Quality by Design: Development of the Quality Target Product Profile (QTPP) for Semisolid Topical Products

Abstract

In recent years, the “quality by design” (QbD) approach has been used for developing pharmaceutical formulations. This is particularly important for complex dosage forms such as topical semisolid products. The first step for developing a product using this efficient approach is defining the quality target product profile (QTPP), a list of quality attributes (QAs) that are required to be present in the final product. These quality attributes are affected by the ingredients used as well as manufacturing procedure parameters. Hence, critical material attributes (CMAs) and critical process parameters (CPPs) need to be specified. Possible failure modes of a topical semisolid product can be determined based on the physiochemical properties of ingredients and manufacturing procedures. In this review, we have defined and specified QTPP, QAs, CMAs and CPPs that are required for developing a topical semisolid product based on the QbD approach.

Rheology by Design: A Regulatory Tutorial for Analytical Method Validation

“…As such, a given critical stress value (yield stress) is required for the formulation to start to flow. Below this point, the products majorly present elastic properties; on the contrary, above this endpoint, the material predominantly displays a plastic flow [ 10 ].…”

“…For instance, the formulation spreadability and bioadhesion to the skin are highly affected by viscoelastic properties. As patients directly apply topical formulations on their skin, these sensorial attributes are of outmost importance to assure patient acceptability and, therefore, treatment compliance [ 10 , 11 , 12 , 13 ].…”

“…A detailed rheological characterization provides valuable insight on why products may settle or separate over shelf life. Furthermore, this tool can determine if there is a significant impact on product microstructure whenever dispensed from a packaging tube/dosing pump [ 10 ]. Biopharmaceutical characteristics, such as drug release and permeation are also reliant on the formulation rheological profile [ 13 , 14 ].…”

“…Biopharmaceutical characteristics, such as drug release and permeation are also reliant on the formulation rheological profile [ 13 , 14 ]. For all the above reasons, rheology behaviour is a key quality attribute within a target product profile of semisolid formulations [ 5 , 10 , 15 ].…”

The Implications of Regulatory Framework for Topical Semisolid Drug Products: From Critical Quality and Performance Attributes towards Establishing Bioequivalence

“…For immiscible phase formulations, such as creams, globule size may directly affect the product stability and performance. Poor control of globule size may result in phase separation, creaming or cracking of the semisolid products [ 30 ]. On the other hand, the alterations in globule size among the prospective generic and reference semisolid drug products may impact the amount of drug entrapped in the globule, its partitioning between the oil and water phase, and consequently, drug release and partitioning into the skin [ 30 ].…”