Mixture experiment methods in the development and optimization of microemulsion formulations

Journal Article · Sat Jun 25 04:00:00 EDT 2011 · Journal of Pharmaceutical and Biomedical Analysis

DOI:https://doi.org/10.1016/j.jpba.2011.01.008· OSTI ID:1034976

Furlanetto, Sandra; Cirri, Marzia; Piepel, Gregory F; Mennini, Natascia; Mura, Paola

Microemulsion formulations represent an interesting delivery vehicle for lipophilic drugs, allowing for improving their solubility and dissolution properties. This work developed effective microemulsion formulations using glyburide (a very poorly-water-soluble hypoglycaemic agent) as a model drug. First, the area of stable microemulsion (ME) formations was identified using a new approach based on mixture experiment methods. A 13-run mixture design was carried out in an experimental region defined by constraints on three components: aqueous, oil, and surfactant/cosurfactant. The transmittance percentage (at 550 nm) of ME formulations (indicative of their transparency and thus of their stability) was chosen as the response variable. The results obtained using the mixture experiment approach corresponded well with those obtained using the traditional approach based on pseudo-ternary phase diagrams. However, the mixture experiment approach required far less experimental effort than the traditional approach. A subsequent 13-run mixture experiment, in the region of stable MEs, was then performed to identify the optimal formulation (i.e., having the best glyburide dissolution properties). Percent drug dissolved and dissolution efficiency were selected as the responses to be maximized. The ME formulation optimized via the mixture experiment approach consisted of 78% surfactant/cosurfacant (a mixture of Tween 20 and Transcutol, 1:1 v/v), 5% oil (Labrafac Hydro) and 17% aqueous (water). The stable region of MEs was identified using mixture experiment methods for the first time.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1034976
• Report Number(s): PNNL-SA-76828
• Journal Information: Journal of Pharmaceutical and Biomedical Analysis, Journal Name: Journal of Pharmaceutical and Biomedical Analysis Journal Issue: 4 Vol. 55
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
DESIGN
DISSOLUTION
EFFICIENCY
MICROEMULSIONS
MIXTURES
Microemulsion formulation
Mixture design
OPTIMIZATION
PHASE DIAGRAMS
SOLUBILITY
STABILITY
WATER
experimental design
optimization