Downstream Processing Considerations

Page, Susanne; Maurer, Reto

doi:10.1007/978-1-4939-1598-9_13

Cited by 1 publication

(2 citation statements)

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“…Normally, the drug load in ASD is already quite low due to the presence of the stabilizing polymer, and thus using large amounts of extragranular excipients will even further decrease the drug load in the formulation. 12,18,19 A different approach to overcome polymer gelling is the addition of inorganic salts to the tablet formulation. Most inorganic salts decrease the water solubility of organic solutes (salting-out phenomenon), while some of them (iodide and thiocyanate) have an opposite action (salting-in).…”

Section: ■ Introductionmentioning

confidence: 99%

“…It was concluded that the influence of extragranular components on the dissolution behavior of tablets should be carefully evaluated during formulation development, as it varies for each ASD polymer. Normally, the drug load in ASD is already quite low due to the presence of the stabilizing polymer, and thus using large amounts of extragranular excipients will even further decrease the drug load in the formulation. ,, …”

Section: Introductionmentioning

confidence: 99%

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Formulating Amorphous Solid Dispersions: Impact of Inorganic Salts on Drug Release from Tablets Containing Itraconazole-HPMC Extrudate

et al. 2019

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Amorphous solid dispersions (ASD) are increasingly used to improve the oral bioavailability of poorly water-soluble compounds. However, hydrophilic polymers in ASD have high water-binding properties and, upon water contact, they often form a gel on the surface of the tablet, impacting the rate and extent of drug release. Most inorganic salts decrease water solubility of organic solutes, changing the gel properties of hydrophilic polymers. In this study, the effect of inorganic salts on drug release from a tablet formulation containing an itraconazole (ITZ)-hydroxypropyl methyl cellulose (HPMC) extrudate was investigated. The cloud point of a 1% HPMC solution with and without inorganic salts (KCl, KH2PO4, KHCO3, and potassium iodate (KI)) was determined to classify the salts according to their salting-out or salting-in effect. A kosmotropic effect on HPMC was observed for KCl, KH2PO4, and KHCO3, whereas KI exhibited a chaotropic effect. To prove the effect of these salts on drug release, tablets containing 66% of ITZ-HPMC extrudate (20:80 w/w %), 4% croscarmellose sodium, 30% microcrystalline cellulose, and different types and amounts of KHCO3, KH2PO4, KCl, and KI were compressed (same solid fraction of 0.83–0.85). Tablets without salts showed a slow release and low peak concentrations during dissolution in simulated gastric fluids. By adding the kosmotropic salts to the tablets, the rate and extent of drug release were increased, whereas the chaotropic anion iodide had no effect. The effect was pronounced even with the addition of as little as 2% of inorganic salts and tended to increase with the increasing amount of salt in the formulation. Tablets without salt stored under either dry or humid conditions exhibited a large difference in dissolution profiles, whereas little variation was observed for tablets with kosmotropic salts. In conclusion, the effect of inorganic salts was mechanistically clarified on ASD containing commonly used HPMC. This approach can be beneficial to successfully develop robust formulations containing ASD.

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Section: ■ Introductionmentioning

confidence: 99%