DESIGN, PREPARATION, AND EVALUATION OF SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM OF BAMBUTEROL HYDROCHLORIDE
Objective: The self-micro-emulsifying drug delivery system (SMEDDS) of bambuterol hydrochloride was designed, prepared, and evaluated to overcome the problem of poor bioavailability.
Methods: The designing of the formulation included the selection of oil phase, surfactant, and cosolvent/cosurfactant based on the saturated solubility studies. Psuedoternary phase diagram was constructed using aqueous titration method, to identify the self-emulsifying region. Different ratios of the selected surfactant and cosolvent/cosurfactant (Smix) were also studied and used to construct the ternary phase diagram. The prepared formulations of the SMEDDS were evaluated for drug content, morphology, globule size, robustness to dilution, emulsification time, optical clarity, and stability.
Results: The formulation containing 10 mg bambuterol hydrochloride, triacetin (12.50% w/w), Tween 80 (43.75% w/w), and ethanol (43.75% w/w) was concluded to be optimized. The optimized SMEDDS not only showed optimum globule size, zeta potential, and drug content but was also found to be robust to dilution, formed emulsion spontaneously, and was stable. The optimized SMEDDS showed increased permeability of the drug across the intestinal membrane in ex vivo studies.
Conclusion: The results suggest that bambuterol hydrochloride can be formulated as self-microemulsifying drug delivery system, and further, SMEDDS can be used to improve the oral bioavailability of bambuterol hydrochloride.
3. Gershanik T, Benita S. Self-dispersing lipid formulations for improving oral absorption of lipophilic drugs. Eur J Pharm Biopharm 2000;50:179-88.
4. Gursoy RN, Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biome Pharmacother 2004;58:173-82.
5. ?eki? L, Primorac M. Microemulsion and Nanoemulsions as Carrier for Delivery of NSAIDS: Formulation Challenges and Potential Benefits. Cambridge, MA: Academic Press; 2017. p. 69-94.
6. Pouton CW. SEDDS: Assessment of the efficiency of emulsification. Int J Pharm 1985;27:335-48.
7. Shah NH, Carvajal MT, Patel CI, Infeld MH, Malick AW. Self-emulsifying drug delivery systems (SEDDS) with poly glycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophillic drugs. Int J Pharm 1994;106:15-23.
8. Chitneni M, Peh KK, Darwis D, Abdulkarim M, Abdullah GZ, Qureshi MJ, et al. Intestinal permeability studies of sulpiride incorporated into self-microemulsifying drug delivery system (SMEDDS). Pak J Pharm Sci 2011;24:113-21.
9. Wasan KM. Drug Dev Ind Pharm 2001;27:267-76.
10. Serajuddin AT, Sheen PC, Mufson D, Bernstein DF, Augustine MA. Effect of vehicle amphiphilicity on the dissolution and bioavailability of a poorly water-soluble drug from solid dispersions. J Pharm Sci 1988;77:414-7.
11. Porter CJ, Pouton CW, Cuine JF, Charman WN. Enhancing intestinal drug solubilisation using lipid-based delivery systems. Adv Drug Deliv Rev 2008;60:673-91.
12. Porter CJ, Charman WN. In vitro assessment of oral lipid based formulations. Adv Drug Deliv Rev 2001;50 Suppl 1:S127-47.
13. Chen ML. Lipid excipients and delivery systems for pharmaceutical development: A regulatory perspective. Adv Drug Deliv Rev 2008;60:768-77.
14. Stationary Office Books. The British Pharmacopoeia. Vol. 1. London: Stationary Office Books; 2001.
15. Rosenborg J, Larsson P, Nyberg L. Pharmacokinetics of bambuterol during oral administration of plain tablets and solution to healthy adults. Br J Clin Pharmacol Mar 2000;49:199-206.
16. Nyberg L, Rosenborg J, Weibull E, Nilsson M, Jönsson S, Kennedy B. Pharmacokinetics of bambuterol in healthy subjects. Br J Clin Pharmacol 1998;45:471-8.
17. Sabale V, Vora S. Formulation and evaluation of microemulsion-based hydrogel for topical delivery. Int J Pharm Investig 2012;2:140-9.
18. Gaikwad S, Godbole M, Potnis V, Daud A. Formulation and evaluation of self-emulsifying drug delivery system of orlistat. Am J PharmTech Res 2012;2:297-311.
19. Jaiswal P, Aggarwal G, Harikumar SL, Singh K. Development of self-microemulsifying drug delivery system and solid-self-microemulsifying drug delivery system of telmisartan. Int J Pharm Investig 2014;4:195-206.
20. Deshmukh A, Kulkarni S. Novel self-micro-emulsifying drug delivery system (SMEDDS) of efavirez. J Chem Pharm Res 2012;4:3914-19.
21. Modi J. Formulation and evaluation of nanoemulsion based drug delivery of NSAIDS. Int J Pharm Pharm Sci Res 2012;1:6-12.
22. Ahmad J, Amin S, Hohli K, Mir SR. Construction of pseudoternary phase diagram and its evaluation: Development of dispersible oral formulation. Int J Drug Dev Res 2013;5:84-90.
23. Syed HK, Peh KK. Identification of phases of various oil, surfactant/co-surfactants and water system by ternary phase diagram. Acta Poloniae Pharm Drug Res 2014;71:301-9.
24. Prajapati S, Joshi H, Patel C. Preparation and characterization of self-micro-emulsifying drug delivery system of olmesartan medoxomil for bioavailability improvement. J Pharm 2013;Article ID: 728425, 9 Pages.
25. Kasturi M, Aggrawal S, Jadav JK. Self nanoemulsifying drug delivery sytem of ramipril formulation and in vitro evaluation. Int J Pharm Pharm Sci 2016;8:291-6.
26. Deshmukh SR, Bakhle SS, Upadhye K, Dixit GR. Formulation and evaluation of solid self-emulsifying drug delivery system of gliclazide. Int J Pharm Pharm Sci 2016;8:144-51.
27. Liu W, Pan H, Zhang C, Zhao L, Zhao R, Zhu Y, et al. Developments in methods for measuring the intestinal absorption of nanoparticle-bound drugs. Int J Mol Sci 2016;17:pii: E1171.
28. Waiver of in vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System: Guidance for Industry: U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER); 2017.
29. Jang DJ, Jeong EJ, Lee HM, Kim BC, Lim SJ, Kim CK, et al. Improvement of bioavailability and photostability of amlodipine using redispersible dry emulsion. Eur J Pharm Sci 2006;28:405-11.
30. Nazzal S. Preparation and in vitro characterization of a eutectic based semisolid self-nanoemulsified drug delivery system (SNEDDS) of ubiquinone: Mechanism and progress of emulsion formation. Int J Pharm 2002;235:247-65.
31. Raval M, Patel J, Patel A, Sheth N. Formulation and development of a self-nanoemulsifying drug delivery system of irbesartan. AAPS J 2011;2:9-16.
32. Charman SA, Charman WN, Rogge MC, Wilson TD, Dutko FJ, Pouton CW. Self-emulsifying drug delivery systems: Formulation and biopharmaceutic evaluation of an investigational lipophilic compound. Pharm Res 1992;9:87-93.
33. Prieto C, Calvo L. Performance of the biocompatible surfactant tween 80, for the formulation of microemulsions suitable for new pharmaceutical processing. J Appl Chem 2013;Article ID 930356, 10 Pages.
34. Reekmans S, Luo H, Van Der Auweraer M, De Schryver FC. Influence of alcohols and alkanes on the aggregation behavior of ionic surfactants in wate. Langmuir 1990;6:628-37.
35. Bayrak Y, Iscan M. Studies on the phase behavior of the system non-ionic surfactant/alcohol/alkane/H2O/. Colloids Surfaces A 2005;268:99-103.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.