Influence of Solvent Composition on the Miscibility and Physical Stability of Naproxen/PVP K 25 Solid Dispersions Prepared by Cosolvent Spray-Drying

Paudel, Amrit; Mooter, Guy Van den

doi:10.1007/s11095-011-0539-x

Cited by 86 publications

(81 citation statements)

References 38 publications

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“…(4). Physicochemical characteristics of a drug in solid dispersion may be affected by process, process variables, and carrier compositions (13,14). He et al reported that spray freeze drying process provides physically and chemically stable amorphous solid dispersion of baicalein, while the dispersion prepared by solvent evaporation showed recrystallization of the drug (14).…”

Section: Introductionmentioning

confidence: 99%

Effervescence Assisted Fusion Technique to Enhance the Solubility of Drugs

et al. 2015

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Abstract. The solubility of five poorly soluble drugs was enhanced by using an effervescence assisted solid dispersion (EASD) technique. EASDs were prepared by using modified fusion method. Drug and hydrophilic carrier were melted, and in this molten mixture, effervescence was generated by adding effervescence couple comprising organic acid (citric acid) and carbonic base (sodium bicarbonate). Solubility of drug powders, solid dispersions, and EASDs was determined at 25°C using shake flask method. Atorvastatin calcium, cefuroxime axetil, clotrimazole, ketoconazole, and metronidazole benzoate were estimated using a spectrophotometer at 246, 280, 260, 230, and 232 nm (λ max ), respectively. Solubility of atorvastatin calcium (from 100 to 345 μg/ml), cefuroxime axetil (from 441 to 1948 μg/ml), clotrimazole (from 63 to 677 μg/ml), ketoconazole (from 16 to 500 μg/ml), and metronidazole benzoate (from 112 to 208 μg/ml) in EASDs was enhanced by 3.45-, 4.4-, 10.7-, 31.2-, and 1.8-fold, respectively. Scanning electron micrographs of drug powder, solid dispersion, and EASDs were compared. Scanning electron micrographs of EASDs showed a uniform distribution of drug particles in the carrier matrix. Morphology (size and shape) of cefuroxime axetil particles was altered in solid dispersion as well as in EASD. EASDs showed better solubility enhancement than conventional solid dispersions. The present technique is better suitable for drugs having a low melting point or melt without charring. Effervescence assisted fusion technique of preparing solid dispersions can be employed for enhancing solubility, dissolution, and bioavailability of poorly soluble drugs.

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Section: Introductionmentioning

confidence: 99%

Effervescence Assisted Fusion Technique to Enhance the Solubility of Drugs

et al. 2015

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“…This fundamental finding supports our previous hypothesis that melt-homogenized solvent cast films are likely to reflect the intrinsic miscibility of the considered API:excipient in a melt state (26). This hypothesis has recently been verified on Naproxen/PVP K25 solid dispersions (31). …”

Section: Discussionmentioning

confidence: 66%

Rapid Assessment of Homogeneity and Stability of Amorphous Solid Dispersions by Atomic Force Microscopy—From Bench to Batch

et al. 2013

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PurposeTo verify the robustness and fundamental value of Atomic Force Microscopy (AFM) and AFM-based assays to rapidly examine the molecular homogeneity and physical stability of amorphous solid dispersions on Hot-Melt-Extrudates.MethodsAmorphous solid dispersions were prepared with a Hot-Melt Extruder (HME) and profiled by Raman Microscopy and AFM following a sequential analytical routine (Multi-Scale-Imaging-of-Miscibiliy (MIMix)). Extrudates were analyzed before and after incubation at elevated temperature and humidity. The data were compared with published results as collected on miniaturized melt models. The value of molecular phase separation rates for long term stability prediction was assessed.ResultsData recorded on the extrudates are consistent with those published, and they can be compared side by side. Such direct data comparisons allow the identification of possible sources of extrudate heterogeneities. The surface roughness analysis of fracture-exposed interfaces is a novel quantitative way to trace on the nanometer scale the efficiencies of differently conducted HME-processes. Molecular phase separation rates are shown to be relevant for long term stability predictions.ConclusionsThe AFM-based assessment of API:excipient combinations is a robust method to rapidly identify miscible and stable solid dispersions in a routine manner. It provides a novel analytical tool for the optimization of HME processes.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-013-1045-0) contains supplementary material, which is available to authorized users.

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“…The rate of solvent evaporation will be competing with the rate of solvent diffusion out of the drying droplet due to polymer "skinning" at the surface of the droplet as well as the general viscosity increase during glass formation. Consequently, studies have shown that the spray solvent composition can impact the miscibility and physical stability of spray dried amorphous solid dispersions (Paudel and Van den Mooter 2012). This complexity and its implications on surface composition of the resulting droplet will be discussed in a subsequent section of this chapter.…”

Section: Phase State Implications On Kinetics Of Solventmentioning

confidence: 97%

Practical Considerations for Spray Dried Formulation and Process Development

Lowinger

Baumann

Vodak

et al. 2014

Discovering and Developing Molecules With Optimal Drug-Like Properties

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Spray drying is a broadly applicable process for the manufacture of many products in the food, chemical, and pharmaceutical areas. Powders are produced in a continuous process during the drying of liquid feed stocks through an atomization and drying process. The ability to control the final product attributes to maintain the desired physical state, performance, and bulk powder attributes for downstream processing has made spray drying an important unit operation for the manufacture of amorphous solid dispersions. It can enable progression of compounds with poor aqueous solubility throughout the drug development lifecycle from discovery through commercial production.Efficient development of the process for spray dried amorphous solid dispersions has been demonstrated to ensure the critical quality attributes are maintained during development and scale-up, for example with Vertex Pharmaceuticals' Incivek. To successfully achieve these goals, it is necessary to have a deep understanding of the process and the key formulation attributes along with their potential interaction. By developing this understanding, it is possible to achieve a robust process and formulation that have both been designed to maximize the success during drug development and to achieve the target performance and stability goals.

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Influence of Solvent Composition on the Miscibility and Physical Stability of Naproxen/PVP K 25 Solid Dispersions Prepared by Cosolvent Spray-Drying

Abstract: Spray-drying from a cocktail of good solvent and anti-solvent with narrower volatility difference produces solid dispersions with better miscibility and physical stability resulting from the simultaneous effect on the polymer conformation and better dispersivity of drug.

Cited by 86 publications

References 38 publications

Effervescence Assisted Fusion Technique to Enhance the Solubility of Drugs

Effervescence Assisted Fusion Technique to Enhance the Solubility of Drugs

Rapid Assessment of Homogeneity and Stability of Amorphous Solid Dispersions by Atomic Force Microscopy—From Bench to Batch

Practical Considerations for Spray Dried Formulation and Process Development

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