Loading article...
Loading article...
Stream/Area:
-
Subject:
-
Paper ID:
IJSREM63115
Volume:
10 |
5 |
May 2026
Pages:
1-18
Publication Frequency:
Monthly (12 issues per year)
License:International Journal of Scientific Research in Engineering and Management follows the Creative Commons Attribution 4.0 (CC BY 4.0) License, allowing free use and distribution with proper attribution.
Department of Pharmaceutics
Dr. Uttamrao Mahajan College of B. Pharmacy, Chalisgaon
The traditional form of subcutaneous insulin treatment is known to have late onset of action, needle phobia, low patient compliance and lack of post prandial glycemic control and hence the necessity of developing efficient non-invasive delivery approaches. The current paper describes how insulin nano-encapsulated inhalable dry powder was formulated and evaluated in detail in order to achieve quick systemic glycemic regulation through the pulmonary route. A system was optimized by ionic gelation with sodium tripolyphosphate (TPP) as a cross-linker and 5 formulation batches (F1-F5) by the gradual increase and decrease of polymer concentration (0.5-1.5%), drug:polymer ratio (1:1 to 1:5), and stirring speed (500-1000 rpm) to produce insulin-loaded chitosan nanoparticles. The optimized formulation (F5) exhibited a particle size of 148 ± 2 nm, polydispersity index of 0.214, zeta potential of +27.9 mV and entrapment efficiency of 91.4 ± 0.8% of the drug. Spray drying the nanoparticle dispersion with trehalose and mannitol as cryoprotectants transformed the dispersion into inhalable dry powder. The powder showed satisfactory flow characteristics (Carr index: 16.32 ± 0.54, Hausner ratio: 1.19 ± 0.03, angle of repose: 28.6 ± 0.8deg), low moisture (2.3 percent) and the ideal particle size distribution (D50: 3.0 um, D90: 4.8 um). The aerosolization studies showed fine particle fraction of 61.8, aerodynamic particle size of 3.3 um and emitted dose of 87.4 which was suitable to deposit in deep lungs. It exhibited a biphasic in vitro drug release with an initial burst (17.9% at 1 h), and sustained release (96.3 ± 2.3% at 24 h). At 276 nm UV spectrophotometric calibration gave a linear response at 2-10 ug/mL (R2 = 0.9992). FTIR showed compatibility of drugs and excipients. The 6 months studies of stability under conditions suggested by the ICH (25degC/60% RH and 40degC/75% RH) showed that there were slight fluctuations in particle size (≈160 nm) and drug content (≈95.6%), which confirmed the stability of the formulation. These results support the belief that nano-encapsulated inhalable insulin dry powder is a good platform to attain a rapid reproducible glycemic control in Type 1 and Type 2 diabetes mellitus.
KEYWORDS
The present study successfully demonstrated the development and evaluation of nano-encapsulated inhalable insulin dry powder as a non-invasive and fast-acting pulmonary insulin delivery system in patients with Type 1 and Type 2 Diabetes mellitus. Ionic gelation of chitosan nanoparticles resulted in a systematic optimisation of the formulation that produced an optimised formulation (F5) with particle size of 148 ± 2 nm, PDI of 0.214, Zeta potential of +27.9 mV, and drug entrapment efficiency of 91.4 = 0.8, which was the most effective formulation among the five batches of formulations. Treatment of the nanoparticle dispersion to spray drying with trehalose and mannitol was successful in converting the aerosol to an inhalable fine powder with: a mean aerodynamic diameter of 3.3 µm in the critical 1 -5 µm respirable size range; an excellent fine particle fraction of 61.8% higher than published standards; an emitted dose of 87.4% and good powder flowability (CI: 16.32, HR: 1.19, angle of repose: 28 The FTIR proved the full compatibility of the drugs and excipients. Biphasic release in vitro showed clinically favorable biphasic kinetics, i.e. high initial release to provide prandial cover and low release to provide prolonged release, after an aberrant (Korsmeyer-Peppas) transport kinetics. Stability experiments (ICH compliant) carried out at both 25 o C and 40 o C and 60 and 75% RH respectively during 6 months, indicated a high degree of physical and chemical stability with 95.6 and above retention of drug content respectively. All these findings form a solid scientific basis on the potential of nano-encapsulated inhalable insulin dry powder as a clinically viable alternative to subcutaneous injection of insulin with the promise of better post-prandial glycaemic control, fewer adverse effects related to injection, and significantly improved compliance of the patient. Other future work should involve in vivo pharmacokinetic and pharmacodynamic research in diabetic animal models, scale-up process optimization, device optimization, and long-term toxicology research to develop this formulation to a clinical application.
[1] American Diabetes Association. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S19–S40. doi: 10.2337/dc23-S002. [2] International Diabetes Federation. IDF Diabetes Atlas, 10th edn. Brussels, Belgium: International Diabetes Federation; 2021. ISBN: 978-2-930229-98-0. [3] Pearson ER. Type 2 diabetes: a multifaceted disease. Diabetologia. 2019;62(7):1107–1112. doi: 10.1007/s00125-019-4909-y. [4] Karmakar S, Bhowmik M, Laha B, Manna S. Recent advancements on novel approaches of insulin delivery. Medical Novelties in Technology and Devices. 2023;19:100253. doi: 10.1016/j.medntd.2023.100253. [5] Neumiller JJ, Campbell RK, Wood LD. A review of inhaled technosphere insulin. Annals of Pharmacotherapy. 2010;44(7–8):1231–1239. doi: 10.1345/aph.1P055. [6] Imenshahidi M, Kabiri M, Jandaghi M, Razavi Rouhani SS, Abnous K, Karimi GR. Pulmonary delivery of insulin by dry powder inhaler formulations. Iranian Journal of Basic Medical Sciences. 2025;28(1):1–15. doi: 10.22038/IJBMS.2024.79989.17299. [7] Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications. British Journal of Clinical Pharmacology. 2003;56(6):588–599. doi: 10.1046/j.1365-2125.2003.01892.x. [8] Naureen F, Shah Y, Rehman MU, Chaubey P, Nair AK, Khan J, Shah KU. Inhalable dry powder nano-formulations: Advancing lung disease therapy—a review. Frontiers in Nanotechnology. 2024;2:1403313. doi: 10.3389/fnano.2024.1403313. [9] Chan HW, Zhang Y, Leung SSL, Chan JGY, Kwok PCL, Chan HK. Inhalable nanoparticle-based dry powder formulations for pulmonary drug delivery: Challenges and strategies for clinical translation. Journal of Controlled Release. 2023;370:160–182. doi: 10.1016/j.jconrel.2023.08.044. [10] Andrade F, Rafael D, Videira M, Ferreira D, Sosnik A, Sarmento B. Nanotechnology and pulmonary delivery to overcome resistance in infectious diseases. Advanced Drug Delivery Reviews. 2013;65(13–14):1816–1827. doi: 10.1016/j.addr.2013.07.020.
Publication Date
5/13/2026
Peer Review Type
Double-Blind Peer Review
Review Rounds: 2
Documents
Article Views
1
Total views since publication
PDF Downloads
2
Total downloads since publication
Geographic Reach
5
Digital Preservation: This article is permanently archived on Zenodo and complies with all data preservation standards across major indexing platforms.
Plagiarism Screening
This manuscript has been checked for plagiarism using TurnitinPlagiarismChecker software.
Conflict of Interest
The authors declare no conflict of interest related to this research work.
Funding Information
No funding information available for this research.
Related research in the same subject area
Loading similar articles...