A novel architecture for achieving high drug loading in amorphous spray dried dispersion tablets

Mudie, Deanna M.; Buchanan, Stephanie; Stewart, Aaron M.; Smith, Adam J. de; Shepard, Kimberly B.; Biswas, Nishant; Marshall, Derrick; Ekdahl, Alyssa; Pluntze, Amanda M.; Craig, Christopher D.; Morgen, Michael M.; Baumann, John M.; Vodak, David T.

doi:10.1016/j.ijpx.2020.100042

Cited by 20 publications

(30 citation statements)

References 45 publications

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“…The in vitro dissolution performance of the ASD tablet and the commercially available Calquence capsule was evaluated using a controlled-transfer dissolution (CTD) apparatus containing stomach, duodenum, and jejunum/waste compartments [ 15 , 16 ]. The in vitro testing parameters were selected based on acalabrutinib physicochemical properties; the dose; and the average physiology of fasted beagle dogs (1) pretreated with pentagastrin to increase gastric acid secretion and lower stomach pH and (2) pretreated with famotidine to decrease gastric acid secretion and elevate stomach pH [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

Section: Methodsmentioning

confidence: 99%

Amorphous Solid Dispersion Tablets Overcome Acalabrutinib pH Effect in Dogs

et al. 2021

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Calquence® (crystalline acalabrutinib), a commercially marketed tyrosine kinase inhibitor (TKI), exhibits significantly reduced oral exposure when taken with acid-reducing agents (ARAs) due to the low solubility of the weakly basic drug at elevated gastric pH. These drug–drug interactions (DDIs) negatively impact patient treatment and quality of life due to the strict dosing regimens required. In this study, reduced plasma drug exposure at high gastric pH was overcome using a spray-dried amorphous solid dispersion (ASD) comprising 50% acalabrutinib and 50% hydroxypropyl methylcellulose acetate succinate (HPMCAS, H grade) formulated as an immediate-release (IR) tablet. ASD tablets achieved similar area under the plasma drug concentration–time curve (AUC) at low and high gastric pH and outperformed Calquence capsules 2.4-fold at high gastric pH in beagle dogs. In vitro multicompartment dissolution testing conducted a priori to the in vivo study successfully predicted the improved formulation performance. In addition, ASD tablets were 60% smaller than Calquence capsules and demonstrated good laboratory-scale manufacturability, physical stability, and chemical stability. ASD dosage forms are attractive for improving patient compliance and the efficacy of acalabrutinib and other weakly basic drugs that have pH-dependent absorption.

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Section: Methodsmentioning

confidence: 99%

Amorphous Solid Dispersion Tablets Overcome Acalabrutinib pH Effect in Dogs

et al. 2021

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“… Flow property of Granules: The bulk density, tap density, and Hausner ratio of the granules were all measured using following equation [14][15].…”

Section: Tablet Characterizationmentioning

confidence: 99%

Enhancement of Drug Dissolution of Erlotinib Tablets by Micronization Technique Using Pharmaceutical Experimental Design

Kumar

Dureja

Chandra

2021

JPRI

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Lung cancer is the second most frequent cancer and among the top cause of death worldwide. Chemotherapy is the main therapeutic option for non-small-cell lung cancer (NSCLC), which accounts for the majority of all lung malignancies. The aim of the current work was to develop a tablet formulation having increased drug release profile to improve the bioavailability in order to reduce the dose of the drug. In this present study, Erlotinib tablet was prepared using micronization technique which showed increase drug release profile. Film-coated tablets containing Erlotinib hydrochloride (150 mg) were prepared by dry granulation technique and coated using Opadry ready-mix. Tablets were characterized for Hardness, Friability, Potency and Drug release profile. Drug release was checked in 0.1 N HCL containing 0.5 % SLS and biorelevant dissolution media up to 60 minutes. Tablets of the selected batch were subjected to dissolution in biorelevant media and compare with reference product. The improvement in the drug release was observed in the biorelevant media in comparison with reference product. The in-vitrodissolution data demonstrated the potential of micronization technology to prepare tablets with improved bioavailability of the drug.

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“…prevent API crystallization, the ratio between drug and carrier polymer is typically in the range of 1:9 to 4:6. ( Henriques et al, 2020 ; Mudie et al, 2020 ; Schittny et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…In comparison with a SDD with erlotinib:HPMCAS (35:65) which was slugged prior to tablet compression, the release in high gastric pH = 6 was slower and a lower c max was observed. ( Mudie et al, 2020 ). A recent study from Henriques et al describes spray drying and roller compaction of a non-disclosed API with PVP-VA (20:80).…”

Section: Introductionmentioning

confidence: 99%

Downstream processing of spray-dried ASD with hypromellose acetate succinate – Roller compaction and subsequent compression into high ASD load tablets

Sauer¹,

Warashina

Mishra³

et al. 2021

International Journal of Pharmaceutics: X

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Despite wide commercial application of hypromellose acetate succinate (HPMCAS) in spray-dried amorphous solid dispersion (ASD) drug products, little information is available in the references on downstream processing of spray-dried dispersions with HPMCAS. Poor flow and high dilution factor are a challenge in formulating spray-dried ASDs into tablets, leaving little space for other excipients facilitating binding and disintegration. Direct compression is not possible due to the poor powder flow of spray-dried ASDs. Moisture has to be avoided due to the plasticizing properties of water on the ASD, resulting in reduced stability of the amorphous state. Thus, dry granulation by roller compaction and subsequent tablet compression is the preferred downstream process. We report the investigation of downstream processing by roller compaction and tablet compression of a high load formulation with 75% of spray-dried amorphous solid dispersion (Nifedipine:HPMCAS 1:2). A head to head comparison of microcrystalline cellulose/croscarmellose (MCC/cl-NaCMC) as binder/disintegrant vs. MCC and low-substituted hydroxypropyl cellulose (L-HPC) as excipient for binding and disintegration showed improved re-workability of the formulation with MCC/L-HPC after roller compaction. Upon transfer to the rotary press, a 45% higher tensile strength of tablets is observed after dry granulation with MCC/L-HPC.

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A novel architecture for achieving high drug loading in amorphous spray dried dispersion tablets

Cited by 20 publications

References 45 publications

Amorphous Solid Dispersion Tablets Overcome Acalabrutinib pH Effect in Dogs

Amorphous Solid Dispersion Tablets Overcome Acalabrutinib pH Effect in Dogs

Enhancement of Drug Dissolution of Erlotinib Tablets by Micronization Technique Using Pharmaceutical Experimental Design

Downstream processing of spray-dried ASD with hypromellose acetate succinate – Roller compaction and subsequent compression into high ASD load tablets

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