Sensitivity Profiling of Solid Oral Doses

Blister Product Sensitivity of formulated drugs is often described qualitatively as highly sensitive or less sensitive based on the active ingredients properties. Therefore the difference in the sensitivity when changing formulations using the same active ingredients goes unnoticed. Formulation scientists would benefit if the small differences in the environmental sensitivity between the formulations were distinguishable giving them leads to optimize the formulation in terms of stability and other required properties. Often, a conventional stability study in the final packaging format is the only way to understand the sensitivity or stability of the product and leaves little or no opportunity for the formulator to optimize the formulation for better stability.Forced degradation studies are popular in the preformulation stage, but these are more focused on the impurity profiling for analytical method development and to develop the moisture absorption isotherms. Since these studies are concentrated on the ingredient properties, strengths of final formulation with respect to environmental stability is not determined or clearly distinguished in these studies. A new sensitivity profiling method has been developed which looks at the final formulation beyond the chemical stability and diagnoses the external reasons for the deterioration of the characteristic properties of the formulation which is essential to serve its purpose for the patients. It quantitatively evaluates the effect of the environmental parameters on the deterioration of the product and looks not only at its chemical/assay properties, but also various physical properties, such as drug release patterns and the interaction with packaging materials. This method quantifies the various sensitivity parameters of the formulation in an absolute scale of 0 to 10 based on the results of forced degradation experiments and thus gives the formulators a tool to measure the strength of their formulation in a scientific scale prior to finalizing it.Shortcomings of the conventional forced degradation /stress testing studiesThere are no detailed regulatory guidelines that describe how to carry out stress testing and it is often used synonymously with accelerated testing. This is due to the fact that the purpose of both stress testing and accelerated stability testing is to create a path for the product degradation and not to diagnose the causes for degradation. These two tests should be distinctly different. For identifying the factors affecting degradation, it is essential to define the testing protocols in such a way that to be able to understand the cause and effect aspects while accelerating the degradation process, it is only necessary to increase the severity of the parameters causing deterioration. In fact the purpose of the accelerated stability studies is to fasten the degradation, while that of stress testing should be the understanding the degradation process.The ICH defines accelerated testing as: Studies designed to increase the rate of chemical degradation or physical change of an active substance or drug product using exaggerated storage conditions as part of the formal, definitive, storage program. These data, in addition to long-term stability studies, may also be used to assess long-term chemical effects at non-accelerated conditions and to evaluate the impact of short-term excursions outside label-storage conditions such as might occur during shipping. Results from conventional accelerated studies are not always predictive of physical change. Stress testing is defined as: Studies undertaken to elucidate the intrinsic stability of the drug substance. Such testing is part of the development strategy and is normally carried out under more severe conditions than those used for accelerated testing.From a regulatory perspective, stress testing or forced degradation studies are a scientific tool to understand stability issues, and are inherently predictive in nature. Accelerated testing on the other hand is purely focused on whether or not stability is maintained at a pre-set condition.Sensitivity profiling through BilcareOptimaTMIt is essential to look at a formulation beyond the chemical aspects to ensure the efficacy of the product to the patient. As an example, a chemically stable product without any visual degradation over time or due to exposure to humidity/light condition is normally categorized as a stable product. However this product may not be effective, if its drug release property is affected by any environmental factor or if there is a tendency to liberate gases on storage. In conventional stability studies these factors are not studied critically, rather it is only assessed whether the determined values are within the specified limit at the end of the study.BilcareOptima tests the final dosage form under a range of different conditions, aimed at determining the critical characteristics that affects the stability and quantify its severity on a scientific scale.Three batches of dosage forms are studied under various environmental conditions for more precise understanding and the effect of the following parameters:Hygroscopicity - Dehydration - Physical degradation - Chemical degradation - Drug release pattern - Hardness - Photo sensitivity as a function of RH and Temp - Gas liberation tendency - Product packaging material interaction. - Dimensional aspects.Each of the properties are investigated for the influence of various environmental parameters and its impact on the stability and efficacy of the product. These evaluations lead to exact determination of the critical property of the given oral dosage form and influencing environmental parameter. It is further used to determine the threshold values and sensitivity scaling using a mathematical model. This information is used to predict the product behavior at different climatic condition and decide on the storage conditions, protection needs and shelf life.The sensitivity scale gives a quantitative picture about the product sensitivity towards environmental parameters property wise. The property wise sensitivity data is allowed to come down to the most critical property.This also helps us to understand batch to batch and formulation to formulation variations and can be used to differentiate the two.