RESUMEN
Most of the insulin formulations in clinical use contain phenol, meta-cresol or both as excipients. These excipients in insulin preparations provide stability and have antimicrobial properties. However, they are reported to be associated with undesirable side-effects especially localised allergic reactions. Amount of excipients injected per unit dose of insulin is a major determining factor in causation of these reactions. This review discusses the excipients in different insulin formulations available in India with potential of precipitating undesirable effects and the use of concentrated insulins to reduce these complications. To avoid the detrimental effects associated with excipients, removal of preservatives or use of insulin preparations devoid of excipients can be an option. Besides these approaches, one approach that can be considered is the use of concentrated insulin to reduce the volume of insulin dose and thereby the excipients. Concentrated insulins address the high insulin requirements of the growing population of patients with type 2 diabetes who require higher insulin doses. Concentrated insulins help in reduction of dose volume as well as amount of excipients injected per unit dose of insulin. U200 (concentrated r-DNA Human Insulin Premix 30/70-200 IU/ml) can be advantageous with better absorption from smaller quantity injected, lesser variability in absorption, lesser pain and discomfort due to smaller quantity, lesser chances of hypoglycaemia all of which can lead to better patient compliance. Thus, concentrated insulin U200 can be one of the alternatives to prevent/reduce clinical complications with excipients in insulins.
RESUMEN
Rapid and sensitive reversed phase high performance liquid chromatography (RP-HPLC) and ultra performance liquid chromatography (RP-UPLC) method with UV detection has been developed and validated for of parathyroid hormone (PTH)in presence of meta-cresol as a stabilizer in a pharmaceutical formulation.Chromatography was performed with phase containing 0.1％ Trifluoroacetic acid (TFA) in MilliQ water and 0.1％ TFA in acetonitrile with gradient and flow rate at 0.3 mL/min for HPLC and 0.4 mL/min for UPLC.Quantification was accomplished with internal reference standard (qualified against innovator product and National for for Biological Standards and Control (NIBSC) standard).The methods were validated for linearity (correlation coefficient=0.99),range,accuracy,precision and robustness.Robustness was confirmed by considering three factors; mobile phase composition,column temperature and flow rate/age of mobile phase.Intermediate precision was confirmed on different equipments,different columns and on different days.The relative standard deviation (RSD) (＜2％ for RP-HPLC and ＜1％ for UPLC n=30) indicated a good precision.Retention time was found about 17min and 2min by HPLC and UPLC methods,respectively.Both methods are simple,highly sensitive,precise and accurate and have the potential of being useful for routine quality control.