DEVELOPMENT OF SELF NANO-EMULSIFYING DRUG DELIVERY SYSTEM FOR AN ANTI-HYPERTENSIVE AGENT FELODIPINE: A SYSTEMATIC APPROACH FOR LIPID NANO-FORMULATION WITH IMPROVED ORAL BIOAVAILABILITY IN RATS

K. TRIDEVA SASTRI; G. V. RADHA

doi:10.22159/ijap.2020v12i3.37203

Authors

K. TRIDEVA SASTRI GITAM Institute of Pharmacy, GITAM Deemed to be University, Rushikonda, Visakhapatnam, Andhra Pradesh State, India https://orcid.org/0000-0003-3564-4589
G. V. RADHA GITAM Institute of Pharmacy, GITAM Deemed to be University, Rushikonda, Visakhapatnam, Andhra Pradesh State, India https://orcid.org/0000-0001-6726-2185

DOI:

https://doi.org/10.22159/ijap.2020v12i3.37203

Keywords:

Felodipine, Essential oils, Bioavailability enhancement, Self-nano emulsifying systems, Pharmacokinetic study

Abstract

Objective: The present study involves the development of SNEDDS employing essential oils for enhancing biopharmaceutical performance.

Methods: Preliminary investigations suggested the selection of cinnamon oil as an essential oil, tween 60 as a surfactant, while transcutol HP as a cosolvent for formulating SNEDDS. Formulations evaluated for stability, robustness to dilution, and emulsification time, droplet size, zeta potential (ζ), cloud point, in vitro drug release, drug excipient compatibility, TEM, stability assessment and in vivo pharmacokinetic performance in rats.

Results: All formulations were robust, stable, and revealed excellent emulsification time<40 s, with fine droplet size (11.41±2.41 nm), lower PDI (0.028-0.277). Formulation F(FLD)6 exhibited a release of 97.7% within 4h, and TEM photograph confirmed spherical droplets. The bioavailability results revealed a higher rate and extent of absorption, AUC, and Cmax for the formulations found to be 1212.4 and 355.40±13.67 (p<0.05). The results recommend that the developed formulation approach offers bioavailability enhancement of FLD.

Conclusion: The study concluded that SNEDDS would be an effective formulation system in increasing the aqueous solubility and potentially bioavailability. Furthermore, it can be applied for other therapeutic categories of drugs belonging to BCS class II and IV that show comparable biopharmaceutical challenges.

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Author Biographies

K. TRIDEVA SASTRI, GITAM Institute of Pharmacy, GITAM Deemed to be University, Rushikonda, Visakhapatnam, Andhra Pradesh State, India

Pharmaceutics

GITAM Institute of Pharmacy

G. V. RADHA, GITAM Institute of Pharmacy, GITAM Deemed to be University, Rushikonda, Visakhapatnam, Andhra Pradesh State, India

Associate Professor,

Department of Pharmaceutics,

GITAM Institute of Pharmacy,

GITAM Deemed to be University

References

Saltiel E, Ellrodt AG, Monk JP, Langley MS. Felodipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension. Drugs 1988;36:387-428.

Bazzo GC, Caetano DB, Boch ML, Mosca M, Branco LC, Zétola M, et al. Enhancement of felodipine dissolution rate through its incorporation into ∂ E-PHB polymeric microparticles: in vitro characterization and investigation of absorption in rats. J Pharm Sci 2012;101:1518-23.

Sarode AL, Malekar SA, Cote C, Worthen DR. Hydroxypropyl cellulose stabilizes amorphous solid dispersions of the poorly water-soluble drug felodipine. Carbohydr Polym 2014;112:512-9.

Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci 2006;29:278–87.

Parmar N, Singla N, Amin S, Kohli K. Study of cosurfactant effect on nano emulsifying area and development of lercanidipine loaded (SNEDDS) self nano emulsifying drug delivery system. Colloids Surf B 2011;86:327–38.

Humberstone AJ, Charman WN. Lipid-based vehicles for the oral delivery of poorly water-soluble drugs. Adv Drug Delivery Rev 1997;25:103-28.

Holm R, Porter CJ, Edwards GA, Müllertz A, Kristensen HG, Charman WN. Examination of oral absorption and lymphatic transport of halofantrine in a triple-cannulated canine model after administration in self-microemulsifying drug delivery systems (SMEDDS) containing structured triglycerides. Eur J Pharm Sci 2003;20:91–7.

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

Bandopadhyay S, Singh B, Kapil R, Singh R, Katare OP. Self-emulsifying drug delivery systems (SEDDS): formulation development, characterization, and applications. Crit Rev Ther Drug Carrier Syst 2009;26:427–521.

Balakrishnan P, Lee BJ, Oh DH, Kim JO, Lee YI, Kim DD, et al. Enhanced oral bioavailability of coenzyme Q10 by self-emulsifying drug delivery systems. Int J Pharm 2009;74:66-72.

Madhavi K, Shikha A, Suresh B. Formulation and in vitro characterization solid self-emulsifying drug delivery system of ramipril prepared by adsorption technique. Int J Curr Pharm Sci 2016;8:40-5.

Constantinides PP, Welzel G, Ellens H, Smith PL, Sturgis SS, Yiv SH, et al. Water-in-oil microemulsions are containing medium-chain fatty acids/salts: formulation and intestinal absorption evaluation. Pharm Res 1996;13:210-5.

Srikanth reddy S, Suresh G. Design and evaluation of self-nano emulsifying drug delivery systems of manidipine for enhancement of solubility. Asian J Pharm Clin Res 2019;12:288-95.

Zhang P, Liu Y, Feng N, Xu J. Preparation and evaluation of self-microemulsifying drug delivery system of oridonin. Int J Pharm 2008;355:269–76.

Negi LM, Tariq M, Talegaonkar S. Nanoscale self-emulsifying oil-based carrier system for improved oral bioavailability of camptothecin derivative by P-glycoprotein modulation. Colloids Surf B 2013;111:346–53.

Elnaggar YS, El-Massik MA, Abdallah OY. Self-nano emulsifying drug delivery systems of tamoxifen citrate: design and optimization. Int J Pharm 2009;380:133-41.

Khoo SM, Humberstone AJ, Porter CJH, Edwards GA, Charman WN. Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrine. Int J Pharm 1998;167:155–64.

Madhavi K, Shikha A, Yadav JK. Self-nano emulsifying drug delivery system of ramipril: formulation and in vitro evaluation. Int J Pharm Pharm Sci 2016;8:291-6.

Agrawal AG, Kumar A, Gide PS. Self-emulsifying drug delivery system for enhanced solubility and dissolution of glipizide. Colloids Surf B: Biointerfaces 2015;126:553-60.

Wu W, Wang Y, Que L. Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system. Eur J Pharm Biopharm 2006;63:288–94.

Hai Xia Z, Jie XW, Zhi Bing Z, Yuan L, Zhi Gang S, Jian Feng C. Micronization of atorvastatin calcium by antisolvent precipitation process. Int J Pharm 2009;374:106–13.

Sahu BP, Das MK. Preparation and in vitro/in vivo evaluation of felodipine nanosuspension. Eur J Drug Metab Pharmacokinet 2013;39:183-93.

McConville C, Friend D. Development and characterization of a self-micro emulsifying drug delivery systems (SMEDDSs) for the vaginal administration of the antiretroviral UC-781. Eur J Pharm Biopharm 2013;83:322-9.

Palamakula A, Khan MA. Evaluation of cytotoxicity of oils used in coenzyme Q10 self-emulsifying drug delivery systems (SEDDS). Int J Pharm 2004;273:63–73.

Pouton CW. Formulation of self-emulsifying drug delivery systems. Adv Drug Delivery Rev 1997;25:47–58.

Anton N, Gayet P, Benoit JP, Saulnier P. Nano-emulsions and nanocapsules by the PIT method: an investigation on the role of the temperature cycling on the emulsion phase inversion. Int J Pharm 2007;344:44-52.

Davies JT. Drop sizes of emulsions related to turbulent energy dissipation rates. Chem Eng Sci 1985;40:839-42.

Anton N, Gayet P, Benoit JP, Saulnier P. Nano-emulsions and nanocapsules by the PIT method: an investigation on the role of the temperature cycling on the emulsion phase inversion. Int J Pharm 2007;344:44–52.

Craig DQM, Barker SA, Banning D, Booth SW. An investigation into the mechanisms of self-emulsification using particle size analysis and low-frequency dielectric spectroscopy. Int J Pharm 1995;114:103–10.

Griesser J, Hetenyi G, Kadas H, Demarne F, Jannin V, Bernkop Schnürch A. Self-emulsifying peptide drug delivery systems: how to make them highly mucus permeating. Int J Pharm 2018;538:159–66.