Table Info

Table 1.

QTPP of NLC

S. No.	QTPP	Target	Justification
1	Dosage form	Lipid based formulation	Selection of NLC, which is lipid based enhances the oral bioavailability of lipid soluble, BCS class II drugs
2	Dosage shape	Spherical	High surface area, high rate of drug release
3	Dosage type	Controlled release	Low dosing frequency
4	Dosage strength	X (mg)	Required dose to be incorporated in formulation to provide therapeutic benefit
5	Pharmacokinetics	C_max, AUC	High AUC and C_max are required to achieve higher plasma drug concentration and thus higher oral bioavailability
6	Route of administration	Oral	Good patient compliance, non-invasive
7	Container and closure	Air-tight amber color bottle	To protect drug degradation from light and moisture
8	Stability	At least 12 months at room temperature	To maintain the therapeutic activity of the drug during the storage period

AUC: area under curve; BCS: biopharmaceutical classification system; C_max: maximum plasma concentration; S. No.: serial number

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Conflicts of interest

The author declares that he has no conflicts of interest.

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References

Müller RH, Radtke M, Wissing SA. Nanostructured lipid matrices for improved microencapsulation of drugs. Int J Pharm. 2002;242:121–8. [DOI] [PubMed]

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;13:288–303. [DOI] [PubMed] [PMC]

Garg B, Beg S, Kumar R, Katare OP, Singh B. Nanostructured lipidic carriers of lopinavir for effective management of HIV-associated neurocognitive disorder. J Drug Deliv Sci Technol. 2019;53:101220. [DOI]

Gadhave DG, Kokare CR. Nanostructured lipid carriers engineered for intranasal delivery of teriflunomide in multiple sclerosis: optimization and in vivo studies. Drug dev Ind Pharm. 2019;45:839–51. [DOI] [PubMed]

Gonzalez-Mira E, Egea MA, Souto EB, Calpena AC, García ML. Optimizing flurbiprofen-loaded NLC by central composite factorial design for ocular delivery. Nanotechnology. 2010;22:045101. [DOI] [PubMed]

Imran M, Iqubal MK, Imtiyaz K, Saleem S, Mittal S, Rizvi MMA, et al. Topical nanostructured lipid carrier gel of quercetin and resveratrol: formulation, optimization, in vitro and ex vivo study for the treatment of skin cancer. Int J Pharm. 2020;587:119705. [DOI] [PubMed]

Zhang X, Qiao H, Liu J, Dong H, Shen C, Ni J, et al. Dihydroartemisinin loaded nanostructured lipid carriers (DHA-NLC): evaluation of pharmacokinetics and tissue distribution after intravenous administration to rats. Pharmazie. 2010;65:670–8. [PubMed]

Yu Y, Xu S, Yu S, Li J, Tan G, Li S, et al. A hybrid genipin-cross-linked hydrogel/nanostructured lipid carrier for ocular drug delivery: cellular, ex vivo, and in vivo evaluation. ACS Biomater Sci Eng. 2020;6:1543–52. [DOI]

Beloqui A, Solinís MÁ, Rodríguez-Gascón A, Almeida AJ, Préat V. Nanostructured lipid carriers: promising drug delivery systems for future clinics. Nanomedicine. 2016;12:143–61. [DOI] [PubMed]

10.

Li X, Nie S, Kong J, Li N, Ju C, Pan W. A controlled-release ocular delivery system for ibuprofen based on nanostructured lipid carriers. Int J pharm. 2008;363:177–82.

11.

Khosa A, Reddi S, Saha RN. Nanostructured lipid carriers for site-specific drug delivery. Biomed Pharmacother. 2018;103:598–613. [DOI] [PubMed]

12.

Guidance for industry: quality systems approach to pharmaceutical cGMP regulations [Internet]. U.S. Food and Drug Administration; 2006 [cited 2021 Jan 15]. Available from: https://www.fda.gov/downloads/Drugs/Guidances/UCM070337.pdf

13.

Bhise K, Kashaw SK, Sau S, Iyer AK. Nanostructured lipid carriers employing polyphenols as promising anticancer agents: quality by design (QbD) approach. Int J Pharm. 2017;526:506–15. [DOI] [PubMed] [PMC]

14.

Bastogne T. Quality-by-design of nanopharmaceuticals – a state of the art. Nanomedicine. 2017;13:2151–7. [DOI] [PubMed]

15.

Sangshetti JN, Deshpande M, Zaheer Z, Shinde DB, Arote R. Quality by design approach: regulatory need. Arab J Chem. 2017;10:S3412–25. [DOI]

16.

Juran JM. Juran on quality by design: the new steps for planning quality into goods and services. New York: Simon & Schuster Adult Publishing Group; 1992.

17.

Pharmaceutical CGMPs for the 21st century—a risk-based approach: final report [Internet]. U.S. Food and Drug Administration; 2004 [cited 2021 Jan 15]. Available from: https://www.fda.gov/media/77391/download

18.

Guidance for Industry: Q8(R2) pharmaceutical development [Internet]. U.S. Food and Drug Administration; 2009 [cited 2021 Jan 22]. Available from: https://www.fda.gov/media/71535/download

19.

ICH Q9 quality risk management - scientific guideline [Internet]. European Medicines Agency; [cited 2021 Jan 22]. Available from: https://www.ema.europa.eu/en/ich-q9-quality-risk-management-scientific-guideline

20.

Guidance for Industry: Q10 pharmaceutical quality system (step 4) [Internet]. U.S. Food and Drug Administration; 2009 [cited 2021 Jan 22]. Available from: https://www.fda.gov/media/71553/download

21.

Beg S, Hasnain MS, Rahman M, Swain S. Chapter 1 - Introduction to quality by design (QbD): fundamentals, principles, and applications. In: Beg S, Hasnain MS, editors. Pharmaceutical quality by design: principles and applications. Academic Press; 2019. pp. 1–17. [DOI]

22.

Buttini F, Rozou S, Rossi A, Zoumpliou V, Rekkas DM. The application of quality by design framework in the pharmaceutical development of dry powder inhalers. Eur J Pharm Sci. 2018;113:64–76. [DOI] [PubMed]

23.

Yuangyai C, Nembhard H. Chapter 8 - Design of experiments: a key to innovation in nanotechnology. In: Ahmed W, Jackson MJ, editors. Emerging nanotechnologies for manufacturing. 2nd ed. Boston: William Andrew Publishing; 2015. pp. 230–54. [DOI]

24.

Rapalli VK, Khosa A, Singhvi G, Girdhar V, Jain R, Dubey SK. Chapter 13 - Application of QbD principles in nanocarrier-based drug delivery systems. In: Beg S, Hasnain MS, editors. Pharmaceutical quality by design: principles and applications. Academic Press; 2019. pp. 255–96. [DOI]

25.

Adebileje T, Adebileje S, Aye PO. Ciprofloxacin hydrochloride encapsulated into PLGA nanoparticles for drug delivery application: fractional factorial design. Open Access Library J. 2018;5:e4294. [DOI]

26.

Yu LX. Pharmaceutical quality by design: product and process development, understanding, and control. Pharm Res. 2008;25:781–91. [DOI] [PubMed]

27.

Beg S, Rahman M, Kohli K. Quality-by-design approach as a systematic tool for the development of nanopharmaceutical products. Drug Discov Today. 2019;24:717–25. [DOI] [PubMed]

28.

Waghule T, Dabholkar N, Gorantla S, Rapalli VK, Saha RN, Singhvi G. Quality by design (QbD) in the formulation and optimization of liquid crystalline nanoparticles (LCNPs): a risk based industrial approach. Biomed Pharmacother. 2021;141:111940. [DOI] [PubMed]

29.

Zhang L, Mao S. Application of quality by design in the current drug development. Asian J Pharm Sci. 2017;12:1–8. [DOI] [PubMed] [PMC]

30.

Javed MN, Kohli K, Amin S. Risk assessment integrated QbD approach for development of optimized bicontinuous mucoadhesive limicubes for oral delivery of rosuvastatin. AAPS PharmSciTech. 2018;19:1377–91. [DOI] [PubMed]

31.

Patel D, Patel M, Soni T, Suhagia B. Topical arginine solid lipid nanoparticles: development and characterization by QbD approach. J Drug Deliv Sci Technol. 2021;61:102329. [DOI]

32.

Subramaniam B, Siddik ZH, Nagoor NH. Optimization of nanostructured lipid carriers: understanding the types, designs, and parameters in the process of formulations. J Nanopart Res. 2020;22:141. [DOI]

33.

Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular drug delivery. AAPS J. 2010;12:348–60. [DOI] [PubMed] [PMC]

34.

Van Santvliet L, Ludwig A. Determinants of eye drop size. Surv Ophthalmol. 2004;49:197–213. [DOI] [PubMed]

35.

Alam T, Pandit J, Vohora D, Aqil M, Ali A, Sultana Y. Optimization of nanostructured lipid carriers of lamotrigine for brain delivery: in vitro characterization and in vivo efficacy in epilepsy. Expert opin drug deliv. 2015;12:181–94.

36.

Lakhani P, Patil A, Wu KW, Sweeney C, Tripathi S, Avula B, et al. Optimization, stabilization, and characterization of amphotericin B loaded nanostructured lipid carriers for ocular drug delivery. Int J Pharm. 2019;572:118771. [DOI] [PubMed] [PMC]

37.

Cunha S, Costa CP, Moreira JN, Sousa Lobo JM, Silva AC. Using the quality by design (QbD) approach to optimize formulations of lipid nanoparticles and nanoemulsions: a review. Nanomedicine. 2020;28:102206. [DOI] [PubMed]

38.

Lepore J, Spavins J. PQLI design space. J Pharm Innov. 2008;3:79–87. [DOI]

39.

Rouco H, Diaz-Rodriguez P, Rama-Molinos S, Remuñán-López C, Landin M. Delimiting the knowledge space and the design space of nanostructured lipid carriers through Artificial Intelligence tools. Int J Pharm. 2018;553:522–30. [DOI] [PubMed]

40.

Ohage E, Iverson R, Krummen L, Taticek R, Vega M. QbD implementation and Post Approval Lifecycle Management (PALM). Biologicals. 2016;44:332–40. [DOI] [PubMed]

41.

Rathore AS, Winkle H. Quality by design for biopharmaceuticals. Nat Biotechnol. 2009;27:26–34. [DOI] [PubMed]

42.

Li J, Qiao Y, Wu Z. Nanosystem trends in drug delivery using quality-by-design concept. J Control Rel. 2017;256:9–18. [DOI] [PubMed]

43.

Fernández-Castané A, Li H, Joseph S, Ebeler M, Franzreb M, Bracewell DG, et al. Nanoparticle tracking analysis as a process analytical tool for characterising magnetosome preparations. Food Bioprod Process. 2021;127:426–34. [DOI]

44.

Besseling R, Damen M, Wijgergangs J, Hermes M, Wynia G, Gerich A. New unique PAT method and instrument for real-time inline size characterization of concentrated, flowing nanosuspensions. Eur J Pharm Sci. 2019;133:205–13. [DOI] [PubMed]

45.

Shah RB, Zidan AS, Funck T, Tawakkul MA, Nguyenpho A, Khan MA. Quality by design: characterization of self-nano-emulsified drug delivery systems (SNEDDs) using ultrasonic resonator technology. Int J Pharm. 2007;341:189–94. [DOI] [PubMed]

46.

Ahmed OAA, Kurakula M, Banjar ZM, Afouna MI, Zidan AS. Quality by design coupled with near infrared in formulation of transdermal glimepiride liposomal films. J Pharm Sci. 2015;104:2062–75. [DOI] [PubMed]

47.

Fukuda IM, Pinto CFF, Moreira CdS, Saviano AM, Lourenço FR. Design of Experiments (DoE) applied to Pharmaceutical and Analytical Quality by Design (QbD). Braz J Pharm Sci. 2018;54:e01006. [DOI]

48.

Javed MN, Alam MS, Waziri A, Pottoo FH, Yadav AK, Hasnain MS, et al. Chapter 12 - QbD applications for the development of nanopharmaceutical products. In: Beg S, Hasnain MS, editors. Pharmaceutical quality by design: principles and applications. Academic Press; 2019. pp. 229–53. [DOI]

49.

Negi LM, Jaggi M, Talegaonkar S. A logical approach to optimize the nanostructured lipid carrier system of irinotecan: efficient hybrid design methodology. Nanotechnology. 2013;24:015104. [DOI] [PubMed]

50.

Cacicedo ML, Ruiz MC, Scioli-Montoto S, Ruiz ME, Fernández MA, Torres-Sanchez RM, et al. Lipid nanoparticles–Metvan: revealing a novel way to deliver a vanadium compound to bone cancer cells. New J Chem. 2019;43:17726–34. [DOI]

51.

Montgomery DC. Introduction to statistical quality control. 5th ed. New York: John Wiley & Sons, Inc.; 2007.

52.

Dong Z, Iqbal S, Zhao Z. Preparation of ergosterol-loaded nanostructured lipid carriers for enhancing oral bioavailability and antidiabetic nephropathy effects. AAPS PharmSciTech. 2020;21:64. [DOI] [PubMed]

53.

Candioti LV, De Zan MM, Cámara MS, Goicoechea HC. Experimental design and multiple response optimization. Using the desirability function in analytical methods development. Talanta. 2014;124:123–38. [DOI] [PubMed]

54.

Pradhan M, Alexander A, Singh MR, Singh D, Saraf S, Saraf S, et al. Statistically optimized calcipotriol fused nanostructured lipid carriers for effectual topical treatment of psoriasis. J Drug Deliv Sci Technol. 2021;61:102168. [DOI]

55.

Makoni PA, Khamanga SM, Walker RB. Muco-adhesive clarithromycin-loaded nanostructured lipid carriers for ocular delivery: formulation, characterization, cytotoxicity and stability. J Drug Deliv Sci Technol. 2021;61:102171. [DOI]

56.

Rathod VR, Shah DA, Dave RH. Systematic implementation of quality-by-design (QbD) to develop NSAID-loaded nanostructured lipid carriers for ocular application: preformulation screening studies and statistical hybrid-design for optimization of variables. Drug Dev Ind Pharm. 2020;46:443–55. [DOI] [PubMed]

57.

Rangaraj N, Pailla SR, Shah S, Prajapati S, Sampathi S. QbD aided development of ibrutinib-loaded nanostructured lipid carriers aimed for lymphatic targeting: evaluation using chylomicron flow blocking approach. Drug Deliv Transl Res. 2020;10:1476–94. [DOI] [PubMed]

58.

Cavalcanti SMT, Nunes C, Costa Lima SA, Soares-Sobrinho JL, Reis S. Optimization of nanostructured lipid carriers for Zidovudine delivery using a microwave-assisted production method. Eur J Pharm Sci. 2018;122:22–30. [DOI] [PubMed]

59.

Gurumukhi VC, Bari SB. Fabrication of efavirenz loaded nano-formulation using quality by design (QbD) based approach: exploring characterizations and in vivo safety. J Drug Deliv Sci Technol. 2020;56:101545. [DOI]

60.

Singh A, Neupane YR, Mangla B, Kohli K. Nanostructured lipid carriers for oral bioavailability enhancement of exemestane: formulation design, in vitro, ex vivo, and in vivo studies. J Pharm Sci. 2019;108:3382–95. [DOI] [PubMed]

61.

L Kiss E, Berkó S, Gácsi A, Kovács A, Katona G, Soós J, et al. Design and optimization of nanostructured lipid carrier containing dexamethasone for ophthalmic use. Pharmaceutics. 2019;11:679. [DOI] [PubMed] [PMC]

62.

Outuki PM, Kleinubing SA, Hoscheid J, Montanha MC, da Silva EA, do Couto RO, et al. The incorporation of Pterodon pubescens fruit oil into optimized nanostructured lipid carriers improves its effectiveness in colorectal cancer. Industrial Crops and Product. 2018;123:719–30. [DOI]

63.

Awadeen RH, Boughdady MF, Meshali MM. Quality by design approach for preparation of zolmitriptan/chitosan nanostructured lipid carrier particles – formulation and pharmacodynamic assessment. Int J Nanomedicine. 2020;15:8553–68. [DOI] [PubMed] [PMC]

64.

de Souza A, Yukuyama MN, Barbosa EJ, Monteiro LM, Faloppa ACB, Calixto LA, et al. A new medium-throughput screening design approach for the development of hydroxymethylnitrofurazone (NFOH) nanostructured lipid carrier for treating leishmaniasis. Colloids Surf B Biointerfaces. 2020;193:111097. [DOI] [PubMed]

65.

What are response surface designs, central composite designs, and Box-Behnken designs? [Internet] Minitab, LLC; c2022 [cited 2022 May 15]. Available from: https://support.minitab.com/en-us/minitab/21/help-and-how-to/statistical-modeling/doe/supporting-topics/response-surface-designs/response-surface-central-composite-and-box-behnken-designs/

66.

Beg S, Swain S, Rahman M, Hasnain MS, Imam SS. Chapter 3 - Application of design of experiments (DoE) in pharmaceutical product and process optimization. In: Beg S, Hasnain MS, editors. Pharmaceutical quality by design: principles and applications. Academic Press; 2019. pp. 43–64. [DOI]

67.

Beg S, Sandhu PS, Batra RS, Khurana RK, Singh B. QbD-based systematic development of novel optimized solid self-nanoemulsifying drug delivery systems (SNEDDS) of lovastatin with enhanced biopharmaceutical performance. Drug Deliv. 2015;22:765–84. [DOI] [PubMed]

68.

Sharma T, Jain A, Kaur R, Saini S, Katare OP, Singh B. Supersaturated LFCS type III self-emulsifying delivery systems of sorafenib tosylate with improved biopharmaceutical performance: QbD-enabled development and evaluation. Drug Deliv Transl Res. 2020;10:839–61. [DOI] [PubMed]

69.

Pradhan M, Singh D, Singh MR. Fabrication, optimization and characterization of Triamcinolone acetonide loaded nanostructured lipid carriers for topical treatment of psoriasis: application of Box Behnken design, in vitro and ex vivo studies. J Drug Deliv Sci Technol. 2017;41:325–33. [DOI]

70.

Stevens NT, Anderson-Cook CM. Design and analysis of confirmation experiments. J Quality Tech. 2019;51:109–24. [DOI]

71.

Kan S, Lu J, Liu J, Wang J, Zhao Y. A quality by design (QbD) case study on enteric-coated pellets: screening of critical variables and establishment of design space at laboratory scale. Asian J Pharm Sci. 2014;9:268–78. [DOI]

72.

Chabukswar AR, Jagdale SC, Kuchekar BS, Kothawade HS, Kuckekar AB, Joshi VD, et al. Six sigma: process of understanding the control and capability of ranitidine hydrochloride tablet. J Young Pharm. 2011;3:15–25. [DOI] [PubMed] [PMC]