scholarly journals Co-Amorphous Solid Dispersions for Solubility and Absorption Improvement of Drugs: Composition, Preparation, Characterization and Formulations for Oral Delivery

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 98 ◽  
Author(s):  
Anna Karagianni ◽  
Kyriakos Kachrimanis ◽  
Ioannis Nikolakakis
Keyword(s):  
Solid State ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Apparent Solubility ◽  
Amorphous Drugs ◽  
Amorphous Dispersions ◽  
Amorphous Drug ◽  
New Formulation ◽  
Thermodynamic Instability

The amorphous solid state offers an improved apparent solubility and dissolution rate. However, due to thermodynamic instability and recrystallization tendencies during processing, storage and dissolution, their potential application is limited. For this reason, the production of amorphous drugs with adequate stability remains a major challenge and formulation strategies based on solid molecular dispersions are being exploited. Co-amorphous systems are a new formulation approach where the amorphous drug is stabilized through strong intermolecular interactions by a low molecular co-former. This review covers several topics applicable to co-amorphous drug delivery systems. In particular, it describes recent advances in the co-amorphous composition, preparation and solid-state characterization, as well as improvements of dissolution performance and absorption are detailed. Examples of drug-drug, drug-carboxylic acid and drug-amino acid co-amorphous dispersions interacting via hydrogen bonding, π−π interactions and ionic forces, are presented together with corresponding final dosage forms.

scholarly journals Relative Contributions of Solubility and Mobility to the Stability of Amorphous Solid Dispersions of Poorly Soluble Drugs: A Molecular Dynamics Simulation Study

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 101 ◽  
Author(s):  
Michael Brunsteiner ◽  
Johannes Khinast ◽  
Amrit Paudel
Keyword(s):  
Molecular Dynamics ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Dynamics Simulation ◽  
Limiting Factor ◽  
Poorly Soluble Drugs ◽  
Formulation Development ◽  
Amorphous Solid Dispersions ◽  
Poorly Soluble

Amorphous solid dispersions are considered a promising formulation strategy for the oral delivery of poorly soluble drugs. The limiting factor for the applicability of this approach is the physical (in)stability of the amorphous phase in solid samples. Minimizing the risk of reduced shelf life for a new drug by establishing a suitable excipient/polymer-type from first principles would be desirable to accelerate formulation development. Here, we perform Molecular Dynamics simulations to determine properties of blends of eight different polymer–small molecule drug combinations for which stability data are available from a consistent set of literature data. We calculate thermodynamic factors (mixing energies) as well as mobilities (diffusion rates and roto-vibrational fluctuations). We find that either of the two factors, mobility and energetics, can determine the relative stability of the amorphous form for a given drug. Which factor is rate limiting depends on physico-chemical properties of the drug and the excipients/polymers. The methods outlined here can be readily employed for an in silico pre-screening of different excipients for a given drug to establish a qualitative ranking of the expected relative stabilities, thereby accelerating and streamlining formulation development.

Engineering Advances in Spray Drying for Pharmaceuticals

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
John M. Baumann ◽  
Molly S. Adam ◽  
Joel D. Wood
Keyword(s):  
Spray Drying ◽  
Oral Delivery ◽  
Process Development ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Annual Review ◽  
Publication Date ◽  
Dry Powders ◽  
Wide Range ◽  
Pharmaceutical Industries

Spray drying is a versatile technology that has been applied widely in the chemical, food, and, most recently, pharmaceutical industries. This review focuses on engineering advances and the most significant applications of spray drying for pharmaceuticals. An in-depth view of the process and its use is provided for amorphous solid dispersions, a major, growing drug-delivery approach. Enhanced understanding of the relationship of spray-drying process parameters to final product quality attributes has made robust product development possible to address a wide range of pharmaceutical problem statements. Formulation and process optimization have leveraged the knowledge gained as the technology has matured, enabling improved process development from early feasibility screening through commercial applications. Spray drying's use for approved small-molecule oral products is highlighted, as are emerging applications specific to delivery of biologics and non-oral delivery of dry powders. Based on the changing landscape of the industry, significant future opportunities exist for pharmaceutical spray drying. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering, Volume 12 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Influence of Preparation Methods on Solid State Supersaturation of Amorphous Solid Dispersions: A Case Study with Itraconazole and Eudragit E100

2010 ◽  
Vol 27 (5) ◽  
pp. 775-785 ◽  
Author(s):  
Sandrien Janssens ◽  
Ann De Zeure ◽  
Amrit Paudel ◽  
Jan Van Humbeeck ◽  
Patrick Rombaut ◽  
...  
Keyword(s):  
Solid State ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions ◽  
Preparation Methods ◽  
Eudragit E100

scholarly journals Solid-state characterization of Felodipine–Soluplus amorphous solid dispersions

2015 ◽  
Vol 42 (3) ◽  
pp. 485-496 ◽  
Author(s):  
Jiannan Lu ◽  
Kristina Cuellar ◽  
Nathan I. Hammer ◽  
Seongbong Jo ◽  
Andreas Gryczke ◽  
...  
Keyword(s):  
Solid State ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions ◽  
Solid State Characterization

scholarly journals Compression-Induced Phase Transitions of Bicalutamide

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 438 ◽  
Author(s):  
Joanna Szafraniec-Szczęsny ◽  
Agata Antosik-Rogóż ◽  
Justyna Knapik-Kowalczuk ◽  
Mateusz Kurek ◽  
Ewa Szefer ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Active Pharmaceutical Ingredient ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
X Ray ◽  
High Propensity ◽  
Poorly Soluble ◽  
Amorphous Drug

The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively.

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