microemulsions for oral delivery of insulin: Design, development and evaluation in streptozotocin induced diabetic rats. European Journal of Pharmaceutics and Biopharmaceutics. 76: 159–169.

Singh B., Bandopadhyay S., Kapil R., Singh R., Katare OP., 2009. Self-Emulsifying Drug Delivery System (SNEDDS): Formulation Development, Characterization, Application. Crit.Rev.Ther.Drug.Carrier Syst. 26(5), 427, 431, 444-445, 451A

Sintov AC., Shapiro L., 2004. New Microemulsions Vehicle Facilitates Percutaneous Penetration In Vitro and Cutaneous drug Bioavailability In-Vivo. J.Cont.Rel. 95:173-183

Sonaje K., Lin Y., Juang J., Wey S., Chen C., Sung H., 2009. In vivo evaluation of safety and efficacy of self-assembled nanoparticles for Oral Insulin Delivery. Boimaterials. 30(12):2329-2339

Suresh PK., Sharma S., 2011. Formulation and In-vitro Characterization of Self-nanoemulsifying Drug Delivery System of Cinnarzine. Pharmacie Globale (IJCP). 9(08):1-6

Takatsuka S., Kitazawa T., Morita T., Horikiri Y., Yoshino H., 2006.i Enhancement of intestinal absorption of poorly absorbed hydrophilic compounds by simultaneous use of mucolytic agent and non-ionic surfactant. European Journal of Pharmaceutics and Biopharmaceutics. 62: 52–58.

Wang L., Dong J., Chen J., Eastoe J., Li X., 2009. Design and optimization of a new self-nanoemulsifying drug delivery system. Journal of Colloid and Interface Science. 330: 443–448.

Warner Graham Company, 2016. High quality Ingredients for Personal Care and Pharmaceutical Applications. http//:warnergraham.com/products/olefins-surfactants-emollients/cremer-oleo/.accessed 12 February 2016

Weerapol Y., Limmatvapirat S., Nunthanid J., Sriamornsak P., 2014. Self-nanoemulsifying drug delivery system of nifedipine: impact of hydrophilic-lipophilic balance and molecular structure of mixed surfactants.AAPS.Pharm.Sci.Tech.15(2)

Winarti L., Suwaldi, Martien R., Hakim L., 2016. An Experimental Design of SNEDDS Template Loaded with Bovine Serum Albumin and Optimization Using D-Optimal. Int. J. Pharmaceut. Clin. Res. 8(5):425-432.

Wu W., Niu M., Lu Y., Hovgaard L., 2011. Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation. International Journal of Nanomedicine. 1155.

Zhang Q., Na H., Zhang L., Zhu P., Chen Q., Qiu Y., 2012. The In vitro and In Vivo Study on SNEDDS Based on Insulin-Phospholipid Complex. J.Biomed.Nanotechnol. 8(1):90-7




DOI: http://dx.doi.org/10.14499/indonesianjpharm27iss3pp117

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