Lipid based formulations as supersaturating oral delivery systems: From current to future industrial applications

Holm, René; Kuentz, Martin; Ilie-Spiridon, Alexandra-Roxana; Griffin, Brendan T.

doi:10.1016/j.ejps.2023.106556

Cited by 17 publications

(3 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For decades, lipid-based systems have been utilized to enhance qualities of a wide range of medications. 1 , 2 In particular, lipid-based nanoparticles have shown remarkable benefits in pharmaceutical formulations, including excellent biocompatibility, simplicity of fabrication, tissue specificity, avoidance of reticuloendothelial systems, and nontoxicity. 3 Among lipid nanocarriers, solid-lipid nanoparticles (SLNs) have attracted much attention from academia and industry recently due to their fascinating properties.…”

Section: Introductionmentioning

confidence: 99%

Repaglinide–Solid Lipid Nanoparticles in Chitosan Patches for Transdermal Application: Box–Behnken Design, Characterization, and In Vivo Evaluation

Ali,

Namazi,

Elbadawy

et al. 2024

IJN

View full text Add to dashboard Cite

Background Repaglinide (REP) is an antidiabetic drug with limited oral bioavailability attributable to its low solubility and considerable first-pass hepatic breakdown. This study aimed to develop a biodegradable chitosan-based system loaded with REP–solid lipid nanoparticles (REP-SLNs) for controlled release and bioavailability enhancement via transdermal delivery. Methods REP-SLNs were fabricated by ultrasonic hot-melt emulsification. A Box–Behnken design (BBD) was employed to explore and optimize the impacts of processing variables (lipid content, surfactant concentration, and sonication amplitude) on particle size (PS), and entrapment efficiency (EE). The optimized REP-SLN formulation was then incorporated within a chitosan solution to develop a transdermal delivery system (REP-SLN-TDDS) and evaluated for physicochemical properties, drug release, and ex vivo permeation profiles. Pharmacokinetic and pharmacodynamic characteristics were assessed using experimental rats. Results The optimized REP-SLNs had a PS of 249±9.8 nm and EE of 78%±2.3%. The developed REP-SLN-TDDS demonstrated acceptable characteristics without significant aggregation of REP-SLNs throughout the casting and drying processes. The REP-SLN-TDDS exhibited a biphasic release pattern, where around 36% of the drug load was released during the first 2 h, then the drug release was sustained at around 80% at 24 h. The computed flux across rat skin for the REP-SLN-TDDS was 2.481±0.22 μg/cm 2 /h in comparison to 0.696±0.07 μg/cm 2 /h for the unprocessed REP, with an enhancement ratio of 3.56. The REP-SLN-TDDS was capable of sustaining greater REP plasma levels over a 24 h period ( p <0.05). The REP-SLN-TDDS also reduced blood glucose levels compared to unprocessed REP and commercial tablets ( p <0.05) in experimental rats. Conclusion Our REP-SLN-TDDS can be considered an efficient therapeutic option for REP administration.

show abstract

Section: Introductionmentioning

confidence: 99%

Repaglinide–Solid Lipid Nanoparticles in Chitosan Patches for Transdermal Application: Box–Behnken Design, Characterization, and In Vivo Evaluation

Ali,

Namazi,

Elbadawy

et al. 2024

IJN

View full text Add to dashboard Cite

show abstract

“…Supersaturation is one such example, whereby a drug is present in lipid excipients at concentrations above the thermodynamic solubility in the formulation, which has been induced through heating the formulation, and this has been extensively reviewed by Holm and colleagues. 6 The addition of fatty acids to the formulation is another method of boosting drug solubility in lipid excipients by leveraging favorable interactions between the basic drug and fatty acids. 7 Finally, conversion of free base forms of a drug to lipophilic salts or ionic liquids through metathesis reactions with acidic counterions has been proven as an efficient means of improving drug solubility in lipid excipients.…”

Section: Introductionmentioning

confidence: 99%

“…One possible reason for this underutilization is inadequate lipid solubility of many novel drug candidates, preventing adequate dosing in LBFs, a process crucial for bypassing the rate-limiting dissolution step. ,, Several methods exist to overcome the challenge of limited drug solubility in lipid vehicles. Supersaturation is one such example, whereby a drug is present in lipid excipients at concentrations above the thermodynamic solubility in the formulation, which has been induced through heating the formulation, and this has been extensively reviewed by Holm and colleagues . The addition of fatty acids to the formulation is another method of boosting drug solubility in lipid excipients by leveraging favorable interactions between the basic drug and fatty acids .…”

Section: Introductionmentioning

confidence: 99%

Rationalizing Counterion Selection for the Development of Lipophilic Salts: A Case Study with Venetoclax

Ryan,

Griffin,

O’Shea

2024

Mol. Pharmaceutics

Self Cite

View full text Add to dashboard Cite

The use of lipid-based formulations (LBFs) can be hindered by low dose loading due to solubility limitations of candidate drugs in lipid vehicles. Formation of lipophilic salts through pairing these drugs with a lipophilic counterion has been demonstrated as a potential means to enhance dose loading in LBFs. This study investigated the screening of appropriate counterions to form lipophilic salts of the BCS class IV drug venetoclax. The physical properties, lipid solubility, and in vitro performance of the salts were analyzed. This study illustrated the versatility of alkyl sulfates and sulfonates as suitable counterions in lipophilic salt synthesis with up to ∼9-fold higher solubility in medium- and long-chain LBFs when compared to that of the free base form of venetoclax. All salts formulated as LBFs displayed superior in vitro performance when compared to the free base form of the drug due to the higher initial drug loadings in LBFs and increased affinity for colloidal species. Further, in vitro studies confirmed that venetoclax lipophilic salt forms using alkyl chain counterions demonstrated comparable in vitro performance to venetoclax docusate, thus reducing the potential for laxative effects related to docusate administration. High levels of the initial dose loading of venetoclax lipophilic salts were retained in a molecularly dispersed state during dispersion and digestion of the formulation, while also demonstrating increased levels of saturation in biorelevant media. The findings of this study suggest that alkyl chain sulfates and sulfonates can act as a suitable alternative counterion to docusate, facilitating the selection of counterions that can unlock the potential to formulate venetoclax as an LBF.

show abstract

New Series of 3-Pyridyl-1,3-Thiazoles: In Vitro and In Vivo Anti-Trypanosomatidae Profile, in vitro and in silico Mechanism of Action approach

Gouveia de Melo Silva,

Manoel da Silva Sousa,

Fernandes Junior

et al. 2024

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

Lipid based formulations as supersaturating oral delivery systems: From current to future industrial applications

Cited by 17 publications

References 107 publications

Repaglinide–Solid Lipid Nanoparticles in Chitosan Patches for Transdermal Application: Box–Behnken Design, Characterization, and In Vivo Evaluation

Repaglinide–Solid Lipid Nanoparticles in Chitosan Patches for Transdermal Application: Box–Behnken Design, Characterization, and In Vivo Evaluation

Rationalizing Counterion Selection for the Development of Lipophilic Salts: A Case Study with Venetoclax

New Series of 3-Pyridyl-1,3-Thiazoles: In Vitro and In Vivo Anti-Trypanosomatidae Profile, in vitro and in silico Mechanism of Action approach

Contact Info

Product

Resources

About