Analysis of model drug permeation through highly crosslinked and biodegradable polyethylene glycol membranes

Microwaved-induced in situ amorphization of a drug in a polymer has been suggested to follow a dissolution process, with the drug dissolving into the mobile polymer at temperatures above the glass transition temperature (Tg) of the polymer. Thus, based on the Noyes–Whitney and the Stoke–Einstein equations, the temperature and the viscosity are expected to directly impact the rate and degree of drug amorphization. By investigating two different viscosity grades of polyethylene glycol (PEG), i.e., PEG 3000 and PEG 4000, and controlling the temperature of the microwave oven, it was possible to study the influence of both, temperature and viscosity, on the in situ amorphization of the model drug celecoxib (CCX) during exposure to microwave radiation. In this study, compacts containing 30 wt% CCX, 69 wt% PEG 3000 or PEG 4000 and 1 wt% lubricant (magnesium stearate) were exposed to microwave radiation at (i) a target temperature, or (ii) a target viscosity. It was found that at the target temperature, compacts containing PEG 3000 displayed a faster rate of amorphization as compared to compacts containing PEG 4000, due to the lower viscosity of PEG 3000 compared to PEG 4000. Furthermore, at the target viscosity, which was achieved by setting different temperatures for compacts containing PEG 3000 and PEG 4000, respectively, the compacts containing PEG 3000 displayed a slower rate of amorphization, due to a lower target temperature, than compacts containing PEG 4000. In conclusion, with lower viscosity of the polymer, at temperatures above its Tg, and with higher temperatures, both increasing the diffusion coefficient of the drug into the polymer, the rate of amorphization was increased allowing a faster in situ amorphization during exposure to microwave radiation. Hereby, the theory that the microwave-induced in situ amorphization process can be described as a dissolution process of the drug into the polymer, at temperatures above the Tg, is further strengthened.

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A stepwise protocol for drug permeation assessment that combines heat-separated porcine ear epidermis and vertical diffusion cells

Hemijska industrija ◽

10.2298/hemind170726019p ◽

2018 ◽

Vol 72 (1) ◽

pp. 47-53 ◽

Cited By ~ 1

Author(s):

Ivana Pantelic ◽

Tanja Ilic ◽

Bojan Markovic ◽

Sanela Savic ◽

Milica Lukic ◽

...

Keyword(s):

Evaluation Method ◽

In Vitro Test ◽

Formulation Development ◽

Vertical Diffusion ◽

Synthetic Membranes ◽

Drug Permeation ◽

Diffusion Cells ◽

Drug Sample ◽

Model Drug

After decades long absence of an official consensus on the most appropriate evaluation method for in vitro skin performance of topical semisolid drugs, United States Pharmacopoeia (USP 39) finally suggested three types of testing equipment; however, all these provide data on drug release using inert synthetic membranes. Considering the need for a readily available membrane that would be more structurally similar to human skin, this paper provides a detailed protocol of a method for drug permeation assessment that uses heat-separated porcine ear epidermis and modified Franz diffusion cells. Phases that were shown to be critical for variability of the results are identified (e.g., membrane preparation), and process parameters optimized. Applicability of the method was tested on four cream samples loaded with aceclofenac as a model drug. Sample compositions were designed in such a way to provide ?large? variations (variation of the main stabilizer: natural-origin versus synthetic emulsifier) and relatively ?minor? variations (co-solvent variation: none/isopropanol/glycerol). The developed protocol is a straightforward and reliable in vitro test for the evaluation of rate and extent of drug delivery into/through the skin. Moreover, this protocol may be routinely applied even in averagely equipped laboratories during formulation development or preliminary bioequivalence assessment of generic topical semisolids.

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Co-surfactant effect of polyethylene glycol 400 on microemulsion using BCS class II model drug

Journal Of Advanced Pharmacy Education And Research ◽

10.51847/1h17tzqgyi ◽

2022 ◽

Vol 12 (1) ◽

pp. 63-69

Author(s):

Salam Shanta Taher ◽

Khalid Kadhem Al-Kinani ◽

Zahraa Mohsen Hammoudi ◽

Mowafaq mohammed Ghareeb

Keyword(s):

Polyethylene Glycol ◽

Class Ii ◽

Polyethylene Glycol 400 ◽

Surfactant Effect ◽

Bcs Class Ii ◽

Model Drug

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EVALUATING THE BEST POLYETHYLENE GLYCOL AS SOLID DISPERSION CARRIER BY TAKING ETORICOXIB AS A MODEL DRUG

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i3.30251 ◽

2019 ◽

pp. 250-255

Author(s):

HEMANTH A ◽

HINDUSTAN ABDUL AHAD ◽

DEVANNA N

Keyword(s):

Polyethylene Glycol ◽

Solid Dispersion ◽

Solid Dispersions ◽

Physicochemical Characteristics ◽

Peg 6000 ◽

Good Solubility ◽

Peg 4000 ◽

Tablet Compression ◽

Model Drug ◽

Peg 8000

Objective: The main objective of the current research is focused in discovering the best polyethylene glycol (PEG) as solid dispersion carrier using etoricoxib (ECB) as a model drug. Methods: Varieties of PEG, namely PEG - 3350, PEG - 4000, PEG - 6000, PEG - 8000, and PEG - 20000, were evaluated as a carrier for making ECB solid dispersions. ECB:PEG was taken in the ratios of 1:1, 1:2, 1:4, and 1:6. The solid dispersions were prepared by microwave fusion method and compressed using 8 station tablet compression machine. The fabricated solid dispersion tablets were tested for physicochemical characteristics and drug release rates. The release of ECB from the prepared solid dispersions was further analyzed kinetically using the first order and Hixson-Crowell’s plots. Results: All the solid dispersion batches were shown satisfactory physicochemical characteristics. ECB solid dispersion batches with PEG - 6000 showed good solubility in distilled water (up to 2.29±0.01 μg/ml) and in 0.1 N HCl (up to 2.18±0.01 μg/ml) when compared with ECB alone (0.21±0.01 μg/ml and 0.32±0.01 μg/ml). The prepared solid dispersions with PEG 6000 are shown good ECB release. Conclusion: Among PEG carriers, PEG - 6000 was found to be the best carrier for increasing the solubility and release rate of ECB form the solid dispersions compared to PEG - 3350, PEG - 4000, PEG - 8000, and PEG - 20000.

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DESIGN AND EVALUATION OF CHITOSAN-HPMC POLYMERIC FILMS FOR TRANSDERMAL DELIVERY OF CAPTOPRIL

INDIAN DRUGS ◽

10.53879/id.57.06.12317 ◽

2020 ◽

Vol 57 (06) ◽

pp. 69-72

Author(s):

Rajesh Sreedharan Nair ◽

Manickam Balamurugan ◽

Meng Sheng Teng

Keyword(s):

Transdermal Delivery ◽

Moisture Absorption ◽

Hydroxypropyl Methylcellulose ◽

Physicochemical Characterization ◽

Scanning Calorimetry ◽

Drug Permeation ◽

Evaporation Technique ◽

Model Drug ◽

The Stability

Drug permeation through the skin layers remains a major challenge in transdermal drug delivery. In this study, the permeation enhancing property of chitosan together with its rate-controlling property has been utilized in the development of an efficient transdermal delivery system, using captopril as a model drug. Chitosan-hydroxypropyl methylcellulose (HPMC) films were developed by solvent evaporation technique. The films were characterized for appearance, thickness, weight uniformity, drug content, folding endurance and moisture absorption. Drug-polymer interaction was assessed using ATR-FTIR spectroscopy and Differential Scanning Calorimetry. The in vitro permeation carried out in Franz-type diffusion cells using synthetic Strat-M® membrane, demonstrated that the film coded F2 (Chitosan:HPMC = 50:50) showed a significant increase in drug permeation than F1 (Chitosan:HPMC = 90:10) with a flux value 86.7 µg/cm2/h. The physicochemical characterization and the stability studies confirmed that the formulated films were chemically and physically stable.

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Synergistic Effect of Ultrasound and Polyethylene Glycol on the Mechanism of the Controlled Drug Release from Polylactide Matrices

Polymers ◽

10.3390/polym11050880 ◽

2019 ◽

Vol 11 (5) ◽

pp. 880

Author(s):

Wenting Bao ◽

Xianlong Zhang ◽

Hong Wu ◽

Rong Chen ◽

Shaoyun Guo

Keyword(s):

Polyethylene Glycol ◽

Controlled Release ◽

Drug Release ◽

Synergistic Effect ◽

In Vitro Release ◽

Structure And Properties ◽

Melt Extrusion ◽

Model Drug ◽

Vitro Release

In this paper, the synergistic effect of ultrasound and polyethylene glycol (PEG) on the controlled release of a water soluble drug from polylactide (PLA) matrices was studied. When ultrasound was used following the hot melt extrusion (HME) of the PLA/model drug release system, the release of the model drug (Methylene Blue (MB)) from the PLA when immersed in phosphate buffered saline (PBS) was affected by the variation of the parameters of ultrasound. It was found that no more than 2% PLA dissolved during the in-vitro release study, and the release of the MB from the PLA was diffusion controlled and fit well with the Higuchi diffusion model. Polyethylene glycol (PEG), which has high hydrophilicity and rapid dissolution speed, was blended with the PLA during the melt extrusion to enhance the release of the MB. The analysis of the structure and properties of the in-vitro release tablets of PLA/PEG/MB indicated that the ultrasound could improve the dispersion of MB in the PLA/PEG blends and it could also change the structure and properties of the PLA/PEG blends. Due to the dissolution of the PEG in PBS, the release of the MB from the PLA/PEG drug carrier was a combination of diffusion and erosion controlled release. Thus a new mechanism combining of diffusion and erosion models and modified kinetics model was proposed to explain the release behavior.

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Influence of Lactobacillus Biosurfactants on Skin Permeation of Hydrocortisone

Pharmaceutics ◽

10.3390/pharmaceutics13060820 ◽

2021 ◽

Vol 13 (6) ◽

pp. 820

Author(s):

Angela Abruzzo ◽

Carola Parolin ◽

Elisa Corazza ◽

Barbara Giordani ◽

Massimiliano Pio di Cagno ◽

...

Keyword(s):

Skin Permeation ◽

Aqueous Solubility ◽

Skin Hydration ◽

Permeation Enhancers ◽

Scanning Calorimetry ◽

Drug Permeation ◽

Diffusion Studies ◽

Model Drug ◽

Dsc Curves

One of the most widely used strategies to improve drug diffusion through the skin is the use of permeation enhancers. The aim of this work was to investigate the effect of two biosurfactants (BS), produced by Lactobacillus crispatus BC1 and Lactobacillus gasseri BC9, on the skin permeation profile of hydrocortisone (HC, model drug). HC aqueous solubility and in vitro diffusion studies through porcine skin were performed in the presence of BC1-BS and BC9-BS at concentrations below and above critical micellar concentrations (CMC). Moreover, skin hydration tests and differential scanning calorimetry (DSC) analysis were performed to further investigate BS interaction with the outermost layer of the skin. Both BS increased HC solubility, especially at concentrations above their CMC. At concentrations below the CMC, drug permeation through the skin was improved, as the result of a dual effect: a) the formation of a superficial lipophilic environment, as confirmed by the reduction in skin hydration and b) the interaction between BS and the stratum corneum (SC), as demonstrated by the DSC curves. From the obtained data, it appears that BC1-BS and BC9-BS could represent new promising green excipients for drug permeation enhancement through the skin.

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Xylan-Based Hydrogels as a Potential Carrier for Drug Delivery: Effect of Pore-Forming Agents

Pharmaceutics ◽

10.3390/pharmaceutics10040261 ◽

2018 ◽

Vol 10 (4) ◽

pp. 261 ◽

Cited By ~ 7

Author(s):

Minmin Chang ◽

Xinxin Liu ◽

Ling Meng ◽

Xiaohui Wang ◽

Junli Ren

Keyword(s):

Drug Delivery ◽

Polyethylene Glycol ◽

Drug Release ◽

Pore Structure ◽

Significant Influence ◽

Radical Copolymerization ◽

Cross Linking ◽

Swelling Ratio ◽

Model Drug ◽

Carboxymethyl Xylan

Pore-forming agents have a significant influence on the pore structure of hydrogels. In this study, a porogenic technique was employed to investigate the preparation of macroporous hydrogels which were synthesized by radical copolymerization of carboxymethyl xylan with acrylamide and N-isopropylacrylamide under the function of a cross-linking agent. Six kinds of pore-forming agents were used: polyvinylpyrrolidone K30, polyethylene glycol 2000, carbamide, NaCl, CaCO3, and NaHCO3. The application of these hydrogels is also discussed. The results show that pore-forming agents had an important impact on the pore structure of the hydrogels and consequently affected properties of the hydrogels such as swelling ratio and mechanical strength, while little effect was noted on the thermal property of the hydrogels. 5-Fluorouracil was used as a model drug to study the drug release of the as-prepared hydrogels, and it was found that the drug release was substantially improved after using the NaHCO3 pore-forming agent: a cumulative release rate of up to 71.05% was achieved.

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Impact of Chain Length on Release Behavior of Modified Polyethylene Glycol Intercalated-Montmorillonite Nanocomposite

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2020.17860 ◽

2020 ◽

Vol 20 (9) ◽

pp. 5546-5554

Author(s):

Mosaed Al-Sahly ◽

Hany El-Hamshary ◽

Salem S. Al-Deyab

Keyword(s):

Electron Microscopy ◽

Polyethylene Glycol ◽

Ion Exchange ◽

Chain Length ◽

Fickian Diffusion ◽

Release Behavior ◽

Molecular Weights ◽

Peg 4000 ◽

Model Drug ◽

Peg Chain Length

A new drug delivery nanocomposite system was prepared from sodium montmorillonite (Na+Mt) intercalated with modified polyethylene glycol (PEG). PEGs of different molecular weights (400, 4000, and 8000) were modified with glycidyltrimethylammonium chloride (GTMAC) to provide terminal quaternary ammonium sites capable for attaching with Mt or other materials through ion exchange. The modified PEG-GTMAC derivatives were reacted in excess amount with Na+Mt through ion exchange. The remaining quaternary sites were used for the attachment of sodium diclofenac as a model drug. The structures of the prepared clay-modified PEG-diclofenac systems were characterized using Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The release behavior of diclofenac from the different nanocomposites was studied at different pH values. With regard to the PEG chain length, the drug release increased with increasing PEG molecular weight (GCDIII > GCD-III > GCDII > GCDI). The kinetics of the release models was discussed using Korsmeyer–Peppas, Higuchi, and zero- and first-order models. The results of the kinetics study revealed that modified samples with PEG 400 and PEG 4000 (GCD-I and GCDII) exhibited non-Fickian diffusion (anomalous transport) while modified samples with PEG 8000 (GCDIII) exhibited super case-II transport.

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Fully Supramolecular Polyrotaxanes as Biphase Drug Delivery Systems

International Journal of Polymer Science ◽

10.1155/2014/829474 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Abdolhossien Massoudi ◽

Mohsen Adeli ◽

Leila Khosravi far

Keyword(s):

Drug Delivery ◽

Polyethylene Glycol ◽

Citric Acid ◽

Hydrogen Bonds ◽

Drug Delivery Systems ◽

Noncovalent Interactions ◽

Delivery Systems ◽

End Groups ◽

Model Drug ◽

Primary Drug

Pseudopolyrotaxanes (PPR) consisting ofα-cyclodextrin rings and polyethylene glycol axes with end thymine groups have been synthesized and characterized successfully. Fluorescein (Fl) as a model drug was conjugated to the hydroxyl functional groups of cyclodextrin rings of PPR via ester bonds and PPR-Fl as the primary drug delivery system was obtained. Finally PPR-Fl was capped by hydrogen bonds between end thymine groups and a suitable complementary molecule such as polycitric acid, citric acid, or adenine. The aim of this work was to control the release of the fluorescein-cyclodextrin (Fl-CD) conjugates, as the secondary drug delivery systems, from PPR-Fl by controlling the noncovalent interactions between stoppers and thymine end groups. It was found that the rate of release of the Fl-CD from PPR-Fl could be controlled by pH and the ratio of citric acid or adenine to the PPR-Fl.

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