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Pharmaceutics
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Buccal Drug Delivery
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Buccal Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (31 January 2019) | Viewed by 26570

Special Issue Editors

Prof. Dr. Dimitrios G. Fatouros

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Guest Editor
Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Interests: pharmaceutical nanotechnology; mucosal delivery; poorly soluble drugs; additive manufacturing
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Zeeshan Ahmad

E-Mail Website
Guest Editor
Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK
Interests: nanotechnology; pharmaceutical engineering; fibers; nanoparticles; manufacturing; biomaterials; dosage forms
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Buccal delivery is an alternative route of administration for either local delivery to the oral cavity or systemic release. The buccal route offers many advantages over conventional routes of drug delivery with an improved bioavailability at smaller doses than oral formulations due to the avoidance of degradation in the gastrointestinal tract and hepatic first-pass metabolism. Drugs can reach the systemic circulation directly through the capillary vessels, bypassing the first-pass metabolism in the intestine and liver or avoiding inactivation in the stomach. This Special Issue aims to present current state-of-the-art in buccal delivery of small and large molecules focusing on physiology, pharmacology, pathology, and formulation design.

We invite research scientists from the academia and pharmaceutical industry to submit original research articles or review articles.

Assoc. Prof. Dimitrios G. Fatouros
Prof. Zeeshan Ahmad
Guest Editors

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 submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue 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. 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

  • Buccal Delivery
  • Drug Absorption
  • Permeability
  • Absorption Enhancers
  • Passive Diffusion
  • Buccal Mucosa

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Published Papers (6 papers)

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Research

12 pages, 3254 KiB  
Article
In Vitro and Ex Vivo Evaluation of Tablets Containing Piroxicam-Cyclodextrin Complexes for Buccal Delivery
by Eleni Kontogiannidou, Martina Ferrari, Asteria-Danai Deligianni, Nikolaos Bouropoulos, Dimitrios A. Andreadis, Milena Sorrenti, Laura Catenacci, Kazem Nazari, Muhammad Sohail Arshad, Ming-Wei Chang, Zeeshan Ahmad and Dimitrios G. Fatouros
Pharmaceutics 2019, 11(8), 398; https://doi.org/10.3390/pharmaceutics11080398 - 8 Aug 2019
Cited by 16 | Viewed by 4989
Abstract
In the current study, the development of mucoadhesive tablets for buccal delivery of a non-steroidal anti-inflammatory drug was investigated. Binary complexes with piroxicam and cyclodextrins (β-cyclodextrin (β-CD), methylated-β-cyclodextrin (Me-β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD)) were prepared by the co-evaporation method. All formulations were characterized by [...] Read more.
In the current study, the development of mucoadhesive tablets for buccal delivery of a non-steroidal anti-inflammatory drug was investigated. Binary complexes with piroxicam and cyclodextrins (β-cyclodextrin (β-CD), methylated-β-cyclodextrin (Me-β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD)) were prepared by the co-evaporation method. All formulations were characterized by means of differential scanning calorimetry, infrared spectroscopy and powder X-ray diffractometry. Mucoadhesive tablets of binary systems were formulated by direct compression using chitosan as mucoadhesive polymer. The in vitro release profiles of tablets were conducted in simulated saliva and, the drug permeation studies, across porcine buccal mucosa. The results suggest that the rank order effect of cyclodextrins for the drug release was Me-β-CD > HP-β-CD > β-CD, whereas the ex vivo studies showed that the tablets containing chitosan significantly increased the transport of the drug compared to their free complexes. Finally, histological assessment revealed loss of the superficial cell layers, which might be attributed to the presence of cyclodextrins. Full article
(This article belongs to the Special Issue Buccal Drug Delivery)
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20 pages, 2689 KiB  
Article
Evaluation of Clay-Functionalized Wafers and Films for Nicotine Replacement Therapy via Buccal Mucosa
by Joshua Boateng and Obinna Okeke
Pharmaceutics 2019, 11(3), 104; https://doi.org/10.3390/pharmaceutics11030104 - 1 Mar 2019
Cited by 39 | Viewed by 4804
Abstract
The functional physicochemical properties of nicotine (NIC)-loaded composite freeze-dried wafers and solvent-evaporated films comprising hydroxypropylmethylcellulose (HPMC) and sodium alginate (SA), stabilized with magnesium aluminium silicate (MAS), have been reported. The formulations were characterized for swelling capacity, mucoadhesion, in vitro drug dissolution properties in [...] Read more.
The functional physicochemical properties of nicotine (NIC)-loaded composite freeze-dried wafers and solvent-evaporated films comprising hydroxypropylmethylcellulose (HPMC) and sodium alginate (SA), stabilized with magnesium aluminium silicate (MAS), have been reported. The formulations were characterized for swelling capacity, mucoadhesion, in vitro drug dissolution properties in simulated saliva (SS) and PBS at pH 6.8, and ex vivo and in vitro permeation using pig buccal mucosa membrane and EpiOralTM buccal tissue culture, respectively; finally, the cell viability of the EpiOralTM tissues after contact with the NIC-loaded formulations was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the functional characteristics compared with those of commercially available NIC strips. Swelling and NIC release from the HPMC–SA wafers were more prolonged (30 min) compared to the commercially available NIC strips which disintegrated rapidly and released the drug within 5 min. Generally, swelling, mucoadhesion, and drug release was faster in PBS than in SS, and the presence of MAS was essential for maintaining a high dose recovery compared to non-MAS formulations and commercial NIC strips, which showed lower percentage of NIC content, possibly due to evaporation during analysis. Permeation studies showed that the NIC released was able to cross both porcine buccal membrane and the EpiOralTM buccal tissue, with the latter showing higher permeation flux for all the formulations tested. All the NIC-loaded, MAS-stabilized formulations showed high tissue viability, with values above 80%, showing their great potential for use as buccal delivery platforms for NIC replacement therapy to aid smoking cessation. Full article
(This article belongs to the Special Issue Buccal Drug Delivery)
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9 pages, 589 KiB  
Article
Effect of an Experimental Formulation Containing Chlorhexidine on Pathogenic Biofilms and Drug Release Behavior in the Presence or Absence of Bacteria
by Ana Carolina S. Ré, Maria Carolina Bonjovanni, Maíra P. Ferreira, Osvaldo Freitas and Carolina P. Aires
Pharmaceutics 2019, 11(2), 88; https://doi.org/10.3390/pharmaceutics11020088 - 19 Feb 2019
Cited by 4 | Viewed by 3230
Abstract
(1) Background: For any antibacterial oral formulation to be successful, it must present effects in the presence of biofilms. Therefore, our aim is to analyze the drug release and the antibiofilm effects of a semi-solid formulation containing chlorhexidine (CHX) in the presence of [...] Read more.
(1) Background: For any antibacterial oral formulation to be successful, it must present effects in the presence of biofilms. Therefore, our aim is to analyze the drug release and the antibiofilm effects of a semi-solid formulation containing chlorhexidine (CHX) in the presence of pathogenic biofilms. (2) Methods: The biofilms of Streptococcus mutans (n = 6) or Porphyromonas gingivalis (n = 3) were formed for 6 and 4 days, respectively, being exposed to: 1) a CHX system or 2) vehicle control without CHX. A group without treatment was included as negative control. The acidogenicity, CHX quantification and bacterial viability were determined. A dissolution assay in a buffer and culture medium in the absence of bacteria was also performed. (3) Results: Although the CHX quantification in the culture medium of both biofilms was lower compared to the buffer (p < 0.05) and the culture medium in the absence of bacteria, the CHX system was able to display antibiofilm effects until 96 h for the S. mutans biofilms (p < 0.05) and 72 h for the P. gingivalis biofilms (p < 0.05). (4) Conclusions: The experimental formulation is able to extend chlorhexidine effects, even in challenging conditions such as in the presence of bacteria, allowing the in vitro control of cariogenic biofilms for 4 days and periodontopathogenic biofilms for 3 days. Full article
(This article belongs to the Special Issue Buccal Drug Delivery)
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23 pages, 3130 KiB  
Article
Enhanced In Situ Availability of Aphanizomenon Flos-Aquae Constituents Entrapped in Buccal Films for the Treatment of Oxidative Stress-Related Oral Diseases: Biomechanical Characterization and In Vitro/Ex Vivo Evaluation
by Viviana De Caro, Denise Murgia, Francesco Seidita, Emanuela Bologna, Gioacchino Alotta, Massimiliano Zingales and Giuseppina Campisi
Pharmaceutics 2019, 11(1), 35; https://doi.org/10.3390/pharmaceutics11010035 - 17 Jan 2019
Cited by 26 | Viewed by 4414
Abstract
In recent years, the key role of oxidative stress in pathogenesis of oral diseases has been emphasized and the use of antioxidant agents has been encouraged. Aphanizomenon flos-aquae (AFA) is a unicellular blue-green alga with antioxidant and anti-inflammatory properties. The aim of this [...] Read more.
In recent years, the key role of oxidative stress in pathogenesis of oral diseases has been emphasized and the use of antioxidant agents has been encouraged. Aphanizomenon flos-aquae (AFA) is a unicellular blue-green alga with antioxidant and anti-inflammatory properties. The aim of this study was the formulation and characterization of mucoadhesive thin layer films loaded with AFA, finalized to the treatment of oxidative stress (OS)-related oral diseases. First, to enhance the bioavailability of AFA constituents, the raw food grade material was appropriately treated by a high frequency homogenization able to disrupt cell walls. Thus, Eudragit® E100-based buccal films were produced by the solvent casting method, containing 7% and 18% of AFA. The films, characterized by uniformity in thickness, weight, and drug content, showed low swelling degree, good muco-adhesiveness and controlled drug release. The mechanical tests showed elastic moduli of films of almost 5 MPa that is well-suitable for human buccal applications without discomfort, besides biaxial tests highlighted a marked material isotropy. Permeation studies through porcine mucosae demonstrated the ability of films to promote AFA penetration in the tissues, and when sublingually administered, they produced a drug flux up to six-fold higher than an AFA solution. The new formulations represent an interesting alternative for the development of cosmetics and nutraceuticals with a functional appeal containing plant extracts. Full article
(This article belongs to the Special Issue Buccal Drug Delivery)
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17 pages, 1019 KiB  
Article
Buccal Bullfrog (Rana catesbeiana Shaw) Oil Emulsion: A Mucoadhesive System Intended for Treatment of Oral Candidiasis
by Susiane S. Moreira-Oliveira, Lucas Amaral-Machado, Wógenes Nunes De Oliveira, Éverton N. Alencar, Kelly Cristine Zatta, Luanda B. F. C. De Souza, Aldo da Cunha Medeiros, Guilherme Maranhão Chaves and Eryvaldo S. T. Egito
Pharmaceutics 2018, 10(4), 257; https://doi.org/10.3390/pharmaceutics10040257 - 3 Dec 2018
Cited by 7 | Viewed by 3814
Abstract
Oral candidiasis (OC) is an infectious disease caused by microorganisms of the genus Candida, leading to lesions in the buccal cavity. Its treatment consists of the administration of topical or systemic antifungal agents, which may compromise the patient compliance due to its [...] Read more.
Oral candidiasis (OC) is an infectious disease caused by microorganisms of the genus Candida, leading to lesions in the buccal cavity. Its treatment consists of the administration of topical or systemic antifungal agents, which may compromise the patient compliance due to its side effects, highlighting the need for alternative treatments. In this scenario, bullfrog oil, an animal oil composed of a pool of saturated and unsaturated fatty acids, is introduced as a potential antifungal raw material. Thus, the aim of this work was to produce a mucoadhesive emulsified system able to deliver the bullfrog oil in the buccal cavity to treat the OC. The emulsion was produced and characterized by visual inspection, droplet size, polydispersity index (PdI), and zeta potential over the course of 60 days. In addition, its mucoadhesive ability was evaluated using an in vitro mucin model. The antifungal activity, evaluated by the broth microdilution assay and the biocompatibility, performed against human erythrocytes, were also carried out. The emulsion showed a droplet size of 320.79 ± 35.60 nm, a PdI of 0.49 ± 0.08, and a zeta potential of −38.53 ± 6.23 mV, with no significant changes over 60 days. The mucoadhesive properties of the system was improved by the use of pharmaceutical excipients. The antifungal activity showed that the bullfrog oil and the emulsion were able to inhibit the growth of different Candida species. Furthermore, the emulsion showed no significant hemolytic effect. Overall, the system showed suitable physicochemical characteristics and biocompatibility, with substantial in vitro antifungal activity, suggesting that this system can be further investigated for OC treatment. Full article
(This article belongs to the Special Issue Buccal Drug Delivery)
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10 pages, 908 KiB  
Article
New Insights on the Mechanism of Fatty Acids as Buccal Permeation Enhancers
by Cristina Padula, Silvia Pescina, Sara Nicoli and Patrizia Santi
Pharmaceutics 2018, 10(4), 201; https://doi.org/10.3390/pharmaceutics10040201 - 24 Oct 2018
Cited by 30 | Viewed by 4002
Abstract
Buccal mucosa has recently received much attention as a potential route for systemic delivery of drugs, including biologics and vaccines. The aim of this work was to gain insight into the mechanism of fatty acids as buccal permeation enhancers, by studying the effect [...] Read more.
Buccal mucosa has recently received much attention as a potential route for systemic delivery of drugs, including biologics and vaccines. The aim of this work was to gain insight into the mechanism of fatty acids as buccal permeation enhancers, by studying the effect of a series of medium and long chain fatty acids on the permeation of a model high molecular weight and hydrophilic molecule, fluorescein isothiocyanate labelled dextran (FD-4, m.w. 4 kDa) across porcine esophageal epithelium. A parabolic relationship between fatty acid lipophilicity and enhancement was obtained, regardless of the presence and number of double bonds. The relationship, which resembles the well-known relationship between permeability and lipophilicity of transdermal delivery, presents a maximum value in correspondence of C10 (logP approx. 4). This is probably the ideal lipophilicity for the fatty acid to interact with the lipid domains of the mucosa. When the same analysis was performed on skin data, the same trend was observed, although the maximum value was reached for C12 (logP approx. 5), in agreement with the higher lipophilicity of the skin. The results obtained in the present work represent a significant advancement in the understanding of the mechanisms of action of fatty acids as buccal penetration enhancers. Full article
(This article belongs to the Special Issue Buccal Drug Delivery)
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