Article Review: Glimepiride Solubility Enhancement Strategy as Diabetes Treatment Therapy
DOI:
https://doi.org/10.58344/locus.v4i5.4010Keywords:
formulation, solubility, sulfonylurea group, type 2 diabetesAbstract
Diabetes mellitus (DM) is a chronic metabolic disease characterized by high blood glucose levels due to impaired insulin secretion. The prevalence of diabetes in Indonesia always increases every year. Glimepiride is a type 2 antidiabetic drug of the sulfonylurea class that works by stimulating insulin secretion of pancreatic beta cells. Glimepiride is given through the oral route of administration and is widely used because it has a longer half-life and can be used as treatment monotherapy. Glimepiride itself has physicochemical properties that can penetrate the stratum corneum with a dose of less than 10 mg, a molecular weight of 490.62 g/mol, a melting point of 207°C, and a lipophilicity value (LogP) of 3.5. However, oral glimepiride in therapy has bioavailability problems due to its poor solubility in the gastrointestinal tract. It has very low solubility values at acidic and neutral pH of approximately less than 0.004 mg/mL (BCS 2). Due to the low aqueous solubility of glimepiride is a major challenge in drug formulation development. This low solubility has an impact on its bioavailability, which is not optimal, thus reducing its therapeutics. Various efforts were made in order to increase the solubility of glimepiride, including the use of formulation techniques such as the preparation of solid dispersion systems, the formation of inclusion complexes, as well as the utilization of nanoparticle technologies such as nanosuspensions, nanoemulgels, and nanoemulsions. In addition, chemical modification approaches and various others are used to improve the solubility of glimepiride. Recent studies have shown that the combination of the latest formulation technologies with suitable carrier materials can significantly improve its solubility and stability, thereby enhancing the therapeutic effectiveness of glimepiride in the management of type 2 diabetes. Thus, innovations in glimepiride formulation are expected to provide better therapeutic solutions for patients with type 2 diabetes.
References
Abdallah, M. H., Abu Lila, A. S., El-Nahas, H. M., & Ibrahim, T. M. (2023). Optimization of Potential Nanoemulgels for Boosting Transdermal Glimepiride Delivery and Upgrading Its Anti-Diabetic Activity. Gels,9 (6). https://doi.org/10.3390/gels9060494
Ahmad, A. B. Y. K., & Taghi, H. S. (2022). Formulation and characterization of orodispersible tablets of glimepiride. Journal of Advanced Pharmaceutical Technology and Research,13 (4), 252-260. https://doi.org/10.4103/japtr.japtr_375_22
Ahmed, O. A. A., Zidan, A. S., & Khayat, M. (2016). Mechanistic analysis of zein nanoparticles/PLGA triblock in situ forming implants for glimepiride. International Journal of Nanomedicine,11, 543-555. https://doi.org/10.2147/IJN.S99731
Ahmed, T. A., Alotaibi, H. A., Alharbi, W. S., Safo, M. K., & El-Say, K. M. (2022). Development of 3D-Printed, Liquisolid and Directly Compressed Glimepiride Tablets, Loaded with Black Seed Oil Self-Nanoemulsifying Drug Delivery System: In Vitro and In Vivo Characterization. Pharmaceuticals,15 (1). https://doi.org/10.3390/ph15010068
Ahmed, T. A., Alotaibi, H. A., Almehmady, A. M., Safo, M. K., & El-Say, K. M. (2022). Influences of Glimepiride Self-Nanoemulsifying Drug Delivery System Loaded Liquisolid Tablets on the Hypoglycemic Activity and Pancreatic Histopathological Changes in Streptozotocin-Induced Hyperglycemic Rats. Nanomaterials,12 (22). https://doi.org/10.3390/nano12223966
Ahmed, T. A., Felimban, R. I., Tayeb, H. H., Rizg, W. Y., Alnadwi, F. H., Alotaibi, H. A., Alhakamy, N. A., Abd-Allah, F. I., Mohamed, G. A., Zidan, A. S., & El-Say, K. M. (2021). Development of multi-compartment 3d-printed tablets loaded with self-nanoemulsified formulations of various drugs: A new strategy for personalized medicine. Pharmaceutics,13 (10). https://doi.org/10.3390/pharmaceutics13101733
Akhlaq, M., Azad, A. K., Fuloria, S., Meenakshi, D. U., Raza, S., Safdar, M., Nawaz, A., Subramaniyan, V., Sekar, M., Sathasivam, K. V., Wu, Y. S., Miret, M. M., & Fuloria, N. K. (2021). Fabrication of tizanidine loaded patches using flaxseed oil and coriander oil as a penetration enhancer for transdermal delivery. Polymers,13 (23). https://doi.org/10.3390/polym13234217
Akram, M. R., Ahmad, M., Abrar, A., Sarfraz, R. M., & Mahmood, A. (2018). Formulation design and development of matrix diffusion controlled transdermal drug delivery of glimepiride. Drug Design, Development and Therapy,12 , 349-364. https://doi.org/10.2147/DDDT.S147082
Aldeeb, R. A. E., Ibrahim, S. S. A., Khalil, I. A., Ragab, G. M., El-Gazar, A. A., Taha, A. A., Hassan, D. H., Gomaa, A. A., & Younis, M. K. (2024). Enhancing collagen based nanoemulgel for effective topical delivery of Aceclofenac and Citronellol oil: Formulation, optimization, in-vitro evaluation, and in-vivo osteoarthritis study with a focus on HMGB-1/RAGE/NF-?B pathway, Klotho, and miR-499a. Drug Delivery and Translational Research,14 (11), 3250-3268. https://doi.org/10.1007/s13346-024-01548-3
Aldosari, B. N., Ibrahim, M. A., Alqahtani, Y., & Abou El Ela, A. E. S. F. (2024). Formulation and evaluation of Fluconazole Nanosuspensions: In vitro characterization and transcorneal permeability studies. Saudi Pharmaceutical Journal,32 (7), 102104. https://doi.org/10.1016/j.jsps.2024.102104
Alhasani, K. F., Kazi, M., Ibrahim, M. A., Shahba, A. A., & Alanazi, F. K. (2019). Self-nanoemulsifying ramipril tablets: A novel delivery system for the enhancement of drug dissolution and stability. International Journal of Nanomedicine,14 , 5435-5448. https://doi.org/10.2147/IJN.S203311
Alissa, I., Nair, A. B., Aldhubiab, B., Shah, H., Shah, J., Mewada, V., Almuqbil, R. M., & Jacob, S. (2023). Design, Development, and Evaluation of Treprostinil Embedded Adhesive Transdermal Patch. Pharmaceutics,15 (4), 1-22. https://doi.org/10.3390/pharmaceutics15041226
Alotaibi, F. O., Alhakamy, N. A., Omar, A. M., & El-Say, K. M. (2020). Clinical pharmacokinetic evaluation of optimized liquisolid tablets as a potential therapy for male sexual dysfunction. Pharmaceutics,12 (12), 1-23. https://doi.org/10.3390/pharmaceutics12121187
Azhar, M., Alasmari, M. S., Zamir, A., Saeed, H., Alqahtani, F., Ahmad, T., & Rasool, M. F. (2025). The Clinical Pharmacokinetics and Pharmacodynamics of Glimepiride-A Systematic Review and Meta-Analysis. Pharmaceuticals,18 (1), 1-26. https://doi.org/10.3390/ph18010122
Baloch, J., Sohail, M. F., Sarwar, H. S., Kiani, M. H., Khan, G. M., Jahan, S., Rafay, M., Chaudhry, M. T., Yasinzai, M., & Shahnaz, G. (2019). Self-nanoemulsifying drug delivery system (Snedds) for improved oral bioavailability of chlorpromazine: In vitro and in vivo evaluation. Medicina (Lithuania),55 (5), 1-13. https://doi.org/10.3390/medicina55050210
Basahih, T. S., Alamoudi, A. A., El-Say, K. M., Alhakamy, N. A., & Ahmed, O. A. A. (2020). Improved Transmucosal Delivery of Glimepiride via Unidirectional Release Buccal Film Loaded With Vitamin E TPGS-Based Nanocarrier. Dose-Response,18 (3), 1-12. https://doi.org/10.1177/1559325820945164
Bose, A., Burman, D. R., Sikdar, B., & Patra, P. (2021). Nanomicelles: Types, properties and applications in drug delivery. IET Nanobiotechnology,15 (1), 19-27. https://doi.org/10.1049/nbt2.12018
Bose, S., Sharma, P., Mishra, V., Patial, S., Saraogi, G. K., Tambuwala, M. M., & Dua, K. (2021). Comparative in vitro evaluation of glimepiride containing nanosuspension drug delivery system developed by different techniques. Journal of Molecular Structure,1231 (2021). https://doi.org/10.1016/j.molstruc.2021.129927
Budiman, A., Handini, A. L., Muslimah, M. N., Nurani, N. V., Laelasari, E., Kurniawansyah, I. S., & Aulifa, D. L. (2023). Amorphous Solid Dispersion as Drug Delivery Vehicles in Cancer. Polymers,15 (16). https://doi.org/10.3390/polym15163380
Budiman, A., Rusdin, A., Subra, L., & Aulifa, D. L. (2023). How Key Alterations of Mesoporous Silica Nanoparticles Affect Anti-Lung Cancer Therapy? A Comprehensive Review of the Literature. International Journal of Nanomedicine,18 (September), 5473-5493. https://doi.org/10.2147/IJN.S426120
Chakraborty, S., Sathe, R. Y., Chormale, J. H., Dangi, A., Bharatam, P. V., & Bansal, A. K. (2023). Effect of Deep Eutectic System (DES) on Oral Bioavailability of Celecoxib: In Silico, In Vitro, and In Vivo Study. Pharmaceutics,15 (9). https://doi.org/10.3390/pharmaceutics15092351
Chang, C., Song, M., Ma, M., Song, J., Cao, F., & Qin, Q. (2023). Preparation, Characterization and Molecular Dynamics Simulation of Rutin-Cyclodextrin Inclusion Complexes. Molecules,28 (3). https://doi.org/10.3390/molecules28030955
Chen, M., Chen, Y., Zhao, Y., Zou, X., & Sun, L. (2021). Construction of nanoceria-capped mesoporous silica carriers for redox/pH-responsive drug release. Journal of Drug Delivery Science and Technology,66 (March), 102763. https://doi.org/10.1016/j.jddst.2021.102763
Chergaoui, S., Debecker, D. P., Leyssens, T., & Luis, P. (2023). Key Parameters Impacting the Crystal Formation in Antisolvent Membrane-Assisted Crystallization. Membranes,13 (2). https://doi.org/10.3390/membranes13020140
Cho, D. Y., Lee, J. G., Kim, M. J., Cho, H. J., Cho, J. H., & Kim, K. S. (2025). Approaches for Inclusion Complexes of Ezetimibe with Cyclodextrins: Strategies for Solubility Enhancement and Interaction Analysis via Molecular Docking. International Journal of Molecular Sciences,26 (4). https://doi.org/10.3390/ijms26041686
Choudhary, A. N., & Nayal, S. (2019). A review: Hydrotropy a solubility enhancing technique. ~1149~ The Pharma Innovation Journal,8 (4), 1149-1153. www.thepharmajournal.com
Clemente, N., Miletto, I., Gianotti, E., Sabbatini, M., Invernizzi, M., Marchese, L., Dianzani, U., & Renò, F. (2021). Verteporfin-loaded mesoporous silica nanoparticles' topical applications inhibit mouse melanoma lymphangiogenesis and micrometastasis in vivo. International Journal of Molecular Sciences,22 (24). https://doi.org/10.3390/ijms222413443
Crystal, A. G. M., Bian, X., Jiang, L., Gan, Z., Guan, X., Zhang, L., & Cai, L. (2019). A Glimepiride-Metformin Multidrug Crystal: Synthesis, Crystal Structure Analysis, and Physicochemical Properties.
Cysewski, P., Jeli?ski, T., Przyby?ek, M., Mai, A., & Ku?ak, J. (2024). Experimental and Machine-Learning-Assisted Design of Pharmaceutically Acceptable Deep Eutectic Solvents for the Solubility Improvement of Non-Selective COX Inhibitors Ibuprofen and Ketoprofen. Molecules,29 (10). https://doi.org/10.3390/molecules29102296
Damiri, F., Kommineni, N., Ebhodaghe, S. O., Bulusu, R., Jyothi, V. G. S. S., Sayed, A. A., Awaji, A. A., Germoush, M. O., Al-Malky, H. S., Nasrullah, M. Z., Rahman, M. H., Abdel-Daim, M. M., & Berrada, M. (2022). Microneedle-Based Natural Polysaccharide for Drug Delivery Systems (DDS): Progress and Challenges. Pharmaceuticals,15 (2), 1-26. https://doi.org/10.3390/ph15020190
Darmawan, E. S., Permanasari, V. Y., Nisrina, L. V., Kusuma, D., Hasibuan, S. R., & Widyasanti, N. (2024). Behind the Hospital Ward: In-Hospital Mortality of Type 2 Diabetes Mellitus Patients in Indonesia (Analysis of National Health Insurance Claim Sample Data). International Journal of Environmental Research and Public Health,21 (5). https://doi.org/10.3390/ijerph21050581
Darusman, F., Sopyan, I., Azzahra, N., & Rusdiana, T. (2025). The solid-state modification for solubility enhancement of practically insoluble glimepiride: A systematic review. Journal of Pharmacy and Pharmacognosy Research,13 (2), 497-512. https://doi.org/10.56499/jppres24.2101_13.2.497
Donthi, M. R., Munnangi, S. R., Krishna, K. V., Saha, R. N., Singhvi, G., & Dubey, S. K. (2023). Nanoemulgel: A Novel Nano Carrier as a Tool for Topical Drug Delivery. Pharmaceutics,15 (1), 1-28. https://doi.org/10.3390/pharmaceutics15010164
Dou, Y., Wang, T., Huang, Y., Ping, V., Xie, Y., Lin, X., Gao, J., Su, Z., & Zeng, H. (2018). Self-nanoemulsifying drug delivery system of bruceine D: a new approach for anti-ulcerative colitis. International Journal of Nanomedicine, 13, 5887–5907.
Eid, A. M., & Hawash, M. (2021). Biological evaluation of Safrole oil and Safrole oil Nanoemulgel as antioxidant, antidiabetic, antibacterial, antifungal and anticancer. BMC Complementary Medicine and Therapies,21 (1), 1-12. https://doi.org/10.1186/s12906-021-03324-z
Eid, A. M., Naseef, H., Jaradat, N., Ghanim, L., Moqadeh, R., & Yaseen, M. (2023). Antibacterial and Anti-Acne Activity of Benzoyl Peroxide Nanoparticles Incorporated in Lemongrass Oil Nanoemulgel. Gels,9 (3), 1-12. https://doi.org/10.3390/gels9030186
El-Sayyad, N. M. E.-M., Badawi, A., Abdullah, M. E., & Abdelmalak, N. S. (2017). Dissolution enhancement of leflunomide incorporating self-emulsifying drug delivery systems and liquisolid concepts. Bulletin of Faculty of Pharmacy, Cairo University,55 (1), 53-62. https://doi.org/10.1016/j.bfopcu.2017.02.001
El-Zahabi, M. A., Bamanie, F. H., Ghareeb, S., Alshaeri, H. K., Alasmari, M. M., Moustafa, M., Al-Marzooki, Z., & Zayed, M. F. (2022). Design, Synthesis, Molecular Modeling and Anti-Hyperglycemic Evaluation of Quinazoline-Sulfonylurea Hybrids as Peroxisome Proliferator-Activated Receptor Gamma (PPAR?) and Sulfonylurea Receptor (SUR) Agonists. International Journal of Molecular Sciences,23 (17). https://doi.org/10.3390/ijms23179605
Farjadian, F., Roointan, A., Mohammadi-Samani, S., & Hosseini, M. (2019). Mesoporous silica nanoparticles: Synthesis, pharmaceutical applications, biodistribution, and biosafety assessment. Chemical Engineering Journal,359 , 684-705. https://doi.org/10.1016/j.cej.2018.11.156
FAROOQUI, P., & GUDE, R. (2023). Formulation Development and Optimization of Fast Dissolving Buccal Films Loaded Glimepiride Solid Dispersion With Enhanced Dissolution Profile Using Central Composite Design. International Journal of Pharmacy and Pharmaceutical Sciences,15 (6), 35-54. https://doi.org/10.22159/ijpps.2023v15i6.47992
Ferreira, C., & Sarraguça, M. (2024). A Comprehensive Review on Deep Eutectic Solvents and Its Use to Extract Bioactive Compounds of Pharmaceutical Interest. Pharmaceuticals,17 (1). https://doi.org/10.3390/ph17010124
Gaber, D. A., Alhuwaymili, A. S., Alhawas, H. S., Almutiri, A. A., Alsubaiyel, A. M., Abdoun, S. A., & Almutairi, R. A. (2022). Synthesized nano particles of glimepiride via spray freezing into cryogenic liquid: characterization, antidiabetic activity, and bioavailability. Drug Delivery,29 (1), 364-373. https://doi.org/10.1080/10717544.2021.2018524
Gao, X., Yu, S., Zhang, G., Cheng, Y., Wang, S., & Xue, F. (2022). Solid-liquid equilibrium, thermodynamic modeling, and the solvent effect of glimepiride in mono-solvents and binary mixed solvents. Journal of Molecular Liquids,360 , 119402. https://doi.org/10.1016/j.molliq.2022.119402
Grini, M. I., Benbayer, C., Saidi-Besbes, S., & Elaissari, A. (2025). Advances in mesoporous silica nanoparticles as carriers for drug delivery and other biomedical applications. Microporous and Mesoporous Materials,391 (March), 113603. https://doi.org/10.1016/j.micromeso.2025.113603
Grohganz, H., Löbmann, K., Priemel, P., Tarp Jensen, K., Graeser, K., Strachan, C., & Rades, T. (2013). Amorphous drugs and dosage forms. Journal of Drug Delivery Science and Technology,23 (4), 403-408. https://doi.org/10.1016/S1773-2247(13)50057-8
Gupta, S., Chavhan, S., & Sawant, K. K. (2011). Self-nanoemulsifying drug delivery system for adefovir dipivoxil: Design, characterization, in vitro and ex vivo evaluation. Colloids and Surfaces A: Physicochemical and Engineering Aspects,392 (1), 145-155. https://doi.org/10.1016/j.colsurfa.2011.09.048
Gurkan, B., Squire, H., & Pentzer, E. (2019). Metal-Free Deep Eutectic Solvents: Preparation, Physical Properties, and Significance. Journal of Physical Chemistry Letters,10 (24), 7956-7964. https://doi.org/10.1021/acs.jpclett.9b01980
Han, M. J., & Zou, Z. Z. (2024). Enabling a novel solvent method on Albendazole solid dispersion to improve the in vivo bioavailability. European Journal of Pharmaceutical Sciences,196 (December 2023), 106751. https://doi.org/10.1016/j.ejps.2024.106751
Haskins, M. M., & Zaworotko, M. J. (2021). Screening and Preparation of Cocrystals: A Comparative Study of Mechanochemistry vs Slurry Methods. Crystal Growth and Design,21 (7), 4141-4150. https://doi.org/10.1021/acs.cgd.1c00418
Hassan, S., Prakash, G., Bal Ozturk, A., Saghazadeh, S., Farhan Sohail, M., Seo, J., Remzi Dokmeci, M., Zhang, Y. S., & Khademhosseini, A. (2017). Evolution and clinical translation of drug delivery nanomaterials. Nano Today,15 , 91-106. https://doi.org/10.1016/j.nantod.2017.06.008
Hess, F., Kipping, T., Weitschies, W., & Krause, J. (2024). Understanding the Interaction of Thermal, Rheological, and Mechanical Parameters Critical for the Processability of Polyvinyl Alcohol-Based Systems during Hot Melt Extrusion. Pharmaceutics,16 (4). https://doi.org/10.3390/pharmaceutics16040472
Hindija, L., Hadžiabdi?, J., Haveri?, A., Rahi?, O., Hadži? Omanovi?, M., ?aluk Kla?ar, L., Durmiševi?, I., Tucak Smaji?, A., Šahinovi?, M., & Vrani?, E. (2024). Preparation, characterization, and in vitro cytogenotoxic evaluation of a novel dimenhydrinate-?-cyclodextrin inclusion complex. Biomolecules and Biomedicine,24 (6), 1637-1650. https://doi.org/10.17305/bb.2024.10507
Huang, Z., Staufenbiel, S., & Bodmeier, R. (2022). Combination of co-crystal and nanocrystal techniques to improve the solubility and dissolution rate of poorly soluble drugs. Pharmaceutical Research,39 (5), 949-961. https://doi.org/10.1007/s11095-022-03243-9
Jaafar, I. S., & Radhi, A. A. (2020). Preparation and physicochemical characterization of cocrystals for enhancing the dissolution rate of glimepiride. Journal of Advanced Pharmacy Education and Research, 10(3), 68–76.
Ju, G., Yan, K., Xu, Y., Chen, S., Zheng, Z., & Qiu, W. (2020). Evaluation of bioequivalency and pharmacokinetic parameters for two formulations of glimepiride 1-mg in chinese subjects. Drug Design, Development and Therapy,14 , 2637-2644. https://doi.org/10.2147/DDDT.S249355
Junyaprasert, V. B., & Morakul, B. (2015). Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian Journal of Pharmaceutical Sciences,10 (1), 13-23. https://doi.org/10.1016/j.ajps.2014.08.005
Kaur, H., & Kaur, G. (2014). A Critical Appraisal of Solubility Enhancement Techniques of Polyphenols. Journal of Pharmaceutics,2014 , 1-14. https://doi.org/10.1155/2014/180845
Kazi, M., Gandhi, S. M., Barse, R., & Jagtap, V. (2023). Formulation and Evaluation of Glimepiride Tablets By Improving Aqueous Solubility of Drug Using Hydrotropy Technique. World Journal of Pharmacy and Pharmaceutical Sciences,12 (6), 1041-1054. https://doi.org/10.20959/wjpps20236-24835
Kim, S., Youssef, S. H., Lee, K. M. K., Song, Y., Vaidya, S., & Garg, S. (2024). Enhanced Skin Permeation of 5-Fluorouracil through Drug-in-Adhesive Topical Patches. Pharmaceutics,16 (3). https://doi.org/10.3390/pharmaceutics16030379
Koca, M., Sevinç Özakar, R., Ozakar, E., Sade, R., Pirimo?lu, B., Özek, N. ?., & Aysin, F. (2022). Preparation and Characterization of Nanosuspensions of Triiodoaniline Derivative New Contrast Agent, and Investigation into Its Cytotoxicity and Contrast Properties. Iranian Journal of Pharmaceutical Research,21 (1), 1-18. https://doi.org/10.5812/ijpr.123824
Korni, R. D., & Gonugunta, C. S. R. (2024). Olanzapine Liquisolid Tablets Using Kolliphor EL with Improved Flowability and Bioavailability: In vitro and In vivo Characterization. Turkish Journal of Pharmaceutical Sciences,21 (1), 52-61. https://doi.org/10.4274/tjps.galenos.2023.05752
Kral, Ö., Ilbasmis-Tamer, S., Han, S., & Tirnaksiz, F. (2024). Development of Dermal Lidocaine Nanosuspension Formulation by the Wet Milling Method Using Experimental Design: In Vitro/In Vivo Evaluation. ACS Omega. https://doi.org/10.1021/acsomega.4c05296
Kushwah, V., Succhielli, C., Saraf, I., & Paudel, A. (2024). Amorphous Solid Dispersions: Implication of Method of Preparation and Physicochemical Properties of API and Excipients. Pharmaceutics,16 (8). https://doi.org/10.3390/pharmaceutics16081035
Li, H. Y., Pan, T. T., Cui, Y., Li, X. X., Gao, J. F., Yang, W. Z., & Shen, S. G. (2016). Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique. International Journal of Nanomedicine,11 , 3777-3788. https://doi.org/10.2147/IJN.S105419
Li, X., Luo, Y., Wang, J., & Du, Z. (2024). Formulation, characterization and in vivo and in vitro evaluation of aloe-emodin-loaded solid dispersions for dissolution enhancement. Journal of Traditional Chinese Medicine,44 (1), 54-62. https://doi.org/10.19852/j.cnki.jtcm.20231110.002
Liu, J., Grohganz, H., Löbmann, K., Rades, T., & Hempel, N. J. (2021). Co-amorphous drug formulations in numbers: Recent advances in co-amorphous drug formulations with focus on co-formability, molar ratio, preparation methods, physical stability, in vitro and in vivo performance, and new formulation strategies. Pharmaceutics,13 (3). https://doi.org/10.3390/pharmaceutics13030389
Luo, R., Xu, H., Lin, Q., Chi, J., Liu, T., Jin, B., Ou, J., Xu, Z., Peng, T., Quan, G., & Lu, C. (2024). Emerging Trends in Dissolving-Microneedle Technology for Antimicrobial Skin-Infection Therapies. Pharmaceutics,16 (9), 1188. https://doi.org/10.3390/pharmaceutics16091188
Lyu, S., Dong, Z., Xu, X., Bei, H. P., Yuen, H. Y., James Cheung, C. W., Wong, M. S., He, Y., & Zhao, X. (2023). Going below and beyond the surface: Microneedle structure, materials, drugs, fabrication, and applications for wound healing and tissue regeneration. Bioactive Materials,27 (March), 303-326. https://doi.org/10.1016/j.bioactmat.2023.04.003
Maded, Z. K., Lassoued, M. A., Taqa, G. A. A., Fawzi, H. A., Abdulqader, A. A., Jabir, M. S., Mahal, R. K., & Sfar, S. (2024). Topical Application of Dipyridamole and Roflumilast Combination Nanoparticles Loaded Nanoemulgel for the Treatment of Psoriasis in Rats. International Journal of Nanomedicine,19 (December), 13113-13134. https://doi.org/10.2147/IJN.S492180
Makar, R. R., Latif, R., Hosni, E. A., & El Gazayerly, O. N. (2017). The impact of amorphization and spheronization techniques on the improved in vitro & in vivo performance of glimepiride tablets. Advanced Pharmaceutical Bulletin,7 (4), 557-567. https://doi.org/10.15171/apb.2017.067
Malkawi, R., Malkawi, W. I., Al-Mahmoud, Y., & Tawalbeh, J. (2022). Current Trends on Solid Dispersions: Past, Present, and Future. Advances in Pharmacological and Pharmaceutical Sciences,2022 . https://doi.org/10.1155/2022/5916013
Medarevi?, D., Ibri?, S., Vardaka, E., Mitri?, M., Nikolakakis, I., & Kachrimanis, K. (2020). Insight into the formation of glimepiride nanocrystals by wet media milling. Pharmaceutics,12 (1). https://doi.org/10.3390/pharmaceutics12010053
Miranda, C., Aceituno, A., Fernández, M., Mendes, G., Rodríguez, Y., Llauró, V., & Cabrera-Pérez, M. Á. (2021). Ich guideline for biopharmaceutics classification system-based biowaiver (M9): Toward harmonization in Latin American countries. Pharmaceutics,13 (3). https://doi.org/10.3390/pharmaceutics13030363
Mohammed, M. J., & Ali, W. K. (2023). Formulation and In-vitro Evaluation of Two Layers Tablet for Dual Release of a Model Drug. International Journal of Drug Delivery Technology,13 (1), 45-56. https://doi.org/10.25258/ijddt.13.1.08
Mou, D., Chen, H., Du, D., Mao, C., Wan, J., Xu, H., & Yang, X. (2008). Hydrogel-thickened nanoemulsion system for topical delivery of lipophilic drugs. International Journal of Pharmaceutics,353 (1-2), 270-276. https://doi.org/10.1016/j.ijpharm.2007.11.051
Nair, A. B., Singh, B., Shah, J., Jacob, S., Aldhubiab, B., Sreeharsha, N., Morsy, M. A., Venugopala, K. N., Attimarad, M., & Shinu, P. (2022). Formulation and Evaluation of Self-Nanoemulsifying Drug Delivery System Derived Tablets Containing Sertraline. Pharmaceutics,14 (2), 1-24. https://doi.org/10.3390/pharmaceutics14020336
Namdev, B., Senthil, V., Jawahar, N., & Chorsiya, A. (2022). A Brief Review on Solubility Enhancement Technique: Hydrotropy. Indian Journal of Pharmaceutical Education and Research,56 (2), 347-355. https://doi.org/10.5530/ijper.56.2.54
Nasrallah, S., & Minceva, M. (2025). Solubility Enhancement of Active Pharmaceutical Ingredients through Liquid Hydrotrope Addition: A Thermodynamic Analysis. Molecular Pharmaceutics. https://doi.org/10.1021/acs.molpharmaceut.4c01117
Nguyen, H. X. (2025). Beyond the Needle: Innovative Microneedle-Based Transdermal Vaccination.
Nupur, M. A., Rahman, M. M., Akter, K., Hanif, K. B., Sharna, J. F., Sarker, M. S., & Ibne Wahed, M. I. (2023). Preparation and characterization of naproxen solid dispersion using different hydrophilic carriers and in-vivo evaluation of its analgesic activity in mice. Heliyon,9 (5), e15432. https://doi.org/10.1016/j.heliyon.2023.e15432
Oktay, A. N., Ilbasmis-Tamer, S., Karakucuk, A., & Celebi, N. (2020). Screening of stabilizing agents to optimize flurbiprofen nanosuspensions using experimental design. Journal of Drug Delivery Science and Technology,57 (November 2019), 101690. https://doi.org/10.1016/j.jddst.2020.101690
Ossowicz-Rupniewska, P., Bednarczyk, P., Nowak, M., Nowak, A., Duchnik, W., Kucharski, ?., Klebeko, J., ?wi?tek, E., Bilska, K., Rokicka, J., Janus, E., Klimowicz, A., & Czech, Z. (2022). Evaluation of the Structural Modification of Ibuprofen on the Penetration Release of Ibuprofen from a Drug-in-Adhesive Matrix Type Transdermal Patch. International Journal of Molecular Sciences,23 (14). https://doi.org/10.3390/ijms23147752
Padmnabh, & Bhatt, D. C. (2023). Development, Optimization and Characterization of Glimepiride Nanosuspension with Improved Solubility and Dissolution. International Journal of Drug Delivery Technology,13 (4), 1248-1257. https://doi.org/10.25258/IJDDT.13.4.21
Pal, A., Roy, S., Kumar, A., Mahmood, S., Khodapanah, N., Thomas, S., Agatemor, C., & Ghosal, K. (2020). Physicochemical characterization, molecular docking, and in vitro dissolution of glimepiride-captisol inclusion complexes. ACS Omega,5 (32), 19968-19977. https://doi.org/10.1021/acsomega.0c01228
Park, H., Seo, H. J., Ha, E. S., Hong, S. hyeon, Kim, J. S., Kim, M. S., & Hwang, S. J. (2020). Preparation and characterization of glimepiride eutectic mixture with L-arginine for improvement of dissolution rate. International Journal of Pharmaceutics,581 (December 2019), 119288. https://doi.org/10.1016/j.ijpharm.2020.119288
Pervez, S., Nasir, F., Hidayatullah, T., Khattak, M. A., Alasmari, F., Zainab, S. R., Gohar, S., Tahir, A., & Maryam, G. e. (2023). Transdermal Delivery of Glimepiride: A Novel Approach Using Nanomicelle-Embedded Microneedles. Pharmaceutics,15 (8). https://doi.org/10.3390/pharmaceutics15082019
Ponnusamy, C., Sugumaran, A., Krishnaswami, V., & Palanichamy, R. (2021). Topical Ocular Delivery of Artemisinin. Mdpi, 13, 1–17.
Rahim, H., Sadiq, A., Khan, S., Amin, F., Ullah, R., Shahat, A. A., & Mahmood, H. M. (2019). Fabrication and characterization of glimepiride nanosuspension by ultrasonication-assisted precipitation for improvement of oral bioavailability and in vitro ?-glucosidase inhibition. International Journal of Nanomedicine,14 , 6287-6296. https://doi.org/10.2147/IJN.S210548
Rajpoot, K., Tekade, M., Pandey, V., Nagaraja, S. H., Youngren-Ortiz, S. R., & Tekade, R. K. (2019). Self-microemulsifying drug-delivery system: Ongoing challenges and future ahead. In Drug Delivery Systems. Elsevier Inc. https://doi.org/10.1016/B978-0-12-814487-9.00009-0
Ran, Q., Wang, M., Kuang, W., Ouyang, J., Han, D., Gao, Z., & Gong, J. (2022). Advances of Combinative Nanocrystal Preparation Technology for Improving the Insoluble Drug Solubility and Bioavailability. Crystals,12 (9), 1-21. https://doi.org/10.3390/cryst12091200
Razzaq, F. A., Asif, M., Asghar, S., Iqbal, M. S., Khan, I. U., Khan, S. U. D., Irfan, M., Syed, H. K., Khames, A., Mahmood, H., Ibrahim, A. Y., & El Sisi, A. M. (2021). Glimepiride-loaded nanoemulgel; development, in vitro characterization, ex vivo permeation and in vivo antidiabetic evaluation. Cells,10 (9). https://doi.org/10.3390/cells10092404
Rezazadeh, M., Agah, S., Kamyabi, A., Akbari, A., Ghamkhari Pisheh, R., Eshraghi, A., Babakhani, A., Ahmadi, A., Paseban, M., Heidari, P., Shirinkam, I., & Mehrdad, A. (2024). Effect of type 2 diabetes mellitus and sulfonylurea on colorectal cancer development: a case-control study. BMC Gastroenterology,24 (1). https://doi.org/10.1186/s12876-024-03477-4
Sacks, D. B., Arnold, M., Bakris, G. L., Bruns, D. E., Horvath, A. R., Lernmark, Å., Metzger, B. E., Nathan, D. M., & Kirkman, M. S. (2023). Executive Summary: Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus. Diabetes Care,46 (10), 1740-1746. https://doi.org/10.2337/dci23-0048
Sakthi Velu, K., Jegatheeswaran, S., Akhtar, M. S., Khan, M. R., Mohandoss, S., & Ahmad, N. (2024). Formulation and Characterization of ?-Cyclodextrins-Nitazoxanide Inclusion Complexes: Enhanced Solubility, In Vitro Drug Release, and Antiviral Activity in Vero Cells. Pharmaceutics,16 (12), 1-19. https://doi.org/10.3390/pharmaceutics16121494
Sarabia-Vallejo, Á., Caja, M. del M., Olives, A. I., Martín, M. A., & Menéndez, J. C. (2023). Cyclodextrin Inclusion Complexes for Improved Drug Bioavailability and Activity: Synthetic and Analytical Aspects. Pharmaceutics,15 (9). https://doi.org/10.3390/pharmaceutics15092345
Schmied, F. P., Bernhardt, A., & Klein, S. (2022). Preparation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) by Co-Extrusion of Liquid SNEDDS and Polymeric Carriers-A New and Promising Formulation Approach to Improve the Solubility of Poorly Water-Soluble Drugs. Pharmaceuticals,15 (9). https://doi.org/10.3390/ph15091135
Sengupta, P., & Chatterjee, B. (2017). Potential and future scope of nanoemulgel formulation for topical delivery of lipophilic drugs. International Journal of Pharmaceutics,526 (1-2), 353-365. https://doi.org/10.1016/j.ijpharm.2017.04.068
Shao, S. Z., Stocker, M. W., Zarrella, S., Korter, T. M., Singh, A., & Healy, A. M. (2023). In Situ Cocrystallization via Spray Drying with Polymer as a Strategy to Prevent Cocrystal Dissociation. Molecular Pharmaceutics,20 (9), 4770-4785. https://doi.org/10.1021/acs.molpharmaceut.3c00564
Sharipov, M., Tawfik, S. M., Gerelkhuu, Z., Huy, B. T., & Lee, Y. I. (2017). Phospholipase A2-Responsive Phosphate Micelle-Loaded UCNPs for Bioimaging of Prostate Cancer Cells. Scientific Reports,7 (1), 1-9. https://doi.org/10.1038/s41598-017-16136-4
Shrivastava, A., Kesavadev, J., Mohan, V., Saboo, B., Shrestha, D., Maheshwari, A., Makkar, B. M., Modi, K. D., & Kumar Das, A. (2023). Clinical Evidence and Practice-Based Guidelines on the Utility of Basal Insulin Combined Oral Therapy (Metformin and Glimepiride) in the Current Era. Current Diabetes Reviews,19 (8). https://doi.org/10.2174/1573399819666230109104300
Siebenmorgen, C., Poortinga, A., & van Rijn, P. (2023). Sono-processes: Emerging systems and their applicability within the (bio-)medical field. Ultrasonics Sonochemistry,100 (October), 106630. https://doi.org/10.1016/j.ultsonch.2023.106630
Soliman, W. E., Shehata, T. M., Mohamed, M. E., Younis, N. S., & Elsewedy, H. S. (2021). Enhancement of curcumin anti-inflammatory effect via formulation into myrrh oil-based nanoemulgel. Polymers,13 (4), 1-16. https://doi.org/10.3390/polym13040577
Suponitsky, K. Y., Fedyanin, I. V., Karnoukhova, V. A., Zalomlenkov, V. A., Gidaspov, A. A., Bakharev, V. V., & Sheremetev, A. B. (2021). Energetic co-crystal of a primary metal-free explosive with btf. Ideal pair for co-crystallization. Molecules,26 (24), 1-19. https://doi.org/10.3390/molecules26247452
Sutradhar, K. B., Khatun, S., & Luna, I. P. (2013). Increasing possibilities of nanosuspension. Journal of Nanotechnology,2013 . https://doi.org/10.1155/2013/346581
Tawfik, S. M., Azizov, S., Elmasry, M. R., Sharipov, M., & Lee, Y. I. (2021). Recent advances in nano micelles delivery systems. Nanomaterials,11 (1), 1-36. https://doi.org/10.3390/nano11010070
Tong, Y., Wang, Y., Yang, M., Yang, J., Chen, L., Chu, X., Gao, C., Jin, Q., Gong, W., & Gao, C. (2018). Systematic development of self-nanoemulsifying liquisolid tablets to improve the dissolution and oral bioavailability of an oily drug, vitamin K1. Pharmaceutics,10 (3), 1-20. https://doi.org/10.3390/pharmaceutics10030096
Truzzi, F., Tibaldi, C., Zhang, Y., Dinelli, G., & D?Amen, E. (2021). An overview on dietary polyphenols and their biopharmaceutical classification system (Bcs). International Journal of Molecular Sciences,22 (11). https://doi.org/10.3390/ijms22115514
Tzankov, B., Voycheva, C., Aluani, D., Yordanov, Y., Avramova, K., Tzankova, V., Spassova, I., Kovacheva, D., & Yoncheva, K. (2019). Improvement of dissolution of poorly soluble glimepiride by loading on two types of mesoporous silica carriers. Journal of Solid State Chemistry,271 (December 2018), 253-259. https://doi.org/10.1016/j.jssc.2018.12.062
Ullah, I., Alhodaib, A., Naz, I., Ahmad, W., Ullah, H., Amin, A., & Nawaz, A. (2023). Fabrication of Novel Omeprazole-Based Chitosan Coated Nanoemulgel Formulation for Potential Anti-Microbia; In Vitro and Ex Vivo Characterizations. Polymers,15 (5). https://doi.org/10.3390/polym15051298
Verma, R., Kaushik, A., Almeer, R., Habibur Rahman, M., Abdel-Daim, M. M., & Kaushik, D. (2021). Improved pharmacodynamic potential of rosuvastatin by self-nanoemulsifying drug delivery system: An in vitro and in vivo evaluation. International Journal of Nanomedicine,16 , 905-924. https://doi.org/10.2147/IJN.S287665
Wahidin, M., Achadi, A., Besral, B., Kosen, S., Nadjib, M., Nurwahyuni, A., Ronoatmodjo, S., Rahajeng, E., Pane, M., & Kusuma, D. (2024). Projection of diabetes morbidity and mortality till 2045 in Indonesia based on risk factors and NCD prevention and control programs. Scientific Reports,14 (1), 1-17. https://doi.org/10.1038/s41598-024-54563-2
Wang, Y., Yuan, W., Guo, S., Li, Q., Chen, X., Li, C., Liu, Q., Sun, L., Chen, Z., Yuan, Z., Luo, C., Chen, S., Tong, S., Nassal, M., Wen, Y. M., & Wang, Y. X. (2022). A 33-residue peptide tag increases solubility and stability of Escherichia coli produced single-chain antibody fragments. Nature Communications,13 (1), 1-15. https://doi.org/10.1038/s41467-022-32423-9
Wong, W. F., Ang, K. P., Sethi, G., & Looi, C. Y. (2023). Recent Advancement of Medical Patch for Transdermal Drug Delivery. Medicina (Lithuania),59 (4), 1-20. https://doi.org/10.3390/medicina59040778
Wu, Y., Fu, R., Lei, C., Deng, Y., Lou, W., Wang, L., Zheng, Y., Deng, X., Yang, S., Wang, M., Zhai, Z., Zhu, Y., Xiang, D., Hu, J., Dai, Z., & Gao, J. (2021). Estimates of Type 2 Diabetes Mellitus Burden Attributable to Particulate Matter Pollution and Its 30-Year Change Patterns: A Systematic Analysis of Data From the Global Burden of Disease Study 2019. Frontiers in Endocrinology,12 (August). https://doi.org/10.3389/fendo.2021.689079
Wu, Z., Wang, N., Ye, Z., Xu, H., Chan, G., & Ouyang, D. (2024). FormulationBCS: A Machine Learning Platform Based on Diverse Molecular Representations for Biopharmaceutical Classification System (BCS) Class Prediction. Molecular Pharmaceutics. https://doi.org/10.1021/acs.molpharmaceut.4c00946
Wünsche, S., Yuan, L., Seidel-Morgenstern, A., & Lorenz, H. (2021). A contribution to the solid state forms of bis(Demethoxy)curcumin: Co-crystal screening and characterization. Molecules,26 (3). https://doi.org/10.3390/molecules26030720
Xu, W., Sun, Y., Du, L., Chistyachenko, Y. S., Dushkin, A. V., & Su, W. (2018). Investigations on solid dispersions of valsartan with alkalizing agents: Preparation, characterization and physicochemical properties. Journal of Drug Delivery Science and Technology,44 (October 2017), 399-405. https://doi.org/10.1016/j.jddst.2018.01.012
Xv, L., Qian, X., Wang, Y., Yu, C., Qin, D., Zhang, Y., Jin, P., & Du, Q. (2020). Structural modification of nano micelles through phosphatidylcholine: The enhanced drug-loading capacity and anticancer activity of celecoxib-casein nanoparticles for the intravenous delivery of celecoxib. Nanomaterials,10 (3), 1-13. https://doi.org/10.3390/nano10030451
Yang, J., & Tsai, P. A. (2024). Microfluidic supercritical CO2 applications: Solvent extraction, nanoparticle synthesis, and chemical reaction. Biomicrofluidics,18 (5), 1-13. https://doi.org/10.1063/5.0215567
Yu, Q., Hui, J., Wang, P., Xu, B., Zhuang, J., & Wang, X. (2012). Hydrothermal synthesis of mesoporous silica spheres: Effect of the cooling process. Nanoscale,4 (22), 7114-7120. https://doi.org/10.1039/c2nr31834b
Zhang, J., Xie, Z., Zhang, N., & Zhong, J. (2017). Nanosuspension drug delivery system: preparation, characterization, postproduction processing, dosage form, and application. In Nanostructures for Drug Delivery. Elsevier Inc. https://doi.org/10.1016/B978-0-323-46143-6.00013-0
Zhang, Q., Bao, J., Duan, T., Hu, M., He, Y., Wang, J., Hu, R., & Tang, J. (2022). Nanomicelle-Microsphere Composite as a Drug Carrier to Improve Lung-Targeting Specificity for Lung Cancer. Pharmaceutics,14 (3). https://doi.org/10.3390/pharmaceutics14030510
Zhou, J., Liu, C., Zhong, Y., Luo, Z., & Wu, L. (2024). A Review of Current Developments in Functionalized Mesoporous Silica Nanoparticles: From Synthesis to Biosensing Applications. Biosensors,14 (12). https://doi.org/10.3390/bios14120575
Zhuo, Y., Zhao, Y. G., & Zhang, Y. (2024). Enhancing Drug Solubility, Bioavailability, and Targeted Therapeutic Applications through Magnetic Nanoparticles. Molecules,29 (20), 1-35. https://doi.org/10.3390/molecules29204854
Zidan, M. F., Afouna, M. I., Ismael, H. R., & Ibrahim, M. F. (2023). Enhancement of Glimepiride Bioavailability by Co-Crystallization Technique. International Journal for Research in Applied Science and Engineering Technology,11 (2), 561-568. https://doi.org/10.22214/ijraset.2023.49022
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Valentina Fiftianingrum, Iyan Sopyan, Dolih Gozali
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-ShareAlike 4.0 International (CC-BY-SA). that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
