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

Guowei Zhao,Yashao Chen,Zhenggen Liao,Shoude Zhang,Qingyun Zeng,Youquan Zhong,Liquan Ou,Changhao Wang

doi:10.3390/pharmaceutics11020074

Guowei Zhao, Yashao Chen + Show 6 more

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https://doi.org/10.3390/pharmaceutics11020074

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Abstract

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.

Highlights

In the biopharmaceutics classification system, poorly water-soluble and highly permeable compounds mostly belong to Class II
The Fourier Transform Infrared Spectroscopy (FT-IR) spectra showed the original AG intermolecular hydrogen bond was destroyed in the as-prepared Solid dispersion (SD), which was beneficial to the dissolution of AG
In the AG–SDsPEpGre40p0a0rheadd tbhye wthorestseaffmecet onvaimcupuromvi-ndgrtyhiendgissmoluettihoondratwe oitfhAGd.ifferent grafted polyethylene glycol (PEG) as carrier materials, the crystallinity and Tm decreased, and the dissolution rate of AG increased with the increase of grafted PEG lipophilicity

Summary

Introduction

In the biopharmaceutics classification system, poorly water-soluble and highly permeable compounds mostly belong to Class II. These drugs are poorly soluble with either slow or limited release resulting in solubility or dissolution rate-limited absorption. These drugs have high permeability, but their oral bioavailability is generally low [1–3]. Solid dispersion (SD) is one of the most effective approaches to improve the solubility, dissolution rate, and the bioavailability of poorly water-soluble drugs [4–7]. In SD, the drug can be dispersed as separate molecules, amorphous particles, or crystalline particles, which can reduce the energy barrier associated with dissolution. The interaction between drug and carrier can act to inhibit agglomeration or crystallization

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