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Expedited Tablet Formulation Development of a Highly Soluble Carbamazepine Cocrystal Enabled by Precipitation Inhibition in Diffusion Layer
- Source :
- Pharmaceutical Research. 36
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- To address the problem of precipitation of a poorly soluble drug during dissolution of highly soluble cocrystals by preparing granules intimately mixed with a water-soluble polymer. Effectiveness of polymers as precipitation inhibitors during the dissolution of carbamazepine–nicotinamide (CBZ-NCT) cocrystal was assessed based on induction time of crystallization from a supersaturated solution in presence of different polymers at two concentrations. Dissolution was evaluated by both intrinsic dissolution rate (IDR) and USP dissolution method. Powder manufacturability was assessed using a shear cell and compaction simulator to assess flowability and tabletability, respectively. Hydroxypropyl methylcellulose acetate succinate (HPMCAS) was the most effective polymer against precipitation of CBZ and the IDR of a 1:1 (w/w) CBZ-NCT/HPMCAS mixture was the highest. The final formulation of 1:1 CBZ-NCT/HPMCAS granule exhibited excellent flowability, good tabletability, and significantly improved drug release rate than cocrystal formulations without HPMCAS or the CBZ formulation. The particle engineering strategy of modifying the diffusion layer on the surface of highly soluble cocrystal with a polymer is effective for inhibiting premature precipitation of CBZ. Assisted with predictive tools for characterizing powder flowability and tabletability, the design of high quality tablet product with improved drug release rate and manufacturability can be achieved in an efficient manner.
- Subjects :
- Niacinamide
Surface Properties
Drug Compounding
Pharmaceutical Science
02 engineering and technology
Methylcellulose
030226 pharmacology & pharmacy
Cocrystal
law.invention
Diffusion
Diffusion layer
03 medical and health sciences
0302 clinical medicine
law
Pharmacology (medical)
Crystallization
Dissolution
Pharmacology
chemistry.chemical_classification
Supersaturation
Precipitation (chemistry)
Organic Chemistry
Granule (cell biology)
Polymer
Silicon Dioxide
021001 nanoscience & nanotechnology
Drug Liberation
Carbamazepine
Solubility
chemistry
Chemical engineering
Nanoparticles
Molecular Medicine
Powders
0210 nano-technology
Tablets
Biotechnology
Subjects
Details
- ISSN :
- 1573904X and 07248741
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Pharmaceutical Research
- Accession number :
- edsair.doi.dedup.....c1e4299c4412c9cff75cb5711ba17da5
- Full Text :
- https://doi.org/10.1007/s11095-019-2622-7