Article
Instruments & Instrumentation
Giovanna Rassu, Antonella Obinu, Carla Serri, Sandra Piras, Antonio Carta, Luca Ferraro, Elisabetta Gavini, Paolo Giunchedi, Alessandro Dalpiaz
Summary: In this study, PLGA nanoparticles (SS13NP) and solid lipid nanoparticles (SS13SLN) loaded with SS13 were prepared. SS13NP showed higher drug bioavailability and shorter time to reach peak concentration in oral administration compared with SS13SLN. These results confirm that the chemical composition of nanoparticles significantly affects the in vivo fate of a BCS IV drug. Moreover, PLGA nanoparticles appear more efficient and rapid than SLN in allowing drug absorption and transport to systemic circulation.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Maria Antonia Tanase, Adina Raducan, Petruta Oancea, Lia Mara Ditu, Miruna Stan, Cristian Petcu, Cristina Scomoroscenco, Claudia Mihaela Ninciuleanu, Cristina Lavinia Nistor, Ludmila Otilia Cinteza
Summary: Novel polymeric mixed micelles from Pluronic F127 and Cremophor EL were studied as drug delivery systems for Norfloxacin. The optimal molar ratio of surfactants was determined to prepare carriers with minimal surfactant concentrations. The mixed micelles showed tunable extended release of Norfloxacin and good activity against clinical isolated strains, while some cytotoxicity was found at high concentrations.
Article
Chemistry, Multidisciplinary
Min-Jun Baek, Ju-Hwan Park, Duy-Thuc Nguyen, Dahan Kim, Jaehwan Kim, Il-Mo Kang, Dae-Duk Kim
Summary: This study explores the use of bentonite as a water-insoluble matrix for improving the oral bioavailability of poorly water-soluble drugs. By adsorbing drugs onto bentonite, amorphous composites can be formed, enhancing the dissolution and oral absorption of the drugs.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Pharmacology & Pharmacy
Anum Munir Awan, Arshad Farid, Shefaat Ullah Shah, Dildar Khan, Fiza Ur Rehman, Muhammad Junaid Dar, Tayyaba Iftikhar, Shakira Ghazanfar, Charis M. Galanakis, Abdulhakeem S. Alamri, Syed Mohammed Basheeruddin Asdaq, Kifayat Ullah Shah
Summary: This study successfully developed stabilizer-coated AMH nanocrystals (AMH-NCs) which improved the solubility, dissolution profile, and oral bioavailability of the highly lipophilic drug AMH. The optimized formulation exhibited desirable properties in terms of particle size, zeta potential, and polydispersity index, and demonstrated good stability over a period of three months. In vivo pharmacokinetic study showed that AMH-NCs significantly enhanced the oral bioavailability of AMH compared to the AMH solution.
Article
Biochemistry & Molecular Biology
Li Zhang, Dewen Kong, Hongjuan Wang, Lingtai Jiao, Xiaoyue Zhao, Junke Song, Dezhi Yang, Haiguang Yang, Shiying Yang, Guanhua Du, Yang Lu
Summary: Novel cocrystals composed of two antithrombotic drugs with poor solubility were developed in this study to improve their solubility, bioavailability, and stability. Compared to physical mixtures and individual drugs, the cocrystals showed significantly enhanced dissolution behavior and increased bioavailability. The study provides a novel approach to overcome the limitations of drug combinations.
Article
Pharmacology & Pharmacy
Wei Xin, Yumei Wang, Yan Bian, Jiahui Lin, Wenhao Weng, Xinyi Zhao, Kaijun Gou, Xianmou Guo, Heran Li
Summary: In this study, a novel chiral mesoporous silica PEIs@TA-CMS was successfully synthesized and found to have superior drug loading and release capabilities compared to MCM41. It displayed high efficiency in incorporating nimodipine, with a significant dissolution-promoting effect and improved oral absorption rate. PEIs@TA-CMS could effectively prolong the survival time of mice on cerebral anoxia, showing approximately 3.26-fold higher bioavailability.
Article
Pharmacology & Pharmacy
Ayat Abdelkader, Eduard Preis, Cornelia M. Keck
Summary: smartFilm tablets are an innovative and cost-effective formulation approach for improving the oral delivery of poorly water-soluble drugs, demonstrating enhanced dissolution rate and potential for industrial feasibility.
Article
Pharmacology & Pharmacy
Xinyue Zhang, Jie Li, Rong Rong, Dangge Wang, Donghai Wang, Yanling Yu, Pei Wu, Yaping Li, Zhiwen Zhang
Summary: A solid nanodispersion system of poorly water-soluble amisupride (AMS) was designed by dispersing AMS into a polymeric matrix. The system exhibited a transformation into nanometer-sized particles upon exposure to gastrointestinal fluids and significantly improved the oral bioavailability of AMS. Compared to the AMS suspension, the absorption of AMS in different parts of the gastrointestinal tract increased significantly by 8.02, 32.18, and 9.11-fold, and the oral bioavailability of AMS was enhanced by 8.58-fold.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Article
Nanoscience & Nanotechnology
Junying Zhang, Yiwen Zhang, Hufang Wang, Wenlin Chen, Aiyu Lu, Hailiang Li, Lifeng Kang, Chunyong Wu
Summary: This study prepared a solid dispersion of CUR in Mogroside V (Mog-V), a non-nutritive natural sweetener, which can self-assemble into micelles in water and effectively improve the water solubility and oral absorption of CUR. The results showed that compared with pure CUR crystals, the solid dispersion increased the solubility of CUR by nearly 6000 times and the oral absorption of CUR by 29 folds in rats.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Arvind Sharma, Kanika Arora, Harapriya Mohapatra, Rakesh K. Sindhu, Madalin Bulzan, Simona Cavalu, Gulsheen Paneshar, Hosam O. Elansary, Ahmed M. El-Sabrout, Eman A. Mahmoud, Abdullah Alaklabi
Summary: This review addresses the latest developments in supersaturated drug delivery systems.
Review
Biochemistry & Molecular Biology
Dixit Bhalani, Bhingaradiya Nutan, Avinash Kumar, Arvind K. Singh Chandel
Summary: The low water solubility of pharmacoactive molecules limits their pharmacological potential, and the pharmaceutical industry faces challenges in enhancing the solubility and bioavailability of drugs. However, there are various technologies available to improve the solubility of poorly water-soluble drugs.
Article
Pharmacology & Pharmacy
Phuong Tran, Jeong-Sook Park
Summary: Dexibuprofen-loaded solid dispersion (SD) was formulated to improve solubility and bioavailability, with results demonstrating excellent potential for the SD formulation as a solution for poorly soluble drug Dexibuprofen.
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
(2021)
Review
Pharmacology & Pharmacy
Sara Meirinho, Marcio Rodrigues, Adriana O. Santos, Amilcar Falcao, Gilberto Alves
Summary: Efforts are made to improve the bioavailability of neurotherapeutics through various approaches, with intranasal administration emerging as an attractive option. Self-emulsifying drug delivery systems (SEDDS) as a lipidic nanosystem can overcome the blood-brain barrier and enhance the brain targeting and bioavailability of drugs.
Article
Chemistry, Medicinal
Daniela A. S. Agostinho, Ana R. Jesus, Ana B. P. Silva, Jose M. S. S. Esperanca, Alexandre Paiva, Ana R. C. Duarte, Patricia M. Reis
Summary: New dianionic phosphonate anion based ionic liquids significantly improved the water solubility of piroxicam and ibuprofen with low cytotoxicity, potentially beneficial for oral drug formulation studies.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Review
Chemistry, Physical
Ambreen Shoaib, Bharti Mangla, Shamama Javed, Muhammad H. Sultan, Saad S. Alqahtani, Faiyaz Shakeel
Summary: A drug product should have aqueous solubility to prevent bioavailability issues, which can hinder safety and efficacy. Techniques such as pharmaceutical nanoparticle engineering, specifically liquid crystal technology, have been developed to enhance drug solubility and bioavailability. These new technologies offer potential for improving drug dissolution and efficacy.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Chemistry, Medicinal
Jonas Borregaard Eriksen, Ann-Christin Jacobsen, Katrine Taekker Christensen, Annette Bauer-Brandl, Martin Brandl
Summary: To achieve high sample throughput, permeation experiments are often conducted using 96-well sandwich plates. However, agitation is often omitted in these experiments due to difficulties associated with orbital shaking and limited availability of other agitation techniques. This study compared the effects of orbital shaking and magnetic stirring on the permeability of model compounds with different water-solubilities. The results showed that magnetic stirring was more efficient in distributing dye within the donor compartment and achieving maximum trans-barrier flux compared to orbital shaking. Additionally, insufficient mixing was found to have the greatest impact on permeation, especially for lipophilic compounds. The study also investigated the well-to-well cross-talk during permeation experiments with orbital shaking and found that using a liquid volume of 250-300 μL in the bottom compartment of the plates reduced cross-talk.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Medicinal
Jonas Borregaard Eriksen, Stine Bredow Christensen, Annette Bauer-Brandl, Martin Brandl
Summary: This study aimed to investigate the impact of the interaction between bile salts and cyclodextrins on the dissolution-permeation of poorly soluble drug compounds. The results showed that the interplay between bile salts and cyclodextrins can enhance the free fraction of the drug in solution to a greater extent than using either component alone.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Joseph P. O'Shea, Patrick Augustijns, Martin Brandl, David J. Brayden, Joachim Brouwers, Brendan T. Griffin, Rene Holm, Ann-Christin Jacobsen, Hans Lennernas, Zahari Vinarov, Caitriona M. O'Driscoll
Summary: This article discusses the complexity of oral drug absorption and the importance of evaluating intestinal permeability. It provides a critique of in vivo, in vitro, and ex vivo approaches for assessing drug permeability. Continued improvement and validation of in silico models will enhance early characterization of permeability and facilitate absorption modeling.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Jonas Borregaard Eriksen, Hesham Barakat, Barbara Luppi, Martin Brandl, Annette Bauer-Brandl
Summary: Treating the PermeaPad(R) barrier with low osmolality solutions appears to enhance the transport of hydrophilic compounds by inducing the osmotic shrinking of lipid vesicles, creating wider water channels for compound passage.
Article
Pharmacology & Pharmacy
Florentin Lukas Holzem, Jeannine Petrig Schaffland, Martin Brandl, Annette Bauer-Brandl, Cordula Stillhart
Summary: This study investigated the dissolution, supersaturation, and precipitation behavior of a poorly water-soluble drug using different sampling methods. The results provided insights into the release and absorption mechanisms of the drug, and demonstrated the importance of microdialysis and nanofiltration approaches for the evaluation of drug formulations.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Florentin Lukas Holzem, Anika Weck, Jeannine Petrig Schaffland, Cordula Stillhart, Sandra Klein, Annette Bauer-Brandl, Martin Brandl
Summary: The majority of new drugs have poor water solubility, which requires the development of enabling formulations for sufficient bioavailability upon oral administration. This study compared the biopredictive abilities of two in vitro tools for predicting intestinal supersaturation and systemic absorption of drug formulations. The PermeaLoop™ apparatus showed better predictive ability compared to the mu FLUX™ setup. The study confirms the usefulness of these tools for formulation ranking of weakly basic compounds and supersaturating formulations.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Jonas Borregaard Eriksen, Jeppe Juhl Christiansen, Annette Bauer-Brandl, Marika Ruponen, Jarkko Rautio, Martin Brandl
Summary: Fosamprenavir is a phosphate ester prodrug that can be converted into the parent drug amprenavir. A novel in vitro setup was designed to monitor the dissolution/bioconversion/permeation process of fosamprenavir. The setup consisted of diffusion cells with a biomimetic barrier, and microdialysis sampling was used to follow the enzymatic conversion in real-time. The results showed supersaturation of amprenavir and increased flux across the biomimetic barrier.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Chemistry, Medicinal
Arianna Cuoco, Jonas Borregaard Eriksen, Barbara Luppi, Martin Brandl, Annette Bauer-Brandl
Summary: This study investigated the influence of bile salts and phospholipids on the absorption of itraconazole from Sporanox(R) oral solution. It was found that both bile salts and phospholipids increased the solubility of itraconazole, but higher concentrations of bile salts resulted in a faster decrease in solubility and reduced in vitro permeation.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Mette Sloth Bohsen, Sofie Tandrup Tychsen, Ali Abdul Hussein Kadhim, Holger Grohganz, Alexander H. Treusch, Martin Brandl
Summary: The stability of liposomes against intestinal bile salts is crucial for oral drug delivery. AF4/MALLS/dRI was used to monitor the structural rearrangement of liposomes exposed to bile salt and to predict their in vitro stability. The results showed that liposomes containing cholesterol had increased stability compared to those without cholesterol.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Jakob Tobias Lynnerup, Jonas Borregaard Eriksen, Annette Bauer-Brandl, Ann Mari Holsaeter, Martin Brandl
Summary: As numerous new drug candidates are poorly water soluble, enabling formulations are needed to increase their bioavailability for oral administration. This study aimed to gain insight into nanoparticle characteristics and performance using an in vitro combined dissolution/permeation setup. The results showed that nanosuspensions exhibited significantly increased dissolution rates and permeation rates compared to the raw APIs.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Patricia D. Nunes, Joao F. Pinto, Annette Bauer-Brandl, Martin Brandl, Joao Henriques, Ana Mafalda Paiva
Summary: With the increasing demand for candidate-enabling formulations, there is a need for in vitro bioavailability forecasting. This study presents a PermeaLoopTM based dissolution/permeation assay for evaluating drug release and permeation simultaneously using different Itraconazole (ITZ)-based amorphous solid dispersions (ASD) formulations. The standardized approach described in this study contributes to the development of in vitro preclinical drug product development.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Patricia D. Nunes, Ana Filipa Ferreira, Joao F. Pinto, Annette Bauer-Brandl, Martin Brandl, Joao Henriques, Ana Mafalda Paiva
Summary: The increasing demand for complex formulations requires appropriate in vitro methodologies to predict their in vivo performance and the mechanisms controlling drug release. In vitro dissolution-permeation (D/P) methodologies are being used to rank the performance of enabling formulations during early development. In this study, two different cell-free in vitro D/P setups were used to evaluate the dissolution-permeation interplay of itraconazole (ITZ)-HPMCAS amorphous solid dispersions (ASDs) with different drug loads. A solvent-shift approach was employed, and microdialysis sampling was used to separate the dissolved drug from other species in solution. The results showed that BioFLUXTM and PermeaLoopTM have different applications in the drug product development pipeline.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Florentin Lukas Holzem, Iben Hojgaard Jensen, Jeannine Petrig Schaffland, Cordula Stillhart, Martin Brandl, Annette Bauer-Brandl
Summary: The combination of microdialysis and dissolution/permeation (D/P) assays can provide more accurate assessment and prediction of drug absorption and dissolution characteristics, especially for poorly soluble drugs and supersaturating formulations.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Mikolaj Czajkowski, Ann-Christin Jacobsen, Annette Bauer-Brandl, Martin Brandl, Paulina Skupin-Mrugalska
Summary: This study aimed to evaluate the feasibility and potential role of hydrogenated phospholipid as a matrix material and solubilizing additive for binary or ternary solid dispersions. It was found that hydrogenated phospholipid has the potential to enhance dissolution and bioavailability, and may be a viable formulation strategy to mitigate the food effect of fenofibrate.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Kimberly Raines, Payal Agarwal, Patrick Augustijns, Alaadin Alayoubi, Lucas Attia, Annette Bauer-Brandl, Martin Brandl, Parnali Chatterjee, Hansong Chen, Yuly Chiang Yu, Carrie Coutant, Ana Luisa Coutinho, David Curran, Jennifer Dressman, Bryan Ericksen, Leah Falade, Yi Gao, Zongming Gao, Debasis Ghosh, Tapash Ghosh, Anitha Govada, Elizabeth Gray, Ruiqiong Guo, Dana Hammell, Andre Hermans, Rohit Jaini, Hanlin Li, Haritha Mandula, Shuaiqian Men, Johanna Milsmann, Huong Moldthan, Rebecca Moody, Dana E. Moseson, Anette Muellertz, Roshni Patel, Kalpana Paudel, Christos Reppas, Rajesh Savkur, Kerstin Schaefer, Abu Serajuddin, Lynne S. Taylor, Rutu Valapil, Kevin Wei, Werner Weitschies, Shinji Yamashita, James E. Polli
Summary: The in-person workshop Drug Dissolution in Oral Drug Absorption was organized into lectures and breakout sessions, focusing on topics such as amorphous solid dispersions, dissolution/permeation interplay, and in vitro methods to predict in vivo biopharmaceutics performance and risk. The discussions highlighted the assessment of dissolved drugs, limitations of current testing methods for poorly water soluble drugs, non-compendial methods and conditions, and the potential benefits of integrating quality control and biopredictive/biorelevant methods.