As a small molecule PDE 4 inhibitor, apremilast has drawn much attention for multiple promising indications. However, apremilast is a poorly water-soluble drug and has multiple polymorphic forms. This study aims to develop a sustained-release (SR) amorphous solid dispersion (ASD) system for apremilast. A streamlined material sparing ASD formulation development approach was utilized to identify candidate polymers and optimize drug loading. HPMCAS-M at a 20% drug loading and Copovidone at a 40% drug loading was selected as the lead formulations. A stable single-phase amorphous system of apremilast via spray drying was generated as revealed by XRPD, DMA, micro-dissolution, and accelerated stability testing. The apparent solubility of apremilast was improved up to 9 folds. HPMC was subsequently utilized to compress the produced ASD system into an SR matrix tablet. Release data demonstrated the capacity of HPMC to gradually hydrate and control drug release while suppressing drug recrystallization during the 20-hours period of sustained drug delivery. The designed SR amorphous based matrix system indicates that the delivery system has the ability to enhance apparent solubility, avoid recrystallization or polymorphic transformation by stabilizing its amorphous form, and provide an opportunity to enhance patient compliance by allowing once-daily administration. / Pharmaceutical Sciences
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/4728 |
| Date | January 2020 |
| Creators | Zhang, Qiangnan |
| Contributors | Fassihi , Reza, Wong, Ho-Lun, Ilies, Marc, Dürig, Thomas |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 169 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/4710, Theses and Dissertations |
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