Drug solubility insulin

Mixing drugs formulated for injection in a syringe may cause interaction, e.g. protamine zinc insulin contains excess of protamine which binds with added soluble insulin and reduces the immediate effect of the dose. 

Antidiabetic Drugs other than Insulin. Figure 8 Structure of human amylin and its soluble analogue pramlintide. 

It is a synthetic, water soluble polymer of molecular weight approximately 40,000. It is 3-5% solution in buffered physiological saline administered intravenously. It produce agglutination of RBC s and therefore interferes with blood grouping and cross matching and also releases histamine. It also binds certain drugs i.e. insulin, penicillin etc. Because of these drawbacks, it is less commonly used. 

In order to overcome the main limitations of the impregnation processes, connected to the limited solubility of the compounds in the supercritical fluids, Perman [68] proposed an alternative method. A supercritical impregnation process was coupled with a liquid solvent (preferentially water) to enhance the drug solubilization. The system composed of a liquid drug solution and the polymeric support was pressurized with the supercritical fluid. Consequently, the swelled polymer allows rapid diffusional transport of the solute into the polymeric substrate. In different examples, bovine serum albumin microspheres were impregnated with insulin, trypsin and gentamicin (see Table 9.9-5). 

These can be sprayed orally onto the buccal or the sublingual membrane to achieve a local or a systemic effect. One such spray called insulin buccal spray (IBS) was developed with soybean lecithin and propanediol [94], Soybean lecithin has high affinity for biomembranes but does not enhance the transport of drugs due to low solubility. Propanediol can improve the solubility of soybean lecithin, and act as an enhancer. IBS was administered to diabetic... 

Another type of absorption enhancer, which has been shown to have a better safety profile, is cyclodextrin (CD) [39]. CDs have been shown to form inclusion complexes with lipophilic drugs, thereby improving their aqueous solubility and stability. A powdered insulin formulation containing dimethyl-(3-cyclodextrin improved the absolute bioavailability of insulin by 13% in rabbits compared to a control liquid formulation (1%) of insulin with dimethyl-(3-cyclodextrin [40]. Recently, hydroxypropyl (3-cyclodextrin has been shown to be more effective for enhancing the nasal absorption of acyclovir than a range of other absorption enhancers in vivo [41]. 

Polymer-based (ethyl vinyl acetate) Changes in solubility of the drug Insulin pH change ... 

For drugs deposited in the proximity of the peripheral capillary beds of muscle and subcutaneous tissue, lipid solubility is considerably less important than the oral route since even ionized forms of drugs are absorbed with relative ease. The capillary wall in these areas is of sufficient porosity that even drugs with molecular weights as great as 60,000 daltons may be absorbed by passive diffusion. This explains why a protein, such as insulin (5808 daltons), can be given subcutaneously and is absorbed into the bloodstream. 

Ester and amide derivatives of lipoic acid (i.e., 360 and 361) are capable of increasing the rate of glucose transport in myotubes in culture in the absence or presence of insulin <2004BMC1183>. Due to the improved lipid solubility, these compounds surpass the potency of LA, which is used as an auxiliary drug for the treatment of diabetes, by a few orders of magnitude. 

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