Abstract
Mixture designs are the specialized experimental designs which provide precise information when the response changes as a function of the relative proportions of the components. All components must be entered in the same units of measure and each run must sum to the same total. These designs are helpful in furnishing maximal information with the help of minimal experimental runs. Different types of mixture designs are available such as simplex (lattice and centroid) mixture designs, optimal mixture (I, A, D) designs, which are used in a variety of experimental optimizations including pharmaceutical drug product development. The number of factors that can be used in simplex lattice, simplex centroid, and optimal design can range from 2 to 30, 3 to 8, and 2 to 24, respectively. As high-resolution designs, the mixture designs are capable of fitting higher-order mathematical models like quadratic and cubic for establishing the factor–response relationships. The design space estimation is very efficient and provides information on optimum solutions. In a nutshell, this chapter provides complete details regarding the basics and applications of mixture designs in pharmaceutical drug product development and optimization.
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References
Beg S, Swain S, Rahman M, Hasnain MS, Imam SS (2019) Application of Design of Experiments (DoE) in pharmaceutical product and process optimization. In: Beg S, Hasnain MS (eds) Pharmaceutical quality by design. Academic Press, New York, pp 43–64
Singh B, Raza K, Beg S (2013) Developing “optimized” drug products employing “designed” experiments. Chem Industry Digest 23:70–76
Beg S, Rahman M, Robaian MA, Alruwaili NK, Imam SS, Panda SK (2020) Pharmaceutical drug product development and process optimization: effective use of quality by design. CRC Press, New York
Singh B, Beg S (2013) Quality by design in product development life cycle. Chronicle Pharmabiz 22:72–79
Beg S, Hasnain MS, Rahman M, Swain S (2019) Introduction to quality by design (QbD): fundamentals, principles, and applications. In: Beg S, Hasnain MS (eds) Pharmaceutical quality by design. Academic Press, New York, pp 1–17
Beg S, Hasnain MS (2019) Pharmaceutical quality by design: principles and applications. Academic Press, New York
Singh B, Sharma T, Saini S, Kaur R, Jain A, Raza K, Beg S (2020) Systematic development of drug nanocargos using formulation by design (FbD): an updated overview. Crit Rev Ther Drug Carrier Syst 37(3):229–269
Myers RH, Montgomery DC (1995) Response Surface methodology: process and product in optimization using designed experiments. Wiley, New York
Beg S, Rahman M, Panda SS (2017) Pharmaceutical QbD: omnipresence in the product development lifecycle. European Pharma Rev 22(1):58–64
Zen NIM, Abd Gani SS, Shamsudin R, Masoumi HRF (2015) The use of D-optimal mixture design in optimizing development of Okara tablet formulation as a dietary supplement. Sci World J 2015:684319
Omar SM, AbdAlla FI, Abdelgawad NM (2018) Preparation and optimization of fast-disintegrating tablet containing naratriptan hydrochloride using D-optimal mixture design. AAPS PharmSciTech 19(6):2472–2487
Mura P, Furlanetto S, Cirri M, Maestrelli F, Marras AM, Pinzauti S (2005) Optimization of glibenclamide tablet composition through the combined use of differential scanning calorimetry and d-optimal mixture experimental design. J Pharm Biomed Anal 37(1):65–71
Das SK, Khanam J, Nanda A (2016) Optimization of preparation method for ketoprofen-loaded microspheres consisting polymeric blends using simplex lattice mixture design. Mater Sci Eng 69:598–608
Maherani B, Arab-tehrany E, Kheirolomoom A, Reshetov V, Stebe MJ, Linder M (2012) Optimization and characterization of liposome formulation by mixture design. Analyst 137(3):773–786
Mura P, Capasso G, Maestrelli F, Furlanetto S (2008) Optimization of formulation variables of benzocaine liposomes using experimental design. J Liposome Res 18(2):113–125
Naguib SS, Hathout RM, Mansour S (2017) Optimizing novel penetration enhancing hybridized vesicles for augmenting the in-vivo effect of an anti-glaucoma drug. Drug Deliv 24(1):99–108
Pires FQ, Angelo T, Silva JKR, Sãi-Barreto LCL, Lima EM, Gelfuso GM, Gratieri T, Cunha-Filho MSS (2017) Use of mixture design in drug-excipient compatibility determinations: thymol nanoparticles case study. J Pharm Biomed Anal 137:196–203
Ven HVd, Vandervoort J, Weyenberg W, Apers S, Ludwig A (2011) Mixture designs in the optimisation of PLGA nanoparticles: influence of organic phase composition on Î2-aescin encapsulation. J Microencapsul 29(2):115–125
Beg S, Sharma G, Thanki K, Jain S, Katare OP, Singh B (2015) Positively charged self-nanoemulsifying oily formulations of olmesartan medoxomil: systematic development, in vitro, ex vivo and in vivo evaluation. Int J Pharm 493(1–2):466–482
Bandyopadhyay S, Beg S, Katare OP, Sharma G, Singh B (2015) QbD-oriented development of self-nanoemulsifying drug delivery systems (SNEDDS) of valsartan with improved biopharmaceutical performance. Curr Drug Deliv 12(5):544–563
Sharma G, Beg S, Thanki K, Katare OP, Jain S, Kohli K, Singh B (2015) Systematic development of novel cationic self-nanoemulsifying drug delivery systems of candesartan cilexetil with enhanced biopharmaceutical performance. RSC Adv 5(87):71500–71513
Beg S, Katare OP, Singh B (2017) Formulation by design approach for development of ultrafine self-nanoemulsifying systems of rosuvastatin calcium containing long-chain lipophiles for hyperlipidemia management. Colloids Surf B: Biointerf 159:869–879
Beg S, Alam MN, Ahmad FJ, Singh B (2019) Chylomicron mimicking nanocolloidal carriers of rosuvastatin calcium for lymphatic drug targeting and management of hyperlipidemia. Colloids Surf B: Biointerf 177:541–549
Khurana RK, Bansal AK, Beg S, Burrow AJ, Katare OP, Singh KK, Singh B (2017) Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: systematic development, characterization and evaluation. Int J Pharm 518(1):289–306
Garg B, Beg S, Kaur R, Kumar R, Katare OP, Singh B (2017) Long-chain triglycerides-based self-nanoemulsifying oily formulations (SNEOFs) of darunavir with improved lymphatic targeting potential. J Drug Target 26(3):252–266
Garg B, Katare OP, Beg S, Lohan S, Singh B (2016) Systematic development of solid self-nanoemulsifying oily formulations (S-SNEOFs) for enhancing the oral bioavailability and intestinal lymphatic uptake of lopinavir. Colloids Surf B: Biointerf 141:611–622
Tripathi CB, Beg S, Kaur R, Shukla G, Bandopadhyay S, Singh B (2016) Systematic development of optimized SNEDDS of artemether with improved biopharmaceutical and antimalarial potential. Drug Deliv 23(9):3209–3223
Beg S, Kaur R, Khurana RK, Rana V, Sharma T, Singh B (2019) QbD-based development of cationic self-nanoemulsifying drug delivery systems of paclitaxel with improved biopharmaceutical attributes. AAPS Pharm Sci Tech 20(3):118
Sandhu PS, Beg S, Mehta F, Singh B, Trivedi P (2015) Novel dietary lipid-based self-nanoemulsifying drug delivery systems of paclitaxel with p-gp inhibitor: implications on cytotoxicity and biopharmaceutical performance. Expert Opin Drug Deliv 12(11):1809–1822
Sandhu PS, Kumar R, Beg S, Jain S, Kushwah V, Katare OP, Singh B (2017) Natural lipids enriched self-nano-emulsifying systems for effective co-delivery of tamoxifen and naringenin: systematic approach for improved breast cancer therapeutics. Nanomedicine 13(5):1703–1713
Jain A, Kaur R, Beg S, Kushwah V, Jain S, Singh B (2018) Novel cationic supersaturable nanomicellar systems of raloxifene hydrochloride with enhanced biopharmaceutical attributes. Drug Deliv Transl Res 8(3):670–692
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Beg, S. (2021). Mixture Designs and Their Applications in Pharmaceutical Product Development. In: Beg, S. (eds) Design of Experiments for Pharmaceutical Product Development. Springer, Singapore. https://doi.org/10.1007/978-981-33-4717-5_8
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DOI: https://doi.org/10.1007/978-981-33-4717-5_8
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