Design and Evaluation of Repaglinide Nanosuspension for Oral Controlled Drug Delivery System by using 32 Factorial Design
Sonali Vijaykumar Magdum1*, Pramodkumar Jaykumar Shirote2
1Department of Pharmaceutics, Dr. J. J. Magdum Pharmacy College, Jaysingpur, Kolhapur, Maharashtra-416101, India
2Department of Pharmaceutical Chemistry, Dr. Bapuji Salunkhe Institute of Pharmacy, Miraj-416410, India
Received: 4th Jan, 2025; Revised: 13th Feb, 2025; Accepted: 21st May, 2025; Available Online: 25th Jun, 2025
ABSTRACT
The current work proposed a nanocrystal-based formulation to overcome the solubility issues of repaglinide. Using the lyophilization procedure, REP nanosuspension was successfully transformed towards solid form. To make also preserve REP nanosuspension, polyvinyl alcohol as well as Eudragit S100 were used as protectors. Lyophilization's suitability for enhancing physical stability was assessed by considering important restrictions, such as the shape of solid dispersion, on the characteristics of nanosuspension. The generated nanocrystals' solid-state characteristics were also evaluated. Process factors that were improved increased the polydispersity index, zeta potential, drug content, also average particle size. Selective cryoprotectants (lactic acid) were used to assess the lyophilization procedure as an appropriate solidification approach. With an average particle diameter of 317 ± 3.4 nm, PDI about 0.150, also zeta potential about -10.2 ± 0.85 mV, formulation remained stable throughout three months at 4°C. The generated nanosuspension's discharge profile showed a cumulative release of over 92.23%, compared to 8.02% during the first ten hours with unprocessed medicine. These findings suggest that the new formulation successfully increases Repaglinide's water solubility.
Keywords: Repaglinide, Factorial Design, Nanosuspension, Nanoprecipitation, Drug release, Stability.
How to cite this article: Sonali Vijaykumar Magdum, Pramodkumar J Shirote. Design and Evaluation of Repaglinide Nanosuspension for Oral controlled Drug Delivery System by using 32 Factorial Design. International Journal of Drug Delivery Technology. 2025;15(2): 416-24. doi:10.25258/ijddt.15.2.6
REFERENCES
- Ma Y, Yang Y, Xie J, Xu J, Yue P, Yang M. Novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide. Int J Nanomedicine. 2018; 13:3763-3779. https://doi.org/10.2147/IJN.S164228.
- Jermain SV, Brough C, Williams III RO. Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery–an update. Int J Pharm. 2018; 535:379-392. https:// doi.org/ 10.1016/j.ijpharm.2017.10.051
- Jakubowska E, Lulek J. The application of freeze-drying as a production method of drug nanocrystals and solid dispersions–a review. J Drug Deliv Sci Technol.2021;62:102357. https://doi.org/10.1016/j.jddst.2021.102357
- Ding Z, Wang L, Xing Y, Zhao Y, Wang Z, Han J. Enhanced oral bioavailability of celecoxib nanocrystalline solid dispersion based on wet media milling technique: formulation, optimization and in vitro/in vivo Pharmaceutics.2019;11:328-345.https://doi.org/ 10.3390/pharmaceutics11070328.
- Kaur A, Parmar PK, Bansal AK. Evaluation of different techniques for size determination of drug nanocrystals: A case study of celecoxib nanocrystalline solid dispersion. Pharmaceutics. 2019; 11:516-533. https:// doi.org/10.3390/pharmaceutics11100516.
- Rahman M, Arevalo F, Coelho A, Bilgili E. Hybrid nanocrystal–amorphous solid dispersions (HyNASDs) as alternative to ASDs for enhanced release of BCS Class II drugs. Eur J Pharm Biopharm. 2019;145:12-26. https:// doi.org/10.1016/j.ejpb.2019.10.002.
- Ahuja M, Dhake AS, Sharma SK, Majumdar DK. Diclofenac-loaded Eudragit S100 nanosuspension for ophthalmic delivery. J Microencapsul. 2011;28(1):37–45. doi:10.3109/02652048.2010.523794
- Schaffazick SR, Pohlmann AR, Dalla-Costa T, Guterres S.l.S. Freeze-drying polymeric colloidal suspensions: Nanocapsules, nanospheres and nanodispersion. A comparative study. Eur J Pharm Biopharm. 2003;56:501–505. doi:10.1016/S0939-6411(03)00139-5
- Abdelwahed W, Degobert G , Serge Stainmesse S, et al. Freeze-drying of nanoparticles: Formulation, process and storage considerations. Adv Drug Deliv Rev. 2006;58(15):1688-1713. doi:10.1016/j.addr.2006.09.017
- Pignatello R, Ricupero N, Bucolo C, Maugeri F, Maltese A, Puglisi G. Preparation and characterization of eudragit retard nanosuspensions for the ocular delivery of cloricromene. AAPS PharmSciTech 2006; 7: E192–E198
- Das S, Suresh P, Deshmukh R. Design of eudragit RL 100 nanoparticles by nanoprecipitation method for ocular drug delivery. Nanomed Nanotech Bio Medi 2010; 6: 318-323.
- Motwani, S. Chopra, S. Talegaonkar , K. Kohli, F.Ahmad, R. Khar, Chitosan-sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: formulation, optimization and in vitro characterization, Eur J Pharm Biopharm 68 (2008) 513–525
- Castelli F, Messina C, Sarpietro M, Pignatello R, Puglisi G. Flurbiprofen release from Eudragit RS and RL aqueous nanosuspension: a kinetic study by DSC and dialysis Experiments. AAPS PharmSciTech 2002; 3: E9.
- Hong, Y. Dang, G. Lin, Y. Yao, Effects of stabilizing agents on the development of myricetin nanosuspension and its characterization: An in vitro and in vivo evaluation, Int. J of Pharm. 477 (2014) 251–260.
- Bilati U, Allémann E, Doelker E. Nanoprecipitation versus emulsion-based techniques for the encapsulation of proteins into biodegradable nanoparticles and process-related stability issues. Aaps Pharmscitech. 2005;6(4):E594–E604. doi:10.1208/pt060474
- Adibkia K, Omidi Y, Siahi M. Inhibition of Endotoxin-Induced uveitis by methylprednisolone acetate nanosuspension in rabbits. J Ocul Pharmacol Ther 2007; 23: 421-432.
- Tran P, Pyo YC, Kim DH, Lee SE, Kim JK, Park JS. Overview of the Manufacturing Methods of Solid Dispersion Technology for Improving the Solubility of Poorly Water-Soluble Drugs and Application to Anticancer Drugs. Pharmaceutics.2019;11:132.https://doi.org/10.3390/pharmaceutics11030132.
- Sarnes A, Kovalainen M, Häkkinen MR, Laaksonen T, Laru J, Kiesvaara J, Ilkka J, Oksala O, Rönkkö S, Järvinen K, Hirvonen J. Nanocrystal-based per-oral itraconazole delivery: Superior in vitro dissolution enhancement versus Sporanox® is not realized in in vivo drug absorption. Control Release. 2014;180:109-116. https://doi.org/ 1016/j.jconrel.2014.02.016.
- Hezha A A, Hunar K O, Solubility Enhancement of a Poorly Water-Soluble Drug Using Hydrotropy and Mixed Hydrotropy-Based Solid Dispersion Techniques. Hindawi Advances in Pharmacological and Pharmaceutical Sciences. 2022; 1-16. https://doi.org/10.1155/2022/7161660.
- Pandi P, Bulusu R, Kommineni N, Khan W, Singh M. Amorphous solid dispersions: An update for preparation, characterization, mechanism on bioavailability, stability, regulatory considerations, and marketed products. Int J Pharm. 2020; 586:119560-119582. https://doi.org/10.1016/j.ijpharm.2020.119560.
- Nkansah P, Antipas A, Lu Y, Varma M, Rotter C, Rago B, El-Kattan A, Taylor G, Rubio M, Litchfield J.J. Development and evaluation of novel solid nanodispersion system for oral delivery of poorly water-soluble drugs. Control.Rel. 2013;169:150-161. doi: 10.1016/j.jconrel.2013.03.032.
- Dash S, S.Murthy, P.Chowdhury, Kinetic modeling on drug release from controlled drug delivery systems, Acta Pol Pharm 2010; 67(3): 217-223.
- Palanisamy M, Khanam J. Solid dispersion of prednisolone: solid state characterization and improvement of dissolution profile. Drug Dev Ind Pharm. 2011;37:373-386.
- Wang Y, Wang W, Yu E, Zhuang W, Sun X, Wang H, Li Q. Preparation of a camptothecin analog FLQY2 self-micelle solid dispersion with improved solubility and bioavailability. J Nanobiotechnology.2022;20:402. doi: 10.1186/s12951-022-01596-2.