CriticalSorb™: A novel efficient nasal delivery system for human growth hormone based on Solutol HS15

Illum, Lisbeth; Jordan, Faron; Lewis, Andrew L.

doi:10.1016/j.jconrel.2012.06.014

Cited by 37 publications

(25 citation statements)

References 34 publications

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“…1) which was visualized by the slightly higher slopes in the linear graph of solubilizing system. HS15 solubilized more CoQ10 than polysorbate 80, which could be explained by the more hydrophobic acyl chain groups in the micellar structure (31,33,34). Furthermore, HS15 had been reported to improve the bioavailability and reduce the cytotoxicity (35)(36)(37).…”

Section: Solubilization By Micellesmentioning

confidence: 99%

Kolliphor® HS 15 Micelles for the Delivery of Coenzyme Q10: Preparation, Characterization, and Stability

et al. 2015

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ABSTRACT. To enhance the stability of coenzyme Q10 (CoQ 10 ), Kolliphor® HS 15 (HS15) was employed as a carrier to build up a stable CoQ10-loaded micelle delivery system. The impact of micellar compositions, the preparation condition, and the preparation method on size characteristics, the solubilization efficiency, and micellar stability were investigated. The optimal preparation conditions were 1:6, 4, 0.2%, 118°C, and 25 min for CoQ10/HS15 mass ratio, pH value, the concentration of glucose, and the sterilization conditions. Upon these conditions, the particle size, polydispersity index (PDI), zeta potential, the entrapment efficiency, drug loading, and the critical micelle concentration (CMC) of CoQ10-loaded micelles were 19.76 nm, 0.112, −3.405 mV, 99.39%, 13.77%, and 5.623×10−4 g/mL, respectively. Differential scanning calorimetry (DSC) analysis collectively corroborated that CoQ10 was entrapped into the micelles in amorphous form. The release pattern of drug was analyzed and proved to follow the first order. Additionally, the samples were exposed to the temperatures of 30°C for 6 months with more significant impact on their stabilities as compared to 4 and 25°C based on particle size and PDI. Under constant humidity with light protection long-term (25±2°C, relative humidity (RH) 60±10%, 18 months) conditions, there was no variation except minor changes of CoQ10 content of the samples. The shelf life of the micellar samples could be predicted as 24 months based on the stability results. Consequently, the CoQ10-loaded micelles showed excellent stabilities below 25°C as a potential drug candidate for further clinical applications.

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Section: Solubilization By Micellesmentioning

confidence: 99%

Kolliphor® HS 15 Micelles for the Delivery of Coenzyme Q10: Preparation, Characterization, and Stability

et al. 2015

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“…1 ) as the principal component, proposed to act as a permeability enhancer. CriticalSorb® technology is currently in early clinical development stage as a nasal spray formulation for delivery of human growth hormone, based on a previously demonstrated enhancement of the bioavailability of human growth hormone and insulin in both animal studies and human trials ( 8 ). In addition, Solutol® HS15 is currently used to increase the aqueous solubility of Biopharmaceutical Classification System (BCS) Class 2 and 4 lipophilic molecules ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Mucosal Permeability Enhancement of CriticalSorb® (Solutol® HS15) Investigated In Vitro in Cell Cultures

et al. 2014

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PurposeCriticalSorb™, with the principal component Solutol® HS15, is a novel mucosal drug delivery system demonstrated to improve the bioavailability of selected biotherapeutics. The intention of this study is to elucidate mechanism(s) responsible for the enhancement of trans-mucosal absorption of biological drugs by Solutol® HS15.MethodsMicelle size and CMC of Solutol® HS15 were determined in biologically relevant media. Polarised airway Calu-3 cell layers were used to measure the permeability of a panel of biological drugs, and to assess changes in TEER, tight junction and F-actin morphology. The rate of cell endocytosis was measured in vitro in the presence of Solutol® HS15 using a membrane probe, FM 2–10.ResultsThis work initially confirms surfactant-like behaviour of Solutol® HS15 in aqueous media, while subsequent experiments demonstrate that the effect of Solutol® HS15 on epithelial tight junctions is different from a ‘classical’ tight junction opening agent and illustrate the effect of Solutol® HS15 on the cell membrane (endocytosis rate) and F-actin cytoskeleton.ConclusionSolutol® HS15 is the principle component of CriticalSorb™ that has shown an enhancement in permeability of medium sized biological drugs across epithelia. This study suggests that its mechanism of action arises primarily from effects on the cell membrane and consequent impacts on the cell cytoskeleton in terms of actin organisation and tight junction opening.

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“…Thus the highest (49%) [68] bioavailability value found with Solutol HS15 followed by starch microspheres/lPC (14.4%) [61], LPC (16.0%) [60] and Chitosan nanoparticle (14% and 15%) [66].…”

Section: Fig 6: Hgh Serum Levels In Rats After Hgh Intranasal Applicmentioning

confidence: 94%

Formulations and Technologies in Growth Hormone Delivery

Mohammed

Obaidat

Assaf

et al. 2017

Int J Pharm Pharm Sci

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Growth hormone (GH) treatment has many indications including the treatment of growth hormone deficiency (GHD), Prader-Willi syndrome, chronic renal insufficiency, Turner syndrome, AIDS-related wasting, idiopathic short stature in children, and accumulation of fat which related in adults with lipodystrophy. Conventional therapy was achieved using daily intramuscular (IM) and subcutaneous (SC) injections. However, patient's noncompliance was very high. To solve this; several studies have been attempted to prepare long-acting formulations and to make prolonged halflife derivatives of GH. New delivery systems were also used such as needle-free and auto-injector devices to enhance the conveniences and adjustability. Furthermore, alternative routes of administration, such as intranasal, pulmonary, transdermal and oral are other strategies used to deliver the GH in a noninvasive way. In this review, we present a summary of various sustained-release formulations and technologies via injection. Noninvasive routes of GH delivery will be also reviewed with the principles of key points, selected additives, and limitations.

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CriticalSorb™: A novel efficient nasal delivery system for human growth hormone based on Solutol HS15

Cited by 37 publications

References 34 publications

Kolliphor® HS 15 Micelles for the Delivery of Coenzyme Q10: Preparation, Characterization, and Stability

Kolliphor® HS 15 Micelles for the Delivery of Coenzyme Q10: Preparation, Characterization, and Stability

Mechanism of Mucosal Permeability Enhancement of CriticalSorb® (Solutol® HS15) Investigated In Vitro in Cell Cultures

Formulations and Technologies in Growth Hormone Delivery

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