Assessing the Interrelationship of Microstructure, Properties, Drug Release Performance, and Preparation Process for Amorphous Solid Dispersions Via Noninvasive Imaging Analytics and Material Characterization

Jia, Wei; Yawman, Phillip D.; Pandya, Keyur M.; Sluga, Kellie; Ng, Tim; Kou, Dawen; Nagapudi, Karthik; Luner, Paul E.; Zhu, Aiden; Zhang, Shawn; Hou, Hao

doi:10.1007/s11095-022-03308-9

Cited by 16 publications

(6 citation statements)

References 59 publications

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“…Though previous work has correlated cPAD particle morphology with reduced in vitro dissolution rate, 71 this work did not find a significant difference in the dissolution rate of cPAD compared to spray-dried or solvent-casted dispersions of the same compositions. 6,38 Additionally, although coprecipitated amorphous dispersions containing neutral polymers (such as VA64) can be produced by precipitation into nonpolar anti-solvents, 32 co-precipitation was not used to generate VA64 ASDs given that residual crystallinity has been observed in posaconazole cPAD formed by precipitation into nonpolar anti-solvents.…”

Section: ■ Results and Discussioncontrasting

confidence: 78%

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: ■ Results and Discussioncontrasting

confidence: 78%

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

et al. 2022

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“…In the past, traditional methods employed a large amount of API material to determine these properties. Considering recent advances, several material-sparing methods were developed for initial preformulation assessment [ 44 , 45 ]. As specified in the available literature, the difference in free energy is one of the notable properties that helps to understand the advantage of solubility for the amorphous form over the crystalline form.…”

Section: Recent Advances In Preformulationmentioning

confidence: 99%

Recent Advances in Amorphous Solid Dispersions: Preformulation, Formulation Strategies, Technological Advancements and Characterization

et al. 2022

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Amorphous solid dispersions (ASDs) are among the most popular and widely studied solubility enhancement techniques. Since their inception in the early 1960s, the formulation development of ASDs has undergone tremendous progress. For instance, the method of preparing ASDs evolved from solvent-based approaches to solvent-free methods such as hot melt extrusion and Kinetisol®. The formulation approaches have advanced from employing a single polymeric carrier to multiple carriers with plasticizers to improve the stability and performance of ASDs. Major excipient manufacturers recognized the potential of ASDs and began introducing specialty excipients ideal for formulating ASDs. In addition to traditional techniques such as differential scanning calorimeter (DSC) and X-ray crystallography, recent innovations such as nano-tomography, transmission electron microscopy (TEM), atomic force microscopy (AFM), and X-ray microscopy support a better understanding of the microstructure of ASDs. The purpose of this review is to highlight the recent advancements in the field of ASDs with respect to formulation approaches, methods of preparation, and advanced characterization techniques

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“…Jia et al investigated the interrelationships among microstructure, properties, and drug dissolution performance of amorphous solid dispersions (ASD) prepared by two distinct processes, i.e., coprecipitation and spray-drying [8]. In addition to conventional techniques, they utilized X-ray microscopy (XRM) to characterize different ASD batches, which revealed a strong relationship between the total solid external surface area normalized by total solid volume and micro dissolution rate.…”

Section: Structure-property-performance Understanding and Enhancementmentioning

confidence: 99%

Crystal and Particle Engineering – An Indispensable Tool for Developing and Manufacturing Quality Pharmaceutical Products

Sun

Davé

2022

Pharm Res

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Design and manufacture of high-quality pharmaceutical products remains challenging due to the inherent complexities arising, in part, from multitudes of components in particulate forms, each having different functionality and potential for unwanted interactions during processing, storage, handling, or administration. Hence, it follows that particles and crystals play an essential role in pharmaceutical manufacturing. Successful manufacturing and quality of finished pharmaceutical products, even if the final dosage form may not be a solid, critically depend on powder properties, such as flowability, tabletability, wettability, and solubility. These powder properties, in turn, are controlled by the properties of constituting particles or crystals of active pharmaceutical ingredients (API) and excipients, such as size, size distribution, shape, porosity, mechanical properties, surface energy, and surface roughness [1,2]. Hence, appropriate engineering of crystals or particles through various processes, such as crystallization, granulation (dry, wet, fluid bed), hot-melt extrusion, spray-drying, and dry coating, is necessary for the purpose of overcoming problems in pharmaceutical manufacturing. Thus, engineering pharmaceutical materials at particle level is an important step in solving many problems in pharmaceutical manufacturing. In summary, the interrelationships among structure, property, performance, and processing, succinctly captured through materials science tetrahedron (MST) [1], could guide research in

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Assessing the Interrelationship of Microstructure, Properties, Drug Release Performance, and Preparation Process for Amorphous Solid Dispersions Via Noninvasive Imaging Analytics and Material Characterization

Cited by 16 publications

References 59 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

Recent Advances in Amorphous Solid Dispersions: Preformulation, Formulation Strategies, Technological Advancements and Characterization

Crystal and Particle Engineering – An Indispensable Tool for Developing and Manufacturing Quality Pharmaceutical Products

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