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Pharmaceutics
Special Issues
Novel Formulation Strategies to Overcome Biological Barrier Permeability Challenges
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Novel Formulation Strategies to Overcome Biological Barrier Permeability Challenges

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Physical Pharmacy and Formulation".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 1574

Special Issue Editors

Dr. Hassan Almoazen

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Guest Editor
College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Ave, Rm 661, Memphis, TN 38163, USA
Interests: pediatric formulations; enhancing drug solubility; enhancing drug stability; enhancing drug permeability; design of prodrugs
Special Issues, Collections and Topics in MDPI journals
Dr. Giovanna Rassu

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Guest Editor
Department of Chemistry and Pharmacy, University of Sassari, via Muroni 23/a, 07100 Sassari, Italy
Interests: mucosal drug delivery; in vitro and ex vivo permeation; mucoadhesive carrier
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Clara Ràfols

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Guest Editor
Department of Chemical Engineering and Analytical Chemistry, University of Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain
Interests: solubility; dissolution; lipophilicity; acidity; permeability; drug-protein/excipients interactions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Drug permeability is one of the most important factors limiting drug bioavailability and pharmacological activity. For any drug to be effective, it has to permeate different tissues and biological barriers to reach the desired target. Recent advancements in science have identified many biological barriers that can limit drug activities. Specifically, these barriers include intestinal epithelium, the blood–brain barrier, the stratum corneum of the skin, tumor microenvironments, and many more. The aim of this Special Issue is to explore new advancements in this area by highlighting prodrugs, novel drug delivery systems, and permeation enhancers and investigating other scientific approaches that can improve drug permeability through tissues.

Dr. Hassan Almoazen
Dr. Giovanna Rassu
Prof. Dr. Clara Ràfols
Guest Editors

Manuscript Submission Information

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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. Pharmaceutics 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 2900 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.

Keywords

  • skin permeability
  • blood–brain barrier
  • tumor permeability
  • intestinal permeability
  • muscle permeability
  • fat tissue permeability
  • cell membrane permeability
  • lung permeability
  • sublingual permeability
  • buccal permeability
  • tissue permeability

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Published Papers (2 papers)

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Research

16 pages, 2463 KB  
Article
Ex Vivo Buccal Permeability of Nanostructured Lipid Carriers (NLCs) Associated with a Peptide Drug Model
by Sebastián Vargas-Valderrama and Javier O. Morales
Pharmaceutics 2026, 18(4), 416; https://doi.org/10.3390/pharmaceutics18040416 - 29 Mar 2026
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Abstract
Background/Objective: Buccal delivery offers a potential route to circumvent gastrointestinal degradation and hepatic first-pass metabolism, but hydrophilic peptides typically exhibit limited mucosal permeation. Nanostructured lipid carriers (NLCs) have been proposed as delivery platforms capable of modulating interfacial interactions and improving mucosal transport. This [...] Read more.
Background/Objective: Buccal delivery offers a potential route to circumvent gastrointestinal degradation and hepatic first-pass metabolism, but hydrophilic peptides typically exhibit limited mucosal permeation. Nanostructured lipid carriers (NLCs) have been proposed as delivery platforms capable of modulating interfacial interactions and improving mucosal transport. This study aimed to quantitatively evaluate the ex vivo buccal permeation of angiotensin II (Ang II), used as a hydrophilic peptide model, when associated with NLCs compared with free peptide under matched Franz diffusion cell conditions. Methods: Ang II-associated NLCs were prepared by melt emulsification combined with a low-energy injection technique. Particle size, polydispersity index, and zeta potential were determined by dynamic light scattering and laser Doppler electrophoresis. Association efficiency and drug loading were quantified by indirect spectrofluorometric analysis. Ex vivo permeation studies were conducted using porcine buccal mucosa mounted in Franz diffusion cells, and cumulative permeation, steady-state flux, and apparent permeability coefficients were calculated. Results: The NLCs exhibited nanometric size, moderate polydispersity, and association efficiency above 80%, and remained colloidally stable at 4 °C for 28 days. In ex vivo experiments, Ang II-associated NLCs showed measurable cumulative permeation, reaching approximately 9% after 2 h, whereas free Ang II was not detected in the receptor compartment under the tested conditions. Conclusions: This work provides a quantitative ex vivo buccal transport comparison of a hydrophilic peptide model delivered as NLC-associated versus free peptide under matched Franz cell conditions. The findings support further investigation of NLC-based approaches for buccal delivery of vasoactive peptides and provide a rational basis for future in vivo evaluation of mucosal delivery performance and systemic exposure. Full article
(This article belongs to the Special Issue Novel Formulation Strategies to Overcome Biological Barrier Permeability Challenges)
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21 pages, 14299 KB  
Article
Mechanochemical Activation of Olanzapine in Mixed Solid Dispersions: Impact of Excipients on Release and Permeation Rates
by Tatyana Volkova, Olga Simonova and German Perlovich
Pharmaceutics 2026, 18(4), 411; https://doi.org/10.3390/pharmaceutics18040411 - 27 Mar 2026
Viewed by 540
Abstract
Background: The key parameters determining the bioavailability of an active pharmaceutical ingredient are its solubility/dissolution rate in physiological fluids and permeability across biological membranes. Highly accurate in vitro prediction of bioavailability is a key issue that typically arises during the development of [...] Read more.
Background: The key parameters determining the bioavailability of an active pharmaceutical ingredient are its solubility/dissolution rate in physiological fluids and permeability across biological membranes. Highly accurate in vitro prediction of bioavailability is a key issue that typically arises during the development of new drug formulations and the improvement of existing ones. Objectives: The objective of the present work is to study the dissolution/release and permeation of olanzapine (OLZ) from two- and three-component solid dispersions (SDs) with sulfobutylether-β-cyclodextrin (SBE-β-CD) and several pharmaceutical adjuvants as solubilizing agents. Methods: Solid dispersions were prepared by mechanical grinding and characterized with X-ray Phase analysis (PXRD), Fourier Transform Infrared (FTIR) and Raman spectroscopy, Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM). Results: Raman spectroscopy was shown to be the best for revealing the interactions of OLZ with SBE-β-CD and γ-aminobutyric acid (GABA) in the three-component SD. The kinetic dependences of OLZ release and diffusion through the cellulose membrane were thoroughly described by quantitative parameters and classified according to the drug release mechanism. Significant improvement of release rate, OLZ concentration, and permeation with SDs compared to the pure OLZ was demonstrated. Conclusions: It was shown that the selected dispersions were stable when stored under normal conditions but underwent changes upon exposure to elevated temperature and humidity. The nature of these changes was determined by the properties of the components and their mutual interactions. Full article
(This article belongs to the Special Issue Novel Formulation Strategies to Overcome Biological Barrier Permeability Challenges)
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