The present invention is directed to a composition that can be used to deliver an antipsychotic drug such as risperidone, paliperidone or a combination thereof, as an injectable in-situ forming biodegradable implant for extended release providing therapeutic plasma levels from the first day. The composition is in the form of drug suspension on a biodegradable and biocompatible copolymer or copolymers solution using water miscible solvents that is administered in liquid form. Once the composition contacts the body fluids, the polymer matrix hardens retaining the drug, forming a solid or semisolid implant that releases the drug in a continuous manner. Therapeutic plasma levels of the drug can be achieved from the first day up to at least 14 days or more even up to at least four weeks.

The present invention relates to pharmaceutical dosage forms, for example to a tamper resistant dosage form including an opioid analgesic, and processes of manufacture, uses, and methods of treatment thereof.

The present disclosure provides extended release trihexyphenidyl compositions suitable for once- or twice-daily administration. The compositions comprise a core comprising at least one organic acid; at least one drug layer comprising trihexyphenidyl or a pharmaceutically acceptable salt thereof over the core; and a functional coat over the drug-layered core. The compositions of the disclosure provide extended release with reduced C.sub.max, a C.sub.min:C.sub.max ratio of ≥0.4, Fluctuation Index of ≤1, while providing and maintaining at least a minimum therapeutically effective plasma concentration, of the trihexyphenidyl or the pharmaceutically acceptable salt thereof for at least about 10 hours. The compositions of the disclosure improve solubility of the trihexyphenidyl or the pharmaceutically acceptable salt thereof at a pH of greater than or equal to 5, to provide and maintain at least a minimum effective concentration of the drug at such pH.

A dosage form with a first portion and a second portion. The first portion can be an immediate release portion and can comprise a pain reliever, which can be naproxen or naproxen sodium. The second portion can be an extended release portion and can comprise pseudoephedrine or a pharmaceutically acceptable salt thereof and/or dextromethorphan or a pharmaceutically acceptable salt thereof. The dosage form can optionally comprise a stabilizing agent. The dosage form can be adapted to maintain a therapeutically effective amount of pain reliever, pseudoephedrine, or a pharmaceutically acceptable salt thereof, and/or dextromethorphan, or a pharmaceutically acceptable salt thereof, for at least eight hours.

Components with relatively high loading of active pharmaceutical ingredients (e.g., drugs), are generally provided. In some embodiments, the component (e.g., a tissue interfacing component) comprises a solid therapeutic agent (e.g., a solid API) and a supporting material (e.g., a binder such as a polymer) such that the solid therapeutic agent is present in the component in an amount of greater than or equal to 10 wt % versus the total weight of the tissue interfacing component. Such tissue-interfacing components may be useful for delivery of API doses e.g., to a subject. Advantageously, in some embodiments, the reduction of volume required to deliver the required API dose as compared to a liquid formulation permits the creation of solid needle delivery systems for a wide variety of drugs in a variety of places/tissues (e.g., tongue, GI mucosal tissue, skin) and/or reduces and/or eliminates the application of an external force in order to inject a drug solution through the small opening in the needle. In some cases, a physiologically relevant dose may be present in a single tissue interfacing component (e.g., having a relatively high API loading).

Self-actuating articles including, for example, self-actuating needles and/or self-actuating biopsy punches, are generally provided. Advantageously, the self-actuating articles described herein may be useful as a general platform for delivery of a wide variety of pharmaceutical drugs that are typically delivered via injection directly into tissue due to degradation in the GI tract. The self-actuating articles described herein may also be used to deliver sensors and/or take biopsies without the need for an endoscopy. In some embodiments, the article comprises a spring (e.g., a coil spring, a beam, a material having particular mechanical recovery characteristics). Those of ordinary skill in the art would understand that the term spring is not intended to be limited to coil springs, but generally encompass any reversibly compressive material and/or component which, after releasing an applied compressive force on the material/component, the material/component substantially returns to an uncompressed length of the material/component (e.g., the within 95% of the length of the material/component prior to compression).

The present invention is directed to a composition that can be used to deliver an antipsychotic drug such as risperidone, paliperidone or a combination thereof, as an injectable in-situ forming biodegradable implant for extended release providing therapeutic plasma levels from the first day. The composition is in the form of drug suspension on a biodegradable and biocompatible copolymer or copolymers solution using water miscible solvents that is administered in liquid form. Once the composition contacts the body fluids, the polymer matrix hardens retaining the drug, forming a solid or semisolid implant that releases the drug in a continuous manner. Therapeutic plasma levels of the drug can be achieved from the first day up to at least 14 days or more even up to at least four weeks.

A drug delivery system is provided in the form of a controlled release, bioerodible pellet for subdermal implantation. The pellet is bioerodible, and provides for the sustained release of a pharmacologically active agent over an extended time period. As such, the drug delivery system finds significant utility in chronic drug administration. Bioerosion products are water soluble, bioresorbed, or both, obviating the need for surgical removal of the implant. Methods for manufacturing and using the drug delivery system are also provided.

Self-righting articles, such as self-righting capsules for administration to a subject, are generally provided. In some embodiments, the self-righting article may be configured such that the article may orient itself relative to a surface (e.g., a surface of a tissue of a subject). The self-righting articles described herein may comprise one or more tissue engaging surfaces configured to engage (e.g., interface with, inject into, anchor) with a surface (e.g., a surface of a tissue of a subject). In some embodiments, the self-righting article may have a particular shape and/or distribution of density (or mass) which, for example, enables the self-righting behavior of the article. In some embodiments, the self-righting article may comprise a tissue interfacing component and/or a pharmaceutical agent (e.g., for delivery of the active pharmaceutical agent to a location internal of the subject). In some cases, upon contact of the tissue with the tissue engaging surface of the article, the self-righting article may be configured to release one or more tissue interfacing components. In some cases, the tissue interfacing component is associated with a self-actuating component. For example, the self-righting article may comprise a self-actuating component configured, upon exposure to a fluid, to release the tissue interfacing component from the self-righting article. In some cases, the tissue interfacing component may comprise and/or be associated with the pharmaceutical agent (e.g., for delivery to a location internal to a subject).

A method for inducing mass apoptosis of cancer cells by enhancing the overall acidity in the tumor. The method enhances overall acidity in tumor internal tissue to reduce overall pH in tumor tissue, last to induce mass apoptosis of cancer cells. When pH of extracellular micro-environment of cancer cells is lower than 5.0, mass apoptosis of cancer cells can be induced. Base on the same direction synergic interaction between the changes of intracellular and extracellular acidity in tumor, the method may be achieved by injecting acid directly into tumor cells, or aggravating the anaerobic respiration of cancer cells through hyperthermia and other ways to enhance overall acidity in tumor tissues. The method may effectively induce mass apoptosis of cancer cells with little damaging to the normal cells, so as to inhibit the differentiation and proliferation of cancer cells, stop the metastasis and diffusion, and realize the radical cure of tumor.