Biorelevant dissolution instruments represent an important tool for pharmaceutical research and development. These instruments are designed to simulate the dissolution of drug formulations in conditions most closely mimicking the gastrointestinal tract. In this work, we focused on the optimization of dissolution compartments/vessels for an updated version of the biorelevant dissolution apparatus-Golem v2. We designed eight compartments of uniform size but different inner geometry. The dissolution performance of the compartments was tested using immediate release caffeine tablets and evaluated by standard statistical methods and principal component analysis. Based on two phases of dissolution testing (using 250 and 100 mL of dissolution medium), we selected two compartment types yielding the highest measurement reproducibility. We also confirmed a statistically ssignificant effect of agitation rate and dissolution volume on the extent of drug dissolved and measurement reproducibility.
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http://dx.doi.org/10.3390/molecules22122042 | DOI Listing |
Pharm Dev Technol
January 2025
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Madhavnagar, Manipal - 576104, Karnataka, India.
Purpose: Supersaturated formulations have been widely explored for improving the oral bioavailability of drugs by using mesoporous silica (MS) to generate supersaturation via molecular adsorption; however, this is followed by precipitation. Several precipitation inhibitors (PI) have been explored to prevent precipitation and maintain the drug in solution for a longer period. However, the combined approach of MS and PIs, the impact of MS and Silica, and the loading of high-molecular-weight neutral molecules such as Cyclosporine A (CsA) have not yet been explored.
View Article and Find Full Text PDFJ Pharm Sci
December 2024
Janssen Research & Development, LLC, Discovery Pharmaceutics, San Diego, CA, USA.
Rat pharmacokinetic studies are commonly utilized in early discovery to support absorption, distribution, metabolism, and excretion optimization of active pharmaceutical ingredients (APIs). The aim of this work was to compare exposures from fit-for-purpose oral suspension and solution formulations in rats to guidance provided by the refined Developability Classification System (rDCS) with respect to identifying potential limits to oral absorption, formulation strategy selection, and to optimize oral bioavailability (BA). This investigation utilized six diverse APIs covering a large range of biorelevant solubility, metabolic stability, and oral BA in rats.
View Article and Find Full Text PDFJ Pharm Sci
December 2024
Department of Physics Chemistry and Pharmacy, University of Southern Denmark, SDU, FKF, Campusvej 52, Odense, 5230, Denmark. Electronic address:
For compendial dissolution testing of solid dosage forms, media volumes of 500 to 900 mL are used in apparatus I and II to ensure sink conditions. However, these volumes are considerably larger than those in the gastrointestinal tract. Thus, the experiments are not biomimetic and possibly not suitable for biopredictive dissolution testing.
View Article and Find Full Text PDFAAPS PharmSciTech
December 2024
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, China.
A slight variation in in vivo exposure for tacrolimus extended-release (ER) capsules, which have a narrow therapeutic index (NTI), significantly affects the pharmacodynamics of the drug. Generic drug bioequivalence (BE) standards are stricter, necessitating accurate assessment of the rate and extent of drug release. Therefore, an in vitro dissolution method with high in vivo predictive power is crucial for developing generic drugs.
View Article and Find Full Text PDFMolecules
November 2024
Department of Chemistry, Physical Chemistry Section & C.S.G.I. (Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase), University of Pavia, Via Taramelli 16, 27100 Pavia, Italy.
Pimozide is a first-generation antipsychotic used in the treatment of schizophrenia, Gilles de la Tourette syndrome, and other chronic psychoses. Its in vivo efficacy is limited by poor solubility and consequent poor bioavailability. Therefore, adipic acid was used as a coformer for the preparation of a binary product with improved pharmaceutical properties.
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