Understanding the effect of lipid formulation loading and ethanol as a diluent on solidification of pitavastatin super-saturable SNEDDS using factorial design approach

Ilham Kuncahyo , Syaiful Choiri , Achmad Fudholi, Abdul Rohman , Ronny Martien

Abstract


Solidification of a preconcentrate lipid formulation namely self-nano emulsifying drug delivery system (SNEDDS) is required to achieve feasibility, flexibility, and a new concept of “dry nano-emulsion”.The purpose of this study was to assess the effect of SNEDDS loading and ethanol as a diluent on the solidification of pitavastatin supersaturable SNEDDS (S-SNEDDS). A 22 full factorial design approach with a center point addition as a curvature was implemented to determine the effect of S-SNEDDS loading and ethanol on the physical characteristics, namely flowability, compactibility, and drug release behavior. Vibrational spectra, thermal behavior, and morphology of solid S-SNEDDS formulation were also evaluated. The results indicated that there was no interaction between S-SNEDDS and carrier, based on vibrational spectra. However, thermal behaviors (enthalpy and weight loss) were depending on SNEDDS loading. Thereafter, the ethanol as a diluent of preconcentrated formulation had no effect on the morphology of carrier structure. However, the S-SNEDDS loading altered the structure of carrier owing to either solubilization or abrasion processes. The statistical model suggested that ethanol as diluent reduced the flowability, compactibility, and drug releases. Meanwhile, the liquid SNEDDS loading affected the reducing of flowability and compactibility. Finally, solidification without diluent and 20% lipid formulation load was recommended. In addition, it was very useful because of ease on handling, flexibility for further formulation, and desired characteristics of final solid dosage form.


Keywords


Pitavastatin; Solidification; Solid SNEDDS; Supersaturable.

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Mokarizadeh M, Kafil HS, 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.

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.

Bandyopadhyay S, Katare OP, 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.

Chavan RB, Modi SR, Bansal AK. Role of solid carriers in pharmaceutical performance of solid supersaturable SEDDS of celecoxib. Int J Pharm. 2015;495(1):374-384.

Pouton CW. 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.

Christophersen PC, Christiansen ML, Holm R, Kristensen J, Jacobsen J, Abrahamsson B, et al. 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.

Inugala S, Eedara BB, Sunkavalli S, Dhurke R, Kandadi P, Jukanti R, et al. 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.

Hassan TH, Metz H, Mäder K. Novel semisolid SNEDDS based on PEG-30-dipolyhydroxystearate: development and characterization. Int J Pharm. 2014;477(1-2):506-518.

Mustapha O, Kim KS, Shafique S, Kim DS, Jin SG, Seo YG, et al. Development of novel cilostazol–loaded solid SNEDDS using a SPG membrane emulsification technique: Physicochemical characterization and in vivo evaluation. Colloids Surf B Biointerfaces. 2017;150:216-222.

Mandić J, Zvonar Pobirk A, Vrečer F, Gašperlin M. Overview of solidification techniques for self-emulsifying drug delivery systems from industrial perspective. Int J Pharm. 2017;533(2): 335-345.

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.

Oh DH, Kang JH, Kim DW, Lee BJ, Kim JO,Yong CS, et al. 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.

Rahman MA, Mujahid M, Rahman MA, Mujahid M. Development of self-nanoemulsifying tablet (SNET) for bioavailability enhancement of sertraline. Braz J Pharm Sci. 2018;54(1):e17232.

Peng T, Zhang X, Huang Y, Zhao Z, Liao Q, Xu J, et al. Nanoporous mannitol carrier prepared by non-organic solvent spray drying technique to enhance the aerosolization performance for dry powder inhalation. Sci Rep. 2017;7:46517-46527.

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.

Agrawal AG, Kumar A, Gide PS. Formulation of solid self-nanoemulsifying drug delivery systems using N-methyl pyrrolidone as cosolvent. Drug Dev Ind Pharm. 2015;41(4):594-604.

Ainurofiq A, Choiri S, Azhari MA, Siagian CR, Suryadi BB, Prihapsara F, et al. 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.

Choiri S, Ainurofiq A, Ratri R, Zulmi MU. 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(1):12064-12070.

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):528-540.

Long AG, Williams RL. The United States Pharmacopoeia 41 - National Formulary 36. Rockville, USA: The United States Pharmacopeial Convention; 2018. pp. 7481-7485.

Gong X, Chang SY, Osei-Yeboah F, Paul S, Perumalla SR, Shi L, et al. Dependence of tablet brittleness on tensile strength and porosity. Int J Pharm. 2015;493(1-2):208-213.

Zhao Y, Wang C, Chow AH, Ren K, Gong T, Zhang Z, et al. Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of Zedoary essential oil: formulation and bioavailability studies. Int J Pharm. 2010;383(1-2):170-177.

Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol. 1975;27(1):48-49.

Ainurofiq A, Choiri S. Development and optimization of a meloxicam/β-cyclodextrin complex for orally disintegrating tablet using statistical analysis. Pharm Dev Technol. 2018;23(5):464-475.

Griesser J, Hetényi G, Kadas H, Demarne F, Jannin V, Bernkop-Schnürch A. Self-emulsifying peptide drug delivery systems: How to make them highly mucus permeating. Int J Pharm. 2018;538(1-2): 159-166.

Masana L. Pitavastatin: Potential in Clinical PracticePitavastatin – from clinical trials to clinical practice. Atheroscler Suppl. 2010;11(3):15–22.

Kim KS, Yang ES, Kim DS, Kim DW, Yoo HH, Yong CS, et al. A novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for improved stability and oral bioavailability of an oily drug, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol. Drug Deliv. 2017;24(1):1018-1025.

Seo YG, Kim DW, Yousaf AM, Park JH, Chang PS, Baek HH, et al. Solid self-nanoemulsifying drug delivery system (SNEDDS) for enhanced oral bioavailability of poorly water-soluble tacrolimus: physicochemical characterisation and pharmacokinetics. J Microencapsul. 2015;32(5): 503-510.

Kuncahyo I, Choiri S. The influence of magnesium stearate, purified talc and combination of both on ternary/quaternary interactive mixture of freely and poorly water-soluble drug. Int J Pharm Pharm Sci. 2014;7(1):397-402.

Mangal S, Gengenbach T, Millington-Smith D, Armstrong B, Morton DAV, Larson I. Relationship between the cohesion of guest particles on the flow behaviour of interactive mixtures. Eur J Pharm Biopharm. 2016;102:168-177.

Tarlier N, Soulairol I, Bataille B, Baylac G, Ravel P, Nofrerias I, et al. Compaction behavior and deformation mechanism of directly compressible textured mannitol in a rotary tablet press simulator. Int J Pharm. 2015;495(1):410-419.

Castrati L, Mazel V, Busignies V, Diarra H, Rossi A, Colombo P, et al. Comparison of breaking tests for the characterization of the interfacial strength of bilayer tablets. Int J Pharm. 2016;513 (1-2):709-716.

Shanmugam S, Baskaran R, Balakrishnan P, Thapa P, Yong CS, Yoo BK. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine for enhanced bioavailability of highly lipophilic bioactive carotenoid lutein. Eur J Pharm Biopharm. 2011;79(2):250-257.

Szumała P. Structure of microemulsion formulated with monoacylglycerols in the presence of polyols and ethanol. J Surfactants Deterg. 2015;18:97-106.


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