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Preparation and Evaluation of Efavirenz Loaded Solid Lipid Nanoparticle for Improving Oral Bioavailability


Affiliations
1 Department of Pharmacy, Pranveer Singh Institute of Technology, Kanpur, India
     

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Efavirenz (EFV) is a highly lipophilic, oral non-nucleoside reverse transcriptase inhibitor reported to have poor aqueous solubility and bioavailability used for the treatment of HIV. In the present research work, solid lipid nanoparticles loaded with efavirenz were formulated for oral drug delivery and to increase the bioavailability of efavirenz. Solid lipid nanoparticles loaded with efavirenz were prepared through the microemulsion method followed by the lyophilization technique using glyceryl monostearate as lipid and Tween 80 as a surfactant. Solid lipid nanoparticle formulation was evaluated using different parameters including Scanning electron microscopy (SEM), drug entrapment efficiency (EE%), in vitro drug release study, differential scanning calorimetry, and powder X-ray diffractometry. Solid lipid nanoparticles loaded efavirenz showed 60.41% drug entrapment. Differential scanning calorimetry and powder X-ray diffractometry study indicate solid lipid nanoparticles loaded efavirenz is crystalline, stable and there is no interaction between the excipients and drug. In vitro drug release study of EFV-SLN showed 88.2±0.12% drug release which is better as compared to marketed formulation drug release. EFV-SLN drug release study data demonstrated a better fit for the first-order kinetics and confirmed the non-Fickian-diffusion mechanism. Prepared SLN formulation has shown good stability at 45∘C and 75% relative humidity (RH) for 150 days. These results determined that the developed EFV-SLN formulation exhibited a promising antiviral activity to treat HIV and has great potential for boosting the oral bioavailability of Efavirenz.

Keywords

Bioavailability, Efavirenz, In vitro drug release study, Microemulsion method, oral drug delivery, Solid lipid nanoparticle.
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  • UNAIDS. Global HIV and AIDS statistics- 2019 fact sheet. Available from: URL:https://www.unaids.org/en/resources/fact-sheet (Accessed 2017).

  • Duzgunes N, et al. Delivery of antiviral agents in liposomes. Methods in Enzymology. 2005; 391:351-73.

  • Clercq ED. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. International Journal of Antimicrobial Agents. 2009; 33:307–320.

  • Gupta U and Jain NK. Non-polymeric nanocarriers in HIV/AIDS drug delivery and targeting. Advanced Drug Delivery Reviews. 2010; 62:478–490.

  • Sosnik A, Chiappetta DA and Carcaboso AM. Drug delivery in HIV pharmacotherapy: what has been done and the challenges standing ahead. Journal of Controlled Release. 2009;138:2–15.

  • Khan MY, et al.. Formulation and Evaluation of Efavirenz 600 mg Tablet. Asian Journal of Research in Pharmaceutical Science. 2015; 5(3):153-167.

  • Vidyadhara S, et al. Simultaneous UV Spectrophotometric Method for the Determination of Tenofovir, Efavirenz and Lamivudine in Bulk and Combined Dosage Form. Asian Journal of Pharmaceutical Analysis. 2016; 6(4):253-258.

  • Rabel SR, Maurin MB, Rowe SM and Hussain M. Determination of the pKa and pH-solubility behavior of an ionizable cyclic carbamate, (S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one(DMP 266). Pharmaceutical Development and Technology. 1996; 1:91–95.

  • DrugBank. Efavirenz. Available from: URL: https://www.drugbank.ca/drugs/DB00625 (Accessed June 13, 2005).

  • Sustiva® Prescribing Information. Bristol-Myers Squibb Company. Available from: URL:http://www.sustiva.com (Accessed October, 2017).

  • Chiappetta DA, Hocht C, Taira C and Sosnik A. Oral pharmacokinetics of the anti-HIV efavirenz encapsulated within polymeric micelles. Biomaterials. 2011; 32:2379–2387.

  • Mistry A, Stolnik S and Illum L. Nanoparticles for direct nose-to-brain delivery of drugs. International Journal of Pharmaceutics. 2009; 379:146–157.

  • Smith PF, DiCenzo R and Morse GD. Clinical pharmacokinetics of non-nucleoside reverse transcriptase inhibitors. Clinical Pharmacokinetic. 2001; 40:893–905.

  • Staszewski S, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. The New England Journal of Medicine. 1999; 341:1865–1873.

  • Wong HL, Wu XY and Bendayan R. Nanotechnological advances for the delivery of CNS therapeutics. Advanced Drug Delivery Reviews. 2012; 64:686–700.

  • Mallipeddi R and Rohan LC. Progress in antiretroviral drug delivery using nanotechnology. International Journal of Nanomedicine. 2010; 5:533–547.

  • Vakhariya RR, et al. Formulation Development and Optimization of Simvastatin Loaded Solid Lipid Nanoparticles. Asian J. Res. Pharm. Sci. 2017; 7(1): 49-52.

  • Bhairav BA, Bachhav JA, Saudagar RB. Review on Solubility Enhancement Techniques. Asian J. Pharm. Res. 2016; 6(3): 147-152.

  • Fundaro A, et al. Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin: pharmacokinetics and tissue distribution after i.v. administration to rats. Pharmacological Research. 2000; 42:337-43.

  • Iqbal MA, et al. Nanostructured lipid carrier’s system: recent advances in drug delivery. Journal of Drug Targeting. 2012; 20:813–830.

  • Mehnert W and Mader K. Solid lipid nanoparticles: production, characterization and applications. Advanced Drug Delivery Reviews. 2001; 47:165–196.

  • Wake PS, Kshirsagar MD. Design and Characterization of Solid Lipid Nanoparticle Based Transdermal Drug Delivery System. Asian J. Res. Pharm. Sci. 2017; 7(2): 87-91.

  • Shah R, Eldridge D, Palombo E and Harding I. Optimisation and stability assessment of solid lipid nanoparticles using particle size and zeta potential. Journal of Physical Science. 2014; 25:59–75.

  • Ebrahimi HA, Javadzadeh Y, Hamidi M and Jalali MB. Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles. DARU Journal of Pharmaceutical Sciences. 2015; 23:1-46.

  • Blasi P, et al. Solid lipid nanoparticles for targeted brain drug delivery. Advanced Drug Delivery Reviews. 2009; 59:454–477.

  • Khairnar DA, et al. A Review on Self- Micro Emulsifying Drug Delivery System: Evident to improve the oral bioavailability of hydrophobic drugs. Asian J. Pharm. Tech. 2016; 6(2): 131-134.

  • Indian Pharmacopoeia. Government of India Ministry of Health and Family Welfare. The Indian Pharmacopoeia Commission, Ghaziabad. 2014.

  • Kalaycioglu GD and Aydogan N. Preparation and investigation of solid lipid nanoparticles for drug delivery. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2016; 510:77-86.

  • Ashok P, et al. Irbesartan Formulation and Evaluation of Loaded Solid Lipid Nanoparticles by Microemulsion Techinque. Asian J. Pharm. Tech. 2020; 10(4):228-230.

  • Gaur PK, Mishra S, Bajpai M and Mishra A. Enhanced Oral Bioavailability of Efavirenz by Solid Lipid Nanoparticles: In Vitro Drug Release and Pharmacokinetics Studies. BioMed Research International. 2014;1:1-9.

  • Zaini E, Wahyu D, Octavia MD and Fitriani L. Influence of Milling Process on Efavirenz Solubility. Journal of Pharmacy and Bioallied Sciences. 2017; 9:22-25.

  • Katara R and Majumdar DK. Eudragit RL 100-based nanoparticulate system of aceclofenac for ocular delivery. Colloids and Surfaces B: Biointerfaces. 2013;103: 455–462.

  • Bisen A, Jain AP, Jain S. Formulation and Evaluation of Zidovudine Loaded Microsphere. Asian J. Res. Pharm. Sci. 2013; 3(4):200-205.

  • Youshia J, Kamel AO, Shamy AE and Mansour S. Design of cationic nanostructured heterolipid matrices for ocular delivery of methazolamide. International Journal of Nanomedicine. 2012; 7:2483–2496.

  • Kulkarni SB, et al. Formulation and Evaluation of Immediate Release Tablet of Efavirenz by Micellar Solubilization Technique. Asian J. Pharm. Res. 2019; 9(1): 12-18.

  • Das S, Suresh PK and Desmukh R. Design of Eudragit RL 100 nanoparticles by nanoprecipitation method for ocular drug delivery. Nanomedicine: Nanotechnology, Biology, and Medicine. 2010; 6:318–323.

  • Khare A, Singh I, Pawar P and Grover K. Design and Evaluation of Voriconazole Loaded Solid Lipid Nanoparticles for Ophthalmic Application. Journal of Drug Delivery. 2016;1:1-11.

  • Rasheed N, et al. Simultaneous Formulation Development, Evaluation and Estimation of Innovative Controlled Release Tablets of Bosentan Formulated with Varied Polymers. Asian J. Pharm. Ana. 2016; 6(4): 235-245.

  • Sruthi S, Kaparthi S, Babu PRS and Subrahmanyam CVS. Formulation and in-vitro evaluation of efavirenz liquisolid compacts. International Journal of Pharmacy and Pharmaceutical Science. 2016; 8(1):137-143.

  • Pokharkar V, Patil-Gadhe A and Palla P. Efavirenz loaded nanostructured lipid carrier engineered for brain targeting through intranasal route: In-vivo pharmacokinetic and toxicity study. Biomedicine and Pharmacotherapy. 2017; 94(1):150–164.


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  • Preparation and Evaluation of Efavirenz Loaded Solid Lipid Nanoparticle for Improving Oral Bioavailability

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Authors

Ashish Srivastava
Department of Pharmacy, Pranveer Singh Institute of Technology, Kanpur, India
Harshita Gupta
Department of Pharmacy, Pranveer Singh Institute of Technology, Kanpur, India

Abstract


Efavirenz (EFV) is a highly lipophilic, oral non-nucleoside reverse transcriptase inhibitor reported to have poor aqueous solubility and bioavailability used for the treatment of HIV. In the present research work, solid lipid nanoparticles loaded with efavirenz were formulated for oral drug delivery and to increase the bioavailability of efavirenz. Solid lipid nanoparticles loaded with efavirenz were prepared through the microemulsion method followed by the lyophilization technique using glyceryl monostearate as lipid and Tween 80 as a surfactant. Solid lipid nanoparticle formulation was evaluated using different parameters including Scanning electron microscopy (SEM), drug entrapment efficiency (EE%), in vitro drug release study, differential scanning calorimetry, and powder X-ray diffractometry. Solid lipid nanoparticles loaded efavirenz showed 60.41% drug entrapment. Differential scanning calorimetry and powder X-ray diffractometry study indicate solid lipid nanoparticles loaded efavirenz is crystalline, stable and there is no interaction between the excipients and drug. In vitro drug release study of EFV-SLN showed 88.2±0.12% drug release which is better as compared to marketed formulation drug release. EFV-SLN drug release study data demonstrated a better fit for the first-order kinetics and confirmed the non-Fickian-diffusion mechanism. Prepared SLN formulation has shown good stability at 45∘C and 75% relative humidity (RH) for 150 days. These results determined that the developed EFV-SLN formulation exhibited a promising antiviral activity to treat HIV and has great potential for boosting the oral bioavailability of Efavirenz.

Keywords


Bioavailability, Efavirenz, In vitro drug release study, Microemulsion method, oral drug delivery, Solid lipid nanoparticle.

References