Is relief from diabetes just a breath away?

Pulmonary insulin delivery is steadily emerging as a promising solution for the treatment of diabetes mellitus. The large as well as thin absorptive area of the lungs has not been explored until now for the treatment of systemic disease like diabetes. With an understanding of the lung anatomy and physiology and the transport mechanism of insulin through lungs, diabetic treatment through the pulmonary route may well become the reality of the 21(st) century. Though the transport of insulin through the lungs itself appears quite encouraging, potential problems concerning the formulation of a peptide like insulin in the form of an aerosol seem to be the most challenging. Stability aspects, stringent control of Mass Median Aerodynamic Diameter, antigenicity, insulin losses due to the device and impaction, sedimentation and diffusion in the nonabsorptive areas of the airway system (especially in the oropharynx) emerge as major concerns. This is in addition to the problems of lack of reproducibility of dose delivery by an inhaler where individual variations due to inspiratory differences and method of use of device come into play. Lung diseases and smoking may alter lung mechanisms and dose alterations are to be studied in such cases. Though almost equally effective, if not more, than the subcutaneous insulin route, even with proved short-term efficacy, insulin delivery through lungs is a potential but not a wholly proven means for blood glucose control.

Study of forced degradation behavior of enalapril maleate by LC and LC-MS and development of a validated stability-indicating assay method.

In the present study, comprehensive stress testing of enalapril maleate was carried out according to ICH guideline Q1A(R2). The drug was subjected to acid (0.1N HCl), neutral and alkaline (0.1N NaOH) hydrolytic conditions at 80 degrees C, as well as to oxidative decomposition at room temperature. Photolysis was carried out in 0.1N HCl, water and 0.1N NaOH at 40 degrees C. Additionally, the solid drug was subjected to 50 degrees C for 60 days in a dri-bath, and to the combined effect of temperature and humidity, with and without light, at 40 degrees C/75% RH. The products formed under different stress conditions were investigated by LC and LC-MS. The LC method that could separate all degradation products formed under various stress conditions involved a C18 column and a mobile phase comprising of ACN and phosphate buffer (pH 3). The flow rate and detection wavelength were 1 ml min(-1) and 210 nm, respectively. The developed method was found to be precise, accurate, specific and selective. It was suitably modified for LC-MS studies by replacing phosphate buffer with water, where pH was adjusted to 3.0 with formic acid. The drug showed instability in solution state (under acidic, neutral, alkaline and photolytic stress conditions), but was relatively stable in the solid-state, except formation of minor products under accelerated conditions. Primarily, maximum degradation products were formed in acid conditions, though the same were also produced variably under other stress conditions. The LC-MS m/z values and fragmentation patterns of two of the five products matched with enalaprilat and diketopiperazine derivative, previously known degradation products of enalapril. Also, m/z value of another product matched with an impurity listed in the drug monograph in European Pharmacopoeia. Rest two were hitherto unknown degradation products. The products were characterized through LC-MS fragmentation studies. Based on the results, a more complete degradation pathway for the drug could be proposed.