title: Rational and precise development of amorphous polymeric systems with dapsone by response surface methodology.
abstract: This work aimed to design dapsone (DAP) amorphous Polymeric Dispersions (PD) using design of experiments (DoE) and response surface methodology (RSM) as optimization tools in order to tailor the biopharmaceutical properties toward its oral delivery. A two-factor, three-level (3(2)) statistical design was implemented to study the influence of input variables (amount of PVP K30 and Pluronic F68) on the equilibrium solubility of DAP of the physical mixture (PM), kneaded (KN) and freeze dried (FD) PDs. Through the analysis, it was found that equilibrium solubility of DAP was improved with increasing of PVP K30, mainly for FD PDs, but decreased with increasing Pluronic F68 concentration. XRD and FTIR spectrum revealed the amorphous characteristic of FD PDs and SEM confirmed the homogeneity of the system leading to enhanced surface area and consequent dissolution rate. The in vitro dissolution rate of PDs was significantly faster compared to DAP and PM, and all the similarity factors (f2) were below 50, demonstrating the differences on the dissolution profiles. The results established the effectiveness of PDs for improvement of dissolution and solubility of DAP and the success in the implementation of DoE and RSM as QbD tools in the design of PDs.
authors: UCIBIO, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
authors: Luíse L
authors: LL
authors: Chaves
authors: UCIBIO, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
authors: Alexandre C C
authors: AC
authors: Vieira
authors: Laboratório de Tecnologia Farmacêutica, Departamento de Ciêncas do Medicamento, Faculdade de Farmácia, Universidade do Porto, Portugal.
authors: Domingos
authors: D
authors: Ferreira
authors: I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Portugal; CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde and Instituto Universitário de Ciências da Saúde, 4585-116 Gandra PRD, Portugal.
authors: Bruno
authors: B
authors: Sarmento
authors: UCIBIO, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal. Electronic address: shreis@ff.up.pt.
authors: Salette
authors: S
authors: Reis
mesh_terms: D002626:Chemistry, Pharmaceutical; D003622:Dapsone / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D003622:Dapsone
keywords: Design of experiments; Freeze drying; Kneading; PVP K30; Quality by design