Alginate as a diphase solid dispersion carrier to enhance solubility
Abstract
The objective of this study was to explore the feasibility of using alginate as a promising diphase solid dispersion carrier to enhance dissolution rate of BCS II drugs with improved stability. Taking lovastatin and indomethacin as model drugs, solvent evaporation method was used to prepare solid dispersions. The drug/polymer compatibility was predicted by Hansen solubility parameter and the drug/polymer ratio was screened based on dissolution study, drug existing state in solid dispersion was characterized by DSC and XRPD. Accelerated stability of the solid dispersion was assessed and compared with that of HPMCAS based system. Phase behavior of the solid dispersion before and after stability study was characterized using polar microscope and Raman mapping. It was found that the optimal drug/alginate ratio was drug dependent and drug existing state was related to drug/alginate miscibility. Stability studies revealed that alginate improved the stability of solid dispersions regardless of drug existing state and a better stability was obtained compared to HPMCAS based system. Raman mapping and SEM study revealed that micro phase separation of solid dispersion was the main reason for the slight decrease in drug dissolution after accelerating experiment. In conclusion, alginate can be used as a promising diphase solid dispersion carrier with significantly improved dissolution rate and storage stability.
Conclusion
This study demonstrated that alginate can be used as a diphase solid dispersion carrier with significant improvement in drug dissolution and stability. The optimal drug/alginate ratio was drug type dependent. In alginate based solid dispersion, the drug existing state in alginate matrix was related to drug-alginate miscibility, which can be predicted by Hansen solubility parameter. Stability studies revealed that alginate improved the stability of solid dispersions regardless of drug existing state and a better stability was obtained compared to HPMCAS based systems. Raman mapping and SEM study revealed that phase separation in microstructure was the main reason for the decreased in-vitro release rate of accelerated lovastatin / alginate solid dispersions but this minor structure change caused no statistical influence on drug dissolution. In conclusion, alginate can be used a promising solid dispersion carrier for a wide range of drugs with preferable system stability.
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