Assessment of the Inter-Batch Variability of Microstructure Parameters in Topical Semisolids and Impact on the Demonstration of Equivalence
Víctor Mangas-Sanjuán,
María Pleguezuelos-Villa,
Matilde Merino-Sanjuán,
Mª Jesús Hernández,
Amparo Nácher,
Alfredo García-Arieta,
Daniel Peris,
Irene Hidalgo,
Lluís Soler,
Marta Sallan,
Virginia Merino
Affiliations
Víctor Mangas-Sanjuán
Departamento de Farmacia y Tecnología Farmacéutica y Parasitología, Facultad de Farmacia, Universitat de València, Av. Vicente Andrés Estellés s/n, Burjassot, 46100 Valencia, Spain
María Pleguezuelos-Villa
Departamento de Farmacia y Tecnología Farmacéutica y Parasitología, Facultad de Farmacia, Universitat de València, Av. Vicente Andrés Estellés s/n, Burjassot, 46100 Valencia, Spain
Matilde Merino-Sanjuán
Departamento de Farmacia y Tecnología Farmacéutica y Parasitología, Facultad de Farmacia, Universitat de València, Av. Vicente Andrés Estellés s/n, Burjassot, 46100 Valencia, Spain
Mª Jesús Hernández
Departament de Fisica de la Terra i Termodinàmica, Universitat de València, Vicente Andrés Estelles s/n. Burjassot, 46100 Valencia, Spain
Amparo Nácher
Departamento de Farmacia y Tecnología Farmacéutica y Parasitología, Facultad de Farmacia, Universitat de València, Av. Vicente Andrés Estellés s/n, Burjassot, 46100 Valencia, Spain
Alfredo García-Arieta
División de Farmacología y Evaluación Clínica, Departamento de Medicamentos de Uso Humano, Agencia Española de Medicamentos y Productos Sanitarios, Calle Campezo 1, Ed 8, 28022 Madrid, Spain
Daniel Peris
Pharmacokinetics and Clinical Affairs Department, Strategy and Development Area, Kern Pharma S.L., Calle Venus 72, Terrassa, 08228 Barcelona, Spain
Irene Hidalgo
Pharmacokinetics and Clinical Affairs Department, Strategy and Development Area, Kern Pharma S.L., Calle Venus 72, Terrassa, 08228 Barcelona, Spain
Lluís Soler
Formulation and Late Scale Development Department, Strategy and Development Area. Kern Pharma S.L., Calle Venus 72, Terrassa, 08228 Barcelona, Spain
Marta Sallan
Formulation and Late Scale Development Department, Strategy and Development Area. Kern Pharma S.L., Calle Venus 72, Terrassa, 08228 Barcelona, Spain
Virginia Merino
Departamento de Farmacia y Tecnología Farmacéutica y Parasitología, Facultad de Farmacia, Universitat de València, Av. Vicente Andrés Estellés s/n, Burjassot, 46100 Valencia, Spain
Demonstration of similar microstructure is essential for demonstrating the equivalence of generic topical products since the microstructure of semisolids may affect the drug release. The objective of this study was to compare the microstructure-defining physical parameters of different batches of a reference ointment containing calcipotriol and betamethasone (Daivobet 50 µg/0.5 mg/g) in order to define the acceptance range that allows concluding equivalence between these batches. Being batches of the same reference product, they are expected to be clinically equivalent and possess similar microstructure. The 90% confidence intervals for the test/reference ratio of these physical parameters were calculated with parametric and non-parametric approaches. Both methods conclude that equivalent microstructure between batches cannot be demonstrated with a reasonable sample size when the acceptance range was set at ±10%, since several physical parameters exhibit inter-batch variability >10%. An acceptance range of ±10% is therefore too strict to conclude equivalence in the microstructure of semisolid dosage forms, given the inter-batch variability observed between batches of the reference product. A wider fixed acceptance range or an acceptance range widened based on the inter-batch variability of the reference product would be advisable.
