title: Comparison of spray freeze drying and the solvent evaporation method for preparing solid dispersions of baicalein with Pluronic F68 to improve dissolution and oral bioavailability.
abstract: The objective of this study was to prepare solid dispersions consisting of baicalein and a carrier with a low glass transition/melting point (Pluronic F68) by spray freeze drying (SFD). We compared these powders to those produced from the conventional solvent evaporation method. In the SFD process, a feeding solution was atomized above the surface of liquid nitrogen following lyophilization, which resulted in instantaneously frozen microparticles. However, solid dispersions prepared by the solvent evaporation method formed a sticky layer on the glass flask with crystalline baicalein separated out from the carrier. The powder samples were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), surface area measurement, differential scanning calorimetry, and Fourier transform infrared spectrometry. SEM and PXRD results suggested that the majority of baicalein in the SFD-processed solid dispersion was in the amorphous state, which has a higher specific surface area than pure baicalein. However, the majority of baicalein was recrystallized in the solid dispersion at the same composition prepared by the solvent evaporation method, which showed a similar dissolution rate to the physical mixture. SFD product was physically and chemically stable after being stored at 40 °C with low humidity for 6 months. After enzyme hydrolysis, baicalein in the SFD product displayed a significantly shorter T (max) and higher C (max) than pure baicalein after oral dosing. The relative bioavailability of the SFD product versus pure baicalein determined by comparing the AUC(0-12) was 233%, which demonstrated the significantly improved oral bioavailability of baicalein produced by the SFD technique.
authors.affiliation: Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
authors.forename: Xiuqiong
authors.initials: X
authors.lastname: He
authors.forename: Lixia
authors.initials: L
authors.lastname: Pei
authors.forename: Henry H Y
authors.initials: HH
authors.lastname: Tong
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D004304:Dosage Forms; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D045703:Emulsifying Agents / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D044950:Flavanones / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D005612:Freeze Drying; D006801:Humans; D008297:Male; D020442:Poloxamer / Q000737:chemistry*; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D004304:Dosage Forms; D045703:Emulsifying Agents; D005079:Excipients; D044950:Flavanones; D011208:Powders; D012997:Solvents; D020442:Poloxamer; C006680:baicalein