The role of carboxyl group of pressure sensitive adhesive in controlled release of propranolol in transdermal patch: Quantitative determination of ionic interaction and molecular mechanism characterization

Yang, Degong; Wan, Xiaocao; Quan, Peng; Liu, Chao; Fang, Liang

doi:10.1016/j.ejps.2018.01.038

Cited by 41 publications

(17 citation statements)

References 33 publications

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“…The better permeation profile and adhesive properties were achieved by combing Duro-Tak 87-4098 along with a Functional -OH group Duro-Tak 387-2510. This synergistic combination of DT 87-4098 with DT 387-2051 suggests us to choose formulation S1 for further studies [13]. In vivo studies were done to assess the efficiency of transdermal patches of carvedilol in Wistar rats.…”

Section: Discussionmentioning

confidence: 99%

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The effect of combination of functional and nonfunctional acrylic polymers on transdermal patches of : in vitro permeation, in vivo evaluation using biochemical parameters, and stability studies

Lal

Verma

2021

Futur J Pharm Sci

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Background A double-layer transdermal drug-in-adhesive patch of carvedilol was developed using functional and nonfunctional grades of acrylic adhesives, DURO-TAK® 387-2051, DURO-TAK® 387-2510, and DURO-TAK® 87-4098. The patch was designed to provide adequate permeation of the drug up to 2 days, with effective adhesion attributes. An optimized formulation was selected, the effect of the combination was studied and a 180° peel strength test was performed to evaluate adhesive properties. Further, the patch was assessed for in vivo studies on basis of biochemical parameters, skin irritation, and stability studies. The stability study was carried out on optimized fresh (S1) and 6 months old patches stored at room, and accelerated condition (40 ± 2 °C/75 ± 5% RH) using FTIR, DSC, and SEM techniques. Result It was studied that the steady-state flux (Jss) or permeation rate of the drug through excised rat skin has relied on the nature of acrylic and the combination of acrylic polymers. The TDDS containing –OH functional group DT 387-2510 with nonfunctional pressure-sensitive adhesives (PSAs) DT 87-4098, with Span 80 as penetration enhancer exhibited maximum flux (19.12 ± 0.64 μg/cm2/h) and form homogeneous and stable blends, controlling permeation of drug at a desired steady rate for 48 h. The data obtained from in vivo studies using biochemical parameters suggested that there were no statistical differences observed in results for the control and treated group while analyzing observations for serum creatinine, glucose test, sodium test, albumin, and potassium (p > 0.05). Also, the optimized formulation showed no sign of localized reactions and was confirmed by a skin histological study indicating the formulation was safe and compatible with the skin. A significant shift of peaks was not observed in FTIR spectra and DSC thermograms of the patches after the stability period. Conclusion The investigation reveals that the drug-in-adhesive patch of carvedilol, by a combination of functional and nonfunctional PSAs, provides a good and effective option for controlled delivery of carvedilol. From our findings, it has been concluded that drug in the adhesive patch has been able to provide satisfactory adhesion, drug uniformity, drug permeation, marked positive biochemical results, and good stability.

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Section: Discussionmentioning

confidence: 99%

“…It was also noted that release of drug from its polymer depends on the solubility and diffusion coefficient of drug in a polymer. Perhaps the interaction between drug and polymer could affect drug coefficient [13,14].…”

Section: The Effect Of Adhesives On Permeation Of CV From Double-layer Patchmentioning

confidence: 99%

The effect of combination of functional and nonfunctional acrylic polymers on transdermal patches of : in vitro permeation, in vivo evaluation using biochemical parameters, and stability studies

Lal

Verma

2021

Futur J Pharm Sci

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“…Snapshots of SD systems loading MG and LA are shown in Figure 12. The diffusion coefficient was used to represent the lateral movement of the drug molecules, and the cohesive energy density was used to measure the intensity of the interaction of the ion pair complexes [69]. The diffusion coefficients of MG-TSD and LA-TSD were 4.52 × 10 −11 and 3.68 × 10 −11 m 2 /s, respectively.…”

Section: Molecular Dynamic Simulationmentioning

confidence: 99%

Mechanism and Improved Dissolution of Glycyrrhetinic Acid Solid Dispersion by Alkalizers

et al. 2020

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The purpose of this study was to increase the dissolution of glycyrrhetinic acid (GA) by preparing ternary solid dispersion (TSD) systems containing alkalizers, and to explore the modulating mechanism of alkalizers in solid dispersion systems. GA TSDs were prepared by hot melt extrusion (HME) with Kollidon® VA64 as the carrier and L-arginine/meglumine as the alkalizers. The in vitro release of the TSD was investigated with a dissolution test, and the dissociation constant (pKa) was used to describe the ionization degree of the drug in different pH buffers. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier Transform Infrared Spectroscopy (FTIR), Raman spectra, X-ray photoelectron spectroscopy (XPS), and a molecular model were used for solid-state characterizations and to study the dissolution mechanism of the TSDs. It was evident that the dissolution of GA significantly increased as a result of the TSD compared to the pure drug and binary solid dispersion. SEM, DSC, and XPRD data showed that GA transformed into an amorphous form in TSD. As illustrated by FTIR, Raman, XPS, and molecular docking, high binding energy ion-pair complexes formed between GA and the alkalizers during the process of HME. These can destroy the H-bond between GA molecules. Further, intermolecular H-bonds formed between the alkalizers and Kollidon® VA64, which can increase the wettability of the drug. Our results will significantly improve the solubility and dissolution of GA. In addition, the lower pKa value of TSD indicates that higher ionization is beneficial to the dissolution of the drug. This study should facilitate further developments of TSDs containing alkalizers to improve the dissolution of weakly acidic drugs and gain a richer understanding of the mechanism of dissolution.

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“…In this approach, at the nano-scale, the penetration of drugs in lipid bilayers of the stratum corneum (SC) is modeled by using molecular dynamics simulation [17]- [19]. One of the results of this set of simulations is the diffusion coefficient for transient diffusion of the drug in the modeled layer [20], [21]. At the meso-and micro-scale, brick-and-mortar and cellular models of the SC are being used to model the drug transport [22]- [24].…”

Section: Introductionmentioning

confidence: 99%

Predicting transdermal fentanyl delivery using physics-based simulations for tailored therapy

Bahrami

Defraeye

2021

Preprint

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Transdermal fentanyl patches are an effective alternative to the sustained-release of oral morphine for chronic pain treatment. Due to the narrow therapeutic range of fentanyl, the fentanyl concentration in the blood needs to be controlled carefully. Only then, effective pain relief can be reached while avoiding adverse effects such as respiratory depression. In this study, a physics-based digital twin of the patient was developed by implementing mechanistic models for transdermal drug uptake and the patient’s pharmacokinetic and pharmacodynamics response. A digital twin is a virtual representation of the patient and the transdermal drug delivery system, which is linked to the real-world patient by patient feedback, sensor data of specific biomarkers, or customizing the twin to a particular patient characteristic, for example, based on the age. This digital twin can predict the transdermal drug delivery processes in-silico. Our twin is used first to predict conventional therapy’s effect for using fentanyl patches on a virtual patient at different ages. The results show that by aging, the maximum transdermal fentanyl flux and maximum concentration of fentanyl in the blood decrease by 11.4% and 7.0%, respectively. Nonetheless, by aging, the pain relief increases by 45.2% despite the lower concentration of fentanyl in the blood for older patients. As a next step, the digital twin was used to propose a tailored therapy, based on the patient’s age, to deliver fentanyl based on the patient’s needs to alleviate pain. This predesigned therapy consisted of customizing the duration of applying and changing the commercialized fentanyl patches based on the calculated pain intensity. According to this therapy, a patient of 20 years old needs to change the patch 2.1 times more frequently compared to conventional therapy, which led to 30% more pain relief and 315% more time without pain. In addition, the digital twin was updated by the patient’s pain intensity feedback. Such therapy led to an increase in the patient’s breathing rate while having effective pain relief, therefore providing a safer and more comfortable treatment for the patient. We quantified the added value of a patient’s physics-based digital twin and sketched the future roadmap for implementing such twin-assisted treatment into the clinics.NomenclatureSymbolsci The concentration of fentanyl in layer i (in the drug uptake model) [ng ml-1]cp The concentration of fentanyl in the central compartment [ng ml-1]cr The concentration of fentanyl in the rapid equilibrated compartment [ng ml-1]cs The concentration of fentanyl in the slow equilibrated compartment [ng ml-1]cg The concentration of fentanyl in the gastrointestinal compartment [ng ml-1]cl The concentration of fentanyl in the hepatic compartment [ng ml-1]ce The concentration of fentanyl in the effect compartment [ng ml-1]Di Diffusion coefficient of fentanyl in layer i (in the mechanistic model) [m2 s-1]D0 Base diffusion coefficient of fentanyl [m2 s-1]DT Diffusion coefficient of fentanyl at temperature T [m2 s-1]D306 Diffusion coefficient of fentanyl at 306[K] [m2 s-1]dpt The thickness of the transdermal patch [µm]dsc The thickness of the stratum corneum [µm]dvep The thickness of the viable epidermis [µm]dEdm The thickness of the equivalent dermis [µm]Ei The intensity of effect i The baseline of effect i The maximum effect iEC50,i The concentration related to half-maximum effect i [ng ml-1]fu The fraction of unbound fentanyl in plasmaji Fentanyl flux in layer i (in the mechanistic model)Ki/j The partition coefficient of fentanyl between layer i to j (in the mechanistic model)Ki The drug capacity in layer i (in the mechanistic model)kcs Inter-compartmental first-order equilibrium rate constant (central to slow equilibrated) [min-1]kcr Inter-compartmental first-order equilibrium rate constant (central to rapid equilibrated) [min-1]kcg Inter-compartmental first-order equilibrium rate constant (central to gastrointestinal) [min-1]kch Inter-compartmental first-order equilibrium rate constant (central to hepatic) [min-1]ksc Inter-compartmental first-order equilibrium rate constant (slow equilibrated to central) [min-1]krc Inter-compartmental first-order equilibrium rate constant (rapid equilibrated to central) [min-1]khc Inter-compartmental first-order equilibrium rate constant (hepatic to central) [min-1]kgh Inter-compartmental first-order equilibrium rate constant (gastrointestinal to hepatic) [min-1]kmet Metabolization rate constant [min-1]kre Renal clearance rate constant [min-1]ke Inter-compartmental first-order equilibrium rate constant (for effect compartment) [min-1]SI Sensitivity indext Time [h]tD Time lag [h] Dependent variable related to xi for sensitivity analysisVc The apparent volume of the central compartment [L]Vs The apparent volume of the slow equilibrated compartment [L]Vr The apparent volume of the rapid equilibrated compartment [L]Vg The apparent volume of the gastrointestinal compartment [L]Vh The apparent volume of the hepatic compartment [L]xi The independent variable which sensitivity analysis is done based on itγ Hill coefficientψi Drug potential in domain i [ng ml-1]

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The role of carboxyl group of pressure sensitive adhesive in controlled release of propranolol in transdermal patch: Quantitative determination of ionic interaction and molecular mechanism characterization

Cited by 41 publications

References 33 publications

The effect of combination of functional and nonfunctional acrylic polymers on transdermal patches of : in vitro permeation, in vivo evaluation using biochemical parameters, and stability studies

The effect of combination of functional and nonfunctional acrylic polymers on transdermal patches of : in vitro permeation, in vivo evaluation using biochemical parameters, and stability studies

Mechanism and Improved Dissolution of Glycyrrhetinic Acid Solid Dispersion by Alkalizers

Predicting transdermal fentanyl delivery using physics-based simulations for tailored therapy

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