Development of PVP/PEG mixtures as appropriate carriers for the preparation of drug solid dispersions by melt mixing technique and optimization of dissolution using artificial neural networks

作者：Barmpalexis Panagiotis; Koutsidis Ioannis; Karavas Evangelos; Louka Dimitra; Papadimitriou Sofia A; Bikiaris Dimitrios N^*

来源：European Journal of Pharmaceutics and Biopharmaceutics, 2013, 85(3): 1219-1231.

DOI：10.1016/j.ejpb.2013.03.013

• Melt mixing
• Solid dispersions
• Tibolone
• PVP/PEG
• Polymer blends
• Artificial neural networks

The effect of plasticizer%26apos;s (PEG) molecular weight (MW) on PVP based solid dispersions (SDs), prepared by melt mixing, was evaluated in the present study using Tibolone as a poorly water soluble model drug. PEGs with MW of 400, 600, and 2000 g/mol were tested, and the effect of drug content, time and temperature of melt mixing on the physical state of Tibolone, and the dissolution characteristics from SDs was investigated. PVP blends with PEG400 and PEG600 were completely miscible, while blends were heterogeneous. Furthermore, a single T-g recorded in all samples, indicating that Tibolone was dispersed in a molecular lever (or in the form of nanodispersions), varied with varying PEG%26apos;s molecular weight, melt mixing temperature, and drug content, while FTIR analysis indicated significant interactions between Tibolone and PVP/PEG matrices. All prepared solid dispersion showed long-term physical stability (18 months in room temperature). The extent of interaction between mixture components was verified using Fox and Gordon-Taylor equations. Artificial neural networks, used to correlate the studied factors with selected dissolution characteristics, showed good prediction ability.

• 出版日期2013-11