Abstract: An electrotransport composition comprises at least one C.sub.2 -C.sub.4 lower alcohol, unsaturated derivatives thereof, or mixtures thereof, and at least one C.sub.8 -C.sub.14 higher alcohol, unsaturated derivatives thereof, or mixtures thereof. An electrotransport device and a method of increasing transdermal electrotransport flux utilize the composition of the invention for delivering pharmaceutically-acceptable agents across a body surface such as skin.

Abstract: A method for manufacturing a transdermal drug delivery device (10) is disclosed wherein a component (32) and/or a subassembly (20) are intentionally adapted to be separable from the rest of the device for disposal which is more medically or environmentally acceptable. In one embodiment, device 10 comprises upper and lower housings (16, 20), with lower housing (20) being separable from upper housing (16) and foldable upon itself to minimize medically unacceptable contact with, e.g., a drug reservoir (26 or 28) contained therein. A device (10) made in accordance with the invention is included.

Abstract: An electrotransport apparatus using dispersed ion exchange material (19,93) is disclosed. The ion exchange material (19,93) may be dispersed in either the donor electrode assembly (10), the counter electrode assembly (10) or both electrode assemblies. The dispersed ion exchange material (93) comprises mobile ionic species (C2) and substantially immobile ionic species (P). The dispersed ion exchange material (93) is consumed during electrotransport of drug or agent (A) in an electrotransport process in which substantially no species which compete with the drug or agent for electrotransport are generated. Electrotransport devices exhibiting reduced polarization are also disclosed.

Abstract: The invention is directed to a composition and product for use in an electrotransport device. The composition includes an ionized drug, an anti-inflammatory agent and a solvent. Preferably, the anti-inflammatory agent is hydrocortisone or esters thereof, and the solvent is an alcohol, a glycol, a glycerol, a cyclodextrin, a nonionic surfactant or mixtures thereof. The composition preferably further includes a gel matrix that is a swellable, hydrophilic polymer, a water soluble hydrophilic polymer or a solid polymer. A hydrophobic polymer and/or additives may also be included.

Abstract: A selectively permeable membrane (14) is positioned between the agent reservoir (15) and the electrode (11) of a donor electrode assembly (8) in an iontophoretic delivery device (10). Optionally, an electrolyte reservoir (13) is positioned intermediate the electrode (11) and the agent reservoir (15). In certain embodiments, the membrane (14) is permeable to species of less than a predetermined molecular weight and substantially less permeable to species of greater than the predetermined molecular weight. The agent is capable of dissociating into agent ions and counter ions.

Abstract: A method is provided for preparing drug formulations suitable for electrotransport drug delivery. The drug to be delivered, present in salt form, is contacted with an ion exchange material prior to incorporation into the reservoir (26) of an electrotransport delivery system (10). In this way, the drug salt is partially or completely neutralized. This technique is useful for adjusting the pH of the drug formulation without incorporating extraneous materials, e.g., competing ions or the like, into the reservoir (26).

Abstract: An electrotransport delivery device (10) with a display (14) having only on and off states, and a method of operating the display (14), are provided. Preferably, the display 14 is a light (e.g., a light emitting diode) with lit and unlit states or an audible alarm (e.g., a beeper) with sounding and silent states. The device (10) counts and stores the number of events (e.g., patient initiated drug delivery or sensed patient condition) which occur over a predetermined period of time (e.g., the period of time over which the device is worn by the patient). The event count is displayed by cycling the display (14) between on and off states according to a predetermined regimen which correlates the number of on/off cycles to the number of events. The device and method permit the use of a simple and inexpensive means (e.g., an LED) to display (e.g., to a medical technician) the number of e.g., patient initiated doses delivered over a previous period of therapy.

Abstract: Compression forces (F) in a rotary tablet compressing machine (40) are monitored and controlled to provide enhanced accuracy in determining peak compression value and continuous validation of a compression waveform. The compression waveform is repetitively sampled under computer control at a sampling frequency that is many times the frequency of the compression events. The samples are stored in a computer memory (26) until at least one complete compression event is recorded. Identification of beginning and ending samples of an individual tablet compression event are obtained from the waveform itself by locating minimum amplitude samples, or by use of a separate signal that is derived from a transducer which is responsive to the angular position of a rotating turret. Stored samples representing the compression waveform as time and amplitude data are passed to a processor (23) that statistically fits the data to an equation form which represents the ideal shape of a compression event.

Abstract: An electrotransport drug-containing composition is provided. The composition includes a drug to be delivered through a body surface (eg, skin) of a patient, and a permeation enhancer which is solid or semisolid at temperatures typically encountered during storage of pharmaceuticals (eg, temperatures up to at least about 25.degree. C). The composition of the invention may be applied from a device 10 suitable for electrotransport delivery. A method for increasing electrotransport agent delivery rate and reducing body surface resistance relies on applying the composition of the invention to the body surface, and applying an electric current through the composition and the body surface.

Abstract: Methods for modifying polypeptide agents to enhance their transdermal electrotransport flux are provided. The polypeptide is modified by reducing the potential of the polypeptide for forming .alpha.-helical or .beta.-sheet segments. In particular, amino acid residues known to stabilize .alpha.-helical and .beta.-sheet segments can be replaced with destabilizing residues and known helix breakers. Modified molecules and compositions including the molecules are also provided.

Abstract: Improved methods of ionophoretic drug delivery are described. By the intentional selection of drug(s) with specific characteristics, of ionotophoresis device, components or both permits the efficiency of drug delivery is increased.

Abstract: An electrotransport delivery device (410) includes control circuitry for discontinuously delivering a beneficial agent (eg, a drug) through a body surface (eg, skin 400). For example, the device may be the type which is manually activated by the patient or other medical personnel to activate electrotransport drug delivery. Once electrotransport delivery has been activated, a timer (221) counts a transition interval, typically about one minute, during which the device is allowed to operate and the impedance of the body surface (400) is allowed to stabilize. Thereafter, the electrotransport current and voltage are then monitored and compared to predetermined limits. Allowing for the transition interval permits tighter tolerances in monitoring the applied current.

Abstract: An electrotransport drug delivery device which delivers an anti-inflammatory agent in order to reduce skin irritation associated with electrotransport delivery of the drug is provided. The anti-inflammatory agent is selected from hydrocortisone, esters of hydrocortisone and salts thereof.

Abstract: A composition comprises an agent to be delivered through a body surface and an electrotransport enhancer having a hydrophobic tail and a polar head of specific characteristics. An electrotransport delivery device is also provided having a reservoir comprising the agent to be delivered and the electrotransport enhancer of the invention. The electrotransport enhancers increase the electrotransport delivery rate of the agent through the surface while reducing the electrical resistance of the surface during electrotransport of the agent.

Abstract: An implantable dispenser is enclosed comprising a wall surrounding a compartment containing a first composition comprising a beneficial agent, an oil, a cosolvent and a polymer gellant, a second expandable composition, a third boundary maintaining composition between the first and second composition, and an exit port.

Abstract: A method of laser drilling a delivery port (37) in a beneficial agent dispenser (30) is disclosed. A dispenser (30) has a compartment (32) formed by a wall (31) for containing a beneficial agent (33) to be delivered. A laser beam is employed for burning at least partially through the wall (31). The laser beam and the dispenser (30) are positioned relative to one another such that the laser beam is aimed at a predetermined port site (35) on the dispenser (30). The laser beam is turned off (unenergized) during the positioning period. The laser beam is then energized and moved relative to the dispenser (30) for scribing a delivery port (37) proximate the port site (35). The scribing motion moves the laser beam from the port site (35) along a course (37). Preferably the course (37) is closed. The scribing motion causes the burning of the wall (31) by the laser beam to scribe the delivery port (37). The positioning motion and the scribing motion are controlled by a scanning system (16).

Abstract: A selectively permeable membrane (14) is positioned between the agent reservoir (15) and the electrode (11) of a donor electrode assembly (8) in an iontophoretic delivery device (10). Optionally, an electrolyte reservoir (13) is positioned intermediate the electrode (11) and the agent reservoir (15). In certain embodiments, the membrane (14) is permeable to species of less than a predetermined molecular weight and substantially less permeable to species of greater than the predetermined molecular weight. The agent is capable of dissociating into agent ions and counter ions.

Abstract: An electrotransport delivery device utilizing reservoir buffering at a select pH ranges in order to reduce skin irritation and skin resistance is provided. Cathodic reservoirs are buffered to a pH of less than about 4, preferably to a pH in the range of about 2 to 4, while anodic reservoirs are buffered to a pH above about 4, preferably to a pH in the range of about 4 to 10. Another electrotransport delivery device utilizes a potassium sensor to monitor potassium efflux from the skin. Potassium efflux above a certain predetermined level has been found to be a precursor to skin irritation/erythema. Operation of the device is modified (eg, terminated) when the predetermined potassium efflux level is sensed.

Abstract: An electrically powered transdermal iontophoretic delivery device (10, 20) and a method of making same is provided. The device utilizes electrode assemblies (8, 9 ) composed of a substantially homogenous blend of a polymeric matrix containing about 5 to 50 vol % of a conductive filler which forms a conductive network through the matrix, and up to about 50 vol % of the agent to be iontophoretically delivered through the skin. In the case of the donor electrode assembly, the agent is typically a drug and preferably a water soluble drug salt. In the case of the counter electrode assembly, the agent is typically an electrolyte salt. The homogenous blend eliminates the need for separate electrode and agent containing layers which require lamination.