Conceptual design and optimization of self microemulsifying drug delivery systems for dapsone by using Box-Behnken design

Year 2021, Volume: 25 Issue: 2, 179 - 195, 27.06.2025

Jayashri Mahore Aniket Shelar Sanjeevani Deshkar Ghansham More

https://doi.org/10.29228/jrp.9

Abstract

Dapsone is a class II BCS with antibacterial and anti-inflammatory action. The goal of this study was to devise a dapsone (DP) system of solid self-microemulsifying drug delivery (S-SMEDDS). Various proportions of capryol 90 as an oil form, tween 80 as a surfactant and Labrasol as a co-surfactant were selected to prepare a pseudo ternary diagram for the self-microemulsifying drug delivery system (L-SMEDDS). The optimized formulation of L- SMEDDS (F8) containing capryol 90 (10 percent w/w), Tween 80 (67.5/5 w/w), and labrasol (22.5 percent w/w) showed the smallest particle size, less emulsification time, high optical clarity, in-vitro release and improved ex-vivo permeation. L-SMEDDDS was converted to S-SMEDDS by adsorbing on neusilin US2 and spray drying with aerosil 200. The effect of inlet temperature (A), feed flow rate (B) and carrier concentration (C) on particle size (Y1) and % practical yield (Y2) was studied using Box-Behnken design. Using the results of dependent variables, polynomial equations, surface response plots, and contour plots were developed. S-SMEDDS have been tested for flow properties, drug quality, reconstitution properties, DSC, XRD, SEM, drug release in vitro and anti-inflammatory activity in vivo. The present study showed the applicability of design of experiments (DOE) to optimize the process parameters needed to produce DP S-SMEDDS as an effective approach to improving its solubility.

Keywords

Self micro-emulsifying drug delivery system , labrasol , capryol 90 , Box-Behnken design , neusilin US2.

References

• [1] Kovvasu S, Kunamaneni P, Joshi R, Betageri G. Self-emulsifying drug delivery systems and their marketed products: a review. Asian J Pharm. 2019; 13(2): 73-84. [CrossRef]
• [2] Pouton C. 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(3-4): 278-87. [CrossRef]
• [3] Agrawal S, Giri T, Tripathi D, Azazuddin, Alexander A. A review on novel therapeutic srategies for the enhancement of solubiltiy for hydrophobic drugs through lipid and surfactant based Self micro emulsifying drug delivery system: A novel approach. Am J Drug Discov Dev. 2012; 2(4): 143-183. [CrossRef]
• [4] Shafiq S, Shakeel F, Talegaonkar S, Ahmad F, Khar R, Ali M. Development and bioavailability assessment of ramipril nanoemulsion formulation. Eur J Pharm Biopharm. 2007; 66(2): 227-243. [CrossRef]
• [5] Constantinides P. Lipid microemulsions for improving drug dissolution and oral absorption: physical andbiopharmaceutical aspects. Pharm Res. 1995; 12(11): 1561-1572. [CrossRef]
• [6] Sanghai B, Aggarwal G, HariKumar S. Solid self microemulsifying drug delivery system: a review. J Drug Deliv ther. 2013; 3(3): 168-174. [CrossRef]
• [7] Midha K, Nagpal M, Singh G, Aggarwal G. Prospectives of solid self-microemulsifying systems in novel drug delivery. Curr Drug Deliv. 2017; 14(8): 1078-1096. [CrossRef]
• [8] Mahore J, Suryawanshi S, Shirolkar S, Deshkar S. Enhancement of percutaneous delivery of dapsone by microemulsion gel. J Young Pharm. 2017; 9(4): 507. [CrossRef]
• [9] Legendre D, Muzny C, Swiatlo E. Hansen's disease (leprosy): current and future pharmacotherapy and treatment of disease‐related ımmunologic reactions. Pharmacotherapy. 2012; 32(1): 27-37. [CrossRef]
• [10] Bachhav Y, Patravale V. Microemulsion based vaginal gel of fluconazole: formulation, in-vitro and in-vivoevaluation. Int J Pharm. 2009; 365(1-2): 175-179. [CrossRef]
• [11] Deshkar SS, Bhalerao SG, Jadhav MS, Shirolkar SV. Formulation and optimization of topical solid lipid nanoparticles based gel of dapsone using design of experiment. Pharm Nanotechnol. 2018; 6(4): 264-75. [CrossRef]
• [1] Kovvasu S, Kunamaneni P, Joshi R, Betageri G. Self-emulsifying drug delivery systems and their marketed products: a review. Asian J Pharm. 2019; 13(2): 73-84. [CrossRef]
• [2] Pouton C. 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(3-4): 278-87. [CrossRef]
• [3] Agrawal S, Giri T, Tripathi D, Azazuddin, Alexander A. A review on novel therapeutic srategies for the enhancement of solubiltiy for hydrophobic drugs through lipid and surfactant based Self micro emulsifying drug delivery system: A novel approach. Am J Drug Discov Dev. 2012; 2(4): 143-183. [CrossRef]
• [4] Shafiq S, Shakeel F, Talegaonkar S, Ahmad F, Khar R, Ali M. Development and bioavailability assessment of ramipril nanoemulsion formulation. Eur J Pharm Biopharm. 2007; 66(2): 227-243. [CrossRef]
• [5] Constantinides P. Lipid microemulsions for improving drug dissolution and oral absorption: physical andbiopharmaceutical aspects. Pharm Res. 1995; 12(11): 1561-1572. [CrossRef]
• [6] Sanghai B, Aggarwal G, HariKumar S. Solid self microemulsifying drug delivery system: a review. J Drug Deliv ther. 2013; 3(3): 168-174. [CrossRef]
• [7] Midha K, Nagpal M, Singh G, Aggarwal G. Prospectives of solid self-microemulsifying systems in novel drug delivery. Curr Drug Deliv. 2017; 14(8): 1078-1096. [CrossRef]
• [8] Mahore J, Suryawanshi S, Shirolkar S, Deshkar S. Enhancement of percutaneous delivery of dapsone by microemulsion gel. J Young Pharm. 2017; 9(4): 507. [CrossRef]
• [9] Legendre D, Muzny C, Swiatlo E. Hansen's disease (leprosy): current and future pharmacotherapy and treatment of disease‐related ımmunologic reactions. Pharmacotherapy. 2012; 32(1): 27-37. [CrossRef]
• [10] Bachhav Y, Patravale V. Microemulsion based vaginal gel of fluconazole: formulation, in-vitro and in-vivoevaluation. Int J Pharm. 2009; 365(1-2): 175-179. [CrossRef]
• [11] Deshkar SS, Bhalerao SG, Jadhav MS, Shirolkar SV. Formulation and optimization of topical solid lipid nanoparticles based gel of dapsone using design of experiment. Pharm Nanotechnol. 2018; 6(4): 264-75. [CrossRef]
• [33] Wu X, Xu J, Huang X, Wen C. Self-microemulsifying drug delivery system improves curcumin dissolution and bioavailability. Drug Dev Ind Pharm. 2011; 37(1): 15-23. [CrossRef]
• [34] Parmar N, Singla N, Amin S, Kohli K. Study of cosurfactant effect on nanoemulsifying area and development of lercanidipine loaded (SNEDDS) self nanoemulsifying drug delivery system. Colloids Surf B. 2011; 86(2): 327-38. [CrossRef]
• [35] Patel A, Shelat P, Lalwani A. Development and optimization of solid self nanoemulsifying drug delivery (S-SNEDDS) using D-optimal design for improvement of oral bioavailability of amiodarone hydrochloride. Curr Drug Deliv. 2015; 12(6): 745-60. [CrossRef]
• [36] Kang B, Lee J, Chon S, Jeong S, Yuk S, Khang G, Lee H, Cho S. Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. Int J Pharm. 2004; 274(1-2): 65-73. [CrossRef]
• [37] Silva L, Almeida S, Alonso E, Rocha P, Martins F, Freitas L, Taveira S, Cunha-Filho M, Marreto R. Preparation of a solid self-microemulsifying drug delivery system by hot-melt extrusion. Int J Pharm. 2018; 541(1-2): 1-10. [CrossRef]
• [38] Patel P, Patel H, Panchal S, Mehta T. Self micro-emulsifying drug delivery system of tacrolimus: formulation, in vitro evaluation and stability studies. Int J Pharm Investig. 2013; 3(2): 95. [CrossRef]
• [39] Singh D, Tiwary A, Bedi N. Role of porous carriers in the biopharmaceutical performance of solid SMEDDS of canagliflozin. Recent patents on drug delivery & formulation. 2018; 12(3): 179-98. [CrossRef]
• [40] Monteiro L, Lione V, do Carmo F, do Amaral L, da Silva J, Nasciutti L, Rodrigues C, Castro H, de Sousa V, Cabral L. Development and characterization of a new oral DP nanoemulsion system: permeability and in silico bioavailability studies. Int J Nanomedicine 2012; (7): 5175. [CrossRef]
• [41] Dhome A, Deshkar S, Shirolkar S. Gliclazide solid lipid nanoparticles: formulation, optimization and ın vitrocharacterization. Pharmaceutical Resonance. 2018; 1(1): 8-16.
• [42] Bhagwat D, Souza J. Formulation and evaluation of solid self micro emulsifying drug delivery system using aerosil 200 as solid carrier. Int J Curr Pharm Res. 2012; 1(12): 414-419. [CrossRef]