Topical Collection "Poorly Soluble Drugs"
Prof. Dr. Holger Grohganz
Former Guest Editor
Prof. Dr. Thomas Rades
Reseach Chair in Pharmaceutical Design and Drug Delivery Faculty of Health and Medical Sciences, Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 København Ø, Denmark
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Interests: the solid state of drugs and dosage forms; poorly water soluble drugs; amorphous drugs and drug delivery systems; lipid based drug delivery systems; analytical techniques in the solid state
Increasingly important bottlenecks for the development of medicines result from the poor aqueous solubilities and low dissolution rates of many small molecular weight drugs in the pipelines of pharmaceutical companies. To increase the solubilities and dissolution rates of drugs, and thus their bioavailabilities, several feasible approaches can be taken, and are of special interest, both in academia, and in the pharmaceutical industry. These include the conversion of crystalline drugs to their respective amorphous forms, the use of lipid based drug delivery systems, particle size reduction, salt-, co-crystal, and pro-drug formations, and the use of cyclodextrin complexes, to name but a few. This Special Issue aims to provide a forum for the dissemination of the latest information on new approaches and methods for dealing with poorly soluble drugs, and with methods of testing their success.
Prof. Dr. Korbinian Löbmann
Prof. Dr. Holger Grohganz
Prof. Dr. Guy Van den Mooter
Manuscript Submission Information
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.
- dissolution rate
- amorphous systems
- lipid based drug delivery systems
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Solid dispersions containing bicalutamide: effect of preparation method and excipients on dissolution rate
Abstract: Binary solid dispersions containing bicaludamide and poloxamer as a carrier were obtained using spray drying and solvent evaporation method. Both processes led to morphological changes and reduction of particle size what was confirmed by scanning electron microscopy and laser diffraction measurements. The effect of alteration of the crystal structure was followed by powder X-ray diffractometry while thermal properties of solid dispersions were determined using differential scanning calorimetry. Interestingly, while bicalutamide exhibited slight decrease in the crystallinity after processing, poloxamer underwent partial amorphization. Moreover, the surface activity of the carrier makes the binary systems formed nanoaggregates in water as confirmed using dynamic light scattering measurements. The aggregates having 200-300 nm in diameter were able to solubilize bicalutamide inside the hydrophobic inner parts. The self-assembly of binary systems was found to improve the dissolution of bicalutamide by 4 to 8-fold in comparison to untreated drug. Given the dissolution rate-limited absorption of bicalutamide, formation of solid dispersions exhibiting enhanced dissolution of the drug is of particular importance.
Predicting the in vivo performance of amorphous solid dispersions based on molecular properties of drug entities by statistical analysis
The manufacture of amorphous solid dispersions (ASD) circumvents the problem of low solubility in water of a large number of drugs. Unfortunately, the manufacture is time and resources consuming often leading to non-optimized results. Consequently an in silico model should provide a good approach to the design of a formulation for an optimal in vivo output. The work proposes a new statistical computational screening method to predict drug-polymer kinetic miscibility and in vivo performance [assessed by the area under the curve (AUC) and the maximum concentration (Cmax) in a plasmatic concentration*time plot] of an ASD based on a drug (API) and polymer (POL) molecular descriptors in combination with thermodynamic, kinetic and process considerations. The model also considers the presence of a solvent (ternary system) and the time dependency phenomena (components’ diffusion and solvent evaporation). The latter was demonstrated in the development of ASD produced by spray drying. The results obtained with the model not only enabled the ranking of the polymers according to their miscibility ability for the drug, but also the narrowing of an optimal drug load range within which drug-polymer miscibility was guaranteed.
The model was obtained by considering principal components analysis (PCA) of the results to enhance the relative importance of the variables and partial least squares (PLS) for the establishment of relationships between the descriptors and the pharmacokinetics variables. For the variability associated to the variables, the degree of correlation (R2=0.7) and the degree of predictability (Q2=0.5) can be considered acceptable for the model. Overall the model produced generalized performance trends and managed to identify the molecular descriptors with higher influence on the in vivo performance of ASDs.