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A Novel Protocol Using Small-Scale Spray-Drying for the Efficient Screening of Solid Dispersions in Early Drug Development and Formulation, as a Straight Pathway from Screening to Manufacturing Stages
| Content Provider | Directory of Open Access Journals (DOAJ) |
|---|---|
| Author | Martin Alexander Schubert Kalliopi Dodou Florent Robin Pascal Somville Rosanna Chirico Aymeric Ousset |
| Abstract | This work describes a novel screening strategy that implements small-scale spray-drying in early development of binary amorphous solid dispersions (ASDs). The proposed methodology consists of a three-stage decision protocol in which small batches (20–100 mg) of spray-dried solid dispersions (SDSDs) are evaluated in terms of drug–polymer miscibility, physical stability and dissolution performance in bio-predictive conditions. The objectives are to select the adequate carrier and drug-loading (DL) for the manufacturing of robust SDSD; and the appropriate stabilizer dissolved in the liquid vehicle of SDSD suspensions, which constitutes the common dosage form used during non-clinical studies. This methodology was verified with CDP146, a poorly water soluble (<2 µg/mL) API combined with four enteric polymers and four stabilizers. CDP146/HPMCAS-LF 40:60 (w/w) and 10% (w/v) PVPVA were identified as the lead SDSD and the best performing stabilizer, respectively. Lead SDSD suspensions (1–50 mg/mL) were found to preserve complete amorphous state during 8 h and maintain supersaturation in simulated rat intestinal fluids during the absorption window. Therefore, the implementation of spray-drying as a small-scale screening approach allowed maximizing screening effectiveness with respect to very limited API amounts (735 mg) and time resources (9 days), while removing transfer steps between screening and manufacturing phases. |
| Related Links | http://www.mdpi.com/1424-8247/11/3/81 |
| e-ISSN | 14248247 |
| DOI | 10.3390/ph11030081 |
| Journal | Pharmaceuticals |
| Issue Number | 3 |
| Volume Number | 11 |
| Language | English |
| Publisher | MDPI AG |
| Publisher Date | 2018-01-01 |
| Publisher Place | Switzerland |
| Access Restriction | Open |
| Subject Keyword | Medicine Pharmacy and Materia Medica Amorphous Solid Dispersions Screening Spray-dryer Downscaling Polymers Miscibility Dissolution Supersaturation Stability |
| Content Type | Text |
| Resource Type | Article |
