Development of Darunavir Loaded Solid Self Micro Emulsifying Drug Delivery System for Enhanced Solubility and Dissolution using Box–Behnken designs

Main Article Content

Mahesh Manohar Biradar
Parul Mehta

Abstract

The purpose of the current work was to develop S-SMEDDS of Darunavir (DRV), which falls under BCS Class II, by using Box-Behnken designs for improved solubility and dissolution. In the solubility investigation of DRV, oleic acid, Tween 80, and Transcutol P were selected as oils, surfactants, and co-surfactants, respectively, and the impact of their concentrations on globule size, zeta potential, and liquid SMEDDS was investigated using a box-Behnken design. Liquid SMEDDS were developed and evaluated in twelve separate batches (DRVL1 to DRVL12). As a solid carrier, Neusilin US2 is used in an adsorption method; four successful batches (DRVS1 to DRVS4) of liquid SMEDDS were then transformed into solid form. In-vitro drug release study DRVS4 of batch S-SMEDDS released 85.792 percent of DRV in 60 min, as compared to 22.532 percent of plain DRV. The study's findings suggest that a potential method for improving the solubility, dissolution, and simultaneous bioavailability of DRV is S-SMEDDS.

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How to Cite
Mahesh Manohar Biradar, & Parul Mehta. (2022). Development of Darunavir Loaded Solid Self Micro Emulsifying Drug Delivery System for Enhanced Solubility and Dissolution using Box–Behnken designs. Journal of Coastal Life Medicine, 10(3), 414–432. Retrieved from https://www.jclmm.com/index.php/journal/article/view/215
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References

Corrêa JC, D’Arcy DM, dos Reis Serra CH, Salgado HR. Darunavir: a critical review of its properties, use and drug interactions. Pharmacology. 2012;90(1-2):102-9.

Deeks ED. Darunavir: a review of its use in the management of HIV-1 infection. Drugs. 2014 ;74(1):99-125.

Lascar RM, Benn P. Role of darunavir in the management of HIV infection. HIV/AIDS (Auckland, NZ). 2009;1:31.

Desai J, Thakkar H. Enhanced oral bioavailability and brain uptake of Darunavir using lipid nanoemulsion formulation. Colloids Surf B Biointerfaces. 2019;175:143-149.

McKeage K, Perry CM, Keam SJ. Darunavir. Drugs. 2009;69(4):477-503.

Rittweger M, Arastéh K. Clinical pharmacokinetics of darunavir. Clin Pharmacokinet. 2007;46(9):739-56. doi: 10.2165/00003088-200746090-00002. PMID: 17713972.

Sosnik A, Chiappetta DA, Carcaboso AM. Drug delivery systems in HIV pharmacotherapy: what has been done and the challenges standing ahead. J Control Release. 2009;138(1):2-15. doi: 10.1016/j.jconrel.2009.05.007. Epub 2009 May 13. PMID: 19445981.

Dash RN, Mohammed H, Humaira T, Ramesh D. Design, optimization and evaluation of glipizide solid self-nanoemulsifying drug delivery for enhanced solubility and dissolution. Saudi Pharm J. 2015;23(5):528-40. doi: 10.1016/j.jsps.2015.01.024. Epub 2015 Feb 19. PMID: 26594119; PMCID: PMC4605912.

Parmar K, Patel J, Sheth N. Self nano-emulsifying drug delivery system for Embelin: Design, characterization and in-vitro studies. Asian Journal of Pharmaceutical Sciences. 2015;10:396–404. doi: 10.1016/j.ajps.2015.04.006.

Nazzal S, Smalyukh II, Lavrentovich OD, Khan MA. 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(1-2):247-65. doi: 10.1016/s0378-5173(02)00003-0. PMID: 11879759.

Oh DH, Kang JH, Kim DW, Lee BJ, Kim JO, Yong CS, Choi HG. Comparison of solid self-microemulsifying drug delivery system (solid SMEDDS) prepared with hydrophilic and hydrophobic solid carrier. Int J Pharm. 2011;420(2):412-8. doi: 10.1016/j.ijpharm.2011.09.007. Epub 2011 Sep 16. PMID: 21944892.

Cho HJ, Lee DW, Marasini N, Poudel BK, Kim JH, Ramasamy T, Yoo BK, Choi HG, Yong CS, Kim JO. Optimization of self-microemulsifying drug delivery system for telmisartan using Box-Behnken design and desirability function. J Pharm Pharmacol. 2013;65(10):1440-50. doi: 10.1111/jphp.12115. Epub 2013 Jul 24. PMID: 24028611.

Singh M. K., Chandel V., Gupta V., Ramteke S. Formulation development and characterization of microemulsion for topical delivery of Glipizide, Der Pharmacia Lettre.2010; 2(3): 33-42.

Mandal S, Mandal SnigdhaS. Microemulsion Drug Delivery System: A Platform for Improving Dissolution Rate of Poorly Water Soluble Drug. International Journal of Pharmaceutical Sciences and Nanotechnology. 2011;3:1214–1219. doi: 10.37285/ijpsn.2010.3.4.6.

Kang BK, Lee JS, Chon SK, Jeong SY, Yuk SH, Khang G, Lee HB, Cho SH. 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. doi: 10.1016/j.ijpharm.2003.12.028. PMID: 15072783.

Cho HJ, Lee DW, Marasini N, Poudel BK, Kim JH, Ramasamy T, Yoo BK, Choi HG, Yong CS, Kim JO. Optimization of self-microemulsifying drug delivery system for telmisartan using Box-Behnken design and desirability function. J Pharm Pharmacol. 2013;65(10):1440-50. doi: 10.1111/jphp.12115. Epub 2013 Jul 24. PMID: 24028611.

Shafiq S, Shakeel F, Talegaonkar S, Ahmad FJ, Khar RK, Ali M. Development and bioavailability assessment of ramipril nanoemulsion formulation. European Journal of Pharmaceutics and Biopharmaceutics. 2007;66:227–243. doi: 10.1016/j.ejpb.2006.10.014.

Bhagwat DA, D’Souza JI. Formulation and evaluation of solid self micro emulsifying drug delivery system using aerosil 200 as solid carrier. International Current Pharmaceutical Journal [Internet]. 2012;1:414–419. doi: 10.3329/icpj.v1i12.12451.

Khoo S-M, Humberstone AJ, Porter CJH, Edwards GA, Charman WN. Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrine. International Journal of Pharmaceutics. 1998;155 – 164.

Bhagwat DA, Swami PA, Nadaf SJ, Choudhari PB, Kumbar VM, More HN, Killedar SG, Kawtikwar PS. Capsaicin Loaded Solid SNEDDS for Enhanced Bioavailability and Anticancer Activity: In-Vitro, In-Silico, and In-Vivo Characterization. J Pharm Sci. 2021;110(1):280-291. doi: 10.1016/j.xphs.2020.10.020. Epub 2020 Oct 15. PMID: 33069713.

Patel PV, Patel HK, Panchal SS, Mehta TA. Self micro-emulsifying drug delivery system of tacrolimus: Formulation, in vitro evaluation and stability studies. Int J Pharm Investig. 2013;3(2):95-104. doi: 10.4103/2230-973X.114899. PMID: 24015381; PMCID: PMC3757905.

Dixit AR, Rajput SJ, Patel SG. Preparation and bioavailability assessment of SMEDDS containing valsartan. AAPS PharmSciTech. 2010;11(1):314-21. doi: 10.1208/s12249-010-9385-0. Epub 2010 Feb 25. PMID: 20182825; PMCID: PMC2850450.

Cho W, Kim MS, Kim JS, Park J, Park HJ, Cha KH, Park JS, Hwang SJ. Optimized formulation of solid self-microemulsifying sirolimus delivery systems. Int J Nanomedicine. 2013;8:1673-82. doi: 10.2147/IJN.S43299. Epub 2013 Apr 26. PMID: 23641156; PMCID: PMC3639716.

Kim DS, Cho JH, Park JH, Kim JS, Song ES, Kwon J, Giri BR, Jin SG, Kim KS, Choi HG, Kim DW. Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate. Int J Nanomedicine. 2019 Jul 5;14:4949-4960. doi: 10.2147/IJN.S211014. PMID: 31308665; PMCID: PMC6617838.

Gupta S, Chavhan S, Sawant KK. Self-nanoemulsifying drug delivery system for adefovir dipivoxil: Design, characterization, in vitro and ex vivo evaluation. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2011;392:145–155. doi: 10.1016/j.colsurfa.2011.09.048.

Akula S, Gurram AK, Devireddy SR. Self-Microemulsifying Drug Delivery Systems: An Attractive Strategy for Enhanced Therapeutic Profile. Int Sch Res Notices. 2014;2014:964051. doi: 10.1155/2014/964051. PMID: 27382619; PMCID: PMC4897095.

Gumaste SG, Dalrymple DM, Serajuddin AT. Development of Solid SEDDS, V: Compaction and Drug Release Properties of Tablets Prepared by Adsorbing Lipid-Based Formulations onto Neusilin® US2. Pharm Res. 2013 Jun 25;30(12):3186–99. doi: 10.1007/s11095-013-1106-4. Epub ahead of print. PMID: 23797463; PMCID: PMC3841580.

Bakhle SS. Development and Evaluation of Liquid and Solid Self-microemulsifying Drug Delivery System of Lovastatin. AJP . 2016. 26.

Aulton ME, Taylor K. Pharmaceutics-The Science of Dosage Form Design. Churchill Livingstone. London, England. 2002;133-134

Zolotov SA, Demina NB, Zolotova AS, Shevlyagina NV, Buzanov GA, Retivov VM, Kozhukhova EI, Zakhoda OY, Dain IA, Filatov AR, Cheremisin AM. Development of novel darunavir amorphous solid dispersions with mesoporous carriers. Eur J Pharm Sci. 2021 Apr 1;159:105700. doi: 10.1016/j.ejps.2021.105700. Epub 2021 Jan 8. PMID: 33429047.

Gupta S, Sawarkar S, Ravikumar P. SOLUBILITY ENHANCEMENT OF POORLY WATER SOLUBLE PROTEASE INHIBITOR. International Journal of Pharmaceutical Sciences and Research. 2016;7(1):252.

Kogawa AC, Gutierrez Antonio S. Characterization of Darunavir: Î’-Cyclodextrin complex and Comparison with the Forms of Darunavir Ethanolate and Hydrate. Journal of Pharmaceutical Sciences & Emerging Drugs. 2016;04. doi: 10.4172/2380-9477.1000110.

Kaduk JA, Zhong K, Blanton TN, Gindhart AM, Fawcett TG. Powder X-ray diffraction of darunavir ethanolate, C27H37N3O7S(C2H5OH). Powder Diffraction. 2015;30:298–299. doi: 10.1017/s0885715615000536.

Nair AB, Chaudhary S, Shah H, Jacob S, Mewada V, Shinu P, Aldhubiab B, Sreeharsha N, Venugopala KN, Attimarad M, Shah J. Intranasal Delivery of Darunavir-Loaded Mucoadhesive In Situ Gel: Experimental Design, In Vitro Evaluation, and Pharmacokinetic Studies. Gels. 2022;8(6):342. doi: 10.3390/gels8060342. PMID: 35735686; PMCID: PMC9223067.

Pouton CW. Formulation of self-emulsifying drug delivery systems. Advanced drug delivery reviews. 1997;25(1):47-58.

Cherniakov I, Domb AJ, Hoffman A. Self-nano-emulsifying drug delivery systems: an update of the biopharmaceutical aspects. Expert Opin Drug Deliv. 2015 Jul;12(7):1121-33. doi: 10.1517/17425247.2015.999038. Epub 2015 Jan 5. PMID: 25556987.