TY - JOUR
T1 - QbD based development and evaluation of topical microemulsion-based hydrogel against superficial fungal infections
AU - Choi, Du Hyung
AU - Kim, Yun Sik
AU - Kim, Dae Duk
AU - Jeong, Seong Hoon
N1 - Publisher Copyright:
© 2018, The Korean Society of Pharmaceutical Sciences and Technology.
PY - 2019/1/15
Y1 - 2019/1/15
N2 - Even though quality by design is becoming an essential method for a development of pharmaceutical product, limited studies have been performed to develop topical drug delivery systems. The aim of this study was to apply a quality by design approach to achieve predictable critical quality attributes of a microemulsion-based hydrogel formulation (MBH) contained itraconazole (ITZ). The control and response factors were determined based on a risk assessment with primary knowledge. Benzyl alcohol (x 1 ), Cremophor® EL (x 2 ), and Transcutol® P (x 3 ) were screened out and selected as oil, surfactant, and co-surfactant, respectively. A D-optimal mixture design was used for optimizing the formulation with desirable characteristics. To obtain an optimal formulation, globule size was minimized, while viscosity and pH were in the range of 500–700 cps × 10 3 and pH 5–7, respectively. The optimal formulation was characterized by globule size, pH, rheological properties, in vitro permeability, and drug release simulation with a mathematical model. The optimal formulation was stable when stored at 40 °C/75% relative humidity and at ambient temperature for 6 months. Therefore, this study suggests that the optimized MBH formulation may present a better alternative over conventional ITZ delivery systems against superficial fungal infections.
AB - Even though quality by design is becoming an essential method for a development of pharmaceutical product, limited studies have been performed to develop topical drug delivery systems. The aim of this study was to apply a quality by design approach to achieve predictable critical quality attributes of a microemulsion-based hydrogel formulation (MBH) contained itraconazole (ITZ). The control and response factors were determined based on a risk assessment with primary knowledge. Benzyl alcohol (x 1 ), Cremophor® EL (x 2 ), and Transcutol® P (x 3 ) were screened out and selected as oil, surfactant, and co-surfactant, respectively. A D-optimal mixture design was used for optimizing the formulation with desirable characteristics. To obtain an optimal formulation, globule size was minimized, while viscosity and pH were in the range of 500–700 cps × 10 3 and pH 5–7, respectively. The optimal formulation was characterized by globule size, pH, rheological properties, in vitro permeability, and drug release simulation with a mathematical model. The optimal formulation was stable when stored at 40 °C/75% relative humidity and at ambient temperature for 6 months. Therefore, this study suggests that the optimized MBH formulation may present a better alternative over conventional ITZ delivery systems against superficial fungal infections.
KW - Itraconazole
KW - Microemulsion-based hydrogel
KW - Quality by design
KW - Risk assessment
KW - Topical drug delivery
UR - http://www.scopus.com/inward/record.url?scp=85054731294&partnerID=8YFLogxK
U2 - 10.1007/s40005-018-0386-4
DO - 10.1007/s40005-018-0386-4
M3 - Article
AN - SCOPUS:85054731294
SN - 2093-5552
VL - 49
SP - 87
EP - 103
JO - Journal of Pharmaceutical Investigation
JF - Journal of Pharmaceutical Investigation
IS - 1
ER -