Preclinical evaluation of new formulation concepts for abiraterone acetate bioavailability enhancement based on the inhibition of pH-induced precipitation

Boleslavská, Tereza; Světlík, Svatopluk; Žvátora, Pavel; Bosák, Jan; Dammer, Ondřej; Beránek, Josef; Kozlík, Petr; Křížek, Tomáš; Canová, Nikolina Kutinová; Šíma, Martin; Slanař, Ondřej; Štěpánek, František

doi:10.1016/j.ejpb.2020.04.005

Cited by 7 publications

(11 citation statements)

References 22 publications

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“…Solymosi et al reported a negligible food effect for a novel formulation based on continuous flow precipitation with Soluplus (9,10). Finally, we have shown in a recent study that amorphous solid dispersion (ASD) formulation based on precipitation inhibitor allowed 2.5-fold bioavailability enhancement in fasted rats (11).…”

Section: Electronic Supplementary Materialsmentioning

confidence: 66%

“…The AAPS Journal (2020) 22: 122 release since we believe that tuning the of abiraterone acetate based on pH is crucial for food effect elimination; (ii) in our previous study (11), HPMCAS-LF was identified as a potent precipitation inhibitor-this might allow drug absorption even when supersaturated state is reached in a given environment (this phenomenon is usually referred to as parachute effect) (31). We were able to prepare marbles smaller than 2 mm in diameter that could be filled into capsules for rodents (capsule size 9el) as shown in Fig.…”

Section: Preparation Of Oil Marbles and Their Physicochemical Characterizationmentioning

confidence: 91%

“…In order to select the most appropriate oil for the OMs, the solubility of abiraterone acetate in several candidate oils was determined using the shake flask method. Briefly, an excess of abiraterone acetate was added to an Eppendorf vial containing 1 mL of the oil and the resulting suspension was shaken at 37°C for 24 h. At the end of the experiment, the vials were centrifuged at 10,000 RPM for 10 min, the supernatant was diluted ten times into isopropyl alcohol, and the concentration of abiraterone acetate in the resulting solution was determined by HPLC (method adapted from our previous study) (11).…”

Section: Solubility Measurementsmentioning

confidence: 99%

“…Approximately 80 mg of OMs was weighted into a 20-mL volumetric flask and extracted into methanol. The resulting solution was diluted 10 times, and the concentration of abiraterone acetate was determined on HPLC using a method adapted from our previous study (11).…”

Section: Drug Load Analysismentioning

confidence: 99%

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Bioavailability Enhancement and Food Effect Elimination of Abiraterone Acetate by Encapsulation in Surfactant-Enriched Oil Marbles

Boleslavská

Rychecký

Krov

et al. 2020

AAPS J

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Abiraterone acetate has limited bioavailability in the fasted state and exhibits a strong positive food effect. We present a novel formulation concept based on the so-called oil marbles (OMs) and show by in vitro and in vivo experiments that the food effect can be suppressed. OMs are spherical particles with a core-shell structure, formed by coating oilbased droplets that contain the dissolved drug by a layer of powder that prevents the cores from sticking and coalescence. OMs prepared in this work contained abiraterone acetate in the amorphous form and showed enhanced dissolution properties during in vitro experiments when compared with originally marketed formulation of abiraterone acetate (Zytiga ® ). Based on in vitro comparison of OMs containing different oil/surfactant combinations, the most promising formulation was chosen for in vivo studies. To ensure relevance, it was verified that the food effect previously reported for Zytiga ® in humans was translated into the rat animal model. The bioavailability of abiraterone acetate formulated in OMs in the fasted state was then found to be enhanced by a factor of 2.7 in terms of AUC and by a factor of 4.0 in terms of C max . Crucially, the food effect reported in the literature for other abiraterone acetate formulations was successfully eliminated and OMs showed comparable extent of bioavailability in a fed-fasted study. Oil marbles therefore seem to be a promising formulation concept not only for abiraterone acetate but potentially also for other poorly soluble drugs that reveal a positive food effect.

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Section: Electronic Supplementary Materialsmentioning

confidence: 66%

Section: Preparation Of Oil Marbles and Their Physicochemical Characterizationmentioning

confidence: 91%

Section: Solubility Measurementsmentioning

confidence: 99%

Section: Drug Load Analysismentioning

confidence: 99%

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Bioavailability Enhancement and Food Effect Elimination of Abiraterone Acetate by Encapsulation in Surfactant-Enriched Oil Marbles

Boleslavská

Rychecký

Krov

et al. 2020

AAPS J

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“…The differences in the weights between the groups were not statistically significant. Intra-arterial catheters were implanted into the carotid arteries for the purpose of repeated blood sampling according to our standard protocol described in detail elsewhere [ 25 ]. Briefly, the catheters were implanted after 6-8 hours of fasting in aseptic conditions.…”

Section: Methodsmentioning

confidence: 99%

Rifampin-Releasing Triple-Layer Cross-Linked Fresh Water Fish Collagen Sponges as Wound Dressings

Hartinger

Mlček

Popková

et al. 2020

BioMed Research International

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Objectives. Surgical wounds resulting from biofilm-producing microorganisms represent a major healthcare problem that requires new and innovative treatment methods. Rifampin is one of a small number of antibiotics that is able to penetrate such biofilms, and its local administration has the potential to serve as an ideal surgical site infection protection and/or treatment agent. This paper presents two types (homogeneous and sandwich structured) of rifampin-releasing carbodiimide-cross-linked fresh water fish collagen wound dressings. Methods. The dressings were prepared by means of the double-lyophilization method and sterilized via gamma irradiation so as to allow for testing in a form that is able to serve for direct clinical use. The mechanical properties were studied via the uniaxial tensile testing method. The in vivo rifampin-release properties were tested by means of a series of incubations in phosphate-buffered saline. The microbiological activity was tested against methicillin-resistant staphylococcus aureus (MRSA) employing disc diffusion tests, and the in vivo pharmacokinetics was tested using a rat model. A histological examination was conducted for the study of the biocompatibility of the dressings. Results. The sandwich-structured dressing demonstrated better mechanical properties due to its exhibiting ability to bear a higher load than the homogeneous sponges, a property that was further improved via the addition of rifampin. The sponges retarded the release of rifampin in vitro, which translated into at least 22 hours of rifampin release in the rat model. This was significantly longer than was achieved via the administration of a subcutaneous rifampin solution. Microbiological activity was proven by the results of the disc diffusion tests. Both sponges exhibited excellent biocompatibility as the cells penetrated into the scaffold, and virtually no signs of local irritation were observed. Conclusions. We present a novel rifampin-releasing sandwich-structured fresh water fish collagen wound dressing that has the potential to serve as an ideal surgical site infection protection and/or treatment agent.

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Increasing the efficacy of abiraterone - from pharmacokinetics, through therapeutic drug monitoring to overcoming food effects with innovative pharmaceutical products

Danielak

Krejčí²,

Beránek³

2022

European Journal of Pharmaceutical Sciences

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Preclinical evaluation of new formulation concepts for abiraterone acetate bioavailability enhancement based on the inhibition of pH-induced precipitation

Cited by 7 publications

References 22 publications

Bioavailability Enhancement and Food Effect Elimination of Abiraterone Acetate by Encapsulation in Surfactant-Enriched Oil Marbles

Bioavailability Enhancement and Food Effect Elimination of Abiraterone Acetate by Encapsulation in Surfactant-Enriched Oil Marbles

Rifampin-Releasing Triple-Layer Cross-Linked Fresh Water Fish Collagen Sponges as Wound Dressings

Increasing the efficacy of abiraterone - from pharmacokinetics, through therapeutic drug monitoring to overcoming food effects with innovative pharmaceutical products

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