Abstract: This invention relates to development of an iontotherapeutic device for regulated transdermal systemic administration of ionizable pharmaceutical compounds. It also provides an iontotherapeutic process for transdermal administration of ionized pharmaceuticals, particularly those which are otherwise transdermally absorbed to a small degree or not all, such as peptide pharmaceuticals, for example, insulins. The invention also relates to unit dose forms, for example, those in which an ionized pharmaceutical is dispersed in a hydrophilic polymer. The unit dose is adapted to be assembled as part of the pharmaceutical reservoir electrode, so that the ionized pharmaceutical will be delivered transdermally and then be absorbed systemically when the iontotherapeutic device is in operation.

Abstract: Transdermal polymer dosage units are provided which comprise a backing layer and a reservoir layer. The reservoir layer can have multiple regions which contact the skin during use, optionally may have different pharmaceuticals, may provide variable rate of transdermal absorption, and may provide the pharmaceuticals in the form of microreservoirs or one or more macroreservoirs. The reservoir region can comprise a macroreservoir of one or more pharmaceuticals wherein the reservoir is bounded by a backing layer and a layer of a substantially non-porous permeability-regulating polymer membrane which directly or indirectly contacts the skin during transdermal administration. Also, provided is a process of transdermal administration of pharmaceuticals using the novel dosage units.

Abstract: A transdermal contraceptive delivery system (TCDS) for fertility control in women is described comprising a backing layer, an adjoining layer of a solid absorption adhesive polymer matrix in which minimum effective daily doses of an estrogen and a progestin are dispersed and released for transdermal absorption. Presently preferred is use of the natural estrogen, 17-beta-estradiol, and the synthetic progestin, levonorgestrel. Along with these two steroidal contraceptive agents, a combination of several chemical skin permeation enhancing agents, blended at specific weight ratios, are homogeneously dispersed in the adhesive polymer matrix. The invention also provides a process of fertility control utilizing the transdermal contraceptive delivery system.

Abstract: Mucosal adhesive devices are provided for use in the oral cavity for therapy against infections. The devices are dosage units which comprise a combination of antimicrobial agents such as antifungal agents and anti-inflammatory agents, optionally also a local anesthetic. The dosage units yield a gradual and relatively constant release of the pharmaceuticals over at least a 12-hour period.

Abstract: Transdermal absorption dosage units have been developed which comprise a backing layer and an adjoining polyacrylate adhesive polymer layer in which at least minimum effective daily doses of one or more steroidal hormones are microdispersed. Presently preferred is use of the natural estrogen, 17-beta-estradiol, or ethinyl estradiol or combinations thereof together with an amount of a natural progestogen or a progestin to minimize any potential side effects. The units use bioacceptable polyacrylate adhesive polymer in making the adhesive polymer layer which has a minor percentage of vinyl acetate polymer units effective in providing improved transdermal absorption of the microdispersed steroidal hormone. An effective amount of vinyl acetate units up to about 5 percent has been found suitable. The invention also provides a process for transdermal administration of one or more steroidal hormones using the novel dosage units provided.

Abstract: Provided are disposable dosage units for use in iontophoresis-facilitated transdermal delivery which have hydrophilic polymer first and second layers, the first layer having ionic resin particles dispersed therein and the second layer having an ionized pharmaceutical contained. The second layer having on its surface a thin fabric layer bearing an adhesive layer. The polymer first and second layers are separated by a permselective membrane. Also provided are related devices and processes using the novel disposable dosage units.

Abstract: Transdermal fertility-controlling absorption polymer matrix dosage units have been developed which comprise a backing layer, an adjoining layer of a solid polymer matrix in which minimum effective daily doses of an estrogen and a progestin are microdispersed and released for transdermal absorption. Presently preferred is use of the natural estrogen, 17-beta-estradiol, and of the progestin, levonorgestrel. The units have a biologically acceptable adhesive polymer layer. The polymer matrix as well as the adhesive layer can have dispersed one or more skin permeation enhancers. Dosage units are provided which transdermally deliver at least minimum daily doses of the estrogen and progestin for multiple days, such as for one week. The invention also provides a process of fertility control using the novel polymer matrix dosage units for the first three weeks of consecutive menstrual cycles of the subject desiring fertility control.

Abstract: Provided are reservoir electrodes for iontotherapeutic devices which have two chambers; the first chamber is electrically connected to the iontotherapeutic device and is designed to contain electrolytic solution and the second chamber has ionized pharmaceutical dissolved in electrolytic solution. The two chambers are separated by a permselective membrane. The first chamber has means to inhibit increase in ionic content caused by the operation of the iontotherapeutic device. Also provided are unit dose forms adapted for insertion into the reservoir electrodes. The dose unit forms are made of crosslinked polymer and contain ionizable pharmaceutical which is released for absorption during operation of the iontotherapeutic process. Also provided are novel iontotherapeutic devices and processes.

Abstract: Transdermal absorption dosage units have been developed for treatment of postmenopausal syndrome which comprise a backing layer, an adjoining adhesive polymer layer in which at least minimum effective daily doses of an estrogen is microdispersed. Presently preferred is use of the natural estrogen, 17-beta-estradiol, or ethinyl estradiol or combinations thereof together with an amount of a natural progestogen or a progestin to minimize any potential side effects. The units use bioacceptable adhesive and polymers. An additional polymer layer in intimate contact with the estrogen-containing layer can be used. Also, a separating layer can optionally be used in making the dosage units, which separate the two adhesive polymer layers, which permits estrogen transmission from the first adhesive polymer layer during treatment. Dosage units are provided which transdermally deliver at least minimum daily doses of the estrogen for at least one day or for multiple days, such as for one week.

Abstract: Provided by this invention are novel transdermal dosage units for administering cardiovascular pharmaceuticals, whereby enhanced absorption with essentially zero-order kinetics is obtained. Also provided is a process for administration of cardiovascular pharmaceuticals by use of said dosage units.

Abstract: This invention relates to development of an iontotherapeutic device for regulated transdermal systemic administration of ionizable pharmaceutical compounds.It also provides an iontotherapeutic process for transdermal administration of ionized pharmaceuticals, particularly those which are otherwise transdermally absorbed to a small degree or not all, such as peptide pharmaceuticals, for example, insulins. The invention also relates to unit dose forms, for example, those in which an ionized pharmaceutical is dispersed in a hydrophilic polymer. The unit dose is adapted to be assembled as part of the pharmaceutical reservoir electrode, so that the ionized pharmaceutical will be delivered transdermally and then be absorbed systemically when the iontotherapeutic device is in operation.

Abstract: Transdermal estrogen/progestin adsorption dosage units have been developed which comprise a backing layer, an adjoining polymer layer is an adhesive layer in which at least minimum effective dose of an estrogen is dissolved or microdispersed. Adhered to the polymer layer is an adhesive layer in which is dissolved and/or microdispersed at least minimum doses of progestin. Presently preferred is use of the natural estrogen, 17-beta-estradiol, or ethinyl estradiol or combinations thereof and of the progestin. The units have biologically acceptable adhesive and polymer layers. The adhesive layer can have dispersed one or more skin permeation enhancing agents. A separating layer can optionally be used in making the dosage units, which separate the adhesive and polymer layers, which permits estrogen transmission from the polymer layer during treatment. Dosage units are provided which transdermally deliver at least minimum daily doses of the estrogen and progestin for multiple days, such as for one week.

Abstract: A laminar structure for administering a chemical at a controlled release rate is disclosed. The structure comprises a backing member which acts as a boundary through which the chemical does not pass. Contacting at least a portion of the backing member is a chemical containing layer having therein a first chemical portion and a second chemical portion. The first and second chemical portions comprise a mixture of chemical in a first concentration transport mode and a second concentration transport mode. The mixture being in a ratio to give a desired chemical release rate from the chemical containing layer.

Abstract: Transdermal estrogen/progestin absorption dosage unit have been developed which comprise a backing layer, an adjoining polymer layer is an adhesive layer in which at least minimum effective dose of an estrogen is dissolved or microdispersed. Adhered to the polymer layer in an adhesive layer in which is dissolved and/or microdispersed at least minimum doses of progestin. Presently preferred is use of the natural estrogen, 17-beta-estradiol, or ethinyl estradiol or combinations thereof and of the progestin, norethindrone or norgestimate or combinations thereof. The units have biologically acceptable adhesive and polymer layers. The adhesive layer can have dispersed one or more skin permeation enhancing agents. A separating layer can optionally be used in making the dosage units, which separate space the adhesive and polymer layers, which permits estrogen tansmission from the polymer layer during treatment.

Abstract: This invention relates to a novel transdermal absorption dosage unit comprising a backing layer, an adjoining layer of solid polymer matrix in which estradiol or another steroidal pharmaceutical having estrogenic activity is microdispersed; and a biologically acceptable adhesive means by which the dosage unit adheres to the skin of the subject being administered said estradiol or another said steroidal pharmaceutical and adapted to permit transdermal absorption of said estradiol or another said steroidal pharmaceutical. Additionally, the invention relates to improved estradiol or other estrogenic steroid maintenance therapy.

Abstract: Transdermal fertility-controlling absorption polymer matrix dosage units have been developed which comprise a backing layer, an adjoining layer of a solid polymer matrix in which minimum effective daily doses of an estrogen and a progestin are microdispersed and released for transdermal absorption. Presently preferred is use of the natural estrogen, 17-beta-estradiol, and of the progestin, levonorgestrel. The units have a biologically acceptable adhesive polymer layer. The polymer matrix as well as the adhesive layer can have dispersed one or more skin permeation enhancers. Dosage units are provided which transdermally deliver at least minimum daily doses of the estrogen and progestin for multiple days, such as for one week. The invention also provides a process of fertility control using the novel polymer matrix dosage units for the first three weeks of consecutive menstrual cycles of the subject desiring fertility control.

Abstract: Transdermal absorption morphinan narcotic analgesic or antagonist pharmaceutical polymer matrix dosage units have been developed which comprise a backing layer and an adjoining layer of a solid polymer matrix in which minimum effective doses of morphinan narcotic analgesic or antagonist pharmaceuticals are microdispersed and transdermally supplied. A presently preferred analgesic is hydromoprhone. The dosage units use a biologically acceptable adhesive polymer means to adhere the dosage units to the subject to be treated. The polymer matrix has dispersed one or more skin permeation enhancers. The invention also provides a process for transdermal absorption of said pharmaceuticals in at least minimum dosage amounts.

Abstract: A transdermal drug delivery device for administering 5-[(3,4-dimethoxyphenethyl) methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile comprising a permeable matrix of silicone elastomer or other bioacceptable lipophilic polymer material having an effective cardiovascular affecting amount of active drug and an effective drug release promoting amount of a transport enhancing agent dispersed therein. The back of the matrix is covered with an occlusive backing and the face of the matrix is covered with a biocompatible adhesive such as a silicone adhesive also having a transport enhancing agent dispersed therein. A supply of skin permeation enhancing agent may be provided adjacent the adhesive layer such that the skin of a patient to whom the device is applied is pretreated with permeation enhancing agent. Particularly preferred skin permeation and transport enhancing agents include N,N-diethyl-m-toluamide, isopropyl myristate and similar compounds.

Abstract: The present invention is concerned with a pharmaceutical delivery device comprising a biologically acceptable silicone polymer matrix having microsealed compartments of 10-200 microns throughout, wherein the microsealed compartments contain a pharmaceutical in a hydrophilic solvent system. The biologically acceptable silicone polymer matrix is formed by in situ cross linking of a liquid, biologically acceptable silicone polymer in an emulsion of pharmaceutical in the hydrophilic solvent system and liquid biologically acceptable silicone polymer. The biologically acceptable silicone polymer matrix is placed in a sealed or unsealed biologically acceptable polymer container.

Abstract: An injectable solution suitable for the systemic treatment of anaerobic infections is prepared by solubilization of 500-650 mg. metronidazole in 10 ml. of a solvent system comprised of:25-35% v/v N,N-dimethylacetamide40-60% v/v ethanol10-30% v/v aqueous bufferOr,15-25% v/v N,N-dimethylacetamide40-60% v/v ethanol10-30% v/v aqueous bufferAnd including one of the following:1-5% v/v nicotinamide5-15% v/v propylene glycol5-15% v/v 2,2-dimethyl-1,3-dioxolane-4-methanol,The aqueous buffer maintaining the pH at 5.0-7.5.