Author(s):
Padmnabh, D. C. Bhatt, Sunil Shukla, Tanuj Hooda, Ramchander Khatri
Email(s):
tanujhooda2010@gmail.com , padmanabhkm@gmail.com
DOI:
10.52711/0974-360X.2026.00318 
Address:
Padmnabh1*, D. C. Bhatt1, Sunil Shukla1, Tanuj Hooda2,3*, Ramchander Khatri3
1Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, Haryana, India
2MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University) Mullana,Ambala, Haryana, India.
3Delhi Pharmaceutical Sciences and Research University, New Delhi, Delhi, India.
*Corresponding Author
Published In:
Volume - 19,
Issue - 5,
Year - 2026
ABSTRACT:
Background: Glimepiride and Gliclazide are classified as Biopharmaceutical Classification System (BCS) Class II drugs, characterized by low aqueous solubility. Objective: This study aims to evaluate the In Vivo pharmacokinetics of Glimepiride nanosuspension (GLMP-NS) and Gliclazide nanosuspension (GLC-NS), both prepared using the precipitation–ultrasonication method. Methods: The antidiabetic efficacy of GLMP-NS and GLC-NS was assessed in streptozotocin-induced diabetic rats and compared with that of pure Glimepiride (GLMP) and Gliclazide (GLC), respectively, using appropriate analytical techniques. Results: The results demonstrated that the reduced particle size and enhanced entrapment efficiency of GLMP-NS and GLC-NS significantly improved the In Vivo bioavailability of their respective drugs. Both nanosuspensions led to a more rapid and pronounced reduction in blood glucose levels in diabetic rats. Furthermore, pharmacokinetic analysis revealed a 2.9-fold and 7.36-fold increase in the oral bioavailability of Glimepiride and Gliclazide, respectively, when administered as nanosuspensions. Conclusion: This study highlights a significant improvement in the dissolution and bioavailability of pure Glimepiride and Gliclazide when formulated as nanosuspensions, demonstrating their potential for enhanced therapeutic efficacy.
Cite this article:
Padmnabh, D. C. Bhatt, Sunil Shukla, Tanuj Hooda, Ramchander Khatri. Improved Oral Bioavailability of Poorly Water-soluble Glimepiride and Gliclazide by Utilizing Nanosuspension Technique. Research Journal Pharmacy and Technology. 2026;19(5):2207-3. doi: 10.52711/0974-360X.2026.00318
Cite(Electronic):
Padmnabh, D. C. Bhatt, Sunil Shukla, Tanuj Hooda, Ramchander Khatri. Improved Oral Bioavailability of Poorly Water-soluble Glimepiride and Gliclazide by Utilizing Nanosuspension Technique. Research Journal Pharmacy and Technology. 2026;19(5):2207-3. doi: 10.52711/0974-360X.2026.00318 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2026-19-5-39
6. REFERENCES:
1. American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care. 2011 Jan 1; 34(Supplement_1): S11-61. doi:10.2337/dc11-S011.
2. Rendell M. The role of sulphonylureas in the management of type 2 diabetes mellitus. Drugs. 2004 Jun; 64: 1339-58. doi:10.2165/00003495-200464120-00006.
3. Müller G, Satoh Y, Geisen K. Extrapancreatic effects of sulfonylureas—a comparison between glimepiride and conventional sulfonylureas. Diabetes Research and Clinical Practice. 1995 Jan 1; 28: S115-37. doi:10.1016/0168-8227(95)01327-x.
4. Wagh VT, Jagtap VA, Shaikh TJ, Nandedkar SY. Formulation and evaluation of glimepiride solid dispersion tablets for their solubility enhancement. Journal of Advanced Scientific Research. 2012 Nov 10; 3(4): 36-41.
5. Ning X, Sun J, Han X, Wu Y, Yan Z, Han J, He Z. Strategies to improve dissolution and oral absorption of glimepiride tablets: solid dispersion versus micronization techniques. Drug Development and Industrial Pharmacy. 2011 Jun 1; 37(6): 727-36. doi:10.3109/03639045.2010.547241.
6. Badian M, Korn A, Lehr KH, Malerczyk V, Waldhäusl W. Absolute bioavailability of glimepiride (Amaryl®) after oral administration. Drug Metabolism and Drug Interactions. 1994 Dec; 11(4): 331-40. doi:10.1515/dmdi.1994.11.4.331.
7. Chaudhari MD, Sonawane RO, Zawar L, Nayak S, Bari SB. Solubility and dissolution enhancement of poorly water soluble glimepiride by using solid dispersion technique. International Journal of Pharmacy and Pharmaceutical Sciences. 2012; 4(5): 534-9.
8. Vidyadhara S, Babu JR, Sasidhar RL, Ramu A, Prasad SS, Tejasree M. Formulation and evaluation of glimepiride solid dispersions and their tablet formulations for enhanced bioavailability. Pharmanest. 2011 Jan; 1: 15-20.
9. Sharma M, Sharma R, Jain DK, Saraf A. Enhancement of oral bioavailability of poorly water soluble carvedilol by chitosan nanoparticles: Optimization and pharmacokinetic study. International Journal of Biological Macromolecules. 2019 Aug 15; 135: 246-60. doi:10.1016/j.ijbiomac.2019.05.162.
10. Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW, Porter CJ. Strategies to address low drug solubility in discovery and development. Pharmacological Reviews. 2013 Jan 1; 65(1): 315-499. doi:10.1124/pr.112.005660.
11. Campbell DB, Lavielle R, Nathan C. The mode of action and clinical pharmacology of gliclazide: a review. Diabetes Research and Clinical Practice. 1991 Jan 1; 14: S21-36. doi:10.1016/0168-8227(91)90115-H.
12. Nipun TS, Islam SA. SEDDS of gliclazide: preparation and characterization by in-vitro, ex-vivo and in-vivo techniques. Saudi Pharmaceutical Journal. 2014 Sep 1; 22(4): 343-8. doi:10.1016/j.jsps.2013.06.001.
13. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharmaceutical Research. 1995 Mar; 12: 413-20. doi:10.1023/A:1016212804288.
14. Palmer KJ, Brogden RN. Gliclazide: an update of its pharmacological properties and therapeutic efficacy in non-insulin-dependent diabetes mellitus. Drugs. 1993 Jul; 46: 92-125. doi:10.2165/00003495-199346010-00007.
15. Shewale BD, Fursule RA, Sapkal NP. Effect of pH and Hydroxylpropyl-b-Cyclodextrin on solubility and stability of gliclazide. International Journal of Health Research. 2008; 1(2): 95-9.
16. Özkan Y, Atay T, Dikmen N, Işimer A, Aboul-Enein HY. Improvement of water solubility and in vitro dissolution rate of gliclazide by complexation with β-cyclodextrin. Pharmaceutica Acta Helvetiae. 2000 Apr 1; 74(4): 365-70. doi:10.1016/S0031-6865(99)00049-5.
17. Davis TM, Daly F, Walsh JP, Ilett KF, Beilby JP, Dusci LJ, Barrett PH. Pharmacokinetics and pharmacodynamics of gliclazide in Caucasians and Australian Aborigines with type 2 diabetes. British Journal of Clinical Pharmacology. 2000 Mar; 49(3): 223-30. doi:10.1046/j.1365-2125.2000.00144.x.
18. Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. Journal of Pharmacological and Toxicological Methods. 2000 Jul 1; 44(1): 235-49. doi:10.1016/S1056-8719(00)00107-6.
19. Ghadi R, Dand N. BCS class IV drugs: highly notorious candidates for formulation development. Journal of Controlled Release. 2017 Feb 28; 248: 71-95. doi:10.1016/j.jconrel.2017.01.014.
20. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews. 1997 Jan 15; 23(1-3): 3-25. doi:10.1016/S0169-409X(96)00423-1.
21. Patra S, Bhol CS, Panigrahi DP, Praharaj PP, Pradhan B, Jena M, Bhutia SK. Gamma irradiation promotes chemo-sensitization potential of gallic acid through attenuation of autophagic flux to trigger apoptosis in an NRF2 inactivation signalling pathway. Free Radical Biology and Medicine. 2020 Nov 20; 160: 111-24. doi:10.1016/j.freeradbiomed.2020.07.036.
22. Hapse SA, Rachh PR, Nagargoje SS. Nanotechnology based approaches for enhancements of bioavailability of sustain release formulation. Journal of Drug Delivery and Therapeutics. 2019; May 1; 9(3).
23. Ghangas S, Ashok PK, Hooda T. Self-nanoemulsifying isotretinoin topical formulation: development, optimization and characterization, in vitro permeation study by using response surface methodology. Indian Journal of Pharmaceutical Education and Research. 2024; 58(1): 122-30. doi:10.5530/ijper.58.1.12.
24. Ghangas S, Ashok PK, Hooda T. Enhancing oral bioavailability of isotretinoin by using solid lipid nanoparticles (SLNs). Indian Journal of Pharmaceutical Education and Research. 2024; 58(2): 453-9. doi:10.5530/ijper.58.2.51.
25. Simos YV, Spyrou K, Patila M, Karouta N, Stamatis H, Gournis D, Dounousi E, Peschos D. Trends of nanotechnology in type 2 diabetes mellitus treatment. Asian Journal of Pharmaceutical Sciences. 2021 Jan 1; 16(1): 62-76. doi:10.1016/j.ajps.2019.07.002.
26. Zottel A, Videtič Paska A, Jovčevska I. Nanotechnology meets oncology: nanomaterials in brain cancer research, diagnosis and therapy. Materials. 2019 May 15; 12(10): 1588. doi:10.3390/ma12101588
27. Thorat S, Tare M. Formulation and evaluation of quercetin loaded nanosponges of abiraterone acetate. International Journal of Pharmaceutical Quality Assurance. 2023; 14(3): 648-55.
28. Jacob S, Nair AB, Shah J. Emerging role of nanosuspensions in drug delivery systems. Biomaterials Research. 2020; Jan 15; 24(1): 3. doi:10.1186/s40824-019-0185-9
29. Yadollahi R, Vasilev K, Simovic S. Nanosuspension technologies for delivery of poorly soluble drugs. Journal of Nanomaterials. 2015; 2015(1): 216375. doi:10.1155/2015/216375
30. Khandbahale SV. A review – nanosuspension technology in drug delivery system. Asian Journal of Pharmaceutical Research. 2019; 9(2): 130-8.
31. Chougule M, Sirvi A, Saini V, Kashyap M, Sangamwar AT. Enhanced biopharmaceutical performance of brick dust molecule nilotinib via stabilized amorphous nanosuspension using a facile acid–base neutralization approach. Drug Delivery and Translational Research. 2023 Oct; 13(10): 2503-19. doi:10.1007/s13346-023-01334-7.
32. Patel VR, Agrawal YK. Nanosuspension: An approach to enhance solubility of drugs. Journal of Advanced Pharmaceutical Technology and Research. 2011 Apr 1; 2(2): 81-7. doi:10.4103/2231-4040.82950
33. Müller RH, Benita S, Böhm BH, editors. Emulsions and nanosuspensions for the formulation of poorly soluble drugs. CRC Press; 1998.
34. El Maghraby GM, Alomrani AH. Effect of binary and ternary solid dispersions on the in vitro dissolution and in-situ rabbit intestinal absorption of gliclazide. Pakistan Journal of Pharmaceutical Sciences. 2011 Oct 1; 24(4): 459-68.
35. More CG, Dabhade PS, Jain NP, Aher BO. Solubility and dissolution enhancement of gliclazide by solid dispersion technique. International Journal of Pharmaceutical Chemistry and Analysis. 2015; 2(2): 51-8.
36. Syukri Y, Fernenda L, Utami FR, Qiftayati I, Kusuma AP, Istikaharah R. Preperation and characterization of Β-cyclodextrin inclusion complexes oral tablets containing poorly water soluble glimipiride using freeze drying method. Indonesian Journal of Pharmacy. 2015; 26(2): 71. doi:10.14499/INDONESIANJPHARM26ISS2PP71.
37. Hiremath SN, Raghavendra RK, Sunil F, Danki LS, Rampure MV, Swamy PV, Bhosale UV. Dissolution enhancement of gliclazide by preparation of inclusion complexes with β-cyclodextrin. Asian Journal of Pharmacy. 2008 Jan 1; 2(1): 73-6.
38. Du B, Shen G, Wang D, Pang L, Chen Z, Liu Z. Development and characterization of glimepiride nanocrystal formulation and evaluation of its pharmacokinetic in rats. Drug Delivery. 2013 Jan 1; 20(1): 25-33. doi:10.3109/10717544.2012.668443.
39. Ravouru N, Venna RS, Penjuri SC, Damineni S, Kotakadi VS, Poreddy SR. Fabrication and characterization of gliclazide nanocrystals. Advanced Pharmaceutical Bulletin. 2018 Aug 29; 8(3): 419. doi:10.15171/apb.2018.054. doi: 10.5281/zenodo.15720464
40. Kaoud RM, Afouna MI, Samy AM, Kassem AA. Glimepiride-solid lipid nanoparticles as a tool to control blood glucose level in diabetic patients, Part 1: Design, formulation, characterization and rheological properties.
41. Amalia A, Jufri M, Anwar E. Preparation and characterization of solid lipid nanoparticle (SLN) of gliclazide. Jurnal Ilmu Kefarmasian Indonesia. 2015; 13(1): 108-14.
42. Mohd AB, Sanka K, Bandi S, Diwan PV, Shastri N. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of glimepiride: development and antidiabetic activity in albino rabbits. Drug Delivery. 2015 May 19; 22(4):499-508. doi:10.3109/10717544.2013.879753.
43. Nawale RB, Deokate UA, Shahi SR, Lokhande PM. Formulation and characterization of efavirenz nanosuspension by QbD approach. Research Journal of Pharmacy and Technology. 2017;10(9):2960-72. doi:10.5958/0974-360X.2017.00525.X.
44. Rahim H, Sadiq A, Khan S, Amin F, Ullah R, Shahat AA, et al. Fabrication and characterization of glimepiride nanosuspension by ultrasonication-assisted precipitation for improvement of oral bioavailability and in vitro α-glucosidase inhibition. International Journal of Nanomedicine. 2019;14:6287-96. doi:10.2147/IJN.S198390
45. Reichal CR, Pius CR, Manju S, Shobana M. Formulation and characterization of gliclazide nanosuspension. Research Journal of Pharmacy and Technology. 2021;14(2):779-86. doi:10.5958/0974-360X.2021.00136.0.
46. Mistry K, Naik K, Vasanthi, Menezes A, Naha A, Koteshwara KB, Pai KG. Formulation and evaluation of irbesartan nanosuspension for dissolution enhancement. Research Journal of Pharmacy and Technology. 2017;10(9):3043-8. doi:10.5958/0974-360X.2017.00540.6.
47. Patel S, Patel AP. Formulation and evaluation of benidipine nanosuspension. Research Journal of Pharmacy and Technology. 2021;14(8):4111-6. doi:10.52711/0974-360X.2021.00712.
48. Somasundaram, Nagarjuna Yadav BV, Sathesh Kumar S. Formulation of PLGA polymeric nanosuspension containing pramipexole dihydrochloride for improved treatment of Parkinson’s diseases. Research Journal of Pharmacy and Technology. 2016;9(7):810-6. doi:10.5958/0974-360X.2016.00155.4.
49. Santhosh Raja M, Venkataramana K. Formulation and evaluation of stabilized glipizide nanosuspension prepared by precipitation method. Research Journal of Pharmacy and Technology. 2020;13(11):5145-50. doi:10.5958/0974-360X.2020.00900.2.
50. Nawale RB, Deokate UA, Shahi SR, Lokhande PM. Formulation and characterization of efavirenz nanosuspension by QbD approach. Research Journal of Pharmacy and Technology. 2017;10(9):2960-72. doi:10.5958/0974-360X.2017.00525.X.
51. Jadhav PA, Yadav AV. Polymeric nanosuspension loaded oral thin films of flurbiprofen: design, development and in vitro evaluation. Research Journal of Pharmacy and Technology. 2020;13(4):1905-10. doi:10.5958/0974-360X.2020.00343.1.
52. Shinde V, Amsa P, Tamizharasi S, Karthikeyan D, Sivakumar T, Kale A. Formulation and characterization of Eudragit RS 100 nanosuspension for ocular delivery of indomethacin. Research Journal of Pharmacy and Technology. 2010;3(3):854-60.
53. Sharma S, Issarani R, Nagori BP. Development of aceclofenac nanosuspension stabilized by polyvinyl alcohol and sodium dodecyl sulphate. Research Journal of Pharmacy and Technology. 2015;8(3):235-41. doi:10.5958/0974-360X.2015.00027.X.
54. Sreekala MG, Reichal CR, Manju S. Formulation and evaluation of teneligliptin nanosuspension. Research Journal of Pharmacy and Technology. 2024;17(1):96-102. doi:10.52711/0974-360X.2024.00015.
55. Tran TT-D, Tran PH-L, Nguyen MNU, et al. Amorphous isradipine nanosuspension by the sonoprecipitation method. International Journal of Pharmaceutics. 2014;474(1):146-50. doi:10.1016/j.ijpharm.2014.07.056
56. Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, Novelli M, Ribes G. Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes. 1998 Feb 1; 47(2): 224-9. doi:10.2337/diab.47.2.224.
57. Szkudelski T. Streptozotocin–nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Experimental Biology and Medicine. 2012 May; 237(5): 481-90. doi:10.1258/ebm.2012.011372
58. Ghasemi A, Khalifi S, Jedi S. Streptozotocin-nicotinamide-induced rat model of type 2 diabetes. Acta Physiologica Hungarica. 2014 Dec 1;101(4):408-20.
59. Gaber DA, Alhuwaymili AS, Alhawas HS, Almutiri AA, Alsubaiyel AM, Abdoun SA, Almutairi RA. Synthesized nanoparticles of glimepiride via spray freezing into cryogenic liquid: characterization, antidiabetic activity, and bioavailability. Drug Delivery. 2022 Dec 31; 29(1): 364-73. doi:10.1080/10717544.2022.2144579.
60. Kumar D, Kumar S, Raj B, Khatri R, Lather A, Hooda T. Anti-diabetic and wound healing potential of plant Saraca asoca leaves in various diabetic animal models. Research Journal of Pharmacy and Technology. 2024; 17(10): 4685-9. doi:10.52711/0974-360X.2024.00722.
61. Shukla S, Shukla S, Sharma S, Vasudeva N, Khatri R, Lather A, Hooda T. Neuroprotective role of eupalitin in streptozotocin-induced diabetic rats: in silico and in vivo studies. Planta Medica. 2025. doi:10.1055/a-2654-7657.
62. Khalil SS, Ali HA, Al-Saadawy HA, El-Dawy K. Combination of gliclazide drug and lupin seeds powder alleviate hyperglycemia on induced-diabetic rats receiving high-fat high fructose/sucrose diet. Slovenian Veterinary Research. 2018 Oct 2; 55.
63. Pandarekandy ST, Sreejesh PG, Harikumaran Thampi BS, Sreekumaran E. Hypoglycaemic effect of glibenclamide: a critical study on the basis of creatinine and lipid peroxidation status of streptozotocin-induced diabetic rat. Indian Journal of Pharmaceutical Sciences. 2017; Sep 1; 79(5). doi:10.4172/pharmaceutical-sciences.1000290.
64. Shavi GV, Kumar AR, Usha YN, Armugam K, Ranjan OP, Ginjupalli K, Pandey S, Udupa N. Enhanced dissolution and bioavailability of gliclazide using solid dispersion techniques. International Journal of Drug Delivery. 2010 Jan 1;2(1).
65. Lakshmi KS, Rajesh T. Separation and quantification of eight antidiabetic drugs on a high‐performance liquid chromatography: its application to human plasma assay. International Scholarly Research Notices. 2011; 2011(1): 521353.
66. Nazief AM, Hassaan PS, Khalifa HM, Sokar MS, El-Kamel AH. Lipid-based gliclazide nanoparticles for treatment of diabetes: formulation, pharmacokinetics, pharmacodynamics and subacute toxicity study. International Journal of Nanomedicine. 2020; Feb 18: 1129-48. doi:10.2147/IJN.S234058.
67. Qushawy M, Nasr A, Swidan S, Mortagi Y. Development and characterization of glimepiride novel solid nanodispersion for improving its oral bioavailability. Scientia Pharmaceutica. 2020; 88(4): 52. doi:10.3390/scipharm88040052.
68. Li H, Pan T, Cui Y, Li X, Gao J, Yang W, Shen S. Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique. International Journal of Nanomedicine. 2016 Aug 5: 3777-88.
69. Badar A, Pachera S, Ansari AS, Lohiya NK. Nano based drug delivery systems: present and future prospects. Nanomedicine Nanotechnology Journal. 2019; 2(1): 121.
70. Chandrakala V, Aruna V, Angajala G. Review on metal nanoparticles as nanocarriers: current challenges and perspectives in drug delivery systems. Emergent Materials. 2022 Dec; 5(6): 1593-615. doi:10.1007/s42247-021-00308-5.