Increasing the Robustness of Biopharmaceutical Precipitation Assays – Part II: Recommendations on the use of FaSSIF

Krollik, Katharina; Lehmann, Andreas; Wagner, Christian; Kaidas, Jonathan; Bülhoff, Janina; Kubas, Holger

doi:10.1016/j.xphs.2021.08.026

Cited by 4 publications

(8 citation statements)

References 23 publications

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“…A neutral buffer solution was prepared with 6.88 g/L NaH 2 PO 4 of sodium phosphate monobasic (anhydrous), 10.37 g/L NaCl, and dilute NaOH such that a 1:1 mixture of SGF and the buffer solution had a pH of 6.5 and the ionic concentrations of fasted-state intestinal fluid . Bile salts and surfactant components were omitted from each of these buffers to isolate the impact of pH and ionic strength on dissolution and avoid potential complications to UV–vis analysis of drug concentration …”

Section: Methodsmentioning

confidence: 99%

“…43 Bile salts and surfactant components were omitted from each of these buffers to isolate the impact of pH and ionic strength on dissolution and avoid potential complications to UV−vis analysis of drug concentration. 44 Dissolution was performed at 500 μg/mL API in solution in 100 mL of SGF (agitated with a Teflon stir bar at 500 RPM). This concentration of cPAD was selected to approximate the active doses of lumefantrine and posaconazole followed by 240 mL of water.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

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Dissolution Behavior of Weakly Basic Pharmaceuticals from Amorphous Dispersions Stabilized by a Poly(dimethylaminoethyl Methacrylate) Copolymer

et al. 2022

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Amorphous solid dispersions (ASDs) are a well-documented formulation approach to improve the rate and extent of dissolution for hydrophobic pharmaceuticals. However, weakly basic compounds can complicate standard approaches to ASDs due to pH-dependent solubility, resulting in uncontrolled drug release in gastric conditions and unstabilized supersaturated solutions prone to precipitation at neutral pH. This work examines the release mechanisms of amorphous dispersions containing model weakly basic pharmaceuticals posaconazole and lumefantrine from a basic poly(dimethylaminoethyl methacrylate) copolymer (Eudragit EPO) and compares their dissolution behavior with ASDs stabilized by acidic and neutral polymers to understand potential benefits to release from a basic polymeric stabilizer. It was found that dissolution of Eudragit EPO ASDs resulted in supersaturation under gastric conditions, which could be sustained upon adjustment to neutral pH. However, the dissolution behavior of Eudragit EPO ASDs was sensitive to the initial pH of the gastric media. For lumefantrine, elevated initial gastric pH resulted in precipitation of amorphous nanoparticles; for posaconazole, elevated gastric pH led to crystallization of the pharmaceutical from solution. This sensitivity to gastric pH was found to originate from the impact of Eudragit EPO on gastric pH and the solubility of each pharmaceutical in the first stage of dissolution. In total, these data illustrate benefits and liabilities for the use of Eudragit EPO for ASDs containing weak pharmaceutical bases to guide the design of robust pharmaceutical formulations.

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Section: Methodsmentioning

confidence: 99%

Section: ■ Materials and Methodsmentioning

confidence: 99%

Dissolution Behavior of Weakly Basic Pharmaceuticals from Amorphous Dispersions Stabilized by a Poly(dimethylaminoethyl Methacrylate) Copolymer

et al. 2022

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“…Please note that the R script is only applicable if a wavelength can be identified for which solely the API concentration is significant. Sometimes, as seen for example in the second part of this series of publications, 17 it may not be possible to identify a wavelength at which FaSSIF does not interfere. However, since the FaSSIF concentration at a specific time point can be calculated easily, this problem can be solved by implementing [FaSSIF] into the model.…”

Section: Discussionmentioning

confidence: 99%

“…In both cases, the wavelength was 257 nm. The plot is based on data published in an accompanying manuscript ("Increasing the robustness of biopharmaceutical precipitation assays − Part II: Recommendations on the use of FaSSIF") 17 . separated from the bulk liquid when drawing samples.…”

Section: Discussionmentioning

confidence: 99%

“…We aimed to investigate the practicability and method development performance using three model substances, namely ketoconazole, dipyridamole, and cinnarizine. In the second part of this two-part publication, 17 the presented approach is applied to investigate the influence of ageing FaSSIF powder on the precipitation behavior of ketoconazole.…”

Section: Impact Of Limited Api Solubility On Calibration Curvesmentioning

confidence: 99%

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Increasing the Robustness of Biopharmaceutical Precipitation Assays – Part I: Derivative UV Spectrophotometric Method Development for in-line Measurements

Lehmann

Krollik

Beran

et al. 2022

Journal of Pharmaceutical Sciences

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Solution Stability of Pharmaceutical Cocrystals

Alvani

Shayanfar

2022

Crystal Growth & Design

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In recent years, pharmaceutical cocrystals as a new solid form have received considerable attention among the applied novel methods for modifying drug substance characteristics. Crystal engineering offers an excellent opportunity to improve physicochemical and pharmacokinetic properties such as solubility, dissolution rate, permeability, bioavailability, biochemical/physical stability, etc. Application of the cocrystal form in the pharmaceutical industry and in academia is becoming a popular method to overcome solubility disadvantages of the active pharmaceutical ingredient (API). Due to manipulation of the API crystalline structure by cocrystal formation, solubility is not the only affected property; some other properties of the newly produced solid form must be considered to fulfill the desired therapeutic efficacy. The stability of the cocrystal in solution is one of these influential features. Regarding the aqueous nature of the gastrointestinal tract, unwanted solution-mediated phase transformation of a cocrystal to a more stable form causes inefficient drug delivery. It may potentially reduce the drug concentration in the circulation. Cocrystal transformation products could be a different polymorph, hydrated form, or mixture of the API and coformer. This review focuses on the solution stability of cocrystals and the effects of various factors such as polymers, surfactants, biorelevant media, organic solvents, and pH.

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Increasing the Robustness of Biopharmaceutical Precipitation Assays – Part II: Recommendations on the use of FaSSIF

Cited by 4 publications

References 23 publications

Dissolution Behavior of Weakly Basic Pharmaceuticals from Amorphous Dispersions Stabilized by a Poly(dimethylaminoethyl Methacrylate) Copolymer

Dissolution Behavior of Weakly Basic Pharmaceuticals from Amorphous Dispersions Stabilized by a Poly(dimethylaminoethyl Methacrylate) Copolymer

Increasing the Robustness of Biopharmaceutical Precipitation Assays – Part I: Derivative UV Spectrophotometric Method Development for in-line Measurements

Solution Stability of Pharmaceutical Cocrystals

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