Effect of Permeation Enhancer on Bioavailability of Formulated Patches of Glibenclamide

: As a unique and pleiotropic polymer, d-alpha-tocopheryl polyethylene glycol succinate (Tocophersolan) is a polymeric synthetic version of vitamin E. Tocophersolan has attracted enormous attention as a versatile excipient in different biomedical applications including drug delivery systems and nutraceuticals. The multiple inherent properties of Tocophersolan make it play flexible roles in drug delivery system design, including excipients with outstanding biocompatibility, solubilizer with the ability of promoting drug dissolution, drug permeation enhancer, P-glycoprotein inhibitor and anticancer compound. For these reasons, Tocophersolan has been widely used for improving the bioavailability of numerous pharmaceutical active ingredients. Tocophersolan has been approved by stringent regulatory authorities (such as US FDA, EMA, and PMDA) as a safe pharmaceutical excipient. In this review, we systematically curated current advances in nano-based delivery systems consisting of Tocophersolan with possibilities for futuristic applications in drug delivery, gene therapy, and nanotheranostic.

Download Full-text

Enhanced Bioavailability and Efficacy of Silymarin Solid Dispersion in Rats with Acetaminophen-Induced Hepatotoxicity

Pharmaceutics ◽

10.3390/pharmaceutics13050628 ◽

2021 ◽

Vol 13 (5) ◽

pp. 628

Author(s):

Im-Sook Song ◽

So-Jeong Nam ◽

Ji-Hyeon Jeon ◽

Soo-Jin Park ◽

Min-Koo Choi

Keyword(s):

Alkaline Phosphatase ◽

Polyethylene Glycol ◽

Oral Administration ◽

Solid Dispersion ◽

Active Component ◽

Efflux Pump ◽

Therapeutic Effects ◽

Permeation Enhancer ◽

Efflux Ratio ◽

Polyethylene Glycol 1000

We evaluated the bioavailability, liver distribution, and efficacy of silymarin-D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) solid dispersion (silymarin-SD) in rats with acetaminophen-induced hepatotoxicity (APAP) compared with silymarin alone. The solubility of silybin, the major and active component of silymarin, in the silymarin-SD group increased 23-fold compared with the silymarin group. The absorptive permeability of silybin increased by 4.6-fold and its efflux ratio decreased from 5.5 to 0.6 in the presence of TPGS. The results suggested that TPGS functioned as a solubilizing agent and permeation enhancer by inhibiting efflux pump. Thus, silybin concentrations in plasma and liver were increased in the silymarin-SD group and liver distribution increased 3.4-fold after repeated oral administration of silymarin-SD (20 mg/kg as silybin) for five consecutive days compared with that of silymarin alone (20 mg/kg as silybin). Based on higher liver silybin concentrations in the silymarin-SD group, the therapeutic effects of silymarin-SD in hepatotoxic rats were evaluated and compared with silymarin administration only. Elevated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels were significantly decreased by silymarin-SD, silymarin, and TPGS treatments, but these decreases were much higher in silymarin-SD animals than in those treated with silymarin or TPGS. In conclusion, silymarin-SD (20 mg/kg as silybin, three times per day for 5 days) exhibited hepatoprotective properties toward hepatotoxic rats and these properties were superior to silymarin alone, which may be attributed to increased solubility, enhanced intestinal permeability, and increased liver distribution of the silymarin-SD formulation.

Download Full-text

An optimized probucol microencapsulated formulation integrating a secondary bile acid (deoxycholic acid) as a permeation enhancer

Drug Design Development and Therapy ◽

10.2147/dddt.s68247 ◽

2014 ◽

pp. 1673 ◽

Cited By ~ 5

Author(s):

Hani Al-Salami ◽

Armin Mooranian ◽

Rebecca Negrulj ◽

Nigel Chen-Tan ◽

Gerald Watts ◽

...

Keyword(s):

Bile Acid ◽

Deoxycholic Acid ◽

Permeation Enhancer ◽

Secondary Bile Acid

Download Full-text

Transdermal enhancement strategy of ketoprofen and teriflunomide: The effect of enhanced drug-drug intermolecular interaction by permeation enhancer on drug release of compound transdermal patch

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2019.118800 ◽

2019 ◽

Vol 572 ◽

pp. 118800 ◽

Cited By ~ 1

Author(s):

Chao Liu ◽

Yanli Guan ◽

Qi Tian ◽

Xinyu Shi ◽

Liang Fang

Keyword(s):

Drug Release ◽

Intermolecular Interaction ◽

Permeation Enhancer ◽

Transdermal Patch

Download Full-text

Improved Transmucosal Delivery of Glimepiride via Unidirectional Release Buccal Film Loaded With Vitamin E TPGS-Based Nanocarrier

Dose-Response ◽

10.1177/1559325820945164 ◽

2020 ◽

Vol 18 (3) ◽

pp. 155932582094516

Author(s):

Tahani S. Basahih ◽

Abdullah A. Alamoudi ◽

Khalid M. El-Say ◽

Nabil A. Alhakamy ◽

Osama A. A. Ahmed

Keyword(s):

Buccal Mucosa ◽

Ethyl Cellulose ◽

Permeation Enhancer ◽

Box Behnken Design ◽

Hypoglycemic Agent ◽

Vitamin E Tpgs ◽

Initial Release ◽

Polyethylene Glycol 1000 ◽

Formulation Variables ◽

Transmucosal Delivery

Glimepiride (GMD) is a hypoglycemic agent that has variation in bioavailability for its unexpected absorption. Glimepiride was formulated in a buccal film loaded with a nanobased formulation to enhance its absorption via buccal mucosa. Nanostructured lipid carriers (NLCs) and d-α-tocopherol polyethylene glycol 1000 succinate-based micelles enhance GMD solubility and improve its permeation through the buccal mucosa. The formulation variables were optimized using a Box-Behnken design. These factors, such as the percent of micelles relative to NLC ( X 1), the percent of Carbopol ( X 2), and the percent of permeation enhancer ( X 3), were investigated for their effect on the initial release ( Y 1) and the cumulative release after 6 hours ( Y 2). The optimum levels for X 1, X 2, and X 3 were 100%, 0.05%, and 1.8%, respectively. The optimized formulation revealed that the permeation of GMD from the film was in favor of micelles. This optimized film was then coated with ethyl cellulose to direct the release only through the buccal mucosa. The optimized unidirectional GMD transmucosal film showed a release of 93.9% of GMD content at 6 hours compared to 60.41% of GMD release from the raw GMD film. This finding confirmed the suitability of transmucosal delivery of GMD via the buccal mucosa.

Download Full-text

Nasal Administration and Plasma Pharmacokinetics of Parathyroid Hormone Peptide PTH 1-34 for the Treatment of Osteoporosis

Pharmaceutics ◽

10.3390/pharmaceutics11060265 ◽

2019 ◽

Vol 11 (6) ◽

pp. 265 ◽

Cited By ~ 2

Author(s):

Richard G. Pearson ◽

Tahir Masud ◽

Elaine Blackshaw ◽

Andrew Naylor ◽

Michael Hinchcliffe ◽

...

Keyword(s):

Nasal Spray ◽

Subcutaneous Injection ◽

Relative Bioavailability ◽

Nasal Delivery ◽

Absolute Bioavailability ◽

Preclinical Model ◽

Permeation Enhancer ◽

Treatment Of Osteoporosis ◽

Plasma Pharmacokinetics ◽

Spray Formulation

Nasal delivery of large peptides such as parathyroid 1-34 (PTH 1-34) can benefit from a permeation enhancer to promote absorption across the nasal mucosa into the bloodstream. Previously, we have published an encouraging bioavailability (78%), relative to subcutaneous injection in a small animal preclinical model, for a liquid nasal spray formulation containing the permeation enhancer polyethylene glycol (15)-hydroxystearate (Solutol® HS15). We report here the plasma pharmacokinetics of PTH 1-34 in healthy human volunteers receiving the liquid nasal spray formulation containing Solutol® HS15. For comparison, data for a commercially manufactured teriparatide formulation delivered via subcutaneous injection pen are also presented. Tc-99m-DTPA gamma scintigraphy monitored the deposition of the nasal spray in the nasal cavity and clearance via the inferior meatus and nasopharynx. The 50% clearance time was 17.8 min (minimum 10.9, maximum 74.3 min). For PTH 1-34, mean plasma Cmax of 5 pg/mL and 253 pg/mL were obtained for the nasal spray and subcutaneous injection respectively; relative bioavailability of the nasal spray was ≤1%. Subsequently, we investigated the pharmacokinetics of the liquid nasal spray formulation as well as a dry powder nasal formulation also containing Solutol® HS15 in a crossover study in an established ovine model. In this preclinical model, the relative bioavailability of liquid and powder nasal formulations was 1.4% and 1.0% respectively. The absolute bioavailability of subcutaneously administered PTH 1-34 (mean 77%, range 55–108%) in sheep was in agreement with published human data for teriparatide (up to 95%). These findings have important implications in the search for alternative routes of administration of peptides for the treatment of osteoporosis, and in terms of improving translation from animal models to humans.

Download Full-text

Exploring protein stabilized multiple emulsion with permeation enhancer for oral delivery of insulin

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2020.11.190 ◽

2021 ◽

Vol 167 ◽

pp. 491-501

Author(s):

Ishneet Kaur ◽

Bhargavi Nallamothu ◽

Kaushik Kuche ◽

Sameer S. Katiyar ◽

Dasharath Chaudhari ◽

...

Keyword(s):

Oral Delivery ◽

Permeation Enhancer ◽

Multiple Emulsion

Download Full-text

Transmucosal Absorption Enhancers in the Drug Delivery Field

Pharmaceutics ◽

10.3390/pharmaceutics11070339 ◽

2019 ◽

Vol 11 (7) ◽

pp. 339 ◽

Cited By ~ 7

Author(s):

Maher ◽

Casettari ◽

Illum

Keyword(s):

Drug Delivery ◽

Clinical Trials ◽

Drug Delivery Systems ◽

Permeation Enhancer ◽

Special Issue ◽

Permeation Enhancers ◽

Absorption Enhancers ◽

Chemical Permeation Enhancers ◽

Epithelial Barriers ◽

Chemical Permeation

Drug delivery systems that safely and consistently improve transport of poorly absorbed compounds across epithelial barriers are highly sought within the drug delivery field. The use of chemical permeation enhancers is one of the simplest and widely tested approaches to improve transmucosal permeability via oral, nasal, buccal, ocular and pulmonary routes. To date, only a small number of permeation enhancers have progressed to clinical trials, and only one product that includes a permeation enhancer has reached the pharmaceutical market. This editorial is an introduction to the special issue entitled Transmucosal Absorption Enhancers in the Drug Delivery Field (https://www.mdpi.com/journal/pharmaceutics/special_issues/transmucosal_absorption_enhancers). The guest editors outline the scope of the issue, reflect on the results and the conclusions of the 19 articles published in the issue and provide an outlook on the use of permeation enhancers in the drug delivery field.

Download Full-text