BCS class IV drugs: Highly notorious candidates for formulation development

Ghadi, Rohan; Dand, Neha

doi:10.1016/j.jconrel.2017.01.014

Cited by 266 publications

(136 citation statements)

References 166 publications

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“…NLCs are second-generation of lipid nanoparticles developed using a blend of solid and liquid lipid. NLCs offer many advantages such as good biocompatibility, controlled drug release and the possibility of production on the large industrial scale [10,11]. Moreover, a high drug loading efficiency can be achieved with the use of NLC [12,13].…”

Section: Fig 1: Structure Of Exemestane [3]mentioning

confidence: 99%

Study on Cause–effect Relations and Optimization of Exemestane-Loaded Nanostructured Lipid Carriers

Thang

Hanh

Duong

2017

Int J Pharm Pharm Sci

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Objective: Exemestane is an anti-breast cancer drug, possesses low water solubility and low permeability. This work aimed at the cause-effect relations and optimization of exemestane-loaded nanostructured lipid carriers (EXE-NLCs) for oral delivery.Methods: Excipient screening was based on exemestane solubilities and the emulsification efficiency of surfactants. A D-optimal design based on three independent variables was applied to evaluate the cause-effect relations and optimise EXE-NLCs formulation. The particle size (PS), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL) were investigated with respect to three independent variables including liquid lipid to total lipid ratio (X1), surfactant concentration (X2), total lipid concentration (X3).Results: EXE-NLCs were prepared by a hot sonication method employing Labrafac CC and Compritol 888ATO as liquid and solid lipids, respectively, and Cremophor RH40 as a surfactant and Lutrol E-400 as a co-surfactant. All investigated factors: liquid lipid to total lipid ratio, surfactant concentration and total lipid concentration showed significant influences on physicochemical characteristics of EXE-NLCs. The optimal EXE-NLC formulation was composed of liquid lipid to total lipid ratio (X1) of 24 % (w/w), surfactant concentration (X2) of 4 % (w/v) and total lipid concentration (X3) of 4 % (w/v). The PS, PDI, EE and DL of the optimized EXE-NLCs were found to be 41.787 nm; 0.11; 97.605 % and 1.935 %, respectively. The optimized formulation was experimentally examined which demonstrated a good agreement between experimental and predicted values. Conclusion:The cause-effect relations and optimization of EXE-NLCs were investigated and reported for the first time. EXE-NLCs formulation was successfully optimized using D-optimal design and merits further study.

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Section: Fig 1: Structure Of Exemestane [3]mentioning

confidence: 99%

Study on Cause–effect Relations and Optimization of Exemestane-Loaded Nanostructured Lipid Carriers

Thang

Hanh

Duong

2017

Int J Pharm Pharm Sci

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“…It should be noted though that cyclosporine A is a cyclic peptide and belongs to BCS Class IV (i.e. low solubility & low permeability) (28). Therefore, the likelihood of obtaining an in vitro-in vivo correlation (IVIVC) for a cyclosporine A formulation is not that high (28).…”

Section: Discussionmentioning

confidence: 99%

“…low solubility & low permeability) (28). Therefore, the likelihood of obtaining an in vitro-in vivo correlation (IVIVC) for a cyclosporine A formulation is not that high (28). That said, the significant increase in drug release obtained with Neoral ® in SIF at 24 h was associated with a significantly higher CyA concentration (p<0.05) in blood compared to CyA-loaded micelles (361 versus 175 ng/mL, respectively).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Orally Administered Poly(Ethylene Oxide)-block-Poly(ε-Caprolactone) Micelles of Cyclosporine A in Rats: Comparison with Neoral®

et al. 2018

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“…Drug discovery and development are remarkably complex and challenging because numerous attributes should be simultaneously optimized to achieve clinically desirable efficacy and safety. In particular, there has been growing emphasis on drug-like properties such as solubility and permeability being considered in the early phase of drug discovery and development [1]. According to the Biopharmaceutical Classification System (BCS), BCS class II and IV drugs show low oral BA.…”

Section: Introductionmentioning

confidence: 99%

“…For BCS class II drugs, low BA can be mainly due to poor dissolution. In contrast, the low BA of BCS class IV drugs is caused by both poor dissolution and low permeability [1]. Diverse approaches have been attempted to deliver water-insoluble drugs: salt formation, co-solvency and surfactant solubilization, amorphous forms, solid dispersion, co-crystals, polymeric micelles, inclusion complex, size reduction, solid lipid nanoparticles, polymeric nanoparticles and liposomes [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Liposomes for Enhanced Bioavailability of Water-Insoluble Drugs: In Vivo Evidence and Recent Approaches

Lee

2020

Pharmaceutics

174

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It has been known that a considerable number of drugs in clinical use or under development are water-insoluble drugs with poor bioavailability (BA). The liposomal delivery system has drawn attention as one of the noteworthy approaches to increase dissolution and subsequently absorption in the gastrointestinal (GI) tract because of its biocompatibility and ability to encapsulate hydrophobic molecules in the lipid domain. However, there have been several drawbacks, such as structural instability in the GI tract and poor permeability across intestinal epithelia because of its relatively large size. In addition, there have been no liposomal formulations approved for oral use to date, despite the success of parenteral liposomes. Nevertheless, liposomal oral delivery has resurged with the rapid increase of published studies in the last decade. However, it is discouraging that most of this research has been in vitro studies only and there have not been many water-insoluble drugs with in vivo data. The present review focused on the in vivo evidence for the improved BA of water-insoluble drugs using liposomes to resolve doubts raised concerning liposomal oral delivery and attempted to provide insight by highlighting the approaches used for in vivo achievements.Pharmaceutics 2020, 12, 264 2 of 30 However, there have been several drawbacks to be overcome, such as instability in the GI tract and poor permeability across the intestinal epithelia because of liposomes' relatively large size [8]. Moreover, it seemed that liposomal oral delivery was faltering during 1980s due to some disappointing results for insulin [9]. However, liposomal oral delivery resurged with a rapid increase in the number of papers published, as shown in Pubmed search results, mainly due to various advanced modification technologies, even though liposomal oral delivery-related papers account for only 5-6% of the total number of liposomes-related studies (Figure 1). In addition, there was an encouraging meta-analysis report in which phospholipid-based solid formulations were analyzed as being effective for BA enhancement [10]. Although liposomal delivery does not seem to achieve satisfactory improvement of oral BA for peptides and protein drugs yet, it looks more promising for oral delivery of hydrophobic drugs because liposomes can solubilize poorly water-soluble drugs, protect the drug from degradation in the GI tract and enhance permeability through the epithelial cell membrane, consequently increasing oral BA. However, most published papers performed in vitro studies only, thus lacking in vivo pharmacokinetic results. The present review focuses on the in vivo evidence for the improved BA of water-insoluble drugs and highlights the approaches used for in vivo achievements.

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BCS class IV drugs: Highly notorious candidates for formulation development

Cited by 266 publications

References 166 publications

Study on Cause–effect Relations and Optimization of Exemestane-Loaded Nanostructured Lipid Carriers

Study on Cause–effect Relations and Optimization of Exemestane-Loaded Nanostructured Lipid Carriers

Pharmacokinetics of Orally Administered Poly(Ethylene Oxide)-block-Poly(ε-Caprolactone) Micelles of Cyclosporine A in Rats: Comparison with Neoral®

Liposomes for Enhanced Bioavailability of Water-Insoluble Drugs: In Vivo Evidence and Recent Approaches

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