Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate

Schultz, Hayley B.; Meola, Tahlia R.; Prestidge, Clive A.

doi:10.1016/j.ijpharm.2020.119069

Cited by 42 publications

(33 citation statements)

References 84 publications

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“…Due to the low solubility and high permeability through cell membranes of CVD, its solubility is a critical parameter that allows improving bioavailability. Many technological approaches are used to enhance the dissolution rate, including particle size reduction to increase the surface area, solubilization in surfactant system, formation of water-soluble complexes, usage of a prodrug, and manipulation of solid-state of drug substance to improve drug dissolution, i.e., by decreasing drug crystallinity [ 3 , 13 ]. One of the widely developed topics is drug delivery systems preparation using natural carriers, e.g., chitosan [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Chitosan as Valuable Excipient for Oral and Topical Carvedilol Delivery Systems

Sip

Paczkowska-Walendowska

Rosiak

et al. 2021

Pharmaceuticals

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Chitosan is a valued excipient due to its biocompatibility properties and increasing solubility of poorly water-soluble drugs. The research presented in this paper concerns the preparation of binary combinations of chitosan (deacetylated chitin) with carvedilol (beta-blocker) to develop a formulation with a modified carvedilol release profile. As part of the research, six physical mixtures of chitosan with carvedilol were obtained and identified by spectral (PXRD, FT-IR, and Raman), thermal (DSC), and microscopic (SEM) methods. The next stage of the research estimated the profile changes and the dissolution rate for carvedilol in the obtained drug delivery systems; the reference sample was pure carvedilol. The studies were conducted at pH = 1.2 and 6.8, simulating the gastrointestinal tract conditions. Quantitative changes of carvedilol were determined using the developed isocratic UHPLC-DAD method. Established apparent permeability coefficients proved the changes in carvedilol’s permeability after introducing a drug delivery system through membranes simulating the gastrointestinal tract and skin walls. A bioadhesive potential of carvedilol–chitosan systems was confirmed using the in vitro model. The conducted research and the obtained results indicate a significant potential of using chitosan as an excipient in modern oral or epidermal drug delivery systems of carvedilol.

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Section: Introductionmentioning

confidence: 99%

Chitosan as Valuable Excipient for Oral and Topical Carvedilol Delivery Systems

Sip

Paczkowska-Walendowska

Rosiak

et al. 2021

Pharmaceuticals

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“…Given the low absolute bioavailability, this could result in F RL of 10–15% in men. Therefore, other factors than lymphatic transport seem to be more important for the extremely pronounced positive food effect on intestinal absorption of abiraterone, such as intraluminal solubilization in the presence of lipids and bile after food intake (Schultz et al, 2020) or enhanced supersaturation in the gastrointestinal fluids, which seems to be the driving factor for the drug absorption as reported in vitro (Stappaerts et al, 2015).…”

Section: Discussionmentioning

confidence: 96%

Validity of cycloheximide chylomicron flow blocking method for the evaluation of lymphatic transport of drugs

Ryšánek

Grus

Kozlík

et al. 2021

British J Pharmacology

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Background and purpose Lymphatic transport of drugs after oral administration is an important mechanism for absorption of highly lipophilic compounds. Direct measurement in lymph duct cannulated animals is the gold standard method, but non‐invasive cycloheximide chylomicron flow blocking method has gained popularity recently. However, concerns about its reliability have been raised. The aim of this work was to investigate the validity of cycloheximide chylomicron flow blocking method for the evaluation of lymphatic transport using model compounds with high to very high lipophilicity, that is, abiraterone and cinacalcet. Experimental approach Series of pharmacokinetic studies were conducted with abiraterone acetate and cinacalcet hydrochloride after enteral/intravenous administration to intact, lymph duct cannulated and/or cycloheximide pre‐treated rats. Key results Mean total absolute oral bioavailability of abiraterone and cinacalcet was 7.0% and 28.7%, respectively. There was a large and significant overestimation of the lymphatic transport extent by the cycloheximide method. Mean relative lymphatic bioavailability of abiraterone and cinacalcet in cycloheximide method was 28‐fold and 3‐fold higher than in cannulation method, respectively. Conclusion and implications Cycloheximide chylomicron flow blocking method did not provide reliable results on lymphatic absorption and substantially overestimated lymphatic transport for both molecules, that is, abiraterone and cinacalcet. This non‐invasive method should not be used for the assessment of lymphatic transport and previously obtained data should be critically revised.

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Section: Prostate Cancer At a Glance: Progression And Classificationmentioning

confidence: 99%

“…[ 34 ] Abiraterone acetate exhibits poor solubility, thereby resulting in poor bioavailability; however, recent studies have reported novel formulation strategies to improve solubilization and bioavailability. [ 35 ] Radiotherapy includes alpha (Ra‐223) and beta (samarium‐153 and strontium‐89) therapies. Beta emitters are considered of higher risk when compared to alpha emitters due to the potential for bone marrow toxicity.…”

Section: Introductionmentioning

confidence: 99%

Nanomedicine for the Treatment of Advanced Prostate Cancer

Vicente‐Ruiz

Serrano‐Martí

Armiñán

et al. 2020

Advanced Therapeutics

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Current prostate cancer (PCa) treatment options include hormonal therapy, chemotherapy, immunotherapy, and radiotherapy; however, a lack of targeting and overall efficiency has failed to improve survival rates or reduce unwanted side‐effects in advanced stage PCa patients. The modification of existing therapeutics, including their reformulation as nanomedicines, can increase stability in plasma, enhance tumor targeting, and improve pharmacokinetics to foster improvements in patient outcomes. This review now describes those nanomedicinal approaches to advanced PCa treatment under evaluation in both preclinical and clinical studies. Despite the current advantages provided by nanomedicine in PCa treatment, there exists the opportunity to improve the design of novel therapeutic approaches. Therefore, this review also highlights the importance of identifying novel functional biomarkers to stratify patients and guide nanomedicinal design. Finally, the authors describe strategies employed to enhance the passive accumulation of nanomedicines in tumors and discuss the enormous potential of combination therapies that target tumor cells and the all‐important tumor microenvironment to reduce tumor growth and overcome therapeutic resistance.

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Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate

Cited by 42 publications

References 84 publications

Chitosan as Valuable Excipient for Oral and Topical Carvedilol Delivery Systems

Chitosan as Valuable Excipient for Oral and Topical Carvedilol Delivery Systems

Validity of cycloheximide chylomicron flow blocking method for the evaluation of lymphatic transport of drugs

Nanomedicine for the Treatment of Advanced Prostate Cancer

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