Methods And Devices For Thermal Treatment

The present invention comprises methods and devices for thermal treatment of a barrier to increase the permeability of the barrier. One form of increasing the permeability of the barrier comprises forming micropores which may be used for administration of active agents across the barrier, or may be used for sampling or collecting fluids, or may be used for detecting, measuring or determining analytes, or may be used for monitoring of physiological or other conditions. Devices of the present invention may comprise microheaters that are activated by inductive or ohmic heating power supply components.Georgia Tech Research Corporatio

Method Of Applying Acoustic Energy Effective To Alter Transport Or Cell Viability

A method for reversibly, or irreversibly, altering the permeability of cells, tissues or other biological barriers, to molecules to be transported into or through these materials, through the application of acoustic energy, is enhanced by applying the ultrasound in combination with devices for monitoring and/or implementing feedback controls. The acoustic energy is applied directly or indirectly to the cells or tissue whose permeability is to be altered, at a frequency and intensity appropriate to alter the permeability to achieve the desired effect, such as the transport of endogenous or exogenous molecules and/or fluid, for drug delivery, measurement of analyte, removal of fluid, alteration of cell or tissue viability or alteration of structure of materials such as kidney or gall bladder stones. In the preferred embodiment, the method includes measuring the strength of the acoustic field applied to the cell or tissue at the applied frequency or other frequencies, and using the acoustic measurement to modify continued or subsequent application of acoustic energy to the cell or tissue. In another preferred embodiment, the method further includes simultaneously, previously, or subsequently exposing the cell or tissue to the chemical or biological agent to be transported into or across the cell or tissue. In another preferred application, the method includes removing biological fluid or molecules from the cells or tissue simultaneously, previously or subsequently to the application of acoustic energy and, optionally, assaying the biological fluid or molecules.Georgia Tech Research Corporatio

Vesicular systems for delivering conventional small organic molecules and larger macromolecules to and through human skin

The history of using vesicular systems for drug delivery to and through skin started nearly three decades ago with a study utilizing phospholipid liposomes to improve skin deposition and reduce systemic effects of triamcinolone acetonide. Subsequently, many researchers evaluated liposomes with respect to skin delivery, with the majority of them recording localized effects and relatively few studies showing transdermal delivery effects. Shortly after this, Transfersomes were developed with claims about their ability to deliver their payload into and through the skin with efficiencies similar to subcutaneous administration. Since these vesicles are ultradeformable, they were thought to penetrate intact skin deep enough to reach the systemic circulation. Their mechanisms of action remain controversial with diverse processes being reported. Parallel to this development, other classes of vesicles were produced with ethanol being included into the vesicles to provide flexibility (as in ethosomes) and vesicles were constructed from surfactants and cholesterol (as in niosomes). Thee ultradeformable vesicles showed variable efficiency in delivering low molecular weight and macromolecular drugs. This article will critically evaluate vesicular systems for dermal and transdermal delivery of drugs considering both their efficacy and potential mechanisms of action

Solid Lipid Nanoparticles: A Potential Approach for Dermal Drug Delivery

Solid lipid nanoparticles (SLNs) have attracted increasing attention during recent years. Due to their unique size dependent properties, lipid nanoparticles offer possibilities to develop new therapeutics. The ability to incorporate drugs into nanoparticles offers a new prototype in drug delivery thus realizing the dual goal of both controlled release and site-specific drug delivery. Drug delivery to the skin is widely used for local and systemic delivery and has potential to be improved by application of nanoparticulate formulations. If investigated appropriately, solid lipid nanoparticles may open new opportunities in therapy of complex diseases which is difficult to treat

Laminated chemical and physical micro-jet actuators based on conductive media

This dissertation presents the development of electrically-powered, lamination-based microactuators for the realization of large arrays of high impulse and short duration micro-jets with potential applications in the field of micro-electro-mechanical systems (MEMS). Microactuators offer unique control opportunities by converting the input electrical or chemical energy stored in a propellant into useful mechanical energy. This small and precise control obtained can potentially be applied towards aerodynamic control and transdermal drug delivery applications. This thesis discusses the development of both chemical and physical microactuators and characterizes their performance with focus towards the feasibility of using them for a specific application. The development of electrically powered microactuators starts by fabricating an array of radially firing microactuators using lamination-based micro fabrication techniques that potentially enable batch fabrication at low cost. The microactuators developed in this thesis consist of three main parts: a micro chamber in which the propellant is stored; two electrode structures through which electrical energy is supplied to the propellant; and a micro nozzle through which the propellant or released gases from the propellant are expanded as a jet. The fabricated actuators are then integrated with MEMS-process-compatible propellants and optimized to produce rapid ignition of the propellant and generate a fluidic jet. This rapid ignition is achieved either by making the propellant itself conductive, thus, passing an electric current directly through the propellant; or by discharging an arc across the propellant by placing it between two closely spaced electrodes. The first concept is demonstrated with chemical microactuators for the application of projectile maneuvering and the second concept is demonstrated with physical microactuators for transdermal drug delivery application. For both the actuators, the propellant integrated microactuators are characterized for performance in terms of impulse delivered, thrust generated and duration of the jet. The experimentally achieved results are validated by comparing with results from theoretical modeling. Finally, the feasibility of using chemical microactuators for maneuvering the path of a 25 mm projectile spinning at 500 Hz is discussed and the feasibility of applying the physical microactuators for increasing skin's permeability to drug analog molecules is studied.Ph.D.Committee Chair: Allen, Mark; Committee Member: Allen, Sue; Committee Member: Glezer, Ari; Committee Member: Koros, Williams; Committee Member: Prausnitz, Mar

Design and evaluation of controlled release transdermal dosage form of cardiovascular durgs

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Influence of the Component Excipients on the Quality and Functionality of a Transdermal Film Formulation

The influence of formulation variables, i.e., a hydrophilic polymer (Methocel® E15) and a film-forming polymer (Eudragit® RL 100 and Eudragit® RS 100), on the physicochemical and functional properties of a transdermal film formulation was assessed. Several terpenes were initially evaluated for their drug permeation enhancement effects on the transdermal film formulations. d-Limonene was found to be the most efficient permeation enhancer among the tested terpenes. Transdermal film formulations containing granisetron (GRN) as a model drug, d-limonene as a permeation enhancer, and different ratios of a hydrophilic polymer (Methocel® E15) and a film-forming polymer (Eudragit® RL 100 or Eudragit® RS 100) were prepared. The prepared films were evaluated for their physicochemical properties such as weight variation, thickness, tensile strength, folding endurance, elongation (%), flatness, moisture content, moisture uptake, and the drug content uniformity. The films were also evaluated for the in vitro drug release and ex vivo drug permeation. The increasing ratios of Methocel®:Eudragit® polymers in the formulation linearly and significantly increased the moisture content, moisture uptake, water vapor transmission rate (WVTR), and the transdermal flux of GRN from the film formulations. Increasing levels of Methocel® in the formulations also increased the rate and extent of the GRN release and the GRN permeation from the prepared films

Development of non-invasive transdermal patch of Emblica officinalis for anti atherosclerotic activity

The present study was designed to formulate matrix type transdermal patches of a potent anti atherosclerotic botanical Emblica officinalis on a mercury substrate and evaluated for physicochemical parameters like thickness, % flatness, weight variation, moisture uptake, moisture content, folding endurance, elongation and drug content values. Further, in vivo drug release was also observed by HPLC in rabbit serum. Four formulations were prepared using different ratio of matrix forming polymers, plasticizer and penetration enhancers. Formulations E-1, E-2, E-3 and E-4 were composed of Ethyl cellulose (EC) and Hydroxypropyl Methylcellulose (HPMC) with the following ratios: 6:4, 7:3, 8:2 and 9:1. In vitro cumulative amounts of the permeated drug were observed 48.53, 55.46, 73.26 and 99.72% in 48 hrs from the four formulations. The release profile of the optimized formulation E-4; r2 = 0.984 (Higuchi) showed that permeation of the drug controlled by a diffusion mechanism. The cumulative amount of the permeated drug after 48hrs from E-4 was 343.95mcg/cm2. Permeability coefficient was calculated 7.16mcg/cm2/hr. Based on physicochemical and in vitro skin permeation studies, E-4 was chosen for further in vivo studies. Blood plasma concentration of E-4 after 48 hrs was 0.2914mcg/cm2. Skin permeation performance and scanning electron microscopic studies revealed that formulation E-4 was found to be better than other formulations and it was selected as the optimized formulation. The skin irritation tests showed negligible erythema and edema. The developed transdermal patches may increase the efficacy of E. officinalis for the therapy of atherosclerosis

In vitro drug delivery based on a porous membrane-based aqueous-organic partitioning system and its enhancements through mouse skin

Novel approaches for transdermal drug delivery (TDD) based on a porous membrane-based aqueous-organic partitioning system have been investigated and successful deliveries were observed. Doxycycline hydrochloride (HCl), a polar antibiotic drug with a relatively large molecule weight (MW: 480.1) was studied as a basic model agent. Its controlled release using this technique was studied first. Satisfactory release profiles demonstrate the practical potential of such a system to achieve useful controlled release rates. The enhancer linoleic acid was essential to successful release using a mouse skin beneath a porous polymeric membrane. The transport rates of smaller molecules e.g., caffeine and nicotine from the same system without any enhancer were very high. Iontophoretic TDD was studied next using a porous polymeric conducting membrane of polyaniline (PANi). Doxycycline HCl, lidocaine HCl (MW: 271) and caffeine (MW:194) in their aqueous solutions were model agents. Excellent release profiles were achieved; the conducting PANi membrane appeared to be capable of not only replacing the Ag part of Ag|AgCl electrode system but also providing an additional control over agent transport rate. Aqueous-organic partitioning system was tested with this novel technique as well. Because of the rather low porosity of synthesized PANi membrane, such a system did not yield a high release rate. The transport rates through polymeric membrane alone were accurately predicted using simplified mass transport models for both iontophoretic and non-iontophoretic systems. Finally, a further application of this new technique was investigated using a thermo-sensitive TDD system. A hydrophilic porous PVDF membrane immobilized with a thermo-sensitive polymeric gel, poly(Nisopropylacrylamide) (PNIPAAM)-co-2mol% acrylic acid (AA), demonstrated its release- on/off\u27 switch function: at normal skin temperature, no release of doxycycline HCl through the skin occurred; under fever condition, certain amount of this antibiotic accumulated beneath the skin

Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer’s disease: a review

Cholinesterase inhibitors have all been available in oral formulations, but a rivastigmine transdermal patch has now been developed and is approved in many countries worldwide for the treatment of mild-to-moderate Alzheimer's disease (AD) (including the USA, Latin America, Europe and Asia)