Development and characterization of liquid and solid self-microemulsifying drug delivery system of Tacrolimus

Main Article Content

Hitesh K Patel
Pranav V Patel
Chetan K Misan
Dhaval S Mehta
Mandev B Patel

Abstract

Tacrolimus is an immunosuppressant agent for the prevention and treatment of graft rejection in solid organ transplantation patients. Tacrolimus is a poorly water-soluble drug. Its absorption is further limited due to the
involvement of an efflux transporter P-glycoprotein and metabolism via cytochrome P450. The objective of presentinvestigation was to develop and characterize a liquid self-microemulsifying drug delivery system (SMEDDS) and a solid SMEDDS by using bioenhancer excipients like Tween 20 and Tween 80, which are known for their inhibiting action on CYP 450 and P-glycoprotein efflux pump. Solubility of Tacrolimus was determined in various vehicles, including
oils, surfactants and cosolvents. Pseudoternary phase diagrams were constructed to identify the most efficient self-emulsification region. The optimized formulations were characterized by differential scanning calorimetry (DSC), X-ray
diffraction (XRD) and globule size analysis. The optimized liquid SMEDDS formulation contained 20% Phosal 53 MCT as oil, 60% Tween 20 as surfactant and 20% ethanol as cosolvent. Liquid SMEDDS was converted to solid SMEDDS by
using Aerosil-200 and Florite-RE as inert solid adsorbents. The optimized liquid and solid SMEDDS showed higher drug release than the marketed capsule and pure API powder. For optimized liquid SMEDDS and solid SMEDDS, the globule
sizes were found to be 140.9 nm and 304.6 nm, respectively. DSC and XRD results of solid SMEDDS confirmed that the drug present in the formulation was in an amorphous state. Shelf-lives for liquid SMEDDS and solid SMEDDS were
found to be 1.76 and 2.27 years, respectively. The prepared liquid SMEDDS and solid SMEDDS containing bioenhancer excipients increase the in vitro dissolution rate of lipophilic Tacrolimus.

Downloads

Download data is not yet available.

Article Details

How to Cite
Patel, H. K., Patel, P. V., Misan, C. K., Mehta, D. S., & Patel, M. B. (2014). Development and characterization of liquid and solid self-microemulsifying drug delivery system of Tacrolimus. Asian Journal of Pharmaceutics (AJP), 6(3). https://doi.org/10.22377/ajp.v6i3.56
Section
Articles

References

Shoukath MA, Ateeq A, Saifuddin S, Ahmad MU, Rane RC, Kale P,

et al. Polyoxyl 60 hydrogenated castor oil free nanosomal formulation

ofimmunosuppressant Tacrolimus: Pharmacokinetics, safety, and

tolerability inrodents and humans. Int Immunopharmacol 2010;10:325-30.

Honbo T, Kobayashi M, Hane K, Hata T, Ueda Y. The oral dosage form

of FK-506. Transplant Proc 1987;19:17-22.

Park YJ, Ryu DS, Li DX, Quan QZ, Oh DH, Kim JO, et al. Characterization of Tacrolimus-loaded solid dispersion with sodium carboxylmethyl cellulose and sodium lauryl sulfate. Arch Pharm Res 2009;32:893-8.

Kang BK, Lee JS, Chon SK, Jeong SY, Yuk SH, Khang G, et al. Development of self-microemulsifying drug delivery systems for oral bioavailability enhancement of simvastatin in beagle dogs. Int J Pharm 2004;274:65-73.

Ping Z, Ying L, Nianping F, Jie X. Preparation and evaluation of self-

microemulsifying drug delivery system of oridonin. Int J Pharm

;355:269-76.

Saipin S, Sirima M, Narubodee P, Wiwat P, Ruedeekorn W. Development

and evaluation of self-microemulsifying liquid and pellet formulations

of curcumin, and absorption studies in rats. Eur J Pharm Biopharm

;76:475-85.

Elnaggar YS, El-Massik MA, Abdallah OY. Self-nanoemulsifying drug

delivery systems of tamoxifen citrate: Design and optimization. Int J

Pharm 2009;380:133-41.

Rane SS. Anderson BD. What determines drug solubility in lipid vehicles: Is it predictable. Adv Drug Deliv Rev 2008;60:638-56.

Rajan BM, Nirav SS. A review: Self emulsifying drug delivery system.

Int J Pharm Pharm Sci 2011;3:23-8.

Basalious EB, Shawky N, Badr-Eldin SM. SNEDDS containing bioenhancers for improvement of dissolution and oral absorption of lacidipine I:Development and optimization. Int J Pharm 2010;391:203-11.

Tang B, Cheng G, Gu JC, Xu CH. Development of solid self-emulsifying

drug delivery systems: Preparation techniques and dosage forms. Drug

Discov Today 2008;13:606-12.

Zhiyuan W, Jin S, Yongjun W, Xiaohong L, Yanhua L, Qiang F, et al. Solid

self-emulsifying nitrendipine pellets: Preparation and in vitro/in vivo

evaluation. Int J Pharm 2010;383:1-6.

Borhade V, Nair H, Hegde D. Design and evaluation of self-

microemulsifying drug delivery system (SMEDDS) of Tacrolimus. AAPS

PharmSciTech 2008;9:13-21.

Date AA, Nagarsenker MS. Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil. Int J Pharm 2007;329:166-72.

Patel P, Panchal S, Mehta T, Solanki S, Patel C. Reversed-phase high

perforformance liquid chromatographic method for determination of

Tacrolimus in bulk and pharmaceutical formulation. Int J Pharm Pham

Sci 2011;3:220-2.

Singh AK, Chaurasiya A, Singh M, Upadhyay SC, Mukherjee R. Exemestane loaded self-microemulsifying drug delivery system (SMEDDS):Development and Optimization. AAPS PharmSciTech 2008;9:628-34.

Joe JH, Lee WM, Park YJ, Joe KH, Oh DH, Seo YG, et al. Effect of the

solid-dispersion method on the solubility and crystalline property of

Tacrolimus. Int J Pharm 2010;395:161-6.

Prabagar B, Beom-Jin L, Dong HO, Jong OK, Myung JH, Jun-Pil J. Enhanced oral bioavailability of dexibuprofen by a novel solid Self-emulsifying drug delivery system (SEDDS). Eur J Pharm Biopharm 2009;72:539-45.

Bali V, Ali M, Ali J. Studies of surfactant combinations and development

of a novel nanoemulsion for minimising variations in bioavailability of

ezetimibe. Colloids Surf B Biointerfaces 2010;76:410-20.

Chakraborty S, Shukla D, Misha B, Singh S. Lipid -an emerging platform for oral delivery of drugs with poor bioavailability. Eur J Pharm Biopharm 2009;73:1-5.

Nazzal S, Smalyukh II, Lavrentovich OD, Khan MA. Preparation and in vitro characterization of a eutectic based semisolid self-nanoemulsified drug delivery system (SNEDDS) of ubiquinone: Mechanism and progress of

emulsion formation. Int J Pharm 2002;235:247-65.