Technosphere® Insulin: Defining the Role of Technosphere Particles at the Cellular Level

Angelo, Robert; Rousseau, Kathleen; Grant, Martin; Leone-Bay, Andrea; Richardson, Peter

doi:10.1177/193229680900300320

Cited by 66 publications

(55 citation statements)

References 38 publications

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“…These particles are homodisperse, with a mean geometric diameter of about 2 µm and after inhalation dissolve rapidly. High surface area and high internal porosity are some of the features of these particles [28,29].…”

Section: Technospherementioning

confidence: 99%

“…It is administered at the beginning of each meal [32,33]. The Technosphere insulin delivers the insulin directly into the arterial circulation with excellent systemic action as they are rapidly absorbed after inhalation [29]. Afrezza is available in two different strengths identified by color like 4 units (blue cartridge) and 8 units (green cartridge) and both dispensed in foil packages [33].…”

Section: Inhaled Insulinmentioning

confidence: 99%

“…5) [32]. It uses the Technosphere platform Shetty and Srinivasan technology [29,31]. Afrezza consists of a dry powder formulation of human insulin delivered from MedTone® inhaler to help patients achieve blood sugar control as the powder is aerosolized and delivered to the lung.…”

Section: Inhaled Insulinmentioning

confidence: 99%

“…Many of these formulations have been administered via pulmonary route in rat models for systemic delivery [28]. Afrezza uses this technology to deliver insulin by oral inhalation [28,29].…”

Section: Technospherementioning

confidence: 99%

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Advancements in Dry Powder Inhaler

Ganga¹,

Shetty²

2017

Asian J Pharm Clin Res

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The dry powder inhaler (DPI) has become widely known as a very attractive platform for drug delivery. DPIs are being used for the treatment of asthma and chronic obstructive pulmonary disease by many patients. There are over 20 devices presently in the DPI market. DPIs are preferred over nebulizers and pressurized metered dose inhalers. However, some of the challenges of DPI are dependence on inspiratory flow (unsuitable for young children, elderly people), systemic absorption due to deposition of drug in deep lung (unsuitable for local diseases treatment), and increase in upper airway deposition of a large fraction of coarse particles. Hence, there is a need to address these unmet issues. The interpatient variation can be minimized by developing devices independent of patient's inspiratory flow rate or active based powder mechanism. This article reviews DPI devices currently available, advantages of newly developed devices, and formulation technologies. The platform technologies are developed to improve aerosolization and dispersion from the device and decrease the patient related factors. The DPI delivery system has been expanded to treatment of non-respiratory diseases such as migraine and diabetes. The development of innovative DPI device and formulation technologies for delivering therapeutic proteins such as insulin has been accelerated to overcome the problems associated with conventional insulin therapy.

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Section: Technospherementioning

confidence: 99%

Section: Inhaled Insulinmentioning

confidence: 99%

Section: Inhaled Insulinmentioning

confidence: 99%

“…Many of these formulations have been administered via pulmonary route in rat models for systemic delivery [28]. Afrezza uses this technology to deliver insulin by oral inhalation [28,29].…”

Section: Technospherementioning

confidence: 99%

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Advancements in Dry Powder Inhaler

Ganga¹,

Shetty²

2017

Asian J Pharm Clin Res

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“…1a, b) system with the dry powder formulations dissolved in a medium. 17,18) However, it is generally considered that DPIs exhibit the following behavior after inhalation: 1) dispersion, 2) delivery to pulmonary mucosa, 3) deposition, 4) dissolution, and 5) absorption. Therefore, the SUB system is not necessarily suitable for the accurate evaluation of inhaled dry powder formulations since it cannot reflect the actual condition on the lung epithelial surface, including the direct attachment of the powders followed by their dissolution.…”

mentioning

confidence: 99%

Safety Evaluation of Dry Powder Formulations by Direct Dispersion onto Air–Liquid Interface Cultured Cell Layer

Asai

Okuda

Yamauchi

et al. 2016

Biological & Pharmaceutical Bulletin

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Most safety evaluations of dry powder inhalers (DPIs) using cultured cells have been performed with dry powder formulations dissolved in a medium. However, this method is not considered to be suitable to evaluate the safety of inhaled dry powder formulations correctly since it cannot reflect the actual phenomenon on the respiratory epithelial surface. In this study, we established a novel in-vitro safety evaluation system suitable for DPIs by combining an air-liquid interface cultured cell layer and a device for dispersing dry powders, and evaluated the safety of candidate excipients of dry powders for inhalation. The safety of excipients (sugars, amino acids, cyclodextrins, and positive controls) in solutions was compared using submerged cell culture systems with a conventional 96-well plate and Transwell ® . The sensitivity of the cells grown in Transwell ® was lower than that of those grown in the 96-well plate. Dry powders were prepared by spray-drying and we evaluated their safety with a novel in-vitro safety evaluation system using an air-liquid interface cultured cell layer. Dry powders decreased the cell viability with doses more than solutions. On the other hand, dissolving the dry powders attenuated their cytotoxicity. This suggested that the novel in-vitro safety evaluation system would be suitable to evaluate the safety of DPIs with high sensitivity.Key words dry powder; safety evaluation; air-liquid interfaced culture; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; A549 cell Pulmonary drug delivery has been investigated as not only a local treatment for respiratory diseases such as asthma or chronic obstructive pulmonary disease, but also as an alternative route for the systemic delivery of macromolecule drugs such as insulin, calcitonin, and heparin. 1-4)Among the three major systems for pulmonary deliverynebulizers, pressurized metered-dose inhalers (pMDIs), and dry powder inhalers (DPIs)-DPIs have several advantages, including favorable portability, a low cost, and the lack of a need for propellants. Furthermore, the handling of DPIs is easier than that of pMDIs because of breath-actuated passive aerosolization. 5)For effective pulmonary deposition after inhalation, in general, the optimal aerodynamic diameter of drug particles is less than 6 µm.6,7) However, micronized drug particles tend to be highly cohesive and poorly flowable, leading to low-level performance. To solve these problems, it is usual for an excipient, such as coarse lactose monohydrate, to be formulated to physically attach to fine active ingredients. 8,9) It has been recently reported that the addition of amino acids or cyclodextrins (CyDs) as excipients improves pulmonary delivery. 10,11) As for fundamental research on DPIs, evaluation of the physical properties such as particle size and pulmonary deposition is mainstream, whereas biological evaluation such as of the efficacy and safety is essential for clinical application. 12)These biological evaluations of dry powder formulations are often conduct...

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Afrezza: An inhaled approach to insulin delivery

Fleming

Davis

2015

Journal of the American Association of Nurse Practitioners

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Purpose The purpose of this article is to educate nurse practitioners about Afrezza. Data sources A comprehensive literature search was conducted using MEDLINE for clinical trial data. Information from the Centers of Disease Control and Prevention, World Health Organization, clinical guidelines, Food and Drug Administration labeling, briefings, and press releases was also utilized. Conclusions Afrezza represents a promising noninjectable insulin delivery option for type 1 and type 2 diabetes mellitus. According to clinical trial evidence, it appears to be efficacious and comparable to currently available prandial insulin options, and based on current data, it appears to be a safe alternative to injectable insulin with high treatment satisfaction. Implications for practice Afrezza may offer an alternative for insulin naïve patients who are hesitant about initiating traditional insulin. It may cause less weight gain when compared to subcutaneous mealtime insulin with a more rapid absorption and elimination profile, but more long‐term studies are needed. Afrezza is limited in type 1 diabetes to use in combination with basal insulin. It is not recommended in the treatment of diabetic ketoacidosis or for patients who smoke. It is contraindicated during hypoglycemic episodes, in chronic lung diseases, or in those with hypersensitivity to regular human insulin or any of the excipients in Afrezza.

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Technosphere® Insulin: Defining the Role of Technosphere Particles at the Cellular Level

Abstract: Background:

Cited by 66 publications

References 38 publications

Advancements in Dry Powder Inhaler

Advancements in Dry Powder Inhaler

Safety Evaluation of Dry Powder Formulations by Direct Dispersion onto Air–Liquid Interface Cultured Cell Layer

Afrezza: An inhaled approach to insulin delivery

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