Bioavailability Enhancement of Poorly Water-Soluble Drugs via Nanocomposites: Formulation–Processing Aspects and Challenges

Bhakay, Anagha; Rahman, Mahbubur; Davé, Rajesh N.; Bilgili, Ecevit

doi:10.3390/pharmaceutics10030086

Cited by 160 publications

(100 citation statements)

References 227 publications

(478 reference statements)

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“…According to previous reports, Cremophor EL ® , also known as Kolliphor EL (HLB value = 13.5), has often been investigated owing to its better emulsifying capacity than the Tween series [44]. Cremophor EL ® demonstrates enhanced permeability and bioavailability, although it is a nonionic surfactant [45]. Based on our data, Cremophor EL ® showed a higher solubility than Labrasol and Tween 80.…”

Section: Discussionsupporting

confidence: 54%

Topical Delivery of Coenzyme Q10-Loaded Microemulsion for Skin Regeneration

et al. 2020

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The aim of this study was to develop a coenzyme Q10 (CoQ10) microemulsion system with improved solubility, penetration, and wound healing efficacy. Based on the pseudo-ternary diagram, microemulsions containing isopropyl myristate (IPM), Cremophor EL ® , and Transcutol ® HP were selected and confirmed to be nanosized (<20 nm) and thermodynamically stable based on the dilution and thermodynamic stability tests. The CoQ10-loaded microemulsion with a surfactant/co-surfactant (S/CoS) ratio of 2:1 (w/w %) demonstrated a higher permeation efficacy compared to microemulsions with S/CoS ratio of 3:1 or 4:1 (w/w %). Additionally, the CoQ10-loaded microemulsion with an S/CoS ratio of 2:1 demonstrated a relatively rapid wound healing effect in keratinocytes and fibroblasts. Overall, these data suggest that a microemulsion based on IPM, Cremophor EL ® , and Transcutol ® HP could be an effective vehicle for the topical administration of CoQ10 and could be utilized for the application of other therapeutic agents that have difficulty in penetrating the skin.Pharmaceutics 2020, 12, 332 2 of 15 minimal side effects (e.g., systemic toxicity) compared to oral drug delivery [10]. However, due to the skin barrier, the penetration of therapeutics across the stratum corneum remains challenging. Especially, general therapeutic agents demonstrate a considerably low penetration efficacy unlike moderately lipophilic substances (molecular weight < 500 Da and log P of 1 to 4) [11]. Hence, these therapeutic agents require skin penetration enhancement strategies such as physical permeation enhancement (e.g., iontophoresis and microneedle) [12], chemical permeation enhancement (e.g., chemical enhancer and ionic liquid) [13], and nanocarrier-based permeation enhancement (e.g., microemulsion and transfersomes) [14,15].Microemulsions are thermodynamically stable vehicles that contain oil and water stabilized by amphiphiles such as surfactants and co-surfactants [16]. Such microemulsions are transparent, isotropic colloidal systems with a droplet size less than 100 nm and have been widely studied since microemulsions were defined [17,18]. As previously reported, compared with conventional emulsions, these systems demonstrate enhanced transdermal permeation owing to their smaller size and disruption of the stratum corneum [19,20]. In addition, these systems are conventionally advantageous due to the fact of their pharmaceutical stability, easy fabrication, and scale-up [21]. Therefore, microemulsions are preferred in dermatological cosmetic applications over the past decades.Coenzyme Q10 (CoQ10, Mw = 863.3 g/mol) is a quinone with side chains of 10 isoprenoids [22]. CoQ10 generally plays an important role as an electron carrier in the oxidative phosphorylation process of the mitochondria while acting as an antioxidant outside the mitochondria [23]. Recently, CoQ10 has gained attention for its therapeutic application for several disorders including cardiovascular diseases, diabetes mellitus, and even cancer [24]. For example, previous literature has ...

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Section: Discussionsupporting

confidence: 54%

Topical Delivery of Coenzyme Q10-Loaded Microemulsion for Skin Regeneration

et al. 2020

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“…APIs released from ASDs were determined via a Distek 2100C dissolution tester (North Brunswick, NJ) using the United States Pharmacopeia II paddle method. The use of the DI water was based on previous studies [47][48][49] that indicated improved size discrimination. Furthermore, no surfactant was used because for crystalline GF, the use of the surfactants prevents from discerning the effect of particle size on the dissolution behavior of the drug.…”

Section: Dissolution Testmentioning

confidence: 99%

“…The DI water was used based on previous publications identifying that it allows for better discernment of the particle size effect of crystalline GF. [47][48][49] The effect of particle size and recrystallization inhibitor amount on the dissolution rate and the recrystallization rate in solution of ASDs were examined. Finally, dissolution mechanisms and recrystallization rate kinetics were also discussed.…”

Section: Introductionmentioning

confidence: 99%

Effect of Particle Size and Polymer Loading on Dissolution Behavior of Amorphous Griseofulvin Powder

Zheng

Lin

Capece

et al. 2019

Journal of Pharmaceutical Sciences

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The effect of particle size on the dissolution behavior of the particles of amorphous solid dispersions (ASDs) of griseofulvin (GF), with 0%-50% Kollidon ® VA 64 as a crystallization inhibitor is investigated. Both the final dissolved GF concentration and the dissolution rate of GF ASDs were found to be inversely proportional to the particle size. The solution concentrations for the smallest (45-75 mm) size group with different polymer loadings were significantly higher than those for the largest (250-355 mm) group regardless of the initial GF amount. Specifically, the dissolution rate of GF ASDs with 50% polymer loading for the finest group was 2.7 times higher than for the largest group under supersaturating conditions. The rates of dissolution and recrystallization were assessed through surface concentration (C s) and Avrami recrystallization rate kinetics, where the solid-state recrystallization was confirmed using Raman spectroscopy. Outcomes indicated that particle size reduction enhanced ASD drug loading by reducing the amount of polymer necessary as finest size ASDs initially dissolve faster, negating their higher recrystallization rate. Kollidon® VA 64 at 30% loading was sufficient to inhibit the GF recrystallization. Overall, the combination of particle size reduction and recrystallization inhibition is effective for improved dissolution behavior of GF ASDs.

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“…Lastly, the term “nanocomposite” more specifically refers to nanoparticles (nanosuspensions) subjected to a drying process to intentionally recover nanoaggregates that are able to redisperse in a liquid (reversible or irreversible aggregates) [ 52 ].…”

Section: Introductionmentioning

confidence: 99%

Nanocrystals of Poorly Soluble Drugs: Drug Bioavailability and Physicochemical Stability

et al. 2018

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Many approaches have been developed over time to overcome the bioavailability limitations of poorly soluble drugs. With the advances in nanotechnology in recent decades, science and industry have been approaching this issue through the formulation of drugs as nanocrystals, which consist of “pure drugs and a minimum of surface active agents required for stabilization”. They are defined as “carrier-free submicron colloidal drug delivery systems with a mean particle size in the nanometer range, typically between 10–800 nm”. The primary importance of these nanoparticles was the reduction of particle size to nanoscale dimensions, with an increase in the particle surface area in contact with the dissolution medium, and thus in bioavailability. This approach has been proven successful, as demonstrated by the number of such drug products on the market. Nonetheless, despite the definition that indicates nanocrystals as a “carrier-free” system, surface active agents are necessary to prevent colloidal particles aggregation and thus improve stability. In addition, in more recent years, nanocrystal properties and technologies have attracted the interest of researchers as a means to obtain colloidal particles with modified biological properties, and thus their interest is now also addressed to modify the drug delivery and targeting. The present work provides an overview of the achievements in improving the bioavailability of poorly soluble drugs according to their administration route, describes the methods developed to overcome physicochemical and stability-related problems, and in particular reviews different stabilizers and surface agents that are able to modify the drug delivery and targeting.

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Bioavailability Enhancement of Poorly Water-Soluble Drugs via Nanocomposites: Formulation–Processing Aspects and Challenges

Cited by 160 publications

References 227 publications

Topical Delivery of Coenzyme Q10-Loaded Microemulsion for Skin Regeneration

Topical Delivery of Coenzyme Q10-Loaded Microemulsion for Skin Regeneration

Effect of Particle Size and Polymer Loading on Dissolution Behavior of Amorphous Griseofulvin Powder

Nanocrystals of Poorly Soluble Drugs: Drug Bioavailability and Physicochemical Stability

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