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26 pages, 3218 KiB

Open AccessArticle

Lecithin-Linker Microemulsion Gelatin Gels for Extended Drug Delivery

by Xiao-Yue Xuan, Yu-Ling Cheng and Edgar Acosta

Pharmaceutics 2012, 4(1), 104-129; https://doi.org/10.3390/pharmaceutics4010104 - 31 Jan 2012

Cited by 34 | Viewed by 12946

Abstract

This article introduces the formulation of alcohol-free, lecithin microemulsion-based gels (MBGs) prepared with gelatin as gelling agent. The influence of oil, water, lecithin and hydrophilic and lipophilic additives (linkers) on the rheological properties and appearance of these gels was systematically explored using ternary [...] Read more.

This article introduces the formulation of alcohol-free, lecithin microemulsion-based gels (MBGs) prepared with gelatin as gelling agent. The influence of oil, water, lecithin and hydrophilic and lipophilic additives (linkers) on the rheological properties and appearance of these gels was systematically explored using ternary phase diagrams. Clear MBGs were obtained in regions of single phase microemulsions (μEs) at room temperature. Increasing the water content in the formulation increased the elastic modulus of the gels, while increasing the oil content had the opposite effect. The hydrophilic additive (PEG-6-caprylic/capric glycerides) was shown to reduce the elastic modulus of gelatin gels, particularly at high temperatures. In contrast to anionic (AOT) μEs, the results suggest that in lecithin (nonionic) μEs, the introduction of gelatin “dehydrates” the μE. Finally, when the transdermal transport of lidocaine formulated in the parent μE and the resulting MBG were compared, only a minor retardation in the loading and release of lidocaine was observed. Full article

(This article belongs to the Special Issue Transdermal Drug Delivery)

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9 pages, 199 KiB

Open AccessArticle

Effect of Duration and Amplitude of Direct Current when Lidocaine Is Delivered by Iontophoresis

by Susan A. Saliba, Courtney L. Teeter-Heyl, Patrick McKeon, Christopher D. Ingeroll and Ethan N. Saliba

Pharmaceutics 2011, 3(4), 923-931; https://doi.org/10.3390/pharmaceutics3040923 - 6 Dec 2011

Cited by 6 | Viewed by 7531

Abstract

Dosage for the galvanic stimulation for iontophoresis varies. Clinicians manipulate the duration or the amplitude of the current, but it is not known which is more effective. We compared the anesthetic effect of lidocaine HCL (2%) by manipulating the current parameters on 21 [...] Read more.

Dosage for the galvanic stimulation for iontophoresis varies. Clinicians manipulate the duration or the amplitude of the current, but it is not known which is more effective. We compared the anesthetic effect of lidocaine HCL (2%) by manipulating the current parameters on 21 healthy volunteers (age: 21.2 ± 4.2, height 170.7 ± 10.2 cm, mass 82.1 ± 19.2 kg). Three conditions were administered in a random order using a Phoresor II^® with 2 mL, 2% lidocaine HCL in an iontophoresis electrode. (1) HASD (40 mA_*min): High amplitude (4 mA), short duration (10 min); (2) LALD (40 mA^.min): Low amplitude (2 mA), long duration (20 min); (3) Sham condition (0 mA, 20 min). Semmes-Weinstein monofilament (SWM) scores were taken pre and post intervention to measure sensation changes. Two-way ANOVA with repeated measures was used to compare sensation. Both iontophoresis treatments: LALD (4.2 ± 0.32 mm) and HASD (4.2 ± 0.52 mm) significantly increased SWM scores, indicating an increase in anesthesia, compared to the sham condition (3.6 ± 0.06 mm) p < 0.05. Neither LALD nor HASD was more effective and there was no difference in anesthesia with the sham. Lidocaine delivered via iontophoresis reduces cutaneous sensation. However, there was no benefit in either a HASD or LALD treatment. Full article

(This article belongs to the Special Issue Transdermal Drug Delivery)

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9 pages, 193 KiB

Open AccessArticle

Formulation Patents and Dermatology and Obviousness

by Dan-Feng Mei, Josephine Liu and Michael A. Davitz

Pharmaceutics 2011, 3(4), 914-922; https://doi.org/10.3390/pharmaceutics3040914 - 21 Nov 2011

Viewed by 7417

Abstract

Most patents covering dermatologic products contain patent claims directed to the pharmaceutical formulation of the product. Such patents, known as formulation patents, are vulnerable to attacks based on the legal argument that the formulations covered are obvious over formulations already known prior to [...] Read more.

Most patents covering dermatologic products contain patent claims directed to the pharmaceutical formulation of the product. Such patents, known as formulation patents, are vulnerable to attacks based on the legal argument that the formulations covered are obvious over formulations already known prior to the filing of the patent application. Because obviousness is an important concept in patent law, recent court cases concerning obviousness and formulation patents were examined and discussed below. Courts have ruled that patent claims are obvious when features of the claimed formulation are found in the prior art, even if the features or characteristics of the formulation are not explicitly disclosed in the prior art. However, patentees have successfully overcome obviousness challenges where there were unexpected results or properties and/or the prior art taught away from the claimed invention. Full article

(This article belongs to the Special Issue Transdermal Drug Delivery)

13 pages, 1061 KiB

Open AccessArticle

Effect of Penetration Enhancer Containing Vesicles on the Percutaneous Delivery of Quercetin through New Born Pig Skin

by Maura Chessa, Carla Caddeo, Donatella Valenti, Maria Manconi, Chiara Sinico and Anna Maria Fadda

Pharmaceutics 2011, 3(3), 497-509; https://doi.org/10.3390/pharmaceutics3030497 - 12 Aug 2011

Cited by 86 | Viewed by 10230

Abstract

Quercetin (3,3′,4′,5,7-pentahydroxyflavone) exerts multiple pharmacological effects: anti-oxidant activity, induction of apoptosis, modulation of cell cycle, anti-mutagenesis, and anti-inflammatory effect. In topical formulations quercetin inhibits oxidative skin damage and the inflammatory processes induced by solar UV radiation. In this work, quercetin (2 mg/mL) was [...] Read more.

Quercetin (3,3′,4′,5,7-pentahydroxyflavone) exerts multiple pharmacological effects: anti-oxidant activity, induction of apoptosis, modulation of cell cycle, anti-mutagenesis, and anti-inflammatory effect. In topical formulations quercetin inhibits oxidative skin damage and the inflammatory processes induced by solar UV radiation. In this work, quercetin (2 mg/mL) was loaded in vesicular Penetration Enhancer containing Vesicles (PEVs), prepared using a mixture of lipids (Phospholipon^® 50, P50) and one of four selected hydrophilic penetration enhancers: Transcutol^® P, propylene glycol, polyethylene glycol 400, and Labrasol^® at the same concentration (40% of water phase). Photon Correlation Spectroscopy results showed a mean diameter of drug loaded vesicles in the range 80–220 nm. All formulations showed a negative surface charge and incorporation efficiency in the range 48–75%. Transmission Electron Microscopy confirmed that size and morphology varied as a function of the used penetration enhancer. The influence of PEVs on ex vivo quercetin (trans)dermal delivery was evaluated using Franz-type diffusion cells, new born pig skin and Confocal Laser Scanning Microscopy. Results showed that drug delivery is affected by the penetration enhancer used in the PEVs' formulation. Full article

(This article belongs to the Special Issue Transdermal Drug Delivery)

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12 pages, 182 KiB

Open AccessArticle

A Computational Procedure for Assessing the Dynamic Performance of Diffusion-Controlled Transdermal Delivery Devices

by Laurent Simon

Pharmaceutics 2011, 3(3), 485-496; https://doi.org/10.3390/pharmaceutics3030485 - 11 Aug 2011

Cited by 10 | Viewed by 6730

Abstract

Abstract: The dynamic performances of two different controlled-release systems were analyzed. In a reservoir-type drug-delivery patch, the transdermal flux is influenced by the properties of the membrane. A constant thermodynamic drug activity is preserved in the donor compartment. Monolithic matrices are among the [...] Read more.

Abstract: The dynamic performances of two different controlled-release systems were analyzed. In a reservoir-type drug-delivery patch, the transdermal flux is influenced by the properties of the membrane. A constant thermodynamic drug activity is preserved in the donor compartment. Monolithic matrices are among the most inexpensive systems used to direct drug delivery. In these structures, the active pharmaceutical ingredients are encapsulated within a polymeric material. Despite the popularity of these two devices, to tailor the properties of the polymer and additives to specific transient behaviors can be challenging and time-consuming. The heuristic approaches often considered to select the vehicle formulation provide limited insight into key permeation mechanisms making it difficult to predict the device performance. In this contribution, a method to calculate the flux response time in a system consisting of a reservoir and a polymeric membrane was proposed and confirmed. Nearly 8.60 h passed before the metoprolol delivery rate reached ninety-eight percent of its final value. An expression was derived for the time it took to transport the active pharmaceutical ingredient out of the polymer. Ninety-eight percent of alpha-tocopherol acetate was released in 461.4 h following application to the skin. The effective time constant can be computed to help develop optimum design strategies. Full article

(This article belongs to the Special Issue Transdermal Drug Delivery)

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11 pages, 578 KiB

Open AccessArticle

Effects of Chemical and Physical Enhancement Techniques on Transdermal Delivery of Cyanocobalamin (Vitamin B12) In Vitro

by Ye Yang, Haripriya Kalluri and Ajay K. Banga

Pharmaceutics 2011, 3(3), 474-484; https://doi.org/10.3390/pharmaceutics3030474 - 10 Aug 2011

Cited by 31 | Viewed by 9600

Abstract

Vitamin B12 deficiency, which may result in anemia and nerve damage if left untreated, is currently treated by administration of cyanocobalamin via oral or intramuscular routes. However, these routes are associated with absorption and compliance issues which have prompted us to investigate skin [...] Read more.

Vitamin B12 deficiency, which may result in anemia and nerve damage if left untreated, is currently treated by administration of cyanocobalamin via oral or intramuscular routes. However, these routes are associated with absorption and compliance issues which have prompted us to investigate skin as an alternative site of administration. Delivery through skin, however, is restricted to small and moderately lipophilic molecules due to the outermost barrier, the stratum corneum (SC). In this study, we have investigated the effect of different enhancement techniques, chemical enhancers (ethanol, oleic acid, propylene glycol), iontophoresis (anodal iontophoresis) and microneedles (soluble maltose microneedles), which may overcome this barrier and improve cyanocobalamin delivery. Studies with different chemical enhancer formulations indicated that ethanol and oleic acid decreased the lag time while propylene glycol based formulations increased the lag time. The formulation with ethanol (50%), oleic acid (10%) and propylene glycol (40%) showed the maximum improvement in delivery. Iontophoresis and microneedle treatments resulted in enhanced permeation levels compared to passive controls. These enhancement approaches can be explored further to develop alternative treatment regimens. Full article

(This article belongs to the Special Issue Transdermal Drug Delivery)

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Review

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22 pages, 928 KiB

Open AccessReview

Structure Enhancement Relationship of Chemical Penetration Enhancers in Drug Transport across the Stratum Corneum

by Doungdaw Chantasart and S. Kevin Li

Pharmaceutics 2012, 4(1), 71-92; https://doi.org/10.3390/pharmaceutics4010071 - 17 Jan 2012

Cited by 38 | Viewed by 10030 | Correction

Abstract

The stratum corneum is a major barrier of drug penetration across the skin in transdermal delivery. For effective transdermal drug delivery, skin penetration enhancers are used to overcome this barrier. In the past decades, a number of research studies were conducted to understand [...] Read more.

The stratum corneum is a major barrier of drug penetration across the skin in transdermal delivery. For effective transdermal drug delivery, skin penetration enhancers are used to overcome this barrier. In the past decades, a number of research studies were conducted to understand the mechanisms of skin penetration enhancers and to develop a structure enhancement relationship. Such understanding allows effective prediction of the effects of skin penetration enhancers, assists topical and transdermal formulation development, and avoids extensive enhancer screening in the transdermal delivery industry. In the past two decades, several hypotheses on chemical enhancer-induced penetration enhancement for transport across the skin lipoidal pathway have been examined based on a systematic approach. Particularly, a hypothesis that skin penetration enhancement is directly related to the concentration of the enhancers in the stratum corneum lipid domain was examined. A direct relationship between skin penetration enhancer potency (based on enhancer aqueous concentration in the diffusion cell chamber) and enhancer n-octanol-water partition coefficient was also established. The nature of the microenvironment of the enhancer site of action in the stratum corneum lipid domain was found to be mimicked by n-octanol. The present paper reviews the work related to these hypotheses and the relationships between skin penetration enhancement and enhancer concentration in the drug delivery media and stratum corneum lipids. Full article

(This article belongs to the Special Issue Transdermal Drug Delivery)

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16 pages, 414 KiB

Open AccessReview

Tissue Engineered Human Skin Equivalents

by Zheng Zhang and Bozena B. Michniak-Kohn

Pharmaceutics 2012, 4(1), 26-41; https://doi.org/10.3390/pharmaceutics4010026 - 6 Jan 2012

Cited by 142 | Viewed by 14247

Abstract

Human skin not only serves as an important barrier against the penetration of exogenous substances into the body, but also provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin (topical delivery) and/or the body (transdermal delivery). In the [...] Read more.

Human skin not only serves as an important barrier against the penetration of exogenous substances into the body, but also provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin (topical delivery) and/or the body (transdermal delivery). In the past three decades, research and development in human skin equivalents have advanced in parallel with those in tissue engineering and regenerative medicine. The human skin equivalents are used commercially as clinical skin substitutes and as models for permeation and toxicity screening. Several academic laboratories have developed their own human skin equivalent models and applied these models for studying skin permeation, corrosivity and irritation, compound toxicity, biochemistry, metabolism and cellular pharmacology. Various aspects of the state of the art of human skin equivalents are reviewed and discussed. Full article

(This article belongs to the Special Issue Transdermal Drug Delivery)

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