Effect of carrier material on the thermodynamic properties and recrystallization kinetics of andrographolide-solid dispersion.

OBJECTIVES: This work investigated the effect of the lipophilic long carbon chain of carrier material on the thermodynamic properties and the recrystallization kinetics of solid dispersion (SD). METHODS: The thermodynamic properties and recrystallization kinetic parameters of amorphous andrographolide (AG)-PEG8000 laurate (SM12)-SD, AG-PEG8000 palmitate (SM16)-SD and AG-PEG8000 behenate (SM22)-SD were determined and calculated by differential scanning calorimetry combining AGV equation and Avrami equation. KEY FINDINGS: From AG-SM12-SD to AG-SM22-SD with the increase of the carbon chain length of carrier material, the glass transition temperature, the maximum relaxation enthalpy and the mean relaxation time of SD increased at first and then decreased; the isothermal crystallization rate constants at different temperatures and non-isothermal crystallization rate constants at different heating rates of SD showed a trend of decreasing at first and then increasing. CONCLUSIONS: Increasing the carbon chain length of polyethylene glycol fatty acid ester can improve the space-limiting effect of the carrier material on the AG molecule, but the carbon chain length of carrier was not the longer the better. SM16 had the appropriate spatial scale, which better limited the molecular mobility of AG in SD, so AG-SM16-SD has better thermodynamic stability and recrystallization kinetic stability.

Effect of carrier materials on the properties of the andrographolide solid dispersion

Abstract In the work the andrographolide (AG)-solid dispersions (SDs) were prepared by the spray-drying method, using polyethylene glycol 8000 (PEG8000), Poloxamer188, polyvinylpyrrolidone K30 (PVPK30), Soluplus® as carrier materials. The effect of different polymers as carrier materials on the properties of the AG-SDs were studied. The results showed obvious differences in intermolecular interaction, thermal stability, drug state, powder properties, dissolution behavior, and so on of AG-SDs prepared using different polymers as carrier materials. AG-PEG8000-SD was a partial-crystalline and partial-amorphous powder with smaller surface area and pore volume, but it was easy to wetting and did not swell in contact with dissolved medium. AG-Soluplus®-SD was completely amorphous powder with larger specific surface area and pore volume, but it swelled in contact with water. Therefore, the dissolution profile of AG in AG-PEG8000-SD was similar to that in AG-Soluplus®-SD. Soluplus® and PEG8000 were suitable polymers to design AG-SDs, considering both physicochemical properties and dissolution behaviors. The results of this reseach showed that when selecting carrier materials for SD, we should not only consider the state of drugs in SD and the powder properties of SD, but also consider whether there is swelling when the carrier materials are in contact with the dissolution medium.

Improvement of the bioavailability of curcumin by a supersaturatable self nanoemulsifying drug delivery system with incorporation of a hydrophilic polymer: in vitro and in vivo characterisation.

OBJECTIVES: The current study was focused on preparing curcumin (CUR) supersaturated self-nano-emulsion (PI-CUR-SNEDDS) using hydrophilic polymer and to study the influence of polymer precipitation inhibitor on the physicochemical and biopharmaceutical properties of the PI-CUR-SNEDDS. METHODS: PI-CUR-SNEDDS were prepared using hydrophilic polymer in order to maintain the supersaturation of CUR in nano-emulsion solution, artificial gastrointestinal fluid (AGF), and the precipitates formed, and characterised by in vitro dispersion tests, in vitro intestinal absorption and in vivo pharmacokinetic and compared with CUR-SNEDDS. KEY FINDINGS: PI-CUR-SNEDDS prepared with 2% hydroxypropyl methylcellulose 55-60 (HPMC55-60) as precipitation inhibitor (PI) significantly improved the viscosity, physical stability and CUR's equilibrium solubility of nanoemulsion. HPMC55-60 and CUR interact in AGF through intermolecular interactions, form hydrogen bonds, and produce amorphous precipitates. Compared with CUR-SNEDDS, the proportion of CUR in the hydrophilic phase increased by about 3-fold, and apparent permeability coefficient (Papp) in duodenum, jejunum, ileum, and colon increased by 2.30, 3.65, 1.54 and 2.08-fold, respectively, and the area under the plasma concentration-time curve0-12h of PI-CUR-SNEDDS also increased by 3.50-fold. CONCLUSIONS: Our results suggested that HPMC55-60 maintained the CUR supersaturation state by forming hydrogen bonds with CUR, increasing the solution's viscosity and drug solubilisation, thus improving the absorption and bioavailability of CUR.

Effect of Carrier Lipophilicity and Preparation Method on the Properties of Andrographolide⁻Solid Dispersion.

Solid dispersion (SD) is a useful approach to improve the dissolution rate and bioavailability of poorly water-soluble drugs. This work investigated the effects of carrier material lipophilicity and preparation method on the properties of andrographolide (AG)⁻SD. The SDs of AG and the carrier materials, polyethylene glycol (PEG) and PEG grafted with carbon chains of different length (grafted PEG), have been prepared by spray-drying and vacuum-drying methods. In AG⁻SDs prepared by the different preparation methods with the same polymer as carrier material, the intermolecular interaction, 5% weight-loss temperature, the melting temperature (Tm), surface morphology, crystallinity, and dissolution behavior have significant differences. In the AG⁻SDs prepared by the same spray-drying method with different grafted PEG as carrier material, Tm, surface morphology, crystallinity, and dissolution behavior had little difference. In the AG⁻SDs prepared by the same vacuum-drying method with different grafted PEG as carrier material, the crystallinity and Tm decreased, and the dissolution rate of AG increased with the increase of grafted PEG lipophilicity. The preparation method has an important effect on the properties of SD. The increase of carrier material lipophilicity is beneficial to the thermal stability of SD, the decrease of crystallinity and the increase of dissolution rate of a poorly water-soluble drug in the SD.