Quality by design approach to the development of transdermal patch systems and regulatory perspective

Background Although the quality by design (QbD) approach is widely used to develop pharmaceutical products and to consistently ensure and improve product quality, studies on this approach for transdermal patch systems (TPSs) are limited. Due to the various advantages such as reducing invasiveness, avoiding first-pass metabolism, and improving convenience and compliance, the TPS is an appealing dosage form for pharmaceutical product development. Area covered This study investigated the quality target product profile (QTPP), critical quality attributes (CQAs), and critical material attributes (CMAs) of a TPS for QbD. The justification for this approach is presented, comparing standards from regulatory agencies and some implementations of CQAs and CMAs with data from various related literature and pharmacopeias. The QTPP elements were generally as follows: dosage form and strength, shelf life, pharmacokinetics, and drug product quality attributes. The CMAs were as follows: drug (partition coefficient, particle size and shape, polymorph, melting point, solubility, pH, and ionization), pressure-sensitive adhesive (PSA) (viscosity, adhesive type, cold flow, and molecular weight), and other excipients (permeation enhancers, crystallization inhibitors, rate-controlling membranes, and solvents). The CQAs were as follows: physicochemical tests (assay, moisture content, folding endurance, tensile strength, and water vapor permeation), adhesive properties tests (peel adhesion, tack, and shear adhesion), in vitro tests (drug release, drug permeation), impurities and degradation products of drug, and skin irritation test. Expert opinion This study suggests that a QbD approach to TPS development can reduce risk, improve product quality, and consistently produce quality results.