Oral self-emulsifying delivery systems for systemic administration of therapeutic proteins: science fiction?

Phan, Thi Nhu Quynh; Le‐Vinh, Bao; Efiana, Nuri Ari; Bernkop‐Schnürch, Andreas

doi:10.1080/1061186x.2019.1584200

Cited by 23 publications

(5 citation statements)

References 45 publications

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“…As expected, it was observed that the droplet size increased from 11.2 nm to 177 nm when the concentration of lipid in preconcentrates increased from 5% to 40%. The surface charge of blank formulations was found to be negative (−5.6 mV to −21.10 mV) in all cases, which, according to previous studies, can be advantageous and result in higher mucus permeation ability, due to less interaction with the negatively charged cell membrane [ 52 , 53 ]. All blank emulsions showed no phase separation; they were all clear and homogenous after 7 days at 25 °C.…”

Section: Resultsmentioning

confidence: 62%

“…Smaller droplet size facilitates drug absorption through biological membranes, and oil droplets with a negative charge can easily permeate the charged mucus layer, enhancing drug bioavailability. These properties were shown to be highly advantageous in the development of SEDDSs [ 52 , 53 ]. Thus, acceptance criteria for determination of the design space were droplet size smaller than 100 nm, PDI smaller than 0.3, and ZP higher than −3, as shown in Figure 6 a–c.…”

Section: Resultsmentioning

confidence: 99%

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Quality by Design-Based Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) as a Potential Carrier for Oral Delivery of Lysozyme

et al. 2023

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For many years, researchers have been making efforts to find a manufacturing technique, as well as a drug delivery system, that will allow for oral delivery of biopharmaceuticals to their target site of action without impairing their biological activity. Due to the positive in vivo outcomes of this formulation strategy, self-emulsifying drug delivery systems (SEDDSs) have been intensively studied in the last few years as a way of overcoming the different challenges associated with the oral delivery of macromolecules. The purpose of the present study was to examine the possibility of developing solid SEDDSs as potential carriers for the oral delivery of lysozyme (LYS) using the Quality by Design (QbD) concept. LYS was successfully ion paired with anionic surfactant, sodium dodecyl sulphate (SDS), and this complex was incorporated into a previously developed and optimized liquid SEDDS formulation comprising medium-chain triglycerides, polysorbate 80, and PEG 400. The final formulation of a liquid SEDDS carrying the LYS:SDS complex showed satisfactory in vitro characteristics as well as self-emulsifying properties (droplet size: 13.02 nm, PDI: 0.245, and zeta potential: −4.85 mV). The obtained nanoemulsions were robust to dilution in the different media and highly stable after 7 days, with a minor increase in droplet size (13.84 nm) and constant negative zeta potential (−0.49 mV). An optimized liquid SEDDS loaded with the LYS:SDS complex was further solidified into powders by adsorption onto a chosen solid carrier, followed by direct compression into self-emulsifying tablets. Solid SEDDS formulations also exhibited acceptable in vitro characteristics, while LYS preserved its therapeutic activity in all phases of the development process. On the basis of the results gathered, loading the hydrophobic ion pairs of therapeutic proteins and peptides to solid SEDDS may serve as a potential method for delivering biopharmaceuticals orally.

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Section: Resultsmentioning

confidence: 62%

Section: Resultsmentioning

confidence: 99%

Quality by Design-Based Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) as a Potential Carrier for Oral Delivery of Lysozyme

et al. 2023

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“…Maintenance of drug solubility in gastrointestinal tract is the foremost challenges to oral formulation and especially the increased drug solubility at the absorption site of the gut [19]. Lipophilic drug composite that manifest dissolution rate limited absorption, selfemulsifying systems can provide an improvement in absorption in terms of rate and extent, that results in consistent blood time profiles [7,20]. Problem of poor solubility and low bioavailability of drug across all categories of biopharmaceutical classification system can be resolved by formulating into self-emulsifying system, as shown in Table 2 [21].…”

Section: Suitable Drug Candidate Identification For Self-emulsifying Systemsmentioning

confidence: 99%

“…A stable self-micro emulsifying system consists of mixture of drug, oil, surfactant and co-surfactant. Upon dilution with water it results into fine oil-in-water emulsion with a droplets diameter less than 50 nm [7,8]. The microemulsion droplet of self-micro emulsifying systems entraps the drug molecule completely with 100% efficacy, thus self-micro emulsifying systems shows high potential to deliver low water soluble drug [9].…”

Section: Introductionmentioning

confidence: 99%

Self-Microemulsifying System

Shah¹,

Agrawal²

2020

Colloid Science in Pharmaceutical Nanotechnology

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Oral route is preferred for drug administration; however according to the recent scenario 40% of new drug candidates have poor water solubility and low bioavailability. One of the biggest challenges in drug delivery science is to improve low oral bioavailability problem which is associated with the hydrophobic drugs due to their unprecedented potential as a drug deliver with the broad range of application. Self-emulsifying systems have been proved as highly useful technological innovations to vanquish such bioavailability problem by virtue of their diminutive globule size, higher solubilization tendency for hydrophobic drugs, robust formulation advantages, and easy to scale up. Self-microemulsifying systems are isotropic mixers of oil, surfactant, drug and co-emulsifier or solubilizer, which spontaneously form transparent micro-emulsions with oil droplets ranging between 100 and 250 nm. Micro emulsified drug can be easily absorbed through the lymphatic pathway and it bypasses the hepatic first-pass effect. Self-microemulsifying system is a thermodynamically stable system and overcomes the drawback of layering of emulsions after sitting for a long period of time. The present literature gives exhaustive information on the formulation design and characterization of self-microemulsifying systems.

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“…Among the various technologies having been developed to overcome the obstacles limiting oral peptide delivery [9,10], the formation of hydrophobic ion pairs (HIPs) proved to be promising as this can increase the lipophilic character of hydrophilic peptide drugs and thus enhance their permeability of lipophilic membranes [11,12]. Because of a limited stability of HIPs in the GI tract, the incorporation of HIPs into lipophilic carrier systems is advantageous [13][14][15]. In addition to a protective effect towards presystemic metabolism [16][17][18], lipid-based nanocarrier systems in particular proved to be able to facilitate mucus T permeation and to enhance the cellular uptake of peptides [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery

Ismail

Phan

Laffleur

et al. 2020

European Journal of Pharmaceutics and Biopharmaceutics

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The lipophilic character of peptides can be tremendously improved by hydrophobic ion pairing (HIP) with counterions to be efficiently incorporated into lipid-based nanocarriers (NCs). Herein, HIPs of exenatide with the cationic surfactant tetraheptylammonium bromide (THA) and the anionic surfactant sodium docusate (DOC) were formed to increase its lipophilicity. These HIPs were incorporated into lipid based NCs comprising 41% Capmul MCM, 15% Captex 355, 40% Cremophor RH and 4% propylene glycol. Exenatide-THA NCs showed a log D lipophilic phase (LPh)/release medium (RM) of 2.29 and 1.92, whereas the log D LPh/RM of exenatide-DOC was 1.2 and −0.9 in simulated intestinal fluid and Hanks' balanced salts buffer (HBSS), respectively. No significant hemolytic activity was induced at a concentration of 0.25% (m/v) of both blank and loaded NCs. Exenatide-THA NCs and exenatide-DOC NCs showed a 10-fold and 3-fold enhancement in intestinal apparent membrane permeability compared to free exenatide, respectively. Furthermore, orally administered exenatide-THA and exenatide-DOC NCs in healthy rats resulted in a relative bioavailability of 27.96 ± 5.24% and 16.29 ± 6.63%, respectively, confirming the comparatively higher potential of the cationic surfactant over the anionic surfactant. Findings of this work highlight the potential of the type of counterion used for HIP as key to successful design of lipid-based NCs for oral exenatide delivery.

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Oral self-emulsifying delivery systems for systemic administration of therapeutic proteins: science fiction?

Cited by 23 publications

References 45 publications

Quality by Design-Based Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) as a Potential Carrier for Oral Delivery of Lysozyme

Quality by Design-Based Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) as a Potential Carrier for Oral Delivery of Lysozyme

Self-Microemulsifying System

Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery

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