Role of wetting agents and disintegrants in development of danazol nanocrystalline tablets
| Autor: | Shyam Karki, Saikishore Meruva, William Bowen, Yuchuan Gong, Prajwal Thool, Sumit Kumar |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Pharmaceutical Science
02 engineering and technology Poloxamer 030226 pharmacology & pharmacy Dosage form 03 medical and health sciences chemistry.chemical_compound Granulation 0302 clinical medicine Suspensions Wetting Agents Dissolution testing Mannitol Particle Size Cellulose Dissolution Croscarmellose sodium Active ingredient Dioctyl Sulfosuccinic Acid Drug Carriers Danazol Docusate Sodium 021001 nanoscience & nanotechnology Microcrystalline cellulose Drug Liberation chemistry Carboxymethylcellulose Sodium Nanoparticles 0210 nano-technology Nuclear chemistry Tablets |
| Zdroj: | International journal of pharmaceutics. 577 |
| ISSN: | 1873-3476 |
| Popis: | Poor wetting and/or particle aggregation are the shortcomings of the dried nanocrystalline suspensions, which subsequently might hinder the superior dissolution performance of the nano-crystalline suspensions. The objective of this study was to evaluate the effect of wetting agents and disintegrants on the dissolution performance of dried nanocrystals of an active pharmaceutical ingredient (API) with poor wetting property. Danazol, a BCS Class II compound with high LogP and low polar surface area, was chosen as a model compound for this study. Danazol nanocrystalline suspension was prepared by wet-media milling and converted into powder via spray granulation either with mannitol or microcrystalline cellulose as carriers at a drug: carrier ratio of 1:9 w/w. Danazol nanocrystalline suspension showed a superior dissolution performance compared to an un-milled danazol suspension. Dried danazol nanocrystals suffered from poor wetting leading to hindered dissolution performance i.e. ~ 40% and ~ 15% drug dissolution within 15 min for the mannitol and microcrystalline cellulose-based granules, respectively. Addition of a lipophilic surfactant (i.e. docusate sodium) at a surfactant: drug ratio of 0.015: 1 w/w during granulation helped in retaining the superior drug dissolution rates i.e. more than 80% drug dissolution within 15 min for mannitol-based granules by enhancing the wettability of dried danazol nanocrystals when compared to a hydrophilic surfactant (i.e. poloxamer 188) or disintegrant (i.e. sodium starch glycolate or croscarmellose sodium). The fast-dissolving mannitol-based granules containing danazol nanocrystals and docusate sodium were compressed into a tablet dosage form. The tablets containing danazol nanocrystals with docusate sodium showed a superior dissolution performance compared to a tablet containing un-milled danazol with docusate sodium. |
| Databáze: | OpenAIRE |
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