Spectrophotometric method for dissolution analysis of pioglitazone from capsules

Pioglitazone, an anti-diabetic molecule have been analyzed from a marketed capsule consisting of glimepiride and pioglitazone using spectrophotometric method. The method was developed at 270 nm using 0.1 N HCl as diluent. The method was found to be highly specific for pioglitazone in presence of glimepiride and other constituents of the capsule. The developed method is simple, precise, robust and stands validated as per ICH guidelines.


Introduction
Pioglitazone is a diabetes drug (thiazolidinedione-type, also called "glitazones") used along with a proper diet and exercise program to control high blood sugar in patients with type 2 diabetes.It works by helping to restore your body's proper response to insulin, thereby lowering your blood sugar.
Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems.Proper control of diabetes may also lessen your risk of a heart attack or stroke.
Pioglitazone is used either alone or in combination with other diabetes medications (such as metformin or a sulfonylurea such as glyburide).

Chemicals
Hydrochloric acid AR grade and Purified water were procured from Merck India Pvt Ltd.

Standard solution preparations
Weigh pioglitazone HCl equivalent to 30 mg of pioglitazone in 1000 ml volumetric flask.Add 300 ml of methanol to the flask, sonicate, cool and make the content of the flask to 1000 ml using 0.1 N HCl.

Sample solution
Weigh powdered pellets accurately equivalent to 30 mg of pioglitazone in 1000 ml volumetric flask.Add about 300 ml of methanol, sonicate for 10 minutes.Add about 500 ml 0.1 N HCl and sonicate for about 20 minutes.Cool and make up the volume with 0.1N HCl.Filter the solution through 0.45  membrane filter.Determine the absorbance of the standard and test solution at 270 nm using 0.1 N HCl as blank.

Dissolution conditions
The dissolution was carried out in vitro.In each of the 6 vessels, place 900 ml of dissolution medium and allow to equilibrate to 37 °C.Immerse the paddle, put weighed tablet in each of the jars & start rotation at 75 RPM.At the end of the 30 min, 1, 4 and 8 th hour of rotation, withdraw with a pipette 10 ml of solution.Replace the withdrawn solution with 10 ml of dissolution medium.Dilute the aliquots of 30 min as 5 ml to 10 ml with diluting solvent & filter through 0.45 µ filter.

System Suitability
System suitability tests were carried out to ensure reproducibility of the equipment.The test was carried out by measuring of standard solution in 5 replicates.

Precision
Precision is the measure of either the degree of reproducibility or of repeatability of the analytical method under normal conditions.The test were carried out with 6 assay samples in replicate of standard solutions.

Linearity
The linearity of an analytical procedure is its ability to obtain test results which are directly proportionally to the concentration of analyte in the sample.
Linearity of pioglitazone is carried out in the range 1.25 g/ml to 7.5 g/ml.

System suitability
The method was found to be suitable for the proposed analysis as the relative standard deviation of average peak area of system suitability test is not more than 2.0 %.

Precision
Precision measured at all level was within the acceptable criterion of NMT 6.0 % indicating the efficiency of method for the proposed analysis.

Conclusion
The method developed for analysis of pioglitazone in presence of Glimepiride and other matrix stands to be validated as per ICH guidelines.The limits for all the parameters were met with no interference from the placebos of the capsules and hence this method can be used as quality control tool for analysis of the capsules.

Table 1
Dissolution parameters of the experiment