Cross-linking with multifunctional excipients and its effect on the physicochemical properties and release profile of ibuprofen-loaded Digitaria exilis starch nanoparticles

Judith Eloyi John; Babajide Akinyele Tytler; James Habila; Yonni Eshovo Apeji; Olubunmi Olayemi; Christiana Yetunde Isimi

Cross-linking with multifunctional excipients and its effect on the physicochemical properties and release profile of ibuprofen-loaded Digitaria exilis starch nanoparticles

Abstract

Nanoparticles have been used to overcome the limitations of oral drug delivery. This study was performed to examine the effects of modifying Digitaria exilis starch by cross-linking with multifunctional excipients: citric acid (CA) and sodium tripolyphosphate (STPP) to produce starch citrate and phosphate respectively at 20 % concentration. Thereafter, nanoparticles were synthesized via the nanoprecipitation method in the presence of Tween® 80, using ibuprofen as the model drug. The physicochemical properties of the modified starch were evaluated and the nanoparticles characterized by the encapsulation efficiciency, loading capacity, particle size, polydispersity index, scanning electron microscope (SEM), fourier transform infrared spectroscopy(FTIR), in vitro drug release and release kinetics. Results show that both cross-linkers improved the physicochemical properties of the starch, and produced particles in the nanometer range (616 nm and 933 nm) for citric acid and sodium tripolyphosphate nanoparticles respectively. Spherical and pitted particles corresponding to citric acid and sodium tripolyphosphate nanoparticles respectively were produced and they both showed a controlled release of ibuprofen from the formulation and both followed the Higuchi kinetic model with R2 values that exhibited a non-fickian diffusion pattern. This study revealed that the two excipients had different effects on the size and morphology of the nanoparticles and controlled the release of drug from the nanoparticles.

Keywords

References

[1] Lokhande TN, Raut SA. Nanoparticles: an Approach for Novel Drug Delivery System-a Review. Raut al World J Pharm Res. 2019;8(7):652. [CrossRef]
[2] Han J, Zhao D, Li D, Wang X, Jin Z, Zhao K. Polymer-Based Nanomaterials and Applications for Vaccines and Drugs. Polymers (Basel). 2018;10(31):1–14. [CrossRef]
[3] Patra JK, Das G, Fraceto LF, Vangelie E, Campos R, Rodriguez P, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology. 2018;16(71):1–33. [CrossRef]
[4] Rizvi SAA, Saleh AM. Applications of Nanoparticle Systems in Drug Delivery Technology. Saudi Pharm J. 2018;1– 25. [CrossRef]
[5] Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H. Nanoparticles as drug delivery systems. Pharmacol Reports. 2012;64(5):1020–37. [CrossRef]
[6] Singla D, Singh A, Dhull SB, Kumar P, Malik T, Kumar P. Taro starch: Isolation, morphology, modification and novel applications concern - A review. Int J Biol Macromol. 2020;163:1283–90. [CrossRef]
[7] Aravamudhan A, Ramos DM, Nada AA, Kumbar SG. Natural Polymers: Polysaccharides and Their Derivatives for Biomedical Applications. Natural and Synthetic Biomedical Polymers. Elsevier Inc.; 2014. 67–89 p. [CrossRef]
[8] Corre D Le, Bras J, Dufresne A. Starch Nanoparticles: A Review. Biomacromolecules. 2010;11:1139–53. [CrossRef]

[9] Bertoft E, Blennow A. Structure of Potato Starch. In: Advances in Potato Chemistry and Technology. Second Edi. Elsevier Inc.; 2016. p. 57–73. [CrossRef]
[10] Gonz P, Carolina S, Jaramillo M, Pii SG. Biodegradable and non-retrogradable eco-films based on starch-glycerol with citric acid as crosslinking agent. Carbohydr Polym. 2015;11:1–15. [CrossRef]
[11] Silva, N. M. C. D. , de Lima, F. F. , Fialho, R. L. , de Magalhães Cabral Albuquerque, E. C. , Velasco, J. I. , Fakhouri, F. M.. Production and Characterization of Starch Nanoparticles Normane Matta Fakhouri. In: Applications of Modified Starches. IntechOpen; 2018. p. 41–8. [CrossRef]
[12] Ghanbarzadeh B, Almasi H, Entezami AA. Improving the barrier and mechanical properties of corn starch-based edible films: Effect of citric acid and carboxymethyl cellulose. Ind Crops Prod. 2011;33(1):229–35. [CrossRef]
[13] Jyothi AN, Moorthy SN, Rajasekharan KN. Effect of cross-linking with epichlorohydrin on the properties of cassava (Manihot esculenta Crantz) starch. Starch/Staerke. 2006;58(6):292–9. [CrossRef]
[14] Shewry PR. The Major Seed Storage Proteins of Spelt Wheat, Sorghum, Millets and Pseudocereals. In: Pseudocereals and Less Common Cereals. Springer, Berlin, Heidelberg; 2002. p. 1–24. [CrossRef]
[15] Ibrahim HM, Saidu B. Effect of Processed Acha (Digitaria exilis) grain on glycemic index of diabetes induced Wistar Rat model. Sch J Biol Sci. 2017;6(3):89–93.
[16] Musa H, Muazu J, Bhatia PG, Mshelbwala K. Investigation into the Use of Fonio (Digitaria Exilis) Starch as a Tablet Disintegrant. Niger J Pharm Sci. 2008;7(1):67–78.
[17] Odeniyi MA, Adepoju AO, Jaiyeoba KT. Native and Modified Digitaria exilis Starch Nanoparticles as a Carrier System for the Controlled Release of Naproxen. Starch - Stärke. 2019;71:1–10. [CrossRef]
[18] Budavari S, MJ O, A S, Heckelman P. An encyclopedia of chemicals, drugs, and biologicals. The Merck index. USA: Merck & Co., Inc; 1989.
[19] Xie Y, Zhang B, Li M, Chen H. Eff ects of cross-linking with sodium trimetaphosphate on structural and adsorptive properties of porous wheat starches. Food Chem. 2019;289:187–94. [CrossRef]
[20] Lenaerts V, Moussa I, Dumoulin Y, Mebsout F, Chouinard F, Szabo P. Cross-linked high amylose starch for controlled release of drugs: recent advances. J Control Release. 1998;53:225–34.
[21] Singh J, Kaur L, McCarthy OJ. Factors influencing the physico-chemical, morphological, thermal and rheological properties of some chemically modified starches for food applications-A review. Food Hydrocoll. 2007;21(1):1–22. [CrossRef]
[22] El-Feky GS, MH E-R, El-Sheikh M, El-Naggar ME, A H. Utilization of Crosslinked Starch Nanoparticles as a Carrier for Indomethacin and Acyclovir Drugs. J Nanomed Nanotechnol. 2015;6(1):1–9.[CrossRef]
[23] El-Naggar ME, El-Rafie MH, El-sheikh MA, El-Feky GS, Hebeish A. Synthesis , characterization , release kinetics and toxicity profile of drug- loaded starch nanoparticles Related papers. Int J Biol Macromol. 2015;81:718–29. [CrossRef]
[24] Uv B, V KD, Jain N. Formulation and Optimization of Mucoadhesive Nanodrug Delivery System of Acyclovir. J Young Pharm. 2011;3(4):275–83. [CrossRef]
[25] Shen Z, Nieh M-P, Li Y. Decorating Nanoparticle Surface for Targeted Drug Delivery: Opportunities and Challenges. Polymers (Basel). 2016;8(3):83. [CrossRef]
[26] Saliu OD, Olatunji GA, Ajetomobi OO, Olosho AI. Crystalline starch citrate biopolymer nanorods as potential stabilizers in nano and micro emulsions. J Chem Soc. 2017;1(2):191–200.
[27] Shen Y, Zhang N, Xu Y, Huang J, Wu D, Shu X. Physicochemical properties of hydroxypropylated and cross-linked rice starches differential in amylose content. Int J Biol Macromol. 2019;128:775–81. [CrossRef]
[28] Zhang B, Cui D, Liu M, Gong H, Huang Y, Han F. Corn porous starch: Preparation, characterization and adsorption property. Int J Biol Macromol. 2011;50(1):250–6. [CrossRef]
[29] Ibuprofen Modified Release Tablets 800 mg. Auckland: BNM Group; 2011. 1–17 p.
[30] Mehlisch DR, Sykes J. Ibuprofen blood plasma levels and onset of analgesia. Int J Clin Pract. 2013;67:3–8. [CrossRef]
[31] Jain R, Sukla SK, Nema N, Panday A. Drug Nano-particle : A Release Kinetics Nanomedicine & Nanotechnology. J Nanomedicine Nanotechnol. 2015;6(5):1–6. [CrossRef]
[32] Barzegar-jalali M, Adibkia K, Valizadeh H, Reza M, Shadbad S. Kinetic analysis of drug release from nanoparticles. J Pharm Pharm Sci. 2008;11(1):167–77. [CrossRef]
[33] Kunle OO, Ibrahim YE, Emeje MO, Shaba S, Kunle Y. Extraction, physicochemical and compaction properties of tacca starch - A potential pharmaceutical excipient. Starch/Staerke. 2003;55(7):319–25. [CrossRef]
[34] Moses O, Abayomi T, Michael O, Adedayo B. Preparation and physicochemical characterization of icacina starch citrate – a potential pharmaceutical/industrial starch. Agric Biol J North Am. 2012;3(1):11–6. [CrossRef]
[35] Babu AS, Parimalavalli R. " Functional and Chemical Properties of Starch isolated from Tubers ". Int J Agric Food Sci. 2012;2(3):77–80.
[36] Nagarajan E, Shanmugasundaram P, Ravichandiran V, Vijayalakshmi A, Senthilnathan B, Masilamani K. Development and Evaluation of Chitosan Based Polymeric Nanoparticles of an Antiulcer Drug Lansoprazole. J Appl Pharm Sci. 2015;5(04):20–5. [CrossRef]
[37] Álvarez C, Núñez I, Torrado JJ, Gordon J, Potthast H, García-Arieta A. Investigation on the possibility of biowaivers for ibuprofen. J Pharm Sci. 2011;100(6):2343–9. [CrossRef]
[38] Chourasiya V, Bohrey S, Pandey A. Formulation, optimization, characterization and in-vitro drug release kinetics of atenolol loaded PLGA nanoparticles using 33 factorial design for oral delivery. Mater Discov. 2016;1–32. [CrossRef]

Details

Primary Language

English

Subjects

Pharmaceutical Biotechnology, Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Judith Eloyi John This is me
0000-0001-7789-4776
Nigeria

Babajide Akinyele Tytler This is me
0000-0002-0135-0892
Nigeria

James Habila This is me
0000-0003-3518-5271
Nigeria

Yonni Eshovo Apeji ^* This is me
0000-0002-3116-7570
Nigeria

Olubunmi Olayemi
0000-0001-5759-7176
Nigeria

Christiana Yetunde Isimi This is me
0000-0002-9066-9984
Nigeria

Publication Date

June 28, 2025

Submission Date

February 24, 2022

Acceptance Date

May 2, 2022

Published in Issue

Year 2022 Volume: 26 Number: 5

IZ

https://izlik.org/JA88DL62NU

Cite

RIS / Bibtex

APA

John, J. E., Tytler, B. A., Habila, J., Apeji, Y. E., Olayemi, O., & Isimi, C. Y. (2025). Cross-linking with multifunctional excipients and its effect on the physicochemical properties and release profile of ibuprofen-loaded Digitaria exilis starch nanoparticles. Journal of Research in Pharmacy, 26(5), 1190-1201. https://izlik.org/JA88DL62NU

AMA

1.John JE, Tytler BA, Habila J, Apeji YE, Olayemi O, Isimi CY. Cross-linking with multifunctional excipients and its effect on the physicochemical properties and release profile of ibuprofen-loaded Digitaria exilis starch nanoparticles. J. Res. Pharm. 2025;26(5):1190-1201. https://izlik.org/JA88DL62NU

Chicago

John, Judith Eloyi, Babajide Akinyele Tytler, James Habila, Yonni Eshovo Apeji, Olubunmi Olayemi, and Christiana Yetunde Isimi. 2025. “Cross-Linking With Multifunctional Excipients and Its Effect on the Physicochemical Properties and Release Profile of Ibuprofen-Loaded Digitaria Exilis Starch Nanoparticles”. Journal of Research in Pharmacy 26 (5): 1190-1201. https://izlik.org/JA88DL62NU.

EndNote

John JE, Tytler BA, Habila J, Apeji YE, Olayemi O, Isimi CY (June 1, 2025) Cross-linking with multifunctional excipients and its effect on the physicochemical properties and release profile of ibuprofen-loaded Digitaria exilis starch nanoparticles. Journal of Research in Pharmacy 26 5 1190–1201.

IEEE

[1]J. E. John, B. A. Tytler, J. Habila, Y. E. Apeji, O. Olayemi, and C. Y. Isimi, “Cross-linking with multifunctional excipients and its effect on the physicochemical properties and release profile of ibuprofen-loaded Digitaria exilis starch nanoparticles”, J. Res. Pharm., vol. 26, no. 5, pp. 1190–1201, June 2025, [Online]. Available: https://izlik.org/JA88DL62NU

ISNAD

John, Judith Eloyi - Tytler, Babajide Akinyele - Habila, James - Apeji, Yonni Eshovo - Olayemi, Olubunmi - Isimi, Christiana Yetunde. “Cross-Linking With Multifunctional Excipients and Its Effect on the Physicochemical Properties and Release Profile of Ibuprofen-Loaded Digitaria Exilis Starch Nanoparticles”. Journal of Research in Pharmacy 26/5 (June 1, 2025): 1190-1201. https://izlik.org/JA88DL62NU.

JAMA

1.John JE, Tytler BA, Habila J, Apeji YE, Olayemi O, Isimi CY. Cross-linking with multifunctional excipients and its effect on the physicochemical properties and release profile of ibuprofen-loaded Digitaria exilis starch nanoparticles. J. Res. Pharm. 2025;26:1190–1201.

MLA

John, Judith Eloyi, et al. “Cross-Linking With Multifunctional Excipients and Its Effect on the Physicochemical Properties and Release Profile of Ibuprofen-Loaded Digitaria Exilis Starch Nanoparticles”. Journal of Research in Pharmacy, vol. 26, no. 5, June 2025, pp. 1190-01, https://izlik.org/JA88DL62NU.

Vancouver

1.Judith Eloyi John, Babajide Akinyele Tytler, James Habila, Yonni Eshovo Apeji, Olubunmi Olayemi, Christiana Yetunde Isimi. Cross-linking with multifunctional excipients and its effect on the physicochemical properties and release profile of ibuprofen-loaded Digitaria exilis starch nanoparticles. J. Res. Pharm. [Internet]. 2025 Jun. 1;26(5):1190-201. Available from: https://izlik.org/JA88DL62NU