Dataset Information

Preparation, characterization, and pharmacodynamics of insulin-loaded fumaryl diketopiperazine microparticle dry powder inhalation.

ABSTRACT: Purpose: With the increase of population aging and the proportion of overweight and obese, a growing number of people are suffering from diabetes. Insulin (INS) as the most widely used hypoglycemic agent was always chosen as the most effective treatment method of diabetes. In this study, fumaryl diketopiperazine (FDKP) was used as a carrier for the pulmonary delivery of insulin. Patients and methods: The INS-loaded FDKP microspheres (INS@FDKP-MPs) were prepared by spray drying and physicochemical properties (drug loading, particle size, flowability, moisture content, morphology, and crystalline state) were further investigated. Pharmacodynamics was investigated on diabetic model rats administrated by intratracheal insufflation. Results: The INS-loaded FDKP microspheres show satisfied flowability and in vitro deposition with FPF 50.2% and MMAD 3.45?±?0.13??m, and the blood glucose level was significantly decreased. Moreover, no inflammatory reaction was observed during the safety study. Conclusion: To sum up, the aim was to develop a non-injection system for insulin, INS@FDKP-MPs powder inhalation with high dose, low toxicity, and good lung deposition inhalation could rapidly decrease the blood glucose level without immune stimulation, which shows remarkably potential on diabetes treatment by pulmonary delivery route.

SUBMITTER: Xia Y

PROVIDER: S-EPMC6609328 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Preparation, characterization, and pharmacodynamics of insulin-loaded fumaryl diketopiperazine microparticle dry powder inhalation.

Xia Yun Y Su Yipeng Y Wang Qiyue Q Yang Chen C Tang Baoqiang B Zhang Yue Y Tu Jiasheng J Shen Yan Y

Drug delivery 20191201 1

<b>Purpose:</b> With the increase of population aging and the proportion of overweight and obese, a growing number of people are suffering from diabetes. Insulin (INS) as the most widely used hypoglycemic agent was always chosen as the most effective treatment method of diabetes. In this study, fumaryl diketopiperazine (FDKP) was used as a carrier for the pulmonary delivery of insulin. <b>Patients and methods:</b> The INS-loaded FDKP microspheres (INS@FDKP-MPs) were prepared by spray drying and ...[more]

PMID: 31257946

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Project description:A nifedipine (NP) dry emulsion was fabricated by the adsorption of medium internal-phase emulsions (MIPEs). Simple homogenizers were first used to mix conventional liquid MIPEs, and then a microfluidizer was used to reduce the resulting emulsions' droplet sizes. The dry MIPEs (solid) were produced by adsorbing the emulsions onto solid carriers with a high surface area. The dry MIPEs were diluted in a simulated gastric fluid under gentle agitation to form emulsions. The diluted dry MIPEs were divided into three groups based on an NP content of 0.3%, 0.5%, and 0.7%, with sizes of 5026-5404 nm, 2583-3233 nm, and 1318-1618 nm in diameter, respectively. Powder X-ray diffraction (PXRD) measurements and differential scanning calorimetry (DSC) were used to characterize the physical properties of the dry MIPEs. The samples contained 0.5% or 0.7% drug, 2-4% surfactant, and 8-16% oil (5RH2/8, 7RH2/8, and 7RH4/16) and showed the characteristic peak for NP. No NP peak was observed in formulations with 0.3% NP and any oil-phase content (3RH2/8, 3RH4/16, and 3RH8/32). The formulations with 0.5% drug, 4-8% surfactant, 16-32% oil (5RH4/16 and 5RH8/32) and those with 0.7% drug, 8% surfactant, and 32% oil (7RH8/32) also did not show the peak for NP. These findings demonstrated that microfluidization improved the solubility of NP in the formulations. The subsequent drug dissolution results were consistent with the DSC thermogram and PXRD pattern results. 3RH2/8, 3RH4/16, 3RH8/32, 5RH4/16, 5RH8/32, and 7RH8/32 were completely dissolved and showed higher dissolved NP amounts than 5RH2/8, 7RH2/8, 7RH4/16, and NP powder. The lowest mean dissolution time was for 7RH8/32 (13.31 ± 0.87 min). Caco-2 cells were used to determine drug uptake, and 7RH8/32 showed the maximum intracellular uptake (10.89%). After storage under accelerated and normal conditions (3 and 6 months), the selected formulations remained stable. The developed formulations can be used to improve NP solubility and absorption.

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Dataset Information

Preparation, characterization, and pharmacodynamics of insulin-loaded fumaryl diketopiperazine microparticle dry powder inhalation.

Publications

Preparation, characterization, and pharmacodynamics of insulin-loaded fumaryl diketopiperazine microparticle dry powder inhalation.

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