Purpose: The object of this study is to investigate the influence of hydroxypropylmethylcellulose (HPMC) and sodium lauryl sulfate (SLS) on the aqueous solubility, dissolution and crystallinity of poorly water-soluble sirolimus in solvent-evaporated solid dispersion.
Methods: For selection of proper carriers, the effect of polymers and surfactants on the solubility of sirolimus was investigated. Amongst the carriers tested, HPMC and SLS gave most improved drug solubility, resulting in selecting them as a proper polymer and surfactant, respectively. Numerous solvent-evaporated solid dispersions were prepared with various ratios of sirolimus, SLS and HPMC using the spray-drying technique. Their aqueous solubility, dissolution and crystallinity were evaluated.
Results: All generated formulations significantly enhanced the aqueous solubility and dissolution of drug as compared with the sirolimus powder. As the amount of HPMC and SLS were increased, aqueous solubility and dissolution in solvent-evaporated solid dispersion was increased. Moreover, all the solvent-evaporated solid dispersions provided the amorphous form of drug. Among the solvent-evaporated solid dispersions evaluated, the solid dispersion composed of sirolimus, HPMC and SLS at the weight ratio of 1:10:0.1 had most improved aqueous solubility (350.83 ± 11.92 vs. 0.003 ± 0.001 μg/mL) and dissolution (12.58 ± 1.31 vs. 1.13 ± 0.60%, 240 min at 240 min) compared with drug powder, respectively. This solvent-evaporated solid dispersion appeared as the round-shape and reduced the particle sizes.
Conclusion: Thus, HPMC and SLS considerably affected the drug solubility and dissolution. Furthermore, this novel solvent-evaporated solid dispersion would be a potential candidate for oral preparation of sirolimus.
Dong Shik Kim– Hanyang University, Ansan
Jung Suk Kim– Hanyang University, Ansan
Ji Eun Choi– Department of Pharmaceutical Engineering, Dankook University, South Korea
Min-Jong Choi– Department of Pharmaceutical Engineering, Dankook University, South Korea
Min Hyun Sung– Student, Yeungnam University, Gyeongsan
Chul Soon Yong– College of Pharmacy, Yeungnam University, South Korea
Jong Oh Kim– College of Pharmacy, Yeungnam University, South Korea
Sung Giu Jin– Department of Pharmaceutical Engineering, Dankook University, South Korea
Han-Gon Choi– College of Pharmacy, Hanyang University, South Korea