Formulation of Self-micro Emulsifying Drug Delivery Systems (SMEDDS) of Paclitaxel utilizing factorial design
DOI:
https://doi.org/10.37285/ijpsn.2022.15.1.7Abstract
Background: The antineoplastic drugs possess poor aqueous solubility along with low bioavailability. This limits delivery of antineoplastic drugs through oral route. SMEDDS is a well-accepted means for addressing the lower aqueous solubility and bioavailability issues of a lipophilic drugs. Paclitaxel (PTX) is an antineoplastic drug. PTX is found to be very useful in the treatment of ovarian and breast cancers. PTX have very low aqueous solubility (0.3 µg/ml).
Objective: This study aims to formulate SMEDDS incorporating PTX to enhance its aqueous solubility.
Methodology: Isopropyl myristate (IM), tween 80 (T80) and transcutol (TC) were used to formulate SMEDDS. IM was considered as oil, T80 as surfactant and TC as co surfactant. 32 factorial design analysis helps in studying the effect of an independent factor on a dependent factor on statistical principles. Independent factors, first – concentrations of oil, second – mixture of surfactant and co-surfactant (Smix), and two dependent factors, first – emulsification time and second – in vitro drug release were chosen. All the nine formulated B1-B9 were subjected to various physicochemical tests.
Result and discussion: The globule size was found to be 136.38 – 223.14 nm, zeta potential ranges between -31.54 to -7.58, drug content ranges between 65.34 – 83.56%. Statistical analysis shows that an increasing amount of surfactant decreases emulsification time. This may also decrease the average droplet size of resultant SMEDDS. When the concentration of tween 80 was increased, it was observed that the release of PTX also increased. Rapid and more extent of PTX released from formulated SMEDDS indicates that the aqueous solubility of PTX has increased. B9 formulation releases 99.46% PTX at end of 60 minutes whereas 35.23% of pure PTX powder was solubilized in dissolution medium.
Conclusion: This study states that the prepared SMEDDS possess acceptable properties to be considered as immediate release dosage forms. This conclusion was drawn based on in vitro release study.
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Keywords:
self-emulsifying, lipophilic, antineoplastic, bioavailability, paclitaxel, factorial design
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Bahadur S, Yadu K, Baghel P, Naurange T, and Sahu M (2020). Review of formulation and evaluation of self-micro emulsifying drug delivery system (Smedds). ScienceRise: Pharmaceutical Science 26: 25 – 35
Bahadur S, Roy A, Baghel P, and Chanda R (2016). Formulation of Glipizide Tablets using Fenugreek Seed Mucilage: Optimization by Factorial Design. Asian Journal of Pharmaceutics 10: S662–S668.
Cho HJ, Lee DW, Marasini N, Poudel BK, Kim JH, Ramasamy T, Yoo BK, Choi HG, Yong CS, and Kim J O (2013). Optimization of self-microemulsifying drug delivery system for telmisartan using Box-Behnken design and desirability function. Journal of Pharmacy and Pharmacology 65: 1440– 1450
Choi JS, Cho NH, Kim DH, and Park JS (2019). Comparison of paclitaxel solid dispersion and polymeric micelles for improved oral bioavailability and in vitro anti-cancer effects. Materials Science and Engineering C 100: 247–259.
Choi YH, and Han HK (2018). Nanomedicines: current status and future perspectives in aspect of drug delivery and pharmacokinetics. Journal of Pharmaceutical Investigation 48: 43–60.
Deshmukh A, and Kulkarni S (2014). Solid self microemulsifying drug delivery system of ritonavir. Drug Development and Industrial Pharmacy 40: 477–487.
Ding Z, Wang L, Xing Y, Zhao Y, Wang Z, and Han J (2019). Enhanced oral bioavailability of celecoxib nanocrystalline solid dispersion based on wet media milling technique: Formulation, optimization and in Vitro/In Vivo Evaluation. Pharmaceutics 11, 328–345.
Elfiyani R, Amalia A, and Pratama SY (2017). Effect of using the combination of tween 80 and ethanol on the forming and
physical stability of microemulsion of eucalyptus oil as antibacterial. Journal of Young Pharmacists 9: s1–s4. 9. Goddeeris C, Cuppo F, Reynaers H, Bouwman WG, and Van Den Mooter G (2006). Light scattering measurements on microemulsions: Estimation of droplet sizes. International Journal of Pharmaceutics 312: 187–195.
Holm R, Jensen IHM and Sonnergaard J (2006). Optimization of self-microemulsifying drug delivery systems (SMEDDS) using a D-optimal design and the desirability function. Drug Development and Industrial Pharmacy 32: 1025–1032.
Kamboj S, and Rana V (2016). Quality-by-design based development of a self-microemulsifying drug delivery system to reduce the effect of food on Nelfinavir mesylate. International Journal of Pharmaceutics 501: 311–325.
Kim DS, Cho JH, Park JH, Kim JS, Song ES, Kwon J, Giri BR, Jin SG, Kim KS, Choi HG, and Kim DW (2019). Self microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate. International Journal of Nanomedicine 14: 4949–4960.
Kommuru TR, Gurley B, Khan MA, and Reddy IK (2001). Self emulsifying drug delivery systems (SEDDS) of coenzyme Q10: Formulation development and bioavailability assessment. International Journal of Pharmaceutics 212: 233–246.
Mei L, Zhang Z, Zhao L, Huang L, Yang X, Tang J, and Feng S (2013). Pharmaceutical Nanotechnology for Oral Delivery of Anticancer Drugs. Advanced Drug Delivery Reviews 65: 880– 890
Parakh DR, Patil MP, Sonawane SS, and Kshirsagar SJ (2016). Application of factorial design approach in development and evaluation of self microemulsifying drug delivery system (SMEDDS) of mebendazole. Journal of Pharmaceutical Investigation 47: 507–519.
Qiao J, Ji D, Sun S, Zhang G, Liu X, Sun B, and Guan Q (2018). Oral bioavailability and lymphatic transport of pueraria flavone-loaded self-emulsifying drug-delivery systems containing sodium taurocholate in rats. Pharmaceutics 10: 147– 159.
Quan G, Niu B, Singh V, Zhou Y, Wu CY, Pan X, and Wu C (2017). Supersaturable solid self-microemulsifying drug delivery system: Precipitation inhibition and bioavailability enhancement. International Journal of Nanomedicine 12: 8801–8811.
Sawatdee S, Atipairin A, Yoon AS, Srichana T, Changsan N, and Suwandecha T (2019). Formulation development of albendazole-loaded self-microemulsifying chewable tablets to enhance dissolution and bioavailability. Pharmaceutics 11: 134–153.
Shen H, and Zhong M (2006). Preparation and evaluation of self-microemulsifying drug delivery systems (SMEDDS) containing atorvastatin. Journal of Pharmacy and Pharmacology 58: 1183–1191.
Sun Y, Yu B, Wang G, Wu Y, Zhang X, Chen Y, Tang S, Yuan Y, Lee RJ, Teng L, and Xu S (2014). Enhanced antitumor efficacy of vitamin E TPGS-emulsified PLGA nanoparticles for delivery of paclitaxel. Colloids and Surfaces B: Biointerfaces 123: 716–723.
Venkatesh G, Majid MIA, Mansor SM, Nair NK, Croft SL, and Navaratnam V (2010). In vitro and in vivo evaluation of self microemulsifying drug delivery system of buparvaquone. Drug Development and Industrial Pharmacy, 36: 735–743.
Wei L, Sun P, Nie S, and Pan W (2005). Preparation and evaluation of SEDDS and SMEDDS containing carvedilol. Drug Development and Industrial Pharmacy 31: 785–794.
