| Autor: |
Marks JA; Macromolecules Innovation Institute, Department of Sustainable Biomaterials, College of Natural Resources and Environment, Virginia Tech, Blacksburg, Virginia 24061, United States.; Department of Chemistry, University of the West Indies, Mona, Kingston JMAAW15, Jamaica., Nichols BLB; Department of Chemistry, College of Science, Virginia Tech, Blacksburg, Virginia 24061, United States., Mosquera-Giraldo LI; Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States., T Yazdi S; Macromolecules Innovation Institute, Department of Sustainable Biomaterials, College of Natural Resources and Environment, Virginia Tech, Blacksburg, Virginia 24061, United States., Taylor LS; Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States., Edgar KJ; Macromolecules Innovation Institute, Department of Sustainable Biomaterials, College of Natural Resources and Environment, Virginia Tech, Blacksburg, Virginia 24061, United States. |
| Abstrakt: |
Amorphous solid dispersion (ASD) in a polymer matrix is a powerful method for enhancing the solubility and bioavailability of otherwise crystalline, poorly water-soluble drugs. 6-Carboxycellulose acetate butyrate (CCAB) is a relatively new commercial cellulose derivative that was introduced for use in waterborne coating applications. As CCAB is an amphiphilic, carboxyl-containing, high glass transition temperature ( T g ) polymer, characteristics essential to excellent ASD polymer performance, we chose to explore its ASD potential. Structurally diverse drugs quercetin, ibuprofen, ritonavir, loratadine, and clarithromycin were dispersed in CCAB matrices. We evaluated the ability of CCAB to create ASDs with these drugs and its ability to provide solubility enhancement and effective drug release. CCAB/drug dispersions prepared by spray drying were amorphous up to 25 wt % drug, with loratadine remaining amorphous up to 50% drug. CCAB formulations with 10% drug proved effective at providing in vitro solubility enhancement for the crystalline flavonoid drug quercetin as well as ritonavir, but not for the more soluble APIs ibuprofen and clarithromycin and the more hydrophobic loratadine. CCAB did provide slow and controlled release of ibuprofen, offering a simple and promising Long-duration ibuprofen formulation. Formulation with clarithromycin showed the ability of the polymer to protect against degradation of the drug at stomach pH. Furthermore, CCAB ASDs with both loratadine and ibuprofen could be improved by the addition of the water-soluble polymer poly(vinylpyrrolidone) (PVP), with which CCAB shows good miscibility. CCAB provided solubility enhancement in some cases, and the slower drug release exhibited by CCAB, especially in the stomach, could be especially beneficial, for example, in formulations containing known stomach irritants like ibuprofen. |
