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Current Drug Delivery

Author(s): Sridevi Gowripattapu, D. Sathis Kumar and S. Selvamuthukumar*

DOI: 10.2174/1567201819666220517113012

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Formulation and Statistical Evaluation of Tablets Containing Pitavastatin- Self Nano Emulsifying Drug Delivery Systems

Page: [414 - 432] Pages: 19

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Abstract

Purpose: To formulate and characterize tablets containing Pitavastatin that have been loaded with a self-nano emulsifying drug delivery system (SNEDDS).

Methods: Pitavastatin SNEDDS were prepared with a variety of oils, surfactants, co-surfactants, and solvents to improve the dissolution rate and bioavailability of the HMG-CoA reductase inhibitor. The SNEDDS components were preliminarily investigated for drug solubility in various vehicles, excipient miscibility, emulsification rate, and ternary phase diagrams. The tablets were made using a porous carrier made of Aerosil 200 and then loaded with SNEDDS using a simple absorption method. Physical parameters such as tablet hardness, weight variation, disintegration, drug content, and in-vitro drug release were then measured on the tablets.

Results: Labrafac Lipophilewl1349 (Oil), Tween 80 (Surfactant) and Egg lecithin (Co-surfactant) were selected for the preparation of SNEDDS. Tablets with high porosity suitable for loading with SNEDDS and containing the super-disintegrants, achieved complete dissolution of Pitavastatin from the tablets. In vitro release of Pitavastatin from SNEDDS and the tablets was similar (p < 0.05).

Conclusion: SNEDDS of Pitavastatin is a promising approach to achieving a solid dosage form of the liquid-loaded drug delivery systems for enhancing the solubility and dissolution rate of the drug, and hence also its bioavailability.

Keywords: Pitavastatin, drug carrier, SNEDDS, self-nanoemulsifying, solubility, drug release, surfactant, co-surfactant.

Graphical Abstract

[1]
Stegemann, S.; Leveiller, F.; Franchi, D.; de Jong, H.; Lindén, H. When poor solubility becomes an issue: From early stage to proof of concept. Eur. J. Pharm. Sci., 2007, 31(5), 249-261.
[http://dx.doi.org/10.1016/j.ejps.2007.05.110] [PMID: 17616376]
[2]
Liu, Z.P.; Zhang, L.-L.; Yang, Y.-Y.; Wu, D.; Jiang, G.; Yu, D.-G. Preparing composite nanoparticles for immediate drug release by modifying electrohydrodynamic interfaces during electrospraying. Powder Technol., 2018, 327, 179-187.
[http://dx.doi.org/10.1016/j.powtec.2017.12.066]
[3]
Gershanik, T.; Benita, S. Self-dispersing lipid formulations for improving oral absorption of lipophilic drugs. Eur. J. Pharm. Biopharm., 2000, 50(1), 179-188.
[http://dx.doi.org/10.1016/S0939-6411(00)00089-8] [PMID: 10840200]
[4]
Mu, H.; Holm, R.; Müllertz, A. Lipid-based formulations for oral administration of poorly water-soluble drugs. Int. J. Pharm., 2013, 453(1), 215-224.
[http://dx.doi.org/10.1016/j.ijpharm.2013.03.054] [PMID: 23578826]
[5]
Parikh, A.; Kathawala, K.; Tan, C.C.; Garg, S.; Zhou, X.F. Development of a novel oral delivery system of edaravone for enhancing bioavailability. Int. J. Pharm., 2016, 515(1-2), 490-500.
[http://dx.doi.org/10.1016/j.ijpharm.2016.10.052]
[6]
Başpınar, Y.; Gündoğdu, E.; Köksal, Ç.; Karasulu, E. Pitavastatin-containing nanoemulsions: Preparation, characterization and in vitro cytotoxicity. J. Drug Deliv. Sci. Technol., 2015, 29, 117-124.
[http://dx.doi.org/10.1016/j.jddst.2015.07.003]
[7]
Wang, Y.; Wang, C.; Zhao, J.; Ding, Y.; Li, L. A cost-effective method to prepare curcumin nanosuspensions with enhanced oral bioavailability. J. Colloid Interface Sci., 2017, 485, 91-98.
[http://dx.doi.org/10.1016/j.jcis.2016.09.003] [PMID: 27657837]
[8]
Chawla, G.; Bansal, A.K. Improved dissolution of a poorly water soluble drug in solid dispersions with polymeric and non-polymeric hydrophilic additives. Acta Pharm., 2008, 58(3), 257-274.
[http://dx.doi.org/10.2478/v10007-008-0016-1] [PMID: 19103563]
[9]
Hauss, D.J. Oral lipid-based formulations. Adv. Drug Deliv. Rev., 2007, 59(7), 667-676.
[http://dx.doi.org/10.1016/j.addr.2007.05.006] [PMID: 17618704]
[10]
Pouton, C.W. Formulation of self-emulsifying drug delivery systems. Adv. Drug Deliv. Rev., 1997, 25(1), 47-58.
[http://dx.doi.org/10.1016/S0169-409X(96)00490-5]
[11]
Pouton, C.W. Lipid formulations for oral administration of drugs: Non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems. Eur. J. Pharm. Sci., 2000, 11(Suppl. 2), S93-S98.
[http://dx.doi.org/10.1016/S0928-0987(00)00167-6] [PMID: 11033431]
[12]
Abbaspour, M.; Jalayer, N.; Sharif Makhmalzadeh, B. Development and evaluation of a solid self-nanoemulsifying drug delivery system for loratadin by extrusion-spheronization. Adv. Pharm. Bull., 2014, 4(2), 113-119.
[PMID: 24511474]
[13]
Adhikari, C.; Mishra, A.; Nayak, D.; Chakraborty, A. Drug delivery system composed of mesoporous silica and hollow mesoporous silica nanospheres for chemotherapeutic drug delivery. J. Drug Deliv. Sci. Technol., 2018, 45, 303-314.
[http://dx.doi.org/10.1016/j.jddst.2018.03.020]
[14]
Agrawal, A.G.; Kumar, A.; Gide, P.S. Formulation of solid self-nanoemulsifying drug delivery systems using N-methyl pyrrolidone as cosolvent. Drug Dev. Ind. Pharm., 2015, 41(4), 594-604.
[http://dx.doi.org/10.3109/03639045.2014.886695] [PMID: 24517575]
[15]
Bandyopadhyay, S.; Katare, O.P.; Singh, B. Development of optimized supersaturable self-nanoemulsifying systems of ezetimibe: Effect of polymers and efflux transporters. Expert Opin. Drug Deliv., 2014, 11(4), 479-492.
[http://dx.doi.org/10.1517/17425247.2014.877885] [PMID: 24386966]
[16]
Chavan, R.B.; Modi, S.R.; Bansal, A.K. Role of solid carriers in pharmaceutical performance of solid supersaturable SEDDS of celecoxib. Int. J. Pharm., 2015, 495(1), 374-384.
[http://dx.doi.org/10.1016/j.ijpharm.2015.09.011] [PMID: 26364711]
[17]
Mokarizadeh, M.; Kafil, H.S.; Ghanbarzadeh, S.; Alizadeh, A.; Hamishehkar, H. Improvement of citral antimicrobial activity by incorporation into nanostructured lipid carriers: A potential application in food stuffs as a natural preservative. Res. Pharm. Sci., 2017, 12(5), 409-415.
[http://dx.doi.org/10.4103/1735-5362.213986] [PMID: 28974979]
[18]
Ghasemiyeh, P.; Mohammadi-Samani, S. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: Applications, advantages and disadvantages. Res. Pharm. Sci., 2018, 13(4), 288-303.
[http://dx.doi.org/10.4103/1735-5362.235156] [PMID: 30065762]
[19]
Cirri, M.; Roghi, A.; Valleri, M.; Mura, P. Development and characterization of fast-dissolving tablet formulations of glyburide based on solid self-microemulsifying systems. Eur. J. Pharm. Biopharm., 2016, 104, 19-29.
[http://dx.doi.org/10.1016/j.ejpb.2016.04.008] [PMID: 27091783]
[20]
Oh, D.H.; Kang, J.H.; Kim, D.W.; Lee, B.J.; Kim, J.O.; Yong, C.S.; Choi, H.G. Comparison of solid Self-Microemulsifying Drug Delivery System (solid SMEDDS) prepared with hydrophilic and hydrophobic solid carrier. Int. J. Pharm., 2011, 420(2), 412-418.
[http://dx.doi.org/10.1016/j.ijpharm.2011.09.007] [PMID: 21944892]
[21]
Rahman, M.A.; Mujahid, M.; Rahman, M.A.; Mujahid, M. Development of Self-Nanoemulsifying Tablet (SNET) for bioavailability enhancement of sertraline. Braz. J. Pharm. Sci., 2018, 54(1), e17232.
[http://dx.doi.org/10.1590/s2175-97902018000117232]
[22]
Peng, T.; Zhang, X.; Huang, Y.; Zhao, Z.; Liao, Q.; Xu, J.; Huang, Z.; Zhang, J.; Wu, C.Y.; Pan, X.; Wu, C. Nanoporous mannitol carrier prepared by non-organic solvent spray drying technique to enhance the aerosolization performance for dry powder inhalation. Sci. Rep., 2017, 7(1), 46517-46527.
[http://dx.doi.org/10.1038/srep46517] [PMID: 28462948]
[23]
Pomázi, A.; Ambrus, R.; Sipos, P.; Szabó-Révész, P. Analysis of co-spray-dried meloxicam-mannitol systems containing crystalline microcomposites. J. Pharm. Biomed. Anal., 2011, 56(2), 183-190.
[http://dx.doi.org/10.1016/j.jpba.2011.05.008] [PMID: 21652159]
[24]
Rehman, F.U.; Shah, K.U.; Shah, S.U.; Khan, I.U.; Khan, G.M.; Khan, A. From nanoemulsions to self-nanoemulsions, with recent advances in Self-Nanoemulsifying Drug Delivery Systems (SNEDDS). Expert Opin. Drug Deliv., 2017, 14(11), 1325-1340.
[http://dx.doi.org/10.1080/17425247.2016.1218462] [PMID: 27485144]
[25]
Villar, A.M.; Naveros, B.C.; Campmany, A.C.; Trenchs, M.A.; Rocabert, C.B.; Bellowa, L.H. Design and optimization of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for enhanced dissolution of gemfibrozil. Int. J. Pharm., 2012, 431(1-2), 161-175.
[http://dx.doi.org/10.1016/j.ijpharm.2012.04.001] [PMID: 22498011]
[26]
Badawy, M.E.I.; Saad, A.S.A.; Tayeb, E.H.M.; Mohammed, S.A.; Abd-Elnabi, A.D. Optimization and characterization of the formation of oil-in-water diazinon nanoemulsions: Modeling and influence of the oil phase, surfactant and sonication. J. Environ. Sci. Health B, 2017, 52(12), 896-911.
[http://dx.doi.org/10.1080/03601234.2017.1362941] [PMID: 29111904]
[27]
Singh, Y.; Meher, J.G.; Raval, K.; Khan, F.A.; Chaurasia, M.; Jain, N.K.; Chourasia, M.K. Nanoemulsion: Concepts, development and applications in drug delivery. J. Control. Release, 2017, 252, 28-49.
[http://dx.doi.org/10.1016/j.jconrel.2017.03.008] [PMID: 28279798]
[28]
Solans, C.; Morales, D.; Homs, M. Spontaneous emulsification. Curr. Opin. Colloid Interface Sci., 2016, 22, 88-93.
[http://dx.doi.org/10.1016/j.cocis.2016.03.002]
[29]
Solans, C.; Solé, I. Nano-emulsions: Formation by low-energy methods. Curr. Opin. Colloid Interface Sci., 2012, 17(5), 246-254.
[http://dx.doi.org/10.1016/j.cocis.2012.07.003]
[30]
Weerapol, Y.; Limmatvapirat, S.; Nunthanid, J.; Sriamornsak, P. Self-nanoemulsifying drug delivery system of nifedipine: Impact of hydrophilic-lipophilic balance and molecular structure of mixed surfactants. AAPS PharmSciTech, 2014, 15(2), 456-464.
[http://dx.doi.org/10.1208/s12249-014-0078-y] [PMID: 24452500]
[31]
Lefebvre, G.; Riou, J.; Bastiat, G.; Roger, E.; Frombach, K.; Gimel, J.C.; Saulnier, P.; Calvignac, B. Spontaneous nano-emulsification: Process optimization and modeling for the prediction of the nanoemulsion’s size and polydispersity. Int. J. Pharm., 2017, 534(1-2), 220-228.
[http://dx.doi.org/10.1016/j.ijpharm.2017.10.017] [PMID: 29038063]
[32]
Khan, A.W.; Kotta, S.; Ansari, S.H.; Sharma, R.K.; Ali, J. Self-Nanoemulsifying Drug Delivery System (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: Design, characterization, in vitro and in vivo evaluation. Drug Deliv., 2015, 22(4), 552-561.
[http://dx.doi.org/10.3109/10717544.2013.878003] [PMID: 24512268]
[33]
Ainurofiq, A.; Choiri, S.; Azhari, M.A.; Siagian, C.R.; Suryadi, B.B.; Prihapsara, F.; Rohmani, S. Improvement of meloxicam solubility using a β-cyclodextrin complex prepared via the kneading method and incorporated into an orally disintegrating tablet. Adv. Pharm. Bull., 2016, 6(3), 399-406.
[http://dx.doi.org/10.15171/apb.2016.052] [PMID: 27766224]
[34]
Choiri, S.; Ainurofiq, A.; Ratri, R.; Zulmi, M.U. Analytical method development of nifedipine and its degradants binary mixture using high performance liquid chromatography through a quality by design approach. IOP Conf. Ser. Mater. Sci. Eng., 2018, 333, pp. 12064-12070.
[http://dx.doi.org/10.1088/1757-899X/333/1/012064]
[35]
Beg, S.; Katare, O.P.; Singh, B. Formulation by design approach for development of ultrafine self-nanoemulsifying systems of rosuvastatin calcium containing long-chain lipophiles for hyperlipidemia management. Colloids Surf. B Biointerfaces, 2017, 159, 869-879.
[http://dx.doi.org/10.1016/j.colsurfb.2017.08.050] [PMID: 28892871]
[36]
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 Biointerfaces, 2011, 86(2), 327-338.
[http://dx.doi.org/10.1016/j.colsurfb.2011.04.016] [PMID: 21550214]
[37]
Singh, S.K.; Verma, P.R.; Razdan, B. Development and characterization of a lovastatin-loaded self-microemulsifying drug delivery system. Pharm. Dev. Technol., 2010, 15(5), 469-483.
[http://dx.doi.org/10.3109/10837450903286537] [PMID: 19793039]
[38]
Biswas, A.; Das, P.; Mandal, N.K. Factorial designs robust against the presence of an aberration. Stat. Probab. Lett., 2017, 129, 326-334.
[http://dx.doi.org/10.1016/j.spl.2017.06.005]
[39]
Pouton, C.W. 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), 278-287.
[http://dx.doi.org/10.1016/j.ejps.2006.04.016] [PMID: 16815001]
[40]
Christophersen, P.C.; Christiansen, M.L.; Holm, R.; Kristensen, J.; Jacobsen, J.; Abrahamsson, B.; Müllertz, A. Fed and fasted state gastro-intestinal in vitro lipolysis: In vitro in vivo relations of a conventional tablet, a SNEDDS and a solidified SNEDDS. Eur. J. Pharm. Sci., 2014, 57, 232-239.
[http://dx.doi.org/10.1016/j.ejps.2013.09.007] [PMID: 24056027]
[41]
Inugala, S.; Eedara, B.B.; Sunkavalli, S.; Dhurke, R.; Kandadi, P.; Jukanti, R.; Bandari, S. Solid Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) of darunavir for improved dissolution and oral bioavailability: In vitro and in vivo evaluation. Eur. J. Pharm. Sci., 2015, 74, 1-10.
[http://dx.doi.org/10.1016/j.ejps.2015.03.024] [PMID: 25845633]