Development, Optimization, Characterization and Impact of In vitro Lipolysis on Drug Release of Telmisartan Loaded SMEDDS

Author(s): Ravinder Verma, Deepak Kaushik*.

Journal Name: Drug Delivery Letters

Volume 9 , Issue 4 , 2019

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Abstract:

Objective: The objective of the current research is systematic optimization and development of microemulsion preconcentrates to get better solubility that results in improvement of oral bioavailability profile of Telmisartan utilizing D-optimal mixture design.

Methods: Solubility studies in a variety of lipidic ingredients and optimization of formulations were carried out for the development of liquid SMEDDS. D-optimal mixture design was utilized for assessing the interaction performance of desired responses (such as % cumulative drug release and globule size) and optimized using desirability approach. The optimized batch was evaluated for its % cumulative drug release and globule size performance for determining the dissolution rate and oral bioavailability of drug.

Results: The optimized batch (F-8), which contained 10% oil (Capmul MCM EP), 45% surfactant (Labrasol) and 45% co-surfactant (Transcutol HP) resulted in desired qualities of measured responses with 84.6nm globule size and 98.5% drug release within 15 minutes. Optimized SMEDDS showed brilliant goodness of fit between drug release. Stability studies indicated stability of the optimized SMEDDS batch over 3-month storage at 40°C/75% RH and improved dissolution rate in contrast to pure API. The optimized SMEDDS showed no impact of in vitro lipolysis on drug release.

Conclusion: Developed and optimized SMEDDS showed improved in vitro dissolution rate and dissolution profile in contrast to pure drug. These investigations further confirm dose reduction in SMEDDS by gaining an equivalent therapeutic profile with non-SMEDDS formulation. This research work successfully shows the potential usage of SMEDDS for delivery of BCS-II class drugs.

Keywords: SMEDDS, bioavailability, telmisartan, ternary phase diagram, lipolysis, in vitro dissolution, Fasted State Stimulated Intestinal Fluids media (FaSSIF).

[1]
Padia, N.; Shukla, A.K.; Shelat, P. Development and characterization of telmisartan self-microemulsifying drug delivery system for bioavailability enhancement. J. Scientific and Ind. Res, 2015, 4(3), 153-164.
[2]
Lee, J.H.; Kim, H.Y.; Cho, Y.H.; Koo, T.S.; Lee, G.W. Development and evaluation of raloxifene-hydrochloride-loaded supersaturatable SMEDDS containing an acidifier. Pharmaceutics, 2018, 10(78), 1-12.
[3]
Verma, R.; Mittal, V.; Kaushik, D. Self-micro emulsifying drug delivery system: a vital approach for bioavailability enhancement. Int. J. Chemtech Res., 2017, 10(17), 515-528.
[4]
Divya, B.; Pandey, P.; Verma, R.; Kaushik, D. Development and characterization of rosuvastatin loaded self-emulsifying drug delivery system. Appl. Clinc. Res. Clinical Trials and Reg. Affairs., 2018, 5, 1-8.
[5]
Verma, R.; Mittal, V.; Kaushik, D. Quality based design approach for improving oral bioavailability of valsartan loaded SMEDDS and study of impact of lipolysis on the drug diffusion. Drug Deliv. Lett., 2018, 8(2), 130-139.
[6]
Patra, J.K.; Das, G.; Fraceto, L.F.; Sharma, S.; Shin, S.H. Nano based drug delivery systems: recent developments and future prospects. J. of Nanobiotech., 2018, 16(1), 71-104.
[7]
Mottaghitalab, F.; Farokhi, M.; Atyab, F.; Hosseinkhani, H. Silk fibroin nanoparticle as a novel drug delivery system. J. Control. Release, 2015, 206, 161-176.
[8]
Hosseinkhani, H.; Chen, Y.R.; He, W.J.; Hong, P.D.; Yu, D.S.; Domb, A.J. Engineering of magnetic DNA nanoparticles for tumor-targeted therapy. J. Nanopart. Res., 2013, 15, 1345.
[9]
He, W.J.; Hosseinkhani, H.; Hong, P.D.; Chiang, C.H.; Yu, D.S. Magnetic nanoparticles for imaging technology. Int. J. Nanotechnol., 2013, 10, 930-944.
[10]
Abedini, F.; Ebrahimi, M.; Roozbehani, A.H.; Domb, A.J.; Hosseinkhani, H. Overview on natural hydrophilic polysaccharide polymers in drug delivery. Polymers for Advanc. Technol., 2018, 29, 2564-2573.
[11]
Wadhwa, J.; Nair, A.; Kumri, R. Selfemulsifying therapeutic system: A potential approach for delivery of lipophilic drugs. Braz. J. Pharm. Sci., 2011, 47(3), 1-16.
[12]
Anand, S.; Gupta, R. Self-microemulsifying drug delivery system: A review. World J. Pharm. and Pharm. Sci., 2016, 4(8), 506-522.
[13]
Thakare, P.; Mogal, V.; Borase, P.; Dusane, J.; Kshirsagar, A. A review on self-emulsifying drug delivery system. Pharmaceutical and Bio. Evalu., 2016, 3(2), 140-153.
[14]
Paresh, K.; Patel, M.R.; Patel, K.R. Design and development of self-microemulsifying drug delivery system of febuxostat. Int. J. Universal Pharmacy and Bio. Sci., 2014, 3(2), 2212-2231.
[15]
Chaus, H.A.; Chopade, V.V.; Chaudhri, P.D. Self-emulsifying drug delivery system: A Review. Int. J. Pharm. and Chem. Sci., 2013, 2, 34-44.
[16]
Pandya, B.D.; Shah, S.H.; Shah, N. Bioavailability enhancement of poorly water soluble drugs by SMEDDS: A review. Int. J. Pharm. Sci. Res., 2015, 5, 187-206.
[17]
Brahmaiah, B.K.; Sasikanth, A.; Nama, S.; Suresh, P.; Khan, P.A. Formulation and dissolution study of telmisartan immediate release tablets. Int. J. Innovativ. Drug Dis., 2013, 3(1), 33-38.
[18]
Gursoy, R.N.; Benita, S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed. Pharmacother., 2004, 58, 173-182.
[19]
Abhijit, A.; Nagarsenker, M.S. Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil. Int. J. Pharm., 2007, 329, 166-172.
[20]
Patel, J.B.; Patel, M.R. Self-micro emulsifying drug delivery system: A review. World Int. J. Pharma. Pharm. Sci., 2016, 5(4), 2215-2232.
[21]
Potphode, V.R.; Deshmukh, A.S.; Mahajan, V.R. Self-micro emulsifying drug delivery system: an approach for enhancement of bioavailability of poorly water soluble drugs. Asian J. Pharm. Sci., 2016, 6(3), 159-168.
[22]
Hyma, P. Formulation and characterization of novel self micro emulsifying drug delivery system of glimepiride. The Experiment., 2014, 24(1), 1640-1648.
[23]
Midha, K.; Nagpal, M.; Aggarwal, G.; Singh, T.G. Development of dispersible self-microemulsifying tablet of atorvastatin. Pharm. Methods, 2015, 6(1), 9-26.
[24]
Thakkar, H.; Nangesh, J.; Parmar, M.; Patel, D. Formulation and characterization of the lipidbased drug delivery system of raloxifenemicro emulsion and selfmicroemulsifying drug delivery system. J. Pharm. Bioallied Sci., 2011, 3(3), 442-448.
[25]
Mosgaard, M.D.; Sassene, P.; Rades, T.; Müllertz, A. Development of a high-throughput in vitro lipolysis model for rapid screening lipid-based drug delivery systems. Eur. J. Pharm. Biopharm., 2015, 94493500
[26]
Xiao, L.; Yi, T.; Liu, Y.; Zhou, Z. The in vitro lipolysis of lipid-based drug delivery systems: a newly identified relationship between drug release and liquid crystalline phase. BioMed Res. Int., 2016, 4, 1-7.
[27]
Sassene, P.; Karen, K.; Williams, H.D.; Mullertz, A. Toward establishment of standardized in vitro tests for LbDDSs, Part 6: Effect of varying pancreatin and calcium levels. Am. Assoc. Pharma. Soci. J., 2014, 16(6), 1344-1357.
[28]
Williams, H.D.; Anby, M.U.; Sassene, P.; Kleberg, K.; Mullertz, A.; Porter, J.H. Toward the establishment of standardized in vitro tests for lipid-based formulations, Part 2. The effect of bile salt concentration and drug loading on the performance of type I, II, IIIA, IIIB, and IV formulations during in vitro digestion. Mol. Pharmaceutic., 2012, 101(9), 3286-3300.


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Article Details

VOLUME: 9
ISSUE: 4
Year: 2019
Page: [330 - 340]
Pages: 11
DOI: 10.2174/2210303109666190614120556
Price: $25

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