Formulation Development, Statistical Optimization and Characterization of the Self-Microemulsifying Drug Delivery System (SMEDDS) of Irbesartan

Author(s): Suryakanta Swain*, Sarwar Beg*, Prafulla K. Sahu, Bikash R. Jena, Sitty M. Babu

Journal Name: Nanoscience & Nanotechnology-Asia

Volume 9 , Issue 2 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Irbesartan is an anti-hypertensive BCS class II drug exhibiting poor aqueous solubility, which makes it highly challenging for delivery through the oral route. Based on this fact, a self-microemulsifying drug delivery system (SMEDDS) was designed and characterized for augmenting the aqueous solubility and dissolution rate of irbesartan.

Methods: Several blends of oil (Capmul MCM EP), surfactant (Tween 80) and co-surfactant (PEG 600) were screened from the preliminary solubility and pseudo-ternary phase diagram studies. Systematic optimization of the SMEDDS was carried out using 3-factor 3-level Box-Behnken design.

Results: The optimized formulation was identified by numerical optimization technique, which revealed faster emulsification time, high percent transmittance and drug content, lower globule size < 100 nm, zeta potential and excellent thermodynamic stability. The optimal formulation unveiled more than 93.3% drug release in vitro within 60 minutes, while the pure drug exhibited only 20% drug release, respectively.

Conclusion: Ex vivo permeability and in situ intestinal absorption of drugs was improved nearly 2 to 3- fold by the optimal SMEDDS formulation against the pure drug alone (p < 0.001). Overall, the proposed SMEDDS formulation of irbesartan exhibited a superior biopharmaceutical performance.

Keywords: Solubility, experimental design, drug release, in situ perfusion, permeability, bioavailability.

Martin, A. A Book on Physical Pharmaceutical Sciences; Lippincott Williams, 1999, pp. 156-171.
Trevaskis, N.L.; Charman, W.N.; Porter, C.J.H. Lipid-based delivery systems and intestinal lymphatic drug transport: A mechanistic update. Adv. Drug Deliv. Rev., 2008, 60, 702-716.
Driscoll, C.M. Lipid-based formulations for intestinal lymphatic delivery. Eur. J. Pharm. Sci., 2002, 15, 405-415.
Stegemanna, S.; Leveillerb, F. When poor solubility becomes an issue: From early stage to proof of concept. Eur. J. Pharm. Sci., 2007, 31, 249-261.
Swartz, M.A. The physiology of the lymphatic system. Adv. Drug Deliv. Rev., 2001, 50, 3-20.
Hussain, N.V.; Jaitley, F.A.T. Recent advances in the understanding of uptake of microparticulates across the gastrointestinal lymphatics. Adv. Drug Deliv. Rev., 2001, 50, 107-142.
Carey, M.C.; Small, D.M.; Bliss, C.M. Lipid digestion and absorption. Annu. Rev. Physiol., 1983, 45, 51-77.
Porter, C.J.; Charman, W.N. in vitro assessment of oral lipid based formulations. Adv. Drug Deliv. Rev., 2001, 50, 127-147.
Ahsan, M.N.; Verma, P.R.P.; Singh, S.K. Formulation of rosuvastatin-loaded self-nanoemulsifying drug delivery system using Box-Behnken design. Particul. Sci. Technol., 2014, 32, 46-60.
Neslihan, G.R.; Benita, S. Self-Emulsifying Drug Delivery Systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed. Pharmacother., 2004, 58, 173-182.
Date, A.A.; Nagarsenker, M.S. Design and evaluation of Self Nanoemulsified Drug Delivery Systems (SNEDDS) for cefpodoximeproxetil. Int. J. Pharm., 2007, 329, 166-172.
Hirelekar, R.; Kadam, V. Preformulation study of the inclusion complex Irbesartan-β-cyclodextrin. AAPS PharmSciTech, 2009, 10, 276-281.
Azeem, A.; Rizwan, M. Nanoemulsion components screening and selection: A Technical Note. AAPS PharmSciTech, 2009, 10, 69-76.
Singh, A.K.; Chaurasiya, A.; Singh, M. Exemestane loaded self-microemulsifying drug delivery system (SMEDDS): Development and optimization. AAPS PharmSciTech, 2008, 9, 628-634.
Nirmal, M.; Dong, Y. Y.; Bijay K.P.; Han‐Gon, C.; Chul S.Y.; Jong, O.K. Development and optimization of self‐nanoemulsifying drug delivery system with enhanced bioavailability by box-behnken design and desirability function. J. Pharm. Sci., 2012, 101, 4584-4596.
Ansari, D.; Parmar, S.; Bhadra, S. Optimization of self-microemulsifying drug delivery system of clofazimine using Box-Behnken experimental design. Pharmagene, 2013, 1, 53-61.
Mandawgade, S.D.; Sharma, S.; Pathak, S. Development of SMEDDS using natural lipophile: Application to artemether delivery. Int. J. Pharm., 2008, 362, 179-183.
Qi, X.; Wang, L.; Zhu, J. Self-double-emulsifying drug delivery system (SDEDDS): A new way for oral delivery of drugs with high solubility and low permeability. Int. J. Pharm., 2011, 409, 245-251.
Beg, S.; Swain, S.; Singh, H.P. Development, optimization and characterization of solid self-nanoemulsifying drug delivery systems of valsartan using porous carriers. AAPS PharmSciTech, 2012, 13, 1416-1427.
Mandal, S.; Rana, H.; Jesadiya, B. Release kinetic modeling of atorvastatin calcium loaded self microemulsifying drug delivery system. Elixir Pharm., 2012, 53, 11725-11729.
Attama, A.A.; Nkemnele, M.O. In-vitro evaluation of drug release from self-microemulsifying drug delivery systems using biodegradable homolipid from Capra hircus. Int. J. Pharm., 2005, 304, 4-10.
Pandya, D.J.; Patel, S. Formulation & development of Self Micro Emulsifying Drug Delivery System (SMEDDS) containing amiodarone HCl for dissolution enhancement. Discov. Pharm., 2013, 5, 6-12.
Kamble, M.S.; Borwandkar, V.G.; Bodade, S.S. Optimization of Self-Nanoemulsifying Drug Delivery System (SNEDDS) of repaglinide using D-optimal mixture experimental design. J. Biomed. Pharm. Res., 2013, 2, 100-108.
Shaji, J.; Lodha, S. Response surface methodology for the optimization of celecoxib self-microemulsifying drug delivery system. Indian J. Pharm. Sci., 2008, 70, 585-590.
Kanga, B.K.; Lee, J.S.; Chona, S.K. Development of Self-Microemulsifying Drug Delivery Systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. Int. J. Pharm., 2004, 274, 65-73.
Grove, M.A.; Mullertz, N.J.L. Bioavailability of seocalcitol II: Development and characterization of Self-Micro Emulsifying Drug Delivery Systems (SMEDDS) for oral administration containing medium and long chain triglycerides. Eur. J. Pharm. Sci., 2006, 28, 233-242.
Beg, S.; Sharma, G.; Thanki, K.; Jain, S.; Katare, O.P.; Singh, B. Positively charged self-nanoemulsifying oily formulations of olmesartanmedoxomil: Systematic development, in vitro, ex vivo and in vivo evaluation. Int. J. Pharm., 2015, 493, 466-482.
Sandhu, P.S.; Beg, S.; Mehta, F.; Singh, B.; Trivedi, P. Novel dietary lipid-based self-nanoemulsifying drug delivery systems of paclitaxel with p-gp inhibitor: Implications on cytotoxicity and biopharmaceutical performance. Expert Opin. Drug Deliv., 2015, 12, 1809-1822.
Beg, S.; Sandhu, P.S.; Batra, R.S.; Khurana, R.K.; Singh, B. QbD-based systematic development of novel optimized solid Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) of lovastatin with enhanced biopharmaceutical performance. Drug Deliv., 2014, 22, 765-784.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 25 June, 2019
Page: [210 - 228]
Pages: 19
DOI: 10.2174/2210681208666180125143258
Price: $25

Article Metrics

PDF: 14