Research

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17 pages, 2567 KiB

Open AccessArticle

Development of Multi-Compartment 3D-Printed Tablets Loaded with Self-Nanoemulsified Formulations of Various Drugs: A New Strategy for Personalized Medicine

by Tarek A. Ahmed, Raed I. Felimban, Hossam H. Tayeb, Waleed Y. Rizg, Fuad H. Alnadwi, Hanadi A. Alotaibi, Nabil A. Alhakamy, Fathy I. Abd-Allah, Gamal A. Mohamed, Ahmed S. Zidan and Khalid M. El-Say

Pharmaceutics 2021, 13(10), 1733; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101733 - 19 Oct 2021

Cited by 15 | Viewed by 3360

Abstract

This work aimed to develop a three-dimensional printed (3DP) tablet containing glimepiride (GLMP) and/or rosuvastatin (RSV) for treatment of dyslipidemia in patients with diabetes. Curcumin oil was extracted from the dried rhizomes of Curcuma longa and utilized to develop a self-nanoemulsifying drug delivery [...] Read more.

This work aimed to develop a three-dimensional printed (3DP) tablet containing glimepiride (GLMP) and/or rosuvastatin (RSV) for treatment of dyslipidemia in patients with diabetes. Curcumin oil was extracted from the dried rhizomes of Curcuma longa and utilized to develop a self-nanoemulsifying drug delivery system (SNEDDS). Screening mixture experimental design was conducted to develop SNEDDS formulation with a minimum droplet size. Five different semi-solid pastes were prepared and rheologically characterized. The prepared pastes were used to develop 3DP tablets using extrusion printing. The quality attributes of the 3DP tablets were evaluated. A non-compartmental extravascular pharmacokinetic model was implemented to investigate the in vivo behavior of the prepared tablets and the studied marketed products. The optimized SNEDDS, of a 94.43 ± 3.55 nm droplet size, was found to contain 15%, 75%, and 10% of oil, polyethylene glycol 400, and tween 80, respectively. The prepared pastes revealed a shear-thinning of pseudoplastic flow behavior. Flat-faced round tablets of 15 mm diameter and 5.6–11.2 mm thickness were successfully printed and illustrated good criteria for friability, weight variation, and content uniformity. Drug release was superior from SNEDDS-based tablets when compared to non-SNEDDS tablets. Scanning electron microscopy study of the 3DP tablets revealed a semi-porous surface that exhibited some curvature with the appearance of tortuosity and a gel porous-like structure of the inner section. GLMP and RSV demonstrated relative bioavailability of 159.50% and 245.16%, respectively. Accordingly, the developed 3DP tablets could be considered as a promising combined oral drug therapy used in treatment of metabolic disorders. However, clinical studies are needed to investigate their efficacy and safety. Full article

(This article belongs to the Special Issue Oral Drug Delivery Systems Based on Lipid-Based Carriers)

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19 pages, 24854 KiB

Open AccessArticle

Norfloxacin Loaded Lipid Polymer Hybrid Nanoparticles for Oral Administration: Fabrication, Characterization, In Silico Modelling and Toxicity Evaluation

by Muhammad Asghar Khan, Shahzeb Khan, Mohsin Kazi, Sultan M. Alshehri, Muhammad Shahid, Shafi Ullah Khan, Zahid Hussain, Muhammad Sohail, Muhammad Shafique, Hajra Afeera Hamid, Mahwish Kamran, Abdelbary Elhissi, Muhammad Wasim and Hnin Ei Thu

Pharmaceutics 2021, 13(10), 1632; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101632 - 06 Oct 2021

Cited by 7 | Viewed by 2857

Abstract

Norfloxacin (NOR), widely employed as an anti-bacterial drug, has poor oral bioavailability. Nano based drug delivery systems are widely used to overcome the existing oral bioavailability challenges. Lipid–Polymer Hybrid Nanoparticles (LPHNs) exhibit the distinctive advantages of both polymeric and liposomes nanoparticles, while excluding [...] Read more.

Norfloxacin (NOR), widely employed as an anti-bacterial drug, has poor oral bioavailability. Nano based drug delivery systems are widely used to overcome the existing oral bioavailability challenges. Lipid–Polymer Hybrid Nanoparticles (LPHNs) exhibit the distinctive advantages of both polymeric and liposomes nanoparticles, while excluding some of their disadvantages. In the current study, NOR loaded LPHNs were prepared, and were solid amorphous in nature, followed by in vitro and in vivo evaluation. The optimized process conditions resulted in LPHNs with the acceptable particle size 121.27 nm, Polydispersity Index (PDI) of 0.214 and zeta potential of −32 mv. The addition of a helper lipid, oleic acid, and polymers, ethyl cellulose, substantially increased the encapsulation efficiency (EE%) (65% to 97%). In vitro study showed a sustained drug release profile (75% within 12 h) for NOR LPHNs. The optimized NOR LPHNs showed a significant increase (p < 0.05) in bioavailability compared to the commercial product. From the acute toxicity study, the LD50 value was found to be greater than 1600 mg/kg. The molecular modelling studies substantiated the experimental results with the best combination of polymers and surfactants that produced highly stable LPHNs. Therefore, LPHNs proved to be a promising system for the delivery of NOR, as well as for other antibiotics and hydrophobic drugs. Full article

(This article belongs to the Special Issue Oral Drug Delivery Systems Based on Lipid-Based Carriers)

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20 pages, 21772 KiB

Open AccessArticle

Quality-by-Design-Based Development of a Voxelotor Self-Nanoemulsifying Drug-Delivery System with Improved Biopharmaceutical Attributes

by Aristote B. Buya, Romano Terrasi, Jérémie K. Mbinze, Giulio G. Muccioli, Ana Beloqui, Patrick B. Memvanga and Véronique Préat

Pharmaceutics 2021, 13(9), 1388; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091388 - 02 Sep 2021

Cited by 8 | Viewed by 2569

Abstract

Low aqueous solubility and poor oral bioavailability are limiting factors in the oral delivery of voxelotor, an antisickling agent. To overcome these limitations, a voxelotor self-nanoemulsifying drug delivery system was developed. Various oils, surfactants, and cosurfactants were screened for their solubilization potential for [...] Read more.

Low aqueous solubility and poor oral bioavailability are limiting factors in the oral delivery of voxelotor, an antisickling agent. To overcome these limitations, a voxelotor self-nanoemulsifying drug delivery system was developed. Various oils, surfactants, and cosurfactants were screened for their solubilization potential for the drug. The area of nanoemulsification was identified using a ternary phase diagram. An experimental mixture design and a desirability function were applied to select SNEDDSs that contain a maximum amount of lipids and a minimum amount of surfactant, and that possess optimal emulsification properties (i.e., droplet sizes, polydispersity index (PDI), emulsification time, and transmittance percentage). The optimized SNEDDS formulation was evaluated for the self-emulsifying time (32 s), droplet size (35 nm), and zeta potential (−8 mV). In vitro dissolution studies indicated a 3.1-fold improvement in drug solubility from the optimized SNEDDS over pure drug powder. After 60 min of in vitro lipolysis, 88% of the voxelotor loaded in the SNEDDS remained in the aqueous phase. Cytotoxicity evaluation, using Caco-2 cells, indicated the safety of the formulation at 0.9 mg/mL. The transport of the voxelotor SNEDDS across Caco-2 monolayers was significantly enhanced compared to that of the free drug. Compared to the drug suspension, the developed SNEDDS enhanced the oral bioavailability (1.7-fold) of voxelotor in rats. The results suggest that further development of SNEDDSs for the oral delivery of voxelotor is needed. Full article

(This article belongs to the Special Issue Oral Drug Delivery Systems Based on Lipid-Based Carriers)

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16 pages, 5496 KiB

Open AccessArticle

New In Vitro Coculture Model for Evaluating Intestinal Absorption of Different Lipid Nanocapsules

by Norraseth Kaeokhamloed, Emillie Roger, Jérôme Béjaud, Nolwenn Lautram, Florence Manero, Rodolphe Perrot, Marie Briet, Chadi Abbara and Samuel Legeay

Pharmaceutics 2021, 13(5), 595; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13050595 - 21 Apr 2021

Cited by 6 | Viewed by 2929

Abstract

Standard models used for evaluating the absorption of nanoparticles like Caco-2 ignore the presence of vascular endothelium, which is a part of the intestinal multi-layered barrier structure. Therefore, a coculture between the Caco-2 epithelium and HMEC-1 (Human Microvascular Endothelial Cell type 1) on [...] Read more.

Standard models used for evaluating the absorption of nanoparticles like Caco-2 ignore the presence of vascular endothelium, which is a part of the intestinal multi-layered barrier structure. Therefore, a coculture between the Caco-2 epithelium and HMEC-1 (Human Microvascular Endothelial Cell type 1) on a Transwell^® insert has been developed. The model has been validated for (a) membrane morphology by transmission electron microscope (TEM); (b) ZO-1 and β-catenin expression by immunoassay; (c) membrane integrity by trans-epithelial electrical resistance (TEER) measurement; and (d) apparent permeability of drugs from different biopharmaceutical classification system (BCS) classes. Lipid nanocapsules (LNCs) were formulated with different sizes (55 and 85 nm) and surface modifications (DSPE-mPEG (2000) and stearylamine). Nanocapsule integrity and particle concentration were monitored using the Förster resonance energy transfer (FRET) technique. The result showed that surface modification by DSPE-mPEG (2000) increased the absorption of 55-nm LNCs in the coculture model but not in the Caco-2. Summarily, the coculture model was validated as a tool for evaluating the intestinal absorption of drugs and nanoparticles. The new coculture model has a different LNCs absorption mechanism suggesting the importance of intestinal endothelium and reveals that the surface modification of LNCs can modify the in vitro oral absorption. Full article

(This article belongs to the Special Issue Oral Drug Delivery Systems Based on Lipid-Based Carriers)

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18 pages, 3264 KiB

Open AccessArticle

Taking Particle Tracking into Practice by Novel Software and Screening Approach: Case-Study of Oral Lipid Nanocarriers

by María Plaza-Oliver, Emilio L. Cano, María Mar Arroyo-Jimenez, Matías Gámez, María Victoria Lozano-López and Manuel J. Santander-Ortega

Pharmaceutics 2021, 13(3), 370; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13030370 - 10 Mar 2021

Cited by 5 | Viewed by 1793

Abstract

The success on the design of new oral nanocarriers greatly depends on the identification of the best physicochemical properties that would allow their diffusion across the mucus layer that protects the intestinal epithelium. In this context, particle tracking (PT) has arisen in the [...] Read more.

The success on the design of new oral nanocarriers greatly depends on the identification of the best physicochemical properties that would allow their diffusion across the mucus layer that protects the intestinal epithelium. In this context, particle tracking (PT) has arisen in the pharmaceutical field as an excellent tool to evaluate the diffusion of individual particles across the intestinal mucus. In PT, the trajectories of individual particles are characterized by the mean square displacement (MSD), which is used to calculate the coefficient of diffusion (D) and the anomalous diffusion parameter (α) as

M S D = 4 D τ^{α}

. Unfortunately, there is no stablished criteria to evaluate the goodness-of-fit of the experimental data to the mathematical model. This work shows that the commonly used R² parameter may lead to an overestimation of the diffusion capacity of oral nanocarriers. We propose a screening approach based on a combination of R² with further statistical parameters. We have analyzed the effect of this approach to study the intestinal mucodiffusion of lipid oral nanocarriers, compared to the conventional screening approach. Last, we have developed software able to perform the whole PT analysis in a time-saving, user-friendly, and rational fashion. Full article

(This article belongs to the Special Issue Oral Drug Delivery Systems Based on Lipid-Based Carriers)

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Review

Jump to: Research

42 pages, 1452 KiB

Open AccessReview

An Overview of Herbal-Based Antidiabetic Drug Delivery Systems: Focus on Lipid- and Inorganic-Based Nanoformulations

by Espoir K. Kambale, Joëlle Quetin-Leclercq, Patrick B. Memvanga and Ana Beloqui

Pharmaceutics 2022, 14(10), 2135; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14102135 - 08 Oct 2022

Cited by 8 | Viewed by 2971

Abstract

Diabetes is a metabolic pathology with chronic high blood glucose levels that occurs when the pancreas does not produce enough insulin or the body does not properly use the insulin it produces. Diabetes management is a puzzle and focuses on a healthy lifestyle, [...] Read more.

Diabetes is a metabolic pathology with chronic high blood glucose levels that occurs when the pancreas does not produce enough insulin or the body does not properly use the insulin it produces. Diabetes management is a puzzle and focuses on a healthy lifestyle, physical exercise, and medication. Thus far, the condition remains incurable; management just helps to control it. Its medical treatment is expensive and is to be followed for the long term, which is why people, especially from low-income countries, resort to herbal medicines. However, many active compounds isolated from plants (phytocompounds) are poorly bioavailable due to their low solubility, low permeability, or rapid elimination. To overcome these impediments and to alleviate the cost burden on disadvantaged populations, plant nanomedicines are being studied. Nanoparticulate formulations containing antidiabetic plant extracts or phytocompounds have shown promising results. We herein aimed to provide an overview of the use of lipid- and inorganic-based nanoparticulate delivery systems with plant extracts or phytocompounds for the treatment of diabetes while highlighting their advantages and limitations for clinical application. The findings from the reviewed works showed that these nanoparticulate formulations resulted in high antidiabetic activity at low doses compared to the corresponding plant extracts or phytocompounds alone. Moreover, it was shown that nanoparticulate systems address the poor bioavailability of herbal medicines, but the lack of enough preclinical and clinical pharmacokinetic and/or pharmacodynamic trials still delays their use in diabetic patients. Full article

(This article belongs to the Special Issue Oral Drug Delivery Systems Based on Lipid-Based Carriers)

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28 pages, 1018 KiB

Open AccessReview

Fundamental Aspects of Lipid-Based Excipients in Lipid-Based Product Development

by Deepa Nakmode, Valamla Bhavana, Pradip Thakor, Jitender Madan, Pankaj Kumar Singh, Shashi Bala Singh, Jessica M. Rosenholm, Kuldeep K. Bansal and Neelesh Kumar Mehra

Pharmaceutics 2022, 14(4), 831; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14040831 - 11 Apr 2022

Cited by 22 | Viewed by 5135

Abstract

Poor aqueous solubility of drugs is still a foremost challenge in pharmaceutical product development. The use of lipids in designing formulations provides an opportunity to enhance the aqueous solubility and consequently bioavailability of drugs. Pre-dissolution of drugs in lipids, surfactants, or mixtures of [...] Read more.

Poor aqueous solubility of drugs is still a foremost challenge in pharmaceutical product development. The use of lipids in designing formulations provides an opportunity to enhance the aqueous solubility and consequently bioavailability of drugs. Pre-dissolution of drugs in lipids, surfactants, or mixtures of lipid excipients and surfactants eliminate the dissolution/dissolving step, which is likely to be the rate-limiting factor for oral absorption of poorly water-soluble drugs. In this review, we exhaustively summarize the lipids excipients in relation to their classification, absorption mechanisms, and lipid-based product development. Methodologies utilized for the preparation of solid and semi-solid lipid formulations, applications, phase behaviour, and regulatory perspective of lipid excipients are discussed. Full article

(This article belongs to the Special Issue Oral Drug Delivery Systems Based on Lipid-Based Carriers)

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19 pages, 1184 KiB

Open AccessReview

Improved Bioavailability of Poorly Soluble Drugs through Gastrointestinal Muco-Adhesion of Lipid Nanoparticles

by Sui Ling Janet Tan and Nashiru Billa

Pharmaceutics 2021, 13(11), 1817; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13111817 - 31 Oct 2021

Cited by 19 | Viewed by 5127

Abstract

Gastrointestinal absorption remains indispensable in the systemic delivery of most drugs, even though it presents several challenges that, paradoxically, may also provide opportunities that can be exploited to achieve maximal bioavailability. Drug delivery systems made from nanoparticle carriers and especially, lipid carriers, have [...] Read more.

Gastrointestinal absorption remains indispensable in the systemic delivery of most drugs, even though it presents several challenges that, paradoxically, may also provide opportunities that can be exploited to achieve maximal bioavailability. Drug delivery systems made from nanoparticle carriers and especially, lipid carriers, have the potential to traverse gastrointestinal barriers and deploy in the lymphatic pathway, which aptly, is free from first pass via the liver. Several poorly soluble drugs have presented improved systemic bioavailability when couriered in lipid nanoparticle carriers. In this review, we propose an additional frontier to enhancing the bioavailability of poorly soluble drugs when encapsulated in lipid nano-carriers by imparting muco-adhesion to the particles through application of appropriate polymeric coating to the lipid carrier. The combined effect of gastrointestinal muco-adhesion followed by lymphatic absorption is a promising approach to improving systemic bioavailability of poorly soluble drugs following oral administration. Evidence to the potential of this approach is backed-up by recent studies within the review. Full article

(This article belongs to the Special Issue Oral Drug Delivery Systems Based on Lipid-Based Carriers)

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14 pages, 1077 KiB

Open AccessReview

Encapsulation of Active Pharmaceutical Ingredients in Lipid Micro/Nanoparticles for Oral Administration by Spray-Cooling

by Carmen S. Favaro-Trindade, Fernando E. de Matos Junior, Paula K. Okuro, João Dias-Ferreira, Amanda Cano, Patricia Severino, Aleksandra Zielińska and Eliana B. Souto

Pharmaceutics 2021, 13(8), 1186; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081186 - 31 Jul 2021

Cited by 21 | Viewed by 3132

Abstract

Nanoencapsulation via spray cooling (also known as spray chilling and spray congealing) has been used with the aim to improve the functionality, solubility, and protection of drugs; as well as to reduce hygroscopicity; to modify taste and odor to enable oral administration; and [...] Read more.

Nanoencapsulation via spray cooling (also known as spray chilling and spray congealing) has been used with the aim to improve the functionality, solubility, and protection of drugs; as well as to reduce hygroscopicity; to modify taste and odor to enable oral administration; and many times to achieve a controlled release profile. It is a relatively simple technology, it does not require the use of low-cost solvents (mostly associated to toxicological risk), and it can be applied for lipid raw materials as excipients of oral pharmaceutical formulations. The objective of this work was to revise and discuss the advances of spray cooling technology, with a greater emphasis on the development of lipid micro/nanoparticles to the load of active pharmaceutical ingredients for oral administration. Full article

(This article belongs to the Special Issue Oral Drug Delivery Systems Based on Lipid-Based Carriers)

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