Force Degradation Study In Pharmaceutical Industry

 

Force Degradation Study In Pharmaceutical Industry

¨  Force Degradation Study also known as Stress testing is the study in which the Active Pharmaceutical Ingredients (APIs) or formulated products are subjected to extreme chemical or environmental conditions forcefully to determine its breakdown capacity and degradation kinetics.

¨  Force degradation study illustrate how the potential degradants can be detected.

¨  Force degradation study elucidate the degradation pathway of the drug product & formulation.

¨  International Conference on Harmonization (ICH) guideline ICHQ1A, ICHQ1B & ICHQ2B recommend Photo stability, Dry heat, Humidity, Oxidation & Acid Base hydrolytic conditions at which stress testing should be carried out.

¨  The temperature & humidity recommendation is 10◦c above the accelerated conditions i.e   ›50 ◦c and humidity ≥ 75%.

¨  Stress conditions study should be carried out on single batch during 3rd phase  of regulatory submission.

¨  A degradation of 5% to 20% is the acceptable range.

Recommended dose & Parameters of Forced Degradation Study

¨  Usually the stress testing or force degradation study is carried out at 1mg/ml concentration of drug, because there are more chances of degradation at higher concentrations.

¨  Photolysis

¨  Oxidation

¨   Acid Base hydrolysis

¨  Thermal Degradation

Photolysis

¨  Photo Stability: In photo stability stress testing the drug product should be exposed to UV+Visible light in a range of 200 to 800nm for 1.2 million lux hours that is approximately equal to 11.5 days.

¨  During this duration the intensity of light should not be less than 200 watt hours per sq meter.

Oxidative condition

¨  Oxidation: In oxidation stress study the most widely used oxidizing agent is hydrogen peroxide H2O2.

¨  Recommended concentration is vary from 0.1% to 3.0% that should be applied the drug product for 7 days at room temperature.

¨  However if degradation doesn’t occur higher temperature can be applied.

Thermal degradation

¨  Thermal degradation: Thermal degradation studies should be carried out at a high and intense temperature than recommended for accelerated conditions.

¨  Usually the study should be carried at a temperature in the range of 40◦C to 80◦C.

¨  Solid drug products should be exposed to dry and wet heat while liquid products should be exposed to dry heat only.

Acid Base Hydrolysis

¨  Acid Base hydrolysis: Acid Base hydrolysis is one of the main degradation parameters,

¨  In acid base degradation product or material is exposed to acid or base at wide range of pH.

¨  O.1M to 1M hydrochloric acid or sulphuric acid are used in acid hydrolysis.

¨  0.1M to 1M sodium hydroxide or potassium hydroxide are used in base hydrolysis.

¨  Some articles has recommended up 5M of hydrochloric acid, sulphuric acid, sodium hydroxide and potassium hydroxide.

¨  If the recommended drug agent or product is insoluble in the above said medium a co-slovent should be used to enhance solubility.

¨  Hydrolysis is usually carried out at room temperature but if degradation doesn’t occur then elevated temperature from 50 to 70 can be applied.

¨  Study should be carried out for 7 days after that sample should be neutralize with appropriate acid, base or buffer to stop further degradation.

Humidity

¨  Humidity: Stress testing regarding humidity can be carried out at conditions of 90% relative humidity.

Hydrolysis conditions table

Degradation type	Experimental conditions	Storage conditions	Sampling schedule (days)
Hydrolysis	Control API (no acid or base)	40◦c, 60◦c	1, 3, 5
	0.1M -1M HCl	40◦c, 60◦c	1, 3, 5
	0.1M – 1M NaOH	40◦c, 60◦c	1, 3, 5
	Acid control (no API)	40◦c, 60◦c	1, 3, 5
	Base control (no API)	40◦c, 60◦c	1, 3, 5
	pH 2, 4, 6, 8	40◦c, 60◦c	1, 3, 5

 

Oxidative conditions table

Degradation type	Experimetal conditions	Storage conditions	Sampling schedule (days)
Oxidation	0.1%- 3% H2O2	25◦c, 60◦c	1,3,5
	H2O2 control	25◦c, 60◦c	1,3,5
	Azobisisobutyronitrile (AIBN)	40◦c, 60◦c	1,3,5
	AIBN control	40◦c, 60◦c	1,3,5

 

Thermal conditions table

Degradation type	Experimental conditions	Storage conditions	Sampling schedule (days)
Thermal	Heat chamber	60◦c	1,3,5
	Heat chamber	60◦c/75% RH	1,3,5
	Heat chamber	80◦c	1,3,5
	Heat chamber	80◦c/75% RH	1,3,5
	Heat chamber	Room temperature	1,3,5

 

Photolytic conditions table

Degradation type	Experimental conditions	Storage conditions	Sampling schedule (days)
Photolytic	Light 1* ICH	NA	1,3,5
	Light 3* ICH	NA	1,3,5
	Light control	NA	1,3,5

Presented By

Muhammad Atif

PhD Scholar Pharmaceutical Sciences AWKUM

Manager QA Decent Pharma islamabad