Insulin freeze-dried

In insulin powder prepared by freeze drying, the reactions observed were deamidation at AsnA21 and dimer formation [137]. In contrast to suspensions, amorphous insulin in the powder form was more stable than crystalline insulin. In fact, the rate of degradation of crystalline insulin increased with increasing water content, whereas the rate of degradation of amorphous insulin was essentially independent of water content up to the maximum studied (ca. 15%). 

Diabetes mellitus in a 36-year-old man with acute pancreatitis could not be controlled with continuous subcutaneous insulin infusion, even with doses up to 1800 U/ day, because of insulin resistance (168). Intravenous insulin by pump had to be stopped because of a catheter infection. The continuous subcutaneous infusion of freeze-dried insulin and the addition of aprotinin, a protease inhibitor, soluble dexamethasone or prednisolone, and intravenous immunoglobulin was ineffective. An implantable pump for intraperitoneal delivery established good regulation at a dosage of 30 U/day. 

Powdered bioadhesive formulations have attracted much interest for their ability to overcome mucociliary clearance in the nasal cavity. For example, powder formulations of freeze-dried mixtures of insulin and excipients such as crystalline cellulose, hydroxypropyl cellulose, or carbopol 934 have been shown to enhance the absorption of insulin in dogs from the nasal cavity compared to freeze-dried mixtures of insulin and lactose as an excipient [28,31], The improved delivery was attributed to both the improved dispersion of insulin and the high... 

A further approach has been to deliver drugs in the form of a powder (but without a bioadhesive carrier). For example, freeze-dried insulin has been shown to be better absorbed as a powder than in solution, although the absorption of glucagon and dihydroergotamine, when delivered from liquid or powder formulations, was equivalent. 

Fernandez-Urrusuno et al. [30] reported on development of a freeze-dried formulation of CT/TPP nanoparticles loaded with insulin. They tested various cry-protective agents for their ability to maintain the original size/charge of particles upon reconstitution. The best medium appeared to be 5 % trehalose or sucrose. This was confirmed with unloaded nanoparticles from System 2 (Fig. 16). The original suspension, without the trehalose addition, exhibited a size of 185 nm (SD 25 nm). 

Fernandez-Urrusuno R, Romani D, Calvo P, Vila-Jato JL, Alonso MJ (1999) Development of a freeze-dried formulation of insulin-loaded chitosan nanoparticles intended for nasal administration. S.T.P. Pharma Sci 9 429-436... 

Figure 203. Relationship between moisture adsorption (a) mid aggregation (b) for freeze-dried insulin stored at 50°C for 24 h. (Reproduced from Ref. 810 with permission.)...

Another approach for creating integrated microfluidic devices for medical diagnostics is to create a device for the reconstitution (hydration) of a lyophilized (freeze-dried) drug solution, followed by dilution and delivery into a patient at a constant rate. Such a system could utilize freeze-dried antibiotics, analgesics, or insulin for treating a diabetic patient as described in Liepmann et al. [5]. This system. 

Many proteins are not on the market as a ready-to-use solution. The licensed product consists of a vial with freeze dried powder, and sometimes an ampoule of the solvent. This kind of products should be reconstituted just before use. Gently swirling, not shaking, is the way to get such powders into solution. Protein suspensions for example long-acting insulins, should be resuspended by rolling the ampoules between palms instead of shaking. 

Furthermore, in-vivo data has been assessed for the nasal application of spray-freeze-dried insulin particles. SFD insulin applied through the nasal route showed a fast effect in lowering the blood glucose levels of rats (Fig. 10.16) [38]. 

Schiffter, H., Condliffe, J., Vonhoff, S. (2010). Spray-freeze-drying of nano suspensions The manufacture of insulin particles for needle-free ballistic powder delivery. Journal of the Royal Society Interface, 7, S483-S500. 

Bi R, Shao W, Wang Q, Zhang N. Spray-freeze-dried dry powder inhalation of insulin-loaded liposomes for enhanced pulmonary delivery. /Drug Target. 2008 16(9) 639-48. 

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