Amorphous Solid
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Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1467
Anastasia Tsiaxerli ◽  
Anna Karagianni ◽  
Andreas Ouranidis ◽  
Kyriakos Kachrimanis

Polyelectrolyte polymers have been widely used in the pharmaceutical field as excipients to facilitate various drug delivery systems. Polyelectrolytes have been used to modulate the electrostatic environment and enhance favorable interactions between the drug and the polymer in amorphous solid dispersions (ASDs) prepared mainly by hot-melt extrusion. Polyelectrolytes have been used alone, or in combination with nonionic polymers as interpolyelectrolyte complexes, or after the addition of small molecular additives. They were found to enhance physical stability by favoring stabilizing intermolecular interactions, as well as to exert an antiplasticizing effect. Moreover, they not only enhance drug dissolution, but they have also been used for maintaining supersaturation, especially in the case of weakly basic drugs that tend to precipitate in the intestine. Additional uses include controlled and/or targeted drug release with enhanced physical stability and ease of preparation via novel continuous processes. Polyelectrolyte matrices, used along with scalable manufacturing methods in accordance with green chemistry principles, emerge as an attractive viable alternative for the preparation of ASDs with improved physical stability and biopharmaceutic performance.

Polymers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 2922
Afroditi Kapourani ◽  
Artemis Palamidi ◽  
Konstantinos N. Kontogiannopoulos ◽  
Nikolaos D. Bikiaris ◽  
Panagiotis Barmpalexis

Although significant actions have been taken towards the utilization of poly(vinyl alcohol) (PVA) in the preparation of drug amorphous solid dispersions (ASDs) using fusion-based techniques (such as melt-quench cooling and hot-melt extrusion), several drawbacks regarding its rather high melting temperature and its thermal degradation profile make the use of the polymer extremely challenging. This is especially important when the active pharmaceutical ingredient (API) has a lower melting temperature (than PVA) or when it is thermally labile. In this vein, a previous study showed that newly synthesized polyester-based plasticizers may improve the processability and the thermal properties of PVA. However, the effects of such polyester-based plasticizers on the drug’s physicochemical and pharmaco-technical properties are yet unknown. Hence, the aim of the present study is to extend our previous findings and evaluate the use of poly(propylene succinate) (PPSu, i.e., the most promising plasticizer in regard to PVA) in the preparation of drug-loaded PVA-based ASDs. Dronedarone (DRN), a poorly water-soluble API, was selected as a model drug, and drug ASDs (using either neat PVA or PVA-PPSu) were prepared using the melt-mixing/quench cooling approach at low melting temperatures (i.e., 170 °C). DSC and pXRD analysis showed that a portion of the API remained crystalline in the ASDs prepared only with the use of neat PVA, while the samples having PPSu as a plasticizer were completely amorphous. Further evaluation with ATR-FTIR spectroscopy revealed the formation of significant intermolecular interactions between the API and the PVA-PPSu matrix, which could explain the system’s physical stability during storage. Finally, dissolution studies, conducted under nonsink conditions, revealed that the use of PVA-PPSu is able to maintain DRN’s sustained supersaturation for up to 8 h.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1257
Deanna M. Mudie ◽  
Aaron M. Stewart ◽  
Jesus A. Rosales ◽  
Molly S. Adam ◽  
Michael M. Morgen ◽  

Amorphous solid dispersion (ASD) dosage forms can improve the oral bioavailability of poorly water-soluble drugs, enabling the commercialization of new chemical entities and improving the efficacy and patient compliance of existing drugs. However, the development of robust, high-performing ASD dosage forms can be challenging, often requiring multiple formulation iterations, long timelines, and high cost. In a previous study, acalabrutinib/hydroxypropyl methylcellulose acetate succinate (HPMCAS)-H grade ASD tablets were shown to overcome the pH effect of commercially marketed Calquence in beagle dogs. This study describes the streamlined in vitro and in silico approach used to develop those ASD tablets. HPMCAS-H and -M grade polymers provided the longest acalabrutinib supersaturation sustainment in an initial screening study, and HPMCAS-H grade ASDs provided the highest in vitro area under the curve (AUC) in gastric to intestinal transfer dissolution tests at elevated gastric pH. In silico simulations of the HPMCAS-H ASD tablet and Calquence capsule provided good in vivo study prediction accuracy using a bottom–up approach (absolute average fold error of AUC0-inf < 2 except for Calquence + famotidine ≈ 3). This streamlined approach combined an understanding of key drug, polymer, and gastrointestinal properties with in vitro and in silico tools to overcome the acalabrutinib pH effect without the need for reformulation or multiple studies, showing promise for reducing time and costs to develop ASD drug products.

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