International Journal of Drug Delivery Technology
Volume 14, Issue 1

Formulation, Optimization and Evaluation of Solid SMEDDS of Pioglitazone

Manisha R Patil*, Sanjay K Kshirsagar

Department of Pharmaceutics, MET’s Institute of Pharmacy, Affiliated to Savitribai Phule Pune University, Nashik, Maharashtra, India. 

Received: 15th July, 2023; Revised: 31st January, 2024; Accepted: 29th February, 2024; Available Online: 25th March, 2024

ABSTRACT

This investigation assessed 32 formulations of liquid self-microemulsifying drug delivery system (L-SMEDDS) for pioglitazone (PGZ). The optimal PLS12 formulation comprises 40% capmul MC8 (oil), 40% cremophore RH40 (surfactant), and 20% PEG (co-surfactant). PLS12 exhibited approximately 75 nm droplet size, below 200 nm, and a PDI of 0.47, indicating nanosized droplets with uniform distribution. The formulation demonstrated stability, and achieved supreme drug loading capacity. The enhanced L-SMEDDS was solidified into solidified SMEDDS utilizing Sylloid 244 FP, subsequently in a free-flowing powder without drug interactions. Tablets were successfully formulated by incorporating S-SMEDDS with diverse tableting excipients. The selected tablet batch passed quality control and stability tests. The tablet exhibited a rapid and pH-independent release profile. The combined impact of SMEDDS and tablets collectively enhanced the solubility and dissolution of PGZ hydrochloride.

Keywords: Tablets, Solidified SMEDDS, Hardness, PGZ hydrochloride, Solubility enhancement, SEM, Bioavailability

enhancement.

International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.1.21

How to cite this article: Patil MR, Kshirsagar SK. Formulation, Optimization and Evaluation of Solid SMEDDS of Pioglitazone. International Journal of Drug Delivery Technology. 2024;14(1):145-159.

REFERENCE

  1. Lipinski Poor aqueous solubility—an industry wide problem in drug discovery. Am. Pharm. Rev. 2002 Nov;5(3):82-5. DOI: http://www.americanpharmaceuticalreview.com/past_articles/3_ APR_Fall_2002/Lipinski_article.htm
  2. Weuts I, Kempen D, Decorte A, Verreck G, Peeters J, Brewster M, Van den Mooter Phase behaviour analysis of solid dispersions of loperamide and two structurally related compounds with the polymers PVP-K30 and PVP-VA64. European journal of pharmaceutical sciences. 2004 Aug 1;22(5):375-85. DOI: https:// doi.org/10.1016/j.ejps.2004.04.002
  3. Ammar HO, Salama HA, Ghorab M, Mahmoud Implication of inclusion complexation of glimepiride in cyclodextrin–polymer systems on its dissolution, stability and therapeutic efficacy. International journal of pharmaceutics. 2006 Aug 31;320(1-2):53-DOI: https://doi.org/10.1016/j.ijpharm.2006.04.002
  4. Aungst BJ. Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism. Journal of pharmaceutical sciences. 1993 Oct 1;82(10):979-87. DOI: https://doi.org/10.1002/ 2600821008
  5. Kolimi P, Narala S, Youssef AA, Nyavanandi D, Dudhipala N. A systemic review on development of mesoporous nanoparticles as a vehicle for transdermal drug delivery. Nanotheranostics. 2023;7(1):70. DOI: https://doi.org/10.7150/ntno.77395
  6. Humberstone AJ, Charman Lipid-based vehicles for the oral delivery of poorly water soluble drugs. Advanced drug delivery reviews. 1997 Apr 14;25(1):103-28. DOI: https://doi.org/10.1016/ S0169-409X(96)00494-2
  7. Scientific Discussion, European Medicines Agency. Shaping regulatory science to 2025. DOI: https://www.ema.europa. eu/en/news/shaping-regulatory-science-2025 Last accessed December 2023.
  8. Constantinides PP. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharmaceutical research. 1995 Nov;12:1561-72. DOI: https://doi.org/10.1023/A:1016268311867
  9. Ghosh PK, Murthy Microemulsions: a potential drug delivery system. Current drug delivery. 2006 Apr 1;3(2):167-80. DOI: https://doi.org/10.2174/156720106776359168
  10. Shi NQ, Lei YS, Song LM, Yao J, Zhang XB, Wang Impact of amorphous and semicrystalline polymers on the dissolution and crystallization inhibition of pioglitazone solid dispersions. Powder technology. 2013 Oct 1;247:211-21. DOI: https://doi. org/10.1016/j.powtec.2013.06.039
  11. Soltanpour S, Acree WE, Jouyban Solubility of pioglitazone hydrochloride in aqueous solutions of ethanol, propylene glycol, and N-methyl-2-pyrrolidone at 298.2 K. AAPS PharmSciTech. 2009 Dec;10:1153-7. DOI: https://doi.org/10.1208/s12249-009-9322-2
  12. Rafiee MH, Rasool BK, Haider M, Anbar Oral pioglitazone HCl-loaded solid lipid microparticles: Formulation design and bioactivity studies. Journal of Applied Pharmaceutical Science. 2023 Feb 5;13(2):161-74. DOI: http://dx.doi.org/10.7324/ JAPS.2023.130218
  13. Pandit V, Gorantla R, Devi K, Pai RS, Sarasija S. Preparation and characterization of pioglitazone cyclodextrin inclusion Journal of young pharmacists. 2011 Oct 1;3(4):267-74. DOI: https://doi.org/10.4103/0975-1483.90234
  14. Pandit V, Pai RS, Devi K, Suresh S. In vitro-in vivo evaluation of fast-dissolving tablets containing solid dispersion of pioglitazone hydrochloride. Journal of Advanced Pharmaceutical Technology & 2012 Jul;3(3):160-70. DOI: https://doi. org/10.4103%2F2231-4040.101008
  15. Hyma P, Abulu K. SMEDDS formulation: demonstration of enhanced bioavailability of pioglitazone in rats. International journal of pharmacy and pharmaceutical 2014;6(2):662-DOI: ht t ps:// in novareacademics.in / jour nal/ ijpps/ Vol6Suppl2/8564.pdf
  16. Fatouros DG, Karpf DM, Nielsen FS, Mullertz Clinical studies with oral lipid based formulations of poorly soluble compounds. Therapeutics and clinical risk management. 2007 Aug 30;3(4):591-604. DOI: https://doi.org/10.2147/tcrm.s12160436
  17. Gumaste SG, Dalrymple DM, Serajuddin Development of solid SEDDS, V: compaction and drug release properties of tablets prepared by adsorbing lipid-based formulations onto Neusilin® US2. Pharmaceutical research. 2013 Dec;30:3186-99. DOI: https://doi.org/10.1007/s11095-013-1106-4
  18. Shahba AA, Ahmed AR, Alanazi FK, Mohsin K, Abdel-Rahman SI. Multi-layer self-nanoemulsifying pellets: An innovative drug delivery system for the poorly water-soluble drug cinnarizine. Aaps Pharmscitech. 2018 Jul;19:2087-102. DOI: https://doi. org/10.1208/s12249-018-0990-7
  19. Khanfar M, Al-Nimry S. Stabilization and amorphization of lovastatin using different types of silica. AAPS PharmSciTech. 2017 Aug;18:2358-67. DOI: https://doi.org/10.1208/s12249-017-0717-1
  20. Abd-Elhakeem E, Teaima MH, Abdelbary GA, El Mahrouk Bioavailability enhanced clopidogrel-loaded solid SNEDDS: development and in-vitro/in-vivo characterization. Journal of Drug Delivery Science and Technology. 2019 Feb 1;49:603-14. DOI: https://doi.org/10.1016/j.jddst.2018.12.027
  21. Zhang P, Liu Y, Feng N, Xu Preparation and evaluation of self- microemulsifying drug delivery system of oridonin. International journal of pharmaceutics. 2008 May 1;355(1-2):269-76. DOI: https://doi.org/10.1016/j.ijpharm.2007.12.026
  22. Narala S, Komanduri N, Nyavanandi D, Youssef AA, Mandati P, Alzahrani A, Kolimi P, Narala N, Repka MA. Hard gelatin capsules containing hot melt extruded solid crystal suspension of carbamazepine for improving dissolution: Preparation and in vitro Journal of Drug Delivery Science and Technology. 2023 Apr 1; 82:104384. DOI: https://doi. org/10.1016/j.jddst.2023.104384
  23. Shafiq S, Shakeel F, Talegaonkar S, Ahmad FJ, Khar RK, AliDevelopment and bioavailability assessment of ramipril nanoemulsion formulation. European journal of pharmaceutics and biopharmaceutics. 2007 May 1;66(2):227-43. DOI: https://doi.org/10.1016/j.ejpb.2006.10.014
  24. Pandey V, Kohli SMEDDS of pioglitazone: Formulation, in-vitro evaluation and stability studies. Future Journal of Pharmaceutical Sciences. 2017 Jun 1;3(1):53-9. DOI: https://doi. org/10.1016/j.fjps.2017.02.003
  25. Teaima M, Hababeh S, Khanfar M, Alanazi F, Alshora D, El-Nabarawi M. Design and optimization of pioglitazone hydrochloride self-nanoemulsifying drug delivery system (SNEDDS) incorporated into an orally disintegrating tablet. 2022 Feb 16;14(2):425. DOI: https://doi. org/10.3390/pharmaceutics14020425
  26. Kaushik D, Malik J, Sardana S. Formulation and Evaluation of Self Nano- emulsifying Dr ug Deliver y System of Nifedipine. International Journal of Drug Delivery Technology 2015;5(4):132-137. DOI: http://impactfactor.org/PDF/IJDDT/5/ IJDDT,Vol5,Issue4,Article2.pdf
  27. Al-Tamimi DJ, Hussien AA. Preparation and In-vitro Characterization of Tacrolimus as a Solid Self-micro-emulsion. International Journal of Drug Delivery 2021;11(1):70-DOI: 10.25258/ijddt.11.1.12.
  28. Annisa R, Yuwono M, Hendradi Effect of vegetable oil on self- nanoemulsifying drug delivery system of dayak onion [Eleutherine palmifolia (L.) Merr.] extract using hydrophilic-lipophilic balance approach: formulation, characterization. International Journal of Drug Delivery Technology. 2020;10(2):210-216. DOI: 10.25258/ ijddt.10.2.4.
  29. Aarti N, Ravindra Formulation and Evaluation of Fenofibrate Dry Emulsion Tablets by Freeze Drying Method. International Journal of Pharmaceutical Quality Assurance. 2022;13(4):369-76. DOI: 10.25258/ijpqa.13.4.05.