Pharmaceutics

Research

17 pages, 3415 KiB

Open AccessArticle

Study on the Scale-Up Possibility of a Combined Wet Grinding Technique Intended for Oral Administration of Meloxicam Nanosuspension

by Csilla Bartos, Anett Motzwickler-Németh, Dávid Kovács, Katalin Burián and Rita Ambrus

Pharmaceutics 2024, 16(12), 1512; https://doi.org/10.3390/pharmaceutics16121512 - 25 Nov 2024

Viewed by 558

Abstract

Background/Objectives: This article reports on the scalability of a combined wet grinding technique applying planetary ball mill and ZrO₂ pearls as the grinding medium. After the determination of the parameters in a laboratory scale, the tenfold scale-up method was set. Meloxicam (MEL) [...] Read more.

Background/Objectives: This article reports on the scalability of a combined wet grinding technique applying planetary ball mill and ZrO₂ pearls as the grinding medium. After the determination of the parameters in a laboratory scale, the tenfold scale-up method was set. Meloxicam (MEL) was used as a nonsteroidal anti-inflammatory drug (NSAID) intended for per os delivery. During grinding, the PVA solution was used as a dispersion medium. Methods: The influence of the scaling-up on the particle size, morphology, crystallinity, and intra- and interparticulate phenomena has been studied. Formulation investigations of the milled suspensions were carried out. The dissolution test and the cytotoxicity analyses were accomplished. Results: Submicron MEL particle-containing samples were produced in both grinding scales. After the particle size determination was achieved from the suspensions, the wet milled, dried products were studied. The particle size of the dried products fell into the same range for both scales of milling (the maximum particle size was about 580 nm). There was no significant difference in drug crystallinity after the grindings; 70% of MEL remained crystalline in both cases. A remarkable interaction between the components did not develop as a result of milling. The polarity of the products increased, which resulted in a better dissolution, especially in the case of intestinal fluid (~100% in the first 5 min). The products were not found to be toxic. Conclusions: This research demonstrates that the scaling-up of combined wet grinding technique is feasible by adjusting the milling parameters and the adequate amount of excipient. Full article

(This article belongs to the Special Issue Advances in Oral Administration)

► Show Figures

Figure 1

15 pages, 1029 KiB

Open AccessArticle

Pharmacometrics to Evaluate Dosing of the Patient-Friendly Ivermectin CHILD-IVITAB in Children ≥ 15 kg and <15 kg

by Klervi Golhen, Michael Buettcher, Jörg Huwyler, John van den Anker, Verena Gotta, Kim Dao, Laura E. Rothuizen, Kevin Kobylinski and Marc Pfister

Pharmaceutics 2024, 16(9), 1186; https://doi.org/10.3390/pharmaceutics16091186 - 7 Sep 2024

Viewed by 1247

Abstract

The antiparasitic drug ivermectin is approved for persons > 15 kg in the US and EU. A pharmacometric (PMX) population model with clinical PK data was developed (i) to characterize the effect of the patient-friendly ivermectin formulation CHILD-IVITAB on the absorption process and [...] Read more.

The antiparasitic drug ivermectin is approved for persons > 15 kg in the US and EU. A pharmacometric (PMX) population model with clinical PK data was developed (i) to characterize the effect of the patient-friendly ivermectin formulation CHILD-IVITAB on the absorption process and (ii) to evaluate dosing for studies in children < 15 kg. Simulations were performed to identify dosing with CHILD-IVITAB associated with similar exposure coverage in children ≥ 15 kg and < 15 kg as observed in adults receiving the reference formulation STROMECTOL^®. A total of 448 ivermectin concentrations were available from 16 healthy adults. The absorption rate constant was 2.41 h⁻¹ (CV 19%) for CHILD-IVITAB vs. 1.56 h⁻¹ (CV 43%) for STROMECTOL^®. Simulations indicated that 250 µg/kg of CHILD-IVITAB is associated with exposure coverage in children < 15 kg consistent with that observed in children ≥ 15 kg and adults receiving 200 µg/kg of STROMECTOL^®. Performed analysis confirmed that CHILD-IVITAB is associated with faster and more controlled absorption than STROMECTOL^®. Simulations indicate that 250 µg/kg of CHILD-IVITAB achieves equivalent ivermectin exposure coverage in children < 15 kg as seen in children ≥ 15 kg and adults. Full article

(This article belongs to the Special Issue Advances in Oral Administration)

► Show Figures

Figure 1

22 pages, 6720 KiB

Open AccessEditor’s ChoiceArticle

Archaeosomes for Oral Drug Delivery: From Continuous Microfluidics Production to Powdered Formulations

by Ivan Vidakovic, Karin Kornmueller, Daniela Fiedler, Johannes Khinast, Eleonore Fröhlich, Gerd Leitinger, Christina Horn, Julian Quehenberger, Oliver Spadiut and Ruth Prassl

Pharmaceutics 2024, 16(6), 694; https://doi.org/10.3390/pharmaceutics16060694 - 23 May 2024

Cited by 1 | Viewed by 1338

Abstract

Archaeosomes were manufactured from natural archaeal lipids by a microfluidics-assisted single-step production method utilizing a mixture of di- and tetraether lipids extracted from Sulfolobus acidocaldarius. The primary aim of this study was to investigate the exceptional stability of archaeosomes as potential carriers for [...] Read more.

Archaeosomes were manufactured from natural archaeal lipids by a microfluidics-assisted single-step production method utilizing a mixture of di- and tetraether lipids extracted from Sulfolobus acidocaldarius. The primary aim of this study was to investigate the exceptional stability of archaeosomes as potential carriers for oral drug delivery, with a focus on powdered formulations. The archaeosomes were negatively charged with a size of approximately 100 nm and a low polydispersity index. To assess their suitability for oral delivery, the archaeosomes were loaded with two model drugs: calcein, a fluorescent compound, and insulin, a peptide hormone. The archaeosomes demonstrated high stability in simulated intestinal fluids, with only 5% of the encapsulated compounds being released after 24 h, regardless of the presence of degrading enzymes or extremely acidic pH values such as those found in the stomach. In a co-culture cell model system mimicking the intestinal barrier, the archaeosomes showed strong adhesion to the cell membranes, facilitating a slow release of contents. The archaeosomes were loaded with insulin in a single-step procedure achieving an encapsulation efficiency of approximately 35%. These particles have been exposed to extreme manufacturing temperatures during freeze-drying and spray-drying processes, demonstrating remarkable resilience under these harsh conditions. The fabrication of stable dry powder formulations of archaeosomes represents a promising advancement toward the development of solid dosage forms for oral delivery of biological drugs. Full article

(This article belongs to the Special Issue Advances in Oral Administration)

► Show Figures

Graphical abstract

15 pages, 2928 KiB

Open AccessEditor’s ChoiceArticle

Cryo-Milled β-Glucan Nanoparticles for Oral Drug Delivery

by Guanyu Chen, Yi Liu, Darren Svirskis, Hongyu Li, Man Ying, Weiyue Lu and Jingyuan Wen

Pharmaceutics 2024, 16(4), 546; https://doi.org/10.3390/pharmaceutics16040546 - 16 Apr 2024

Viewed by 1679

Abstract

Gemcitabine is a nucleoside analog effective against a number of cancers. However, it has an oral bioavailability of less than 10%, due to its high hydrophilicity and low permeability through the intestinal epithelium. Therefore, the aim of this project was to develop a [...] Read more.

Gemcitabine is a nucleoside analog effective against a number of cancers. However, it has an oral bioavailability of less than 10%, due to its high hydrophilicity and low permeability through the intestinal epithelium. Therefore, the aim of this project was to develop a novel nanoparticulate drug delivery system for the oral delivery of gemcitabine to improve its oral bioavailability. In this study, gemcitabine-loaded β-glucan NPs were fabricated using a film-casting method followed by a freezer-milling technique. As a result, the NPs showed a small particle size of 447.6 ± 14.2 nm, and a high drug entrapment efficiency of 64.3 ± 2.1%. By encapsulating gemcitabine into β-glucan NPs, a sustained drug release profile was obtained, and the anomalous diffusion release mechanism was analyzed, indicating that the drug release was governed by diffusion through the NP matrix as well as matrix erosion. The drug-loaded NPs had a greater ex vivo drug permeation through the porcine intestinal epithelial membrane compared to the plain drug solution. Cytotoxicity studies showed a safety profile of the β-glucan polymers, and the IC_50s of drug solution and drug-loaded β-glucan NPs were calculated as 228.8 ± 31.2 ng·mL⁻¹ and 306.1 ± 46.3 ng·mL⁻¹, respectively. Additionally, the LD₅₀ of BALB/c nude mice was determined as 204.17 mg/kg in the acute toxicity studies. Notably, pharmacokinetic studies showed that drug-loaded β-glucan NPs could achieve a 7.4-fold longer T_1/2 and a 5.1-fold increase in oral bioavailability compared with plain drug solution. Finally, in vivo pharmacodynamic studies showed the promising capability of gemcitabine-loaded β-glucan NPs to inhibit the 4T1 breast tumor growth, with a 3.04- and 1.74-fold reduction compared to the untreated control and drug solution groups, respectively. In conclusion, the presented freezer-milled β-glucan NP system is a suitable drug delivery method for the oral delivery of gemcitabine and demonstrates a promising potential platform for oral chemotherapy. Full article

(This article belongs to the Special Issue Advances in Oral Administration)

► Show Figures

Figure 1

23 pages, 8398 KiB

Open AccessEditor’s ChoiceArticle

Cellular Uptake and Transport Mechanism Investigations of PEGylated Niosomes for Improving the Oral Delivery of Thymopentin

by Mengyang Liu, Darren Svirskis, Thomas Proft, Jacelyn Loh, Yuan Huang and Jingyuan Wen

Pharmaceutics 2024, 16(3), 397; https://doi.org/10.3390/pharmaceutics16030397 - 14 Mar 2024

Viewed by 1629

Abstract

Background: Although its immunomodulatory properties make thymopentin (TP5) appealing, its rapid metabolism and inactivation in the digestive system pose significant challenges for global scientists. PEGylated niosomal nanocarriers are hypothesized to improve the physicochemical stability of TP5, and to enhance its intestinal permeability for [...] Read more.

Background: Although its immunomodulatory properties make thymopentin (TP5) appealing, its rapid metabolism and inactivation in the digestive system pose significant challenges for global scientists. PEGylated niosomal nanocarriers are hypothesized to improve the physicochemical stability of TP5, and to enhance its intestinal permeability for oral administration. Methods: TP5-loaded PEGylated niosomes were fabricated using the thin film hydration method. Co-cultured Caco-2 and HT29 cells with different ratios were screened as in vitro intestinal models. The cytotoxicity of TP5 and its formulations were evaluated using an MTT assay. The cellular uptake and transport studies were investigated in the absence or presence of variable inhibitors or enhancers, and their mechanisms were explored. Results and Discussion: All TP5 solutions and their niosomal formulations were nontoxic to Caco-2 and HT-29 cells. The uptake of TP5-PEG-niosomes by cells relied on active endocytosis, exhibiting dependence on time, energy, and concentration, which has the potential to significantly enhance its cellular uptake compared to TP5 in solution. Nevertheless, cellular transport rates were similar between TP5 in solution and its niosomal groups. The cellular transport of TP5 in solution was carried out mainly through MRP5 endocytosis and a passive pathway and effluxed by MRP5 transporters, while that of TP5-niosomes and TP5-PEG-niosomes was carried out through adsorptive- and clathrin-mediated endocytosis requiring energy. The permeability and transport rate was further enhanced when EDTA and sodium taurocholate were used as the penetration enhancers. Conclusions: This research has illustrated that PEG-niosomes were able to enhance the cellular uptake and maintain the cellular transport of TP5. This study also shows this formulation’s potential to serve as an effective carrier for improving the oral delivery of peptides. Full article

(This article belongs to the Special Issue Advances in Oral Administration)

► Show Figures

Figure 1

19 pages, 1977 KiB

Open AccessArticle

Enhancing Oral Delivery of Biologics: A Non-Competitive and Cross-Reactive Anti-Leptin Receptor Nanofitin Demonstrates a Gut-Crossing Capacity in an Ex Vivo Porcine Intestinal Model

by Solene Masloh, Anne Chevrel, Maxime Culot, Anaëlle Perrocheau, Yogeshvar N. Kalia, Samuel Frehel, Rémi Gaussin, Fabien Gosselet, Simon Huet, Magali Zeisser Labouebe and Leonardo Scapozza

Pharmaceutics 2024, 16(1), 116; https://doi.org/10.3390/pharmaceutics16010116 - 16 Jan 2024

Viewed by 1735

Abstract

Biotherapeutics exhibit high efficacy in targeted therapy, but their oral delivery is impeded by the harsh conditions of the gastrointestinal (GI) tract and limited intestinal absorption. This article presents a strategy to overcome the challenges of poor intestinal permeability by using a protein [...] Read more.

Biotherapeutics exhibit high efficacy in targeted therapy, but their oral delivery is impeded by the harsh conditions of the gastrointestinal (GI) tract and limited intestinal absorption. This article presents a strategy to overcome the challenges of poor intestinal permeability by using a protein shuttle that specifically binds to an intestinal target, the leptin receptor (LepR), and exploiting its capacity to perform a receptor-mediated transport. Our proof-of-concept study focuses on the characterization and transport of robust affinity proteins, known as Nanofitins, across an ex vivo porcine intestinal model. We describe the potential to deliver biologically active molecules across the mucosa by fusing them with the Nanofitin 1-F08 targeting the LepR. This particular Nanofitin was selected for its absence of competition with leptin, its cross-reactivity with LepR from human, mouse, and pig hosts, and its shuttle capability associated with its ability to induce a receptor-mediated transport. This study paves the way for future in vivo demonstration of a safe and efficient oral-to-systemic delivery of targeted therapies. Full article

(This article belongs to the Special Issue Advances in Oral Administration)

► Show Figures

Figure 1

11 pages, 1309 KiB

Open AccessArticle

Compaction Properties of Particulate Proteins in Binary Powder Mixtures with Common Excipients

by Else Holmfred, Cosima Hirschberg and Jukka Rantanen

Pharmaceutics 2024, 16(1), 19; https://doi.org/10.3390/pharmaceutics16010019 - 22 Dec 2023

Cited by 1 | Viewed by 1230

Abstract

The increasing interest in protein- and peptide-based oral pharmaceuticals has culminated in the first protein-based products for oral delivery becoming commercially available. This study investigates the compaction properties of proteins in binary mixtures with common excipients up to 30% (w/w [...] Read more.

The increasing interest in protein- and peptide-based oral pharmaceuticals has culminated in the first protein-based products for oral delivery becoming commercially available. This study investigates the compaction properties of proteins in binary mixtures with common excipients up to 30% (w/w) of particulate protein. Two model proteins, lysozyme and bovine serum albumin, were compacted with either microcrystalline cellulose, spray-dried lactose monohydrate, or calcium hydrogen phosphate dihydrate at two different compaction pressures. Compared to the compacted pure materials, a significant increase in the tensile strength of the compacts was observed for the binary blends containing lysozyme together with the brittle excipients. This could be attributed to the increased bonding forces between the particles in the blend compared to the pure materials. The use of bovine serum albumin with a larger particle size resulted in a decrease in tensile strength for all the compacts. The change in the tensile strength with an increasing protein content was non-linear for both proteins. This work highlights the importance of considering the particulate properties of protein powders and that protein-based compacts can be designed with similar principles as small-molecules in terms of their mechanical tablet properties. Full article

(This article belongs to the Special Issue Advances in Oral Administration)

► Show Figures

Figure 1

Review

Jump to: Research, Other

24 pages, 1540 KiB

Open AccessReview

Research Progress on Peptide Drugs for Type 2 Diabetes and the Possibility of Oral Administration

by Xinxin Yang, Ruiting Lin, Changzhuo Feng, Qiyuan Kang, Peng Yu, Yongzhi Deng and Ye Jin

Pharmaceutics 2024, 16(11), 1353; https://doi.org/10.3390/pharmaceutics16111353 - 23 Oct 2024

Viewed by 982

Abstract

Diabetes is a global disease that can lead to a range of complications. Currently, the treatment of type 2 diabetes focuses on oral hypoglycemic drugs and insulin analogues. Studies have shown that drugs such as oral metformin are useful in the treatment of [...] Read more.

Diabetes is a global disease that can lead to a range of complications. Currently, the treatment of type 2 diabetes focuses on oral hypoglycemic drugs and insulin analogues. Studies have shown that drugs such as oral metformin are useful in the treatment of diabetes but can limit the liver’s ability to release sugar. The development of glucose-lowering peptides has provided new options for the treatment of type 2 diabetes. Peptide drugs have low oral utilization due to their easy degradation, short half-life, and difficulty passing through the intestinal mucosa. Therefore, improving the oral utilization of peptide drugs remains an urgent problem. This paper reviews the research progress of peptide drugs in the treatment of diabetes mellitus and proposes that different types of nano-formulation carriers, such as liposomes, self-emulsifying drug delivery systems, and polymer particles, should be combined with peptide drugs for oral administration to improve their absorption in the gastrointestinal tract. Full article

(This article belongs to the Special Issue Advances in Oral Administration)

► Show Figures

Figure 1

30 pages, 8359 KiB

Open AccessReview

Recent Progress of Oral Functional Nanomaterials for Intestinal Microbiota Regulation

by Wanneng Li, Minle Zhan, Yue Wen, Yu Chen, Zhongchao Zhang, Shuhui Wang, Dean Tian and Sidan Tian

Pharmaceutics 2024, 16(7), 921; https://doi.org/10.3390/pharmaceutics16070921 - 10 Jul 2024

Viewed by 1671

Abstract

The gut microbiota is closely associated with human health, and alterations in gut microbiota can influence various physiological and pathological activities in the human body. Therefore, microbiota regulation has become an important strategy in current disease treatment, albeit facing numerous challenges. Nanomaterials, owing [...] Read more.

The gut microbiota is closely associated with human health, and alterations in gut microbiota can influence various physiological and pathological activities in the human body. Therefore, microbiota regulation has become an important strategy in current disease treatment, albeit facing numerous challenges. Nanomaterials, owing to their excellent protective properties, drug release capabilities, targeting abilities, and good biocompatibility, have been widely developed and utilized in pharmaceuticals and dietary fields. In recent years, significant progress has been made in research on utilizing nanomaterials to assist in regulating gut microbiota for disease intervention. This review explores the latest advancements in the application of nanomaterials for microbiota regulation and offers insights into the future development of nanomaterials in modulating gut microbiota. Full article

(This article belongs to the Special Issue Advances in Oral Administration)

► Show Figures

Figure 1

13 pages, 1853 KiB

Open AccessReview

Oromucosal Administration of Oxytocin: The Development of ‘Oxipops’

by Dan Xu, Chunmei Lan, Juan Kou, Shuxia Yao, Weihua Zhao and Keith M. Kendrick

Pharmaceutics 2024, 16(3), 333; https://doi.org/10.3390/pharmaceutics16030333 - 27 Feb 2024

Cited by 1 | Viewed by 2339

Abstract

The role of the hypothalamic neuropeptide oxytocin in influencing the brain and behavior has been the subject of widespread research over the last few decades due, most notably, to its reported involvement in promoting social cognition and motivation, reducing anxiety, and relieving pain. [...] Read more.

The role of the hypothalamic neuropeptide oxytocin in influencing the brain and behavior has been the subject of widespread research over the last few decades due, most notably, to its reported involvement in promoting social cognition and motivation, reducing anxiety, and relieving pain. It is also increasingly being considered as an important therapeutic intervention in a variety of disorders with social dysfunction as a symptom. While, in recent years, studies in humans have administered oxytocin primarily via an intranasal route, since it may partly enter the brain directly this way via the olfactory and trigeminal nerves, there is increasing evidence that many of its functional effects can be peripherally mediated via increasing its concentration in the blood. This has opened up an oromucosal administration route as an alternative, which is beneficial since the oral consumption of peptides is problematic due to their rapid breakdown in the acidic environment of the gastrointestinal system. In this review we will discuss both the methodologies we have developed for administering oxytocin via lingual application and medicated lollipops, ‘oxipops’, in terms of increasing blood concentrations and the bioavailability of the peptide, and also their validation in terms of functional effects on the brain and behavior. While areas under the curve are significantly greater in terms of plasma oxytocin concentrations following intranasally relative to oromucosally administered oxytocin, with the estimated absolute bioavailability of the latter being around 4.4% compared with 11.1% for intranasal administration, the time to peak concentrations (around 30 min) and functional effects on the brain and behavior are broadly similar. We will also discuss potential therapeutic advantages of the oromucosal administration of oxytocin in different clinical contexts and its wider application for other peptides which are increasingly being developed for therapeutic use. Full article

(This article belongs to the Special Issue Advances in Oral Administration)

► Show Figures

Graphical abstract

25 pages, 2341 KiB

Open AccessReview

Delivery Strategies of Probiotics from Nano- and Microparticles: Trends in the Treatment of Inflammatory Bowel Disease—An Overview

by Sílvio André Lopes, Cesar Augusto Roque-Borda, Jonatas Lobato Duarte, Leonardo Delello Di Filippo, Vinícius Martinho Borges Cardoso, Fernando Rogério Pavan, Marlus Chorilli and Andréia Bagliotti Meneguin

Pharmaceutics 2023, 15(11), 2600; https://doi.org/10.3390/pharmaceutics15112600 - 8 Nov 2023

Cited by 8 | Viewed by 2807

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, most known as ulcerative colitis (UC) and Crohn’s disease (CD), that affects the gastrointestinal tract (GIT), causing considerable symptoms to millions of people around the world. Conventional therapeutic strategies have limitations and side effects, [...] Read more.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, most known as ulcerative colitis (UC) and Crohn’s disease (CD), that affects the gastrointestinal tract (GIT), causing considerable symptoms to millions of people around the world. Conventional therapeutic strategies have limitations and side effects, prompting the exploration of innovative approaches. Probiotics, known for their potential to restore gut homeostasis, have emerged as promising candidates for IBD management. Probiotics have been shown to minimize disease symptoms, particularly in patients affected by UC, opening important opportunities to better treat this disease. However, they exhibit limitations in terms of stability and targeted delivery. As several studies demonstrate, the encapsulation of the probiotics, as well as the synthetic drug, into micro- and nanoparticles of organic materials offers great potential to solve this problem. They resist the harsh conditions of the upper GIT portions and, thus, protect the probiotic and drug inside, allowing for the delivery of adequate amounts directly into the colon. An overview of UC and CD, the benefits of the use of probiotics, and the potential of micro- and nanoencapsulation technologies to improve IBD treatment are presented. This review sheds light on the remarkable potential of nano- and microparticles loaded with probiotics as a novel and efficient strategy for managing IBD. Nonetheless, further investigations and clinical trials are warranted to validate their long-term safety and efficacy, paving the way for a new era in IBD therapeutics. Full article

(This article belongs to the Special Issue Advances in Oral Administration)

► Show Figures

Figure 1

Other

Jump to: Research, Review

13 pages, 921 KiB

Open AccessSystematic Review

Advances in the Oral Administration of Somatostatin Receptor Ligands in Acromegaly: A Systematic Review Focusing on Biochemical Response

by Clémence Reverdiau and Damien Denimal

Pharmaceutics 2024, 16(11), 1357; https://doi.org/10.3390/pharmaceutics16111357 - 24 Oct 2024

Viewed by 735

Abstract

Recent advances in pharmaceutical technology, aimed at overcoming poor drug permeation across the intestinal–epithelial membrane and the challenges posed by the acidic gastrointestinal environment, have led to the development of orally administered somatostatin receptor ligands (SRLs). This development represents a promising step forward [...] Read more.

Recent advances in pharmaceutical technology, aimed at overcoming poor drug permeation across the intestinal–epithelial membrane and the challenges posed by the acidic gastrointestinal environment, have led to the development of orally administered somatostatin receptor ligands (SRLs). This development represents a promising step forward in the management of acromegaly, offering an alternative to the limitations associated with injectable SRLs. Several key clinical findings have emerged in the past two years, notably including the results from the extension phase of the MPOWERED trial, which evaluated oral octreotide capsules (OOCs), and the placebo-controlled PATHFNDR-1 trial using paltusotine. This prompted us to conduct a systematic review of the literature focusing on the efficacy of oral SRLs in controlling acromegaly, based on biochemical response. Of the 136 reports identified through our search on Medline and ClinicalTrials.gov, twelve were included, encompassing data from five interventional trials. Both OOCs and paltusotine demonstrated the ability to maintain biochemical control in patients previously controlled with injectable SRLs. While long-term maintenance was confirmed for OOCs, no data are yet available for paltusotine. Several gaps remain, such as the need for head-to-head comparisons between OOCs and paltusotine, and clinical trials in patients who have not received prior injectable SRL treatment. Full article

(This article belongs to the Special Issue Advances in Oral Administration)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Advances in Oral Administration

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (12 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI