Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Bhujbal, Sonal; Mitra, Biplob; Jain, Uday K.; Gong, Yuchuan; Agrawal, Anjali; Karki, Shyam; Taylor, Lynne S.; Kumar, Sumit; Zhou, Qi Tony

doi:10.1016/j.apsb.2021.05.014

Cited by 244 publications

(146 citation statements)

References 426 publications

Supporting

Mentioning

131

Contrasting

Order By: Relevance

“…Increasing solubility of biopharmaceutical classification system (BCS) class II drugs in combination with a stabilization of the supersaturated state in solution is widely discussed as governing mechanism for enhancing bioavailability ( Alonzo et al, 2010 ; Brouwers et al, 2009 ; Hirlak et al, 2021 ; López Mármol et al, 2021 ). Amongst many enabling approaches amorphous solid dispersions (ASD) and particular molecular dispersions of a drug within a polymer matrix are an established method to enhance solubility in aqueous media ( Bhujbal et al, 2021 ; Chiou and Riegelman, 1971 ). Thereby, the dissolution performance of an ASD is mostly affected by the state of supersaturation of dissolved drug ( Van den Mooter, 2012 ; Vasconcelos et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Boost of solubility and supersaturation of celecoxib via synergistic interactions of methacrylic acid-ethyl acrylate copolymer (1:1) and hydroxypropyl cellulose in ternary amorphous solid dispersions

Pöstges

Kayser

Stoyanov³

et al. 2022

International Journal of Pharmaceutics: X

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Boost of solubility and supersaturation of celecoxib via synergistic interactions of methacrylic acid-ethyl acrylate copolymer (1:1) and hydroxypropyl cellulose in ternary amorphous solid dispersions

Pöstges

Kayser

Stoyanov³

et al. 2022

International Journal of Pharmaceutics: X

View full text Add to dashboard Cite

“…Several published studies have detailed applications of the HME technology in pharmaceutical manufacturing [ 18 , 19 ]. According to recent records, about twelve HME ASD commercial drug products have been approved by the US Food and Drug Administration (FDA) within the last two decades, with about half of them being developed by AbbVie [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development

et al. 2022

View full text Add to dashboard Cite

Several literature publications have described the potential application of active pharmaceutical ingredient (API)–polymer phase diagrams to identify appropriate temperature ranges for processing amorphous solid dispersion (ASD) formulations via the hot-melt extrusion (HME) technique. However, systematic investigations and reliable applications of the phase diagram as a risk assessment tool for HME are non-existent. Accordingly, within AbbVie, an HME risk classification system (HCS) based on API–polymer phase diagrams has been developed as a material-sparing tool for the early risk assessment of especially high melting temperature APIs, which are typically considered unsuitable for HME. The essence of the HCS is to provide an API risk categorization framework for the development of ASDs via the HME process. The proposed classification system is based on the recognition that the manufacture of crystal-free ASD using the HME process fundamentally depends on the ability of the melt temperature to reach the API’s thermodynamic solubility temperature or above. Furthermore, we explored the API–polymer phase diagram as a simple tool for process design space selection pertaining to API or polymer thermal degradation regions and glass transition temperature-related dissolution kinetics limitations. Application of the HCS was demonstrated via HME experiments with two high melting temperature APIs, sulfamerazine and telmisartan, with the polymers Copovidone and Soluplus. Analysis of the resulting ASDs in terms of the residual crystallinity and degradation showed excellent agreement with the preassigned HCS class. Within AbbVie, the HCS concept has been successfully applied to more than 60 different APIs over the last 8 years as a robust validated risk assessment and quality-by-design (QbD) tool for the development of HME ASDs.

show abstract

“…The latter step is important as dosage forms generated from the pure melt (e.g., injection molded or calendering) often result in slow dissolution without disintegration, which can be improved by mixing the ASD powder with tableting excipients [ 5 ]. Commonly used matrix polymers suitable for hot-melt extrusion are polyvinylpyrrolidone (PVP), polyvinylpyrrolidone/vinyl acetate (PVPVA, copovidone), polymethacrylates, hydroxypropyl methylcellulose (HPMC) or hydroxypropyl methylcellulose acetate succinate (HPMCAS), and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus ® ) [ 6 ]. Nevertheless, the final dosage form of ASDs-based drug products is mostly tablets, as demonstrated by recently marketed products [ 3 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Compression Modulus and Apparent Density of Polymeric Excipients during Compression—Impact on Tabletability

2022

View full text Add to dashboard Cite

The present study focuses on the compaction behavior of polymeric excipients during compression in comparison to nonpolymeric excipients and its consequences on commonly used Heckel analysis. Compression analysis at compaction pressures (CPs) from 50 to 500 MPa was performed using a compaction simulator. This study demonstrates that the particle density, measured via helium pycnometer (ρpar), of polymeric excipients (Kollidon®VA64, Soluplus®, AQOAT®AS-MMP, Starch1500®, Avicel®PH101) was already exceeded at low CPs (<200 MPa), whereas the ρpar was either never reached for brittle fillers such as DI-CAFOS®A60 and tricalcium citrate or exceeded at CPs above 350 MPa (FlowLac®100, Pearlitol®100SD). We hypothesized that the threshold for exceeding ρpar is linked with predominantly elastic deformation. This was confirmed by the start of linear increase in elastic recovery in-die (ERin-die) with exceeding particle density, and in addition, by the applicability in calculating the elastic modulus via the equation of the linear increase in ERin-die. Last, the evaluation of “density under pressure” as an alternative to the ρpar for Heckel analysis showed comparable conclusions for compression behavior based on the calculated yield pressures. However, the applicability of Heckel analysis for polymeric excipients was questioned in principle. In conclusion, the knowledge of the threshold provides guidance for the selection of suitable excipients in the formulation development to mitigate the risk of tablet defects related to stored elastic energy, such as capping and lamination.

show abstract

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Cited by 244 publications

References 426 publications

Boost of solubility and supersaturation of celecoxib via synergistic interactions of methacrylic acid-ethyl acrylate copolymer (1:1) and hydroxypropyl cellulose in ternary amorphous solid dispersions

Boost of solubility and supersaturation of celecoxib via synergistic interactions of methacrylic acid-ethyl acrylate copolymer (1:1) and hydroxypropyl cellulose in ternary amorphous solid dispersions

A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development

Compression Modulus and Apparent Density of Polymeric Excipients during Compression—Impact on Tabletability

Contact Info

Product

Resources

About