Factors Affecting Preparation of Repaglinide Nanoparticles for Dissolution Improvement
Repaglinide nanoparticles for improved dissolution
Keywords:
Repaglinide, nanosuspension, nano-precipitation, soluplus, PVP K30
Abstract
This study aimed to develop a stable nanosuspension of repaglinide and improve its dissolution, using the Nano-precipitation method, involving a different concentration of a stabilizer, different co-stabilizers and different solvents. Employment of a systemic approach to optimize the formulation parameters, including stabilizer concentration, solvent choice and co-stabilizer election. Soluplus® (SOL) was used as the primary stabilizer for this research, polyvinyl alcohol (PVA), poloxamer 188 (PXM 188), tween 80 (TW80), and polyvinyl pyrrolidine (PVP k30) were investigated as co-stabilizers to prevent particle agglomeration and ensure long-term stability. In addition to ethanol as a primary solvent, acetone and chloroform were used for solvent-change assessment. Particle size, polydispersity index (PDI), FTIR study to reveal any interactions and particle morphology using scanning electron microscope, and drug crystallinity and thermal changes were evaluated to assess the physicochemical properties of the nanosuspension.
RPG-SOL3 resulted nanoparticle mean size (82.96 nm±3.95) and a PDI of (0.100±0.098). In vitro dissolution studies showed a complete dissolution of the formula and a significant enhancement when compared to RPG drug powder. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirmed the amorphous nature of optimal RPG nanoparticle. This study successfully develops a stable nanosuspension formulation of repaglinide to improve its dissolution properties. We have achieved a nanosuspension with desirable physicochemical characteristics through systematic optimization of formulation parameters, including selecting stabilizers and co-stabilizers.
References
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Abd-Alhammid, H. E. J. a. S. N. (2022). Improvement of the Solubility and Dissolution Characteristics of Risperidone via Nanosuspension Formulations. Iraqi J Pharm Sci,. https://doi.org/10.31351/vol31iss1pp43-56
K. Abbas, H., M. Hussein Wais, F., & N. Abood, A. (2017). Preparation and Evaluation of Ketoprofen Nanosuspension Using Solvent Evaporation Technique. Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512), 41-55.
Fadhila, M. (2023). Effectiveness of Dry Grinding and Wet Grinding Methods on Solution and Dissolution Rate of Nimodipine-HPMC Nanoparticles. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.7267 .
Vishal R. Patel, Y. K. A. (2011). Nanosuspension: An approach to enhance solubility of drugs.
Mandić, Z., & Gabelica, V. (2006). Ionization, lipophilicity and solubility properties of repaglinide. J Pharm Biomed Anal, 41(3), 866-871. https://doi.org/10.1016/j.jpba.2006.01.056
Ebrahimi, H. A., Javadzadeh, Y., Hamidi, M., & Jalali, M. B. (2015). Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles. DARU Journal of Pharmaceutical Sciences, 23(1). https://doi.org/10.1186/s40199-015-0128-3
Jogu, C. (2020). Preparation and evaluation of repaglinide nanosuspensions. International Journal of Novel Trends in Pharmaceutical Sciences, 9(1), 6-11. https://doi.org/10.26452/ijntps.v9i1.1166
Gill, S., & Arora, P. (2020). Improving Physicochemical Properties of Repaglinide Through Pharmaceutical Adduct Formation. Journal of Pharmaceutical Technology, Research and Management, 8(1), 31-37. https://doi.org/10.15415/jptrm.2020.81005
Lokhande, A. B., Mishra, S., Kulkarni, R. D., & Naik, J. B. (2013). Preparation and characterization of repaglinide loaded ethylcellulose nanoparticles by solvent diffusion technique using high pressure homogenizer. Journal of Pharmacy Research, 7(5), 421-426. https://doi.org/10.1016/j.jopr.2013.04.049
Bashar, K. K. G., & Al-Khedairy, E. (2023). Solubility and Dissolution Enhancement of Atorvastatin Calcium using Phospholipid Solid Dispersion Technique. Iraqi Journal of Pharmaceutical Sciences( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512), 32(Suppl.), 244-253.
Rajab, R. M. A. a. N. A. (2021). Nanosuspensions of Selexipag: Formulation, Characterization, and in vitro Evaluation. Iraqi J Pharm Sci,, vol 30. https://doi.org/10.31351/vol30iss1pp144-153
Nawar M. Toma, A. A. A. (2021). Preparation and Evaluation of Microneedles-mediated Transdermal Delivery of Montelukast Sodium Nanoparticles. IJDDT.
Fouad, S. A., Teaima, M. H., Gebril, M. I., Abd Allah, F. I., El-Nabarawi, M. A., & Elhabal, S. F. (2023). Formulation of novel niosomal repaglinide chewable tablets using coprocessed excipients: in vitro characterization, optimization and enhanced hypoglycemic activity in rats. Drug Deliv, 30(1), 2181747. https://doi.org/10.1080/10717544.2023.2181747
Bushra Malik Jassim *, a. E. B. H. A.-K. (2023). Formulation and in vitro /in vivo Evaluation of Silymarin Solid DispersionBased Topical Gel for Wound Healing Iraqi J Pharm Sci.
Thamer, A. K., & Abood, A. N. (2021). Preparation and In vitro Characterization of Aceclofenac Nanosuspension (ACNS) for Enhancement of Percutaneous Absorption using Hydrogel Dosage Form. Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512), 30(2), 86-98. https://doi.org/10.31351/vol30iss2pp86-98
Areej W. Alhagiesa*, & Ghareeb**, a. M. M. (2021). Formulation and Characterization of Nimodipine Nanoparticles for the Enhancement of solubility and dissolution rate.
https://doi.org/10.31351/vol32isssuppl.pp244-253
jassim, Z., & Hussein, A. (2014). Formulation and evaluation of clopidogrel tablet incorporating drug nanoparticles. International Journal of Pharmacy and Pharmaceutical Sciences, 6, 838-851.
Dawood, N., Abdal-Hammid, S., & Hussein, A. (2018). Formulation and characterization of lafutidine nanosuspension for oral drug delivery system. International Journal of Applied Pharmaceutics, 10, 20. https://doi.org/10.22159/ijap.2018v10i2.23075
Ali, A. H., & N. Abd-Alhammid, S. (2019). Enhancement of Solubility and Improvement of Dissolution Rate of Atorvastatin Calcium Prepared as Nanosuspension. Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512), 28(2), 46-57. https://doi.org/10.31351/vol28iss2pp46-57
Mohamed S. Attia a, Ahmed Elshahat a, Ahmed Hamdy b, Ayman M. Fathi a, Mahmoud Emad-Eldin c, Fakhr-Eldin S. Ghazy a, Hitesh Chopra d, Tarek M. Ibrahim. (2023). Soluplus® as a solubilizing excipient for poorly water-soluble drugs: Recent advances in formulation strategies and pharmaceutical product features.
Mohammed, A. A., & Abd Alhammid, S. N. (2024). Formulation and Characterization of Clozapine Nanosuspension as a Sublingual Film. Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ), 6(2), 82-88. https://doi.org/10.54133/ajms.v6i2.772
Gumaste, S. G., Gupta, S. S., & Serajuddin, A. T. M. (2016). Investigation of Polymer-Surfactant and Polymer-Drug-Surfactant Miscibility for Solid Dispersion. The AAPS Journal, 18(5), 1131-1143. https://doi.org/10.1208/s12248-016-9939-5
Emad, H., & Nazar Abd-Alhammid, S. (2022). Improvement of the Solubility and Dissolution Characteristics of Risperidone via Nanosuspension Formulations. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683 - 3597 E-ISSN 2521 - 3512), 31(1), 43-56. https://doi.org/10.31351/vol31iss1pp43-56
Kulshreshtha, A. K., Singh, O. N., & Wall, G. M. (2009). Pharmaceutical suspensions: from formulation development to manufacturing. Springer.
Müller, R. H., Jacobs, C., & Kayser, O. (2001). Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future. Adv Drug Deliv Rev, 47(1), 3-19. https://doi.org/10.1016/s0169-409x(00)00118-6
Weng, J., Tong, H. H. Y., & Chow, S. F. (2020). In Vitro Release Study of the Polymeric Drug Nanoparticles: Development and Validation of a Novel Method. Pharmaceutics, 12(8). https://doi.org/10.3390/pharmaceutics12080732
Hamed, H. E., & A. Hussein, A. (2020). Preparation, in vitro and ex-vivo Evaluation of Mirtazapine Nanosuspension and Nanoparticles Incorporated in Orodispersible Tablets. Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512), 29(1), 62-75. https://doi.org/10.31351/vol29iss1pp62-75
Müller, R. H., Radtke, M., & Wissing, S. A. (2002). Nanostructured lipid matrices for improved microencapsulation of drugs. Int J Pharm, 242(1-2), 121-128. https://doi.org/10.1016/s0378-5173(02)00180-1
Khoza, P. B., Moloto, M. J., & Sikhwivhilu, L. M. (2012). The Effect of Solvents, Acetone, Water, and Ethanol, on the Morphological and Optical Properties of ZnO Nanoparticles Prepared by Microwave. Journal of Nanotechnology, 2012, 1-6. https://doi.org/10.1155/2012/195106
Bose, S., Du, Y., Takhistov, P., & Michniak-Kohn, B. (2013). Formulation optimization and topical delivery of quercetin from solid lipid based nanosystems. Int J Pharm, 441(1-2), 56-66. https://doi.org/10.1016/j.ijpharm.2012.12.013
Li, G., Lu, Y., Fan, Y., Ning, Q., & Li, W. (2020). Enhanced oral bioavailability of magnolol via mixed micelles and nanosuspensions based on Soluplus(®)-Poloxamer 188. Drug Deliv, 27(1), 1010-1017. https://doi.org/10.1080/10717544.2020.1785582
Patnaik, S., Chunduri, L. A. A., Akilesh, M. S., Bhagavatham, S. S., & Kamisetti, V. (2016). Enhanced dissolution characteristics of piroxicam–Soluplus® nanosuspensions. Journal of Experimental Nanoscience, 11(12), 916-929.
Pignatello, R., & Corsaro, R. (2019). Polymeric Nanomicelles of Soluplus® as a Strategy for Enhancing the Solubility, Bioavailability and Efficacy of Poorly Soluble Active Compounds. Current Nanomedicine, 09. https://doi.org/10.2174/2468187309666190314152451
Gadadare, R., Mandpe, L., & Pokharkar, V. (2015). Ultra rapidly dissolving repaglinide nanosized crystals prepared via bottom-up and top-down approach: influence of food on pharmacokinetics behavior. AAPS PharmSciTech, 16(4), 787-799. https://doi.org/10.1208/s12249-014-0267-8
Kocbek, P., Baumgartner, S., & Kristl, J. (2006). Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs. International Journal of Pharmaceutics, 312(1), 179-186. https://doi.org/https://doi.org/10.1016/j.ijpharm.2006.01.008
Yang, X.-D., Li, W.-S., Tian, Y.-J., Liu, C.-G., Gao, D.-H., & Ma, H.-L. (2016). Dissolution rate enhancement of repaglinide by solid dispersion. Tropical Journal of Pharmaceutical Research, 15(6). https://doi.org/10.4314/tjpr.v15i6.2
Abd-Alhammid, H. E. J. a. S. N. (2022). Improvement of the Solubility and Dissolution Characteristics of Risperidone via Nanosuspension Formulations. Iraqi J Pharm Sci,. https://doi.org/10.31351/vol31iss1pp43-56
K. Abbas, H., M. Hussein Wais, F., & N. Abood, A. (2017). Preparation and Evaluation of Ketoprofen Nanosuspension Using Solvent Evaporation Technique. Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512), 41-55.
Fadhila, M. (2023). Effectiveness of Dry Grinding and Wet Grinding Methods on Solution and Dissolution Rate of Nimodipine-HPMC Nanoparticles. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.7267 .
Vishal R. Patel, Y. K. A. (2011). Nanosuspension: An approach to enhance solubility of drugs.
Mandić, Z., & Gabelica, V. (2006). Ionization, lipophilicity and solubility properties of repaglinide. J Pharm Biomed Anal, 41(3), 866-871. https://doi.org/10.1016/j.jpba.2006.01.056
Ebrahimi, H. A., Javadzadeh, Y., Hamidi, M., & Jalali, M. B. (2015). Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles. DARU Journal of Pharmaceutical Sciences, 23(1). https://doi.org/10.1186/s40199-015-0128-3
Jogu, C. (2020). Preparation and evaluation of repaglinide nanosuspensions. International Journal of Novel Trends in Pharmaceutical Sciences, 9(1), 6-11. https://doi.org/10.26452/ijntps.v9i1.1166
Gill, S., & Arora, P. (2020). Improving Physicochemical Properties of Repaglinide Through Pharmaceutical Adduct Formation. Journal of Pharmaceutical Technology, Research and Management, 8(1), 31-37. https://doi.org/10.15415/jptrm.2020.81005
Lokhande, A. B., Mishra, S., Kulkarni, R. D., & Naik, J. B. (2013). Preparation and characterization of repaglinide loaded ethylcellulose nanoparticles by solvent diffusion technique using high pressure homogenizer. Journal of Pharmacy Research, 7(5), 421-426. https://doi.org/10.1016/j.jopr.2013.04.049
Bashar, K. K. G., & Al-Khedairy, E. (2023). Solubility and Dissolution Enhancement of Atorvastatin Calcium using Phospholipid Solid Dispersion Technique. Iraqi Journal of Pharmaceutical Sciences( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512), 32(Suppl.), 244-253.
Rajab, R. M. A. a. N. A. (2021). Nanosuspensions of Selexipag: Formulation, Characterization, and in vitro Evaluation. Iraqi J Pharm Sci,, vol 30. https://doi.org/10.31351/vol30iss1pp144-153
Nawar M. Toma, A. A. A. (2021). Preparation and Evaluation of Microneedles-mediated Transdermal Delivery of Montelukast Sodium Nanoparticles. IJDDT.
Fouad, S. A., Teaima, M. H., Gebril, M. I., Abd Allah, F. I., El-Nabarawi, M. A., & Elhabal, S. F. (2023). Formulation of novel niosomal repaglinide chewable tablets using coprocessed excipients: in vitro characterization, optimization and enhanced hypoglycemic activity in rats. Drug Deliv, 30(1), 2181747. https://doi.org/10.1080/10717544.2023.2181747
Bushra Malik Jassim *, a. E. B. H. A.-K. (2023). Formulation and in vitro /in vivo Evaluation of Silymarin Solid DispersionBased Topical Gel for Wound Healing Iraqi J Pharm Sci.
Thamer, A. K., & Abood, A. N. (2021). Preparation and In vitro Characterization of Aceclofenac Nanosuspension (ACNS) for Enhancement of Percutaneous Absorption using Hydrogel Dosage Form. Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512), 30(2), 86-98. https://doi.org/10.31351/vol30iss2pp86-98
Areej W. Alhagiesa*, & Ghareeb**, a. M. M. (2021). Formulation and Characterization of Nimodipine Nanoparticles for the Enhancement of solubility and dissolution rate.
https://doi.org/10.31351/vol32isssuppl.pp244-253
jassim, Z., & Hussein, A. (2014). Formulation and evaluation of clopidogrel tablet incorporating drug nanoparticles. International Journal of Pharmacy and Pharmaceutical Sciences, 6, 838-851.
Dawood, N., Abdal-Hammid, S., & Hussein, A. (2018). Formulation and characterization of lafutidine nanosuspension for oral drug delivery system. International Journal of Applied Pharmaceutics, 10, 20. https://doi.org/10.22159/ijap.2018v10i2.23075
Ali, A. H., & N. Abd-Alhammid, S. (2019). Enhancement of Solubility and Improvement of Dissolution Rate of Atorvastatin Calcium Prepared as Nanosuspension. Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512), 28(2), 46-57. https://doi.org/10.31351/vol28iss2pp46-57
Mohamed S. Attia a, Ahmed Elshahat a, Ahmed Hamdy b, Ayman M. Fathi a, Mahmoud Emad-Eldin c, Fakhr-Eldin S. Ghazy a, Hitesh Chopra d, Tarek M. Ibrahim. (2023). Soluplus® as a solubilizing excipient for poorly water-soluble drugs: Recent advances in formulation strategies and pharmaceutical product features.
Mohammed, A. A., & Abd Alhammid, S. N. (2024). Formulation and Characterization of Clozapine Nanosuspension as a Sublingual Film. Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ), 6(2), 82-88. https://doi.org/10.54133/ajms.v6i2.772
Gumaste, S. G., Gupta, S. S., & Serajuddin, A. T. M. (2016). Investigation of Polymer-Surfactant and Polymer-Drug-Surfactant Miscibility for Solid Dispersion. The AAPS Journal, 18(5), 1131-1143. https://doi.org/10.1208/s12248-016-9939-5
Emad, H., & Nazar Abd-Alhammid, S. (2022). Improvement of the Solubility and Dissolution Characteristics of Risperidone via Nanosuspension Formulations. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683 - 3597 E-ISSN 2521 - 3512), 31(1), 43-56. https://doi.org/10.31351/vol31iss1pp43-56
Kulshreshtha, A. K., Singh, O. N., & Wall, G. M. (2009). Pharmaceutical suspensions: from formulation development to manufacturing. Springer.
Müller, R. H., Jacobs, C., & Kayser, O. (2001). Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future. Adv Drug Deliv Rev, 47(1), 3-19. https://doi.org/10.1016/s0169-409x(00)00118-6
Weng, J., Tong, H. H. Y., & Chow, S. F. (2020). In Vitro Release Study of the Polymeric Drug Nanoparticles: Development and Validation of a Novel Method. Pharmaceutics, 12(8). https://doi.org/10.3390/pharmaceutics12080732
Hamed, H. E., & A. Hussein, A. (2020). Preparation, in vitro and ex-vivo Evaluation of Mirtazapine Nanosuspension and Nanoparticles Incorporated in Orodispersible Tablets. Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512), 29(1), 62-75. https://doi.org/10.31351/vol29iss1pp62-75
Müller, R. H., Radtke, M., & Wissing, S. A. (2002). Nanostructured lipid matrices for improved microencapsulation of drugs. Int J Pharm, 242(1-2), 121-128. https://doi.org/10.1016/s0378-5173(02)00180-1
Khoza, P. B., Moloto, M. J., & Sikhwivhilu, L. M. (2012). The Effect of Solvents, Acetone, Water, and Ethanol, on the Morphological and Optical Properties of ZnO Nanoparticles Prepared by Microwave. Journal of Nanotechnology, 2012, 1-6. https://doi.org/10.1155/2012/195106
Bose, S., Du, Y., Takhistov, P., & Michniak-Kohn, B. (2013). Formulation optimization and topical delivery of quercetin from solid lipid based nanosystems. Int J Pharm, 441(1-2), 56-66. https://doi.org/10.1016/j.ijpharm.2012.12.013
Li, G., Lu, Y., Fan, Y., Ning, Q., & Li, W. (2020). Enhanced oral bioavailability of magnolol via mixed micelles and nanosuspensions based on Soluplus(®)-Poloxamer 188. Drug Deliv, 27(1), 1010-1017. https://doi.org/10.1080/10717544.2020.1785582
Patnaik, S., Chunduri, L. A. A., Akilesh, M. S., Bhagavatham, S. S., & Kamisetti, V. (2016). Enhanced dissolution characteristics of piroxicam–Soluplus® nanosuspensions. Journal of Experimental Nanoscience, 11(12), 916-929.
Pignatello, R., & Corsaro, R. (2019). Polymeric Nanomicelles of Soluplus® as a Strategy for Enhancing the Solubility, Bioavailability and Efficacy of Poorly Soluble Active Compounds. Current Nanomedicine, 09. https://doi.org/10.2174/2468187309666190314152451
Gadadare, R., Mandpe, L., & Pokharkar, V. (2015). Ultra rapidly dissolving repaglinide nanosized crystals prepared via bottom-up and top-down approach: influence of food on pharmacokinetics behavior. AAPS PharmSciTech, 16(4), 787-799. https://doi.org/10.1208/s12249-014-0267-8
Kocbek, P., Baumgartner, S., & Kristl, J. (2006). Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs. International Journal of Pharmaceutics, 312(1), 179-186. https://doi.org/https://doi.org/10.1016/j.ijpharm.2006.01.008
Yang, X.-D., Li, W.-S., Tian, Y.-J., Liu, C.-G., Gao, D.-H., & Ma, H.-L. (2016). Dissolution rate enhancement of repaglinide by solid dispersion. Tropical Journal of Pharmaceutical Research, 15(6). https://doi.org/10.4314/tjpr.v15i6.2
Published
2025-06-10
How to Cite
Ghadhan, H. Y., & Ahmed, K. K. (2025). Factors Affecting Preparation of Repaglinide Nanoparticles for Dissolution Improvement. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.14273
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Research Article
