Skip to main content
SpringerLink
Log in

Design, formulation, in vitro, in vivo, and pharmacokinetic evaluation of nisoldipine-loaded self-nanoemulsifying drug delivery system

  • Research Paper
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

Abstract

The aim of the present work was to prepare and optimize the self-nanoemulsifying drug delivery system (SNEDDS) of poor aqueous soluble and less bioavailable nisoldipine to improve its solubility and bioavailability. The solubility of nisoldipine was assessed in various vehicles and ternary phase diagram was constructed to identify the efficient self-emulsifying region. The selected formulations were evaluated for self-emulsification time, droplet size analysis, and in vitro drug release profile. The optimized formulation ACP 19 had reduced particle size (118.3 ± 1.53 nm), when compared to PCT 08 (740 ± 1.16 nm). In vitro drug release study revealed that 98.05 ± 0.95 and 93.71 ± 1.05 % of drug was, respectively, released from ACP 19 and PCT 08 formulations at 24 h, whereas only 47.42 ± 0.65 % was released from drug in suspension. ACT 19 and PCT 08, respectively, showed 2.5- and 2.22-folds greater bioavailability than drug in suspension. PK Solver 2.0 was used for analysis of data obtained from in vivo study and the results revealed that both ACP 19 SNEDDS and drug in suspension fit into one-compartment pharmacokinetic model.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ahr HJ, Krause HP, Suwelack D, Weber H (1988) Pharmacokinetics of nisoldipine. II. Distribution to and elimination from tissues and organs following single or repeated administration of [14C] nisoldipine to rats and dogs. Arzneimittelforschung 38:1099–1104

    Google Scholar 

  • Balakumar K, Raghavan CV, Selvan NT, Habibur Rahman SM (2013a) Self emulsifying drug delivery system: optimization and its prototype for various compositions of oils, surfactants and co-surfactants. J Pharm Res 6:510–514

    Article  Google Scholar 

  • Balakumar K, Raghavan CV, Selvan NT, Prasad RH, Abdu S (2013b) Self nanoemulsifying drug delivery system (SNEDDS) of Rosuvastatin calcium: design, formulation, bioavailability and pharmacokinetic evaluation. Colloids Surf, B 112:337–343

    Article  Google Scholar 

  • Chakraborty S, Shukla D, Mishra B, Singh S (2009) Lipid—an emerging platform for oral delivery of drugs with poor bioavailability. Eur J Pharm Biopharm 73:1–15

    Article  Google Scholar 

  • Chavda VP (2012) Are SMEDDS and SNEDDS a same? A gimmick or pharmaceutically relevant. Mintage J Pharm Med Sci 1:7–10

    Google Scholar 

  • Chopra S, Venkatesan N, Betageri GV (2013) Formulation of lipid bearing pellets as a delivery system for poorly soluble drugs. Int J Pharm 446:136–144

    Article  Google Scholar 

  • Christiansen ML, Holma R, Kristensen J, Kreilgaard M, Jacobsen J, Abrahamsson B, Müllertz A (2014) Cinnarizine food-effects in beagle dogs can be avoided by administration in a self nano emulsifying drug delivery system (SNEDDS). Eur J Pharm Sci 57:164–172

    Article  Google Scholar 

  • Constantinides PP (1995) Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res 12:1561–1572

    Article  Google Scholar 

  • Elgart A, Cherniakov I, Aldouby Y, Domb AJ, Hoffman A (2013) Improved oral bioavailability of BCS class 2 compounds by self nano-emulsifying drug delivery systems (SNEDDS): the underlying mechanisms for amiodarone and talinolol. Pharm Res 30:3029–3044

    Article  Google Scholar 

  • Elnaggar YS, El-Massik MA, Abdallah OY (2009) Self-nanoemulsifying drug delivery systems of tamoxifen citrate: design and optimization. Int J Pharm 380:133–141

    Article  Google Scholar 

  • Gaur PK, Mishra S, Bajpai M, Mishra A (2014) Enhanced oral bioavailability of efavirenz by solid lipid nanoparticles: in vitro drug release and pharmacokinetics studies. Biomed Res Int. doi:10.1155/2014/363404

  • Gupta S, Chavhan S, Sawant KK (2011) Self-nanoemulsifying drug delivery system for adefovir dipivoxil: design, characterization, in vitro and ex vivo evaluation. Colloids Surf A: Physicochem Eng Asp 392:145–155

    Article  Google Scholar 

  • Jeevana JB, Sreelakshmi K (2011) Design and Evaluation of Self-Nanoemulsifying Drug Delivery System of Flutamide. J Young Pharm 3:4–8

    Article  Google Scholar 

  • Jiang SP, He SN, Li YL et al (2013) Preparation and characteristics of lipid nanoemulsion formulations loaded with doxorubicin. Int J Nanomedicine 8:3141–3150

    Google Scholar 

  • Jinno J-I, Kamada N, Miyake M, Yamada K, Mukai T, Odomi M, Toguchi H, Liversidge GG, Higaki K, Kimura T (2006) Effect of particle size reduction on dissolution and oral absorption of a poorly water-soluble drug, cilostazol, in beagle dogs. J Controlled Release 111:56–64

    Article  Google Scholar 

  • Kale AA, Patravale VB (2008) Design and evaluation of self-emulsifying drug delivery systems (SEDDS) of nimodipine. AAPS Pharm Sci Tech 9:191–196

    Article  Google Scholar 

  • Kawakami K (2012) Modification of physicochemical characteristics of active pharmaceutical ingredients and application of supersaturatable dosage forms for improving bioavailability of poorly absorbed drugs. Adv Drug Deliv Rev 64:480–495

    Article  Google Scholar 

  • Kawakami K, Yoshikawa T, Mororo Y, Hayashi T (2002) Microemulsion formulation for enhanced absorption of poorly soluble drugs: I. prescription design. J Control Release 81:65–74

    Article  Google Scholar 

  • Khan AW, Kotta S, Ansari SH, Sharma RK, Ali J (2012) Potentials and challenges in self-nanoemulsifying drug delivery systems. Exp Opi Drug Deliv 9:1305–1317

    Article  Google Scholar 

  • Khoo SM, Humberstone AJ, Porter CJH, Edwards GA, Charman WN (1998) Formulation design and bio availability assessment of lipidic self-emulsifying formulations of halofantrine. Int J Pharm 167:155–164

    Article  Google Scholar 

  • Kim HJ, Yoon KA, Hahn M, Park ES, Chi SC (2000) Preparation and in vitro evaluation of self-microemulsifying drug delivery systems containing idebenone. Drug Dev Ind Pharm 26:523–529

    Article  Google Scholar 

  • Kocbek P, Baumgartner S, Kristl J (2006) Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly water-soluble drugs. Int J Pharm 312:179–186

    Article  Google Scholar 

  • Liu H, Shang K, Liu W, Leng D, Li R, Kong Y, Zhang T (2014) Improved oral bioavailability of glyburide by a self-nanoemulsifying drug delivery system. J Microencapsul 31:277–283

    Article  Google Scholar 

  • Maghraby GME, Elsergany RN (2014) Fast disintegrating tablets of nisoldipine for intra-oral administration. Pharm Dev Technol 19:641–650

    Article  Google Scholar 

  • Mahmoud EA, Bendas ER, Mohamed MI (2009) Preparation and evaluation of self nanoemulsifying tablets of carvedilol. AAPS Pharm Sci Tech 10:183–192

    Article  Google Scholar 

  • Mitchell J, Frishman W, Heiman M (1993) Nisoldipine: a new dihydropyridine calcium-channel blocker. J Clin Pharmacol 33:46–52

    Article  Google Scholar 

  • Nagarsenker MS, Date AA (2007) Design and evaluation of self-nanoemulsifying drug delivery (SNEDDS) for cefpodoxime proxetil. Int J Pharm 329:166–172

    Article  Google Scholar 

  • Park MJ, Ren S, Lee BJ (2007) In vitro and in vivo comparative study of itraconazole bioavailability when formulated in highly soluble self-emulsifying system and in solid dispersion. Biopharm Drug Dispos 28:199–207

    Article  Google Scholar 

  • Patel J, Patel A, Raval M, Sheth N (2011) Formulation and development of a self-nanoemulsifying drug delivery system of irbesartan. J Adv Pharm Technol Res 2:9–16

    Article  Google Scholar 

  • Pouton CW (1997) Formulation of self emulsifying drug delivery system. Adv Drug Del Rev 25:47–58

    Article  Google Scholar 

  • Pouton CW (2000) Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and "self-microemulsifying" drug delivery systems. Eur J Pharm Sci 11:S93–S98

    Article  Google Scholar 

  • Pouton CW (2006) Formulation of poorly water soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci 29:278–287

    Article  Google Scholar 

  • Pouton CW (2007) Properties and users of common formulation lipids, surfactants and cosolvents. In: AAPS workshop, www.aapspharmaceutica.com/meetings/files/85/03poultona.pdf

  • Prajapati ST, Joshi HA, Patel CN (2013) Preparation and characterization of self-microemulsifying drug delivery system of olmesartan medoxomil for bioavailability improvement. J Pharm 2013:1–9

    Google Scholar 

  • Safhi MM (2011) Novel spectrophotometric method for the estimation of nisoldipine in bulk and pharmaceutical dosage forms. Der Pharma Chemica 3:275–278

    Google Scholar 

  • Savjani KT, Gajjar AK, Savjani JK (2012) Drug solubility: importance and enhancement techniques. ISRN Pharm. doi:10.5402/2012/195727

    Google Scholar 

  • Shah RB, Zidan AS, Funck T (2007) Quality by design: characterization of self-nano-emulsified drug delivery systems (SNEDDs) using ultrasonic resonator technology. Int J Pharm 341:189–194

    Article  Google Scholar 

  • Shukla JB, Patel SJ (2010) Formulation and evaluation of self micro emulsifying system of candesartan cilexetil. Int J Pharm Pharm Sci 2:143–146

    Google Scholar 

  • Wasan KM (2001) Formulation and physiological and biopharmaceutical issues in the development of oral lipid-based drug delivery systems. Drug Dev Ind Pharm 27:267–276

    Article  Google Scholar 

  • Wu W, Wang Y, Que L (2006) Enhanced bioavailability of silymarin by selfmicroemulsifying drug delivery system. Eur J Pharm Biopharm 63:288–294

    Article  Google Scholar 

  • Xiao Y, Lin Z, Liu J, Zhang W, Wang L, Yu P (2012) A transdermal microemulsion-based hydrogel of nisoldipine: preparation, in vitro characterization and in vivo pharmacokinetic evaluation. Asian J Pharm Sci 7:316–328

    Google Scholar 

  • Yamaoka K, Nakagawa T, Uno T (1978) Application of Akaike’s information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm 6:165–175

    Article  Google Scholar 

  • Yang R, Huang X, Dou J, Zhai G, Su L (2013) Self-microemulsifying drug delivery system for improved oral bioavailability of oleanolic acid: design and evaluation. Int J Nanomed 8:2917–2926

    Google Scholar 

  • Zhang P, Liu Y, Feng N, Xu J (2008) Preparation and evaluation of self microemulsifiying drug delivery system of oridonin. Int J Pharm 355:269–276

    Article  Google Scholar 

  • Zhang H, Zhang FM, Yan SJ (2012) Preparation, in vitro release, and pharmacokinetics in rabbits of lyophilized injection of sorafenib solid lipid nanoparticles. Int J Nanomed 7:2901–2910

    Article  Google Scholar 

Download references

Conflict of interest

All the authors report no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, PSG College of Pharmacy, Peelamedu, Coimbatore, 641004, Tamil Nadu, India

    Balakumar Krishnamoorthy, S. M. Habibur Rahman, N. Tamil selvan, M. Rajkumar, K. Vamshikrishna & Chellan Vijayaraghavan

  2. Department of Pharmaceutical Analysis, PSG College of Pharmacy, Peelamedu, Coimbatore, 641004, Tamil Nadu, India

    R. Hari prasad & M. Siva selvakumar

  3. Department of Biology, University of Minho, Braga, Portugal, Europe

    Marslin Gregory

Authors
  1. Balakumar Krishnamoorthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. M. Habibur Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. Tamil selvan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Hari prasad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Rajkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Siva selvakumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K. Vamshikrishna
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marslin Gregory
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chellan Vijayaraghavan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chellan Vijayaraghavan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Krishnamoorthy, B., Habibur Rahman, S.M., Tamil selvan, N. et al. Design, formulation, in vitro, in vivo, and pharmacokinetic evaluation of nisoldipine-loaded self-nanoemulsifying drug delivery system. J Nanopart Res 17, 34 (2015). https://doi.org/10.1007/s11051-014-2818-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11051-014-2818-z

Keywords

Search

Navigation