Abstract: The present disclosure generally pertains to a medical device and more particularly, a metered-dose inhaler (“MDI”) actuator capable of a targeted delivery of fine API particles having particle diameters of about 1.1 ?m or less to a portion of a patient's lungs where alveoli are located.

Abstract: The present disclosure introduces safe and effective pharmaceutical formulations for intranasal delivery. Specifically, the present disclosure introduces the safe clinical use of bile acids or salts thereof as an enhancer to exhibit improved bioavailability and tissue tolerance. In several embodiments, pharmaceutical formulations including bile acids or salts thereof are provided. In several embodiments, the formulations are suitable and/or configured for the intranasal (IN) delivery, methods of manufacturing such formulations, and methods of treating patients using such formulations. The pharmaceutical formulations comprising bile acids, salts of bile acids, and/or combinations thereof. In several embodiments, bile acids, salts of bile acids, and/or combinations thereof are configured for use as absorption enhancers.

Abstract: The present disclosure introduces methods for characterizing iron core carbohydrate colloid drug products, such as iron sucrose drug products. Disclosed methods enable the characterization of the iron core size of the iron core nanoparticles in iron carbohydrates as they exist in the formulation in solution, such as e.g. iron sucrose drug products, and more particularly, the average particle diameter size and size distribution(s) of the iron core nanoparticles. The disclosed methods apply small-angle X-ray scattering (SAXS) in parallel beam transmission geometry, with a sample mounted inside a capillary and centered in the X-ray beam, to iron carbohydrates, such as iron sucrose, in solution without the need to modify the sample, such as to remove unbound carbohydrates, dilute, or dry the sample, to accurately characterize the average iron core particle diameter size of the iron core nanoparticles.

Abstract: The present disclosure introduces intranasal (IN) pharmaceutical formulations having naloxone or an opioid antagonist as the active agent, and an absorption enhancer, such as a bile acid, or a salt thereof, for IN delivery. The bile acid, or salt thereof, enhances absorption of naloxone or an opioid antagonist into the bloodstream of a human subject.

Abstract: Disclosed herein are pharmaceutical formulations including epinephrine that have increased epinephrine retention over long-term storage, e.g., 30-months. In one aspect, a formulation includes: one or more of 0.1 mg/mL of epinephrine or a pharmaceutically acceptable salt thereof provided without any overage, a tonicity regulating agent including 8.2 mg/mL of sodium chloride, a pH adjusting agent including a mixture of 1.5 mg/mL sodium citrate dihydrate, 3.3 mg/mL of citric acid monohydrate, and, optionally, an as-needed amount of sodium hydroxide to maintain the pH level of the formulation within a range of 3.6 to 4.0, 0.075 mg/mL of sodium metabisulfite, and 4 ?g/mL of ethylene diamine tetra-acetate disodium. The formulation has an API recovery of 94.5% or more after at least 30 months of storage at long-term storage conditions defined as 25° C.±2° C. at 1 atmosphere. In addition, in another aspect, a formulation includes 1 mg/mL of epinephrine and other ingredients.

Abstract: Disclosed herein are pharmaceutical formulations including epinephrine that have increased epinephrine retention over long-term storage, e.g., 30-months. In one aspect, a formulation includes: one or more of 0.1 mg/mL of epinephrine or a pharmaceutically acceptable salt thereof provided without any overage, a tonicity regulating agent including 8.2 mg/mL of sodium chloride, a pH adjusting agent including a mixture of 1.5 mg/mL sodium citrate dihydrate, 3.3 mg/mL of citric acid monohydrate, and, optionally, an as-needed amount of sodium hydroxide to maintain the pH level of the formulation within a range of 3.6 to 4.0, 0.075 mg/mL of sodium metabisulfite, and 4 ?g/mL of ethylene diamine tetra-acetate disodium. The formulation has an API recovery of 94.5% or more after at least 30 months of storage at long-term storage conditions defined as 25° C.±2° C. at 1 atmosphere. In addition, in another aspect, a formulation includes 1 mg/mL of epinephrine and other ingredients.

Abstract: The present disclosure provides NMR relaxation methods for characterizing iron carbohydrate drug products. The methods measure 13C and 1H nuclei relaxation parameters such as T1 and PWHH include performing 2D T1 NMR, 1D 13C NMR and 1H NMR to characterize certain physiochemical properties of iron sucrose drug products, for purposes of assessing bioequivalence between a tested iron sucrose product and a comparator product. The disclosure further provides a novel Fe(III)/Fe(II) reduction method using a new reducing agent Na2S2O5 and an 1H NMR method to monitor the Fe(III)/Fe(II) reduction process.

Abstract: The present disclosure introduces methods for characterizing iron core carbohydrate colloid drug products, such as iron sucrose drug products. Disclosed methods enable the characterization of the iron core size of the iron core nanoparticles in iron carbohydrates as they exist in the formulation in solution, such as e.g. iron sucrose drug products, and more particularly, the average particle diameter size and size distribution(s) of the iron core nanoparticles. The disclosed methods apply small-angle X-ray scattering (SAXS) in parallel beam transmission geometry, with a sample mounted inside a capillary and centered in the X-ray beam, to iron carbohydrates, such as iron sucrose, in solution without the need to modify the sample, such as to remove unbound carbohydrates, dilute, or dry the sample, to accurately characterize the average iron core particle diameter size of the iron core nanoparticles.

Abstract: Disclosed herein are pharmaceutical formulations including epinephrine that have increased epinephrine retention over long-term storage, e.g., 30-months. In one aspect, a formulation includes: one or more of 0.1 mg/mL of epinephrine or a pharmaceutically acceptable salt thereof provided without any overage, a tonicity regulating agent including 8.2 mg/mL of sodium chloride, a pH adjusting agent including a mixture of 1.5 mg/mL sodium citrate dihydrate, 3.3 mg/mL of citric acid monohydrate, and, optionally, an as-needed amount of sodium hydroxide to maintain the pH level of the formulation within a range of 3.6 to 4.0, 0.075 mg/mL of sodium metabisulfite, and 4 ?g/mL of ethylene diamine tetra-acetate disodium. The formulation has an API recovery of 94.5% or more after at least 30 months of storage at long-term storage conditions defined as 25° C.±2° C. at 1 atmosphere. In addition, in another aspect, a formulation includes 1 mg/mL of epinephrine and other ingredients.

Abstract: Methods are disclosed for producing highly purified recombinant human insulin (RHI) having a purity of 99.0% (w/w) or greater, a Total Impurity (not including the related substance desamido AsnA21-RHI, as specified by USP) of 0.8% (w/w) or less, and an impurity C of 0.1% (w/w) or less. Also disclosed are API compositions of highly purified RHI having a purity of 99.0% (w/w) or greater, a Total Impurity of 0.8% (w/w) or less, and an impurity C of 0.1% (w/w) or less.

Abstract: A high-purity inhalable insulin material, used for preparing a pulmonary pharmaceutical product, includes insulin particles having a particle size at the micrometer level and having the following characteristics: (i) the purity of insulin is not less than 96% on the dried basis; (ii) the total amount of insulin-related impurities is not more than 2%; (iii) the total amount of solvent impurities, which is not a co-solvent formulation component for a pulmonary product, is not more than 0.03%; and (iv) the total amount of non-solvent impurities is not more than 0.3%. Up to 99% by volume of the insulin particles in the inhalable insulin have a particle size of less than 5 ?m, based on the total volume of the insulin particles. A high-efficiency method prepares high-purity inhalable insulin material. The yield rate for the high-efficiency method is 75 to 85% or more.

Abstract: Methods are disclosed for producing highly purified recombinant human insulin (RHI) having a purity of 99.0% (w/w) or greater, a Total Impurity (not including the related substance desamido AsnA21-RHI, as specified by USP) of 0.8% (w/w) or less, and an impurity C of 0.1% (w/w) or less. Also disclosed are API compositions of highly purified RHI having a purity of 99.0% (w/w) or greater, a Total Impurity of 0.8% (w/w) or less, and an impurity C of 0.1% (w/w) or less.

Abstract: A high-purity inhalable insulin material, used for preparing a pulmonary pharmaceutical product, includes insulin particles having a particle size at the micrometer level and having the following characteristics: (i) the purity of insulin is not less than 96% on the dried basis; (ii) the total amount of insulin-related impurities is not more than 2%; (iii) the total amount of solvent impurities, which is not a co-solvent formulation component for a pulmonary product, is not more than 0.03%; and (iv) the total amount of non-solvent impurities is not more than 0.3%. Up to 99% by volume of the insulin particles in the inhalable insulin have a particle size of less than 5 ?m, based on the total volume of the insulin particles. A high-efficiency method prepares high-purity inhalable insulin material. The yield rate for the high-efficiency method is 75 to 85% or more.

Abstract: A high-purity inhalable insulin material, used for preparing a pulmonary pharmaceutical product, includes insulin particles having a particle size at the micrometer level and having the following characteristics: (i) the purity of insulin is not less than 96% on the dried basis; (ii) the total amount of insulin-related impurities is not more than 2%; (iii) the total amount of solvent impurities, which is not a co-solvent formulation component for a pulmonary product, is not more than 0.03%; and (iv) the total amount of non-solvent impurities is not more than 0.3%. Up to 99% by volume of the insulin particles in the inhalable insulin have a particle size of less than 5 ?m, based on the total volume of the insulin particles. A high-efficiency method prepares high-purity inhalable insulin material. The yield rate for the high-efficiency method is 75 to 85% or more.

Abstract: A high-purity inhalable insulin material, used for preparing a pulmonary pharmaceutical product, includes insulin particles having a particle size at the micrometer level and having the following characteristics: (i) the purity of insulin is not less than 96% on the dried basis; (ii) the total amount of insulin-related impurities is not more than 2%; (iii) the total amount of solvent impurities, which is not a co-solvent formulation component for a pulmonary product, is not more than 0.03%; and (iv) the total amount of non-solvent impurities is not more than 0.3%. Up to 99% by volume of the insulin particles in the inhalable insulin have a particle size of less than 5 ?m, based on the total volume of the insulin particles. A high-efficiency method prepares high-purity inhalable insulin material. The yield rate for the high-efficiency method is 75 to 85% or more.

Abstract: A method of preparing an inhalable insulin suitable for pulmonary delivery includes: dissolving an insulin raw material in an acidic solution to form a dissolved insulin solution; titrating the dissolved insulin solution with a buffer solution to form a suspension comprising micronized insulin particles; and stabilizing the micronized insulin particles.

Abstract: A high-purity inhalable insulin material, used for preparing a pulmonary pharmaceutical product, includes insulin particles having a particle size at the micrometer level and having the following characteristics: (i) the purity of insulin is not less than 96% on the dried basis; (ii) the total amount of insulin-related impurities is not more than 2%; (iii) the total amount of solvent impurities, which is not a co-solvent formulation component for a pulmonary product, is not more than 0.03%; and (iv) the total amount of non-solvent impurities is not more than 0.3%. Up to 99% by volume of the insulin particles in the inhalable insulin have a particle size of less than 5 ?m, based on the total volume of the insulin particles. A high-efficiency method prepares high-purity inhalable insulin material. The yield rate for the high-efficiency method is 75 to 85% or more.

Abstract: A high-purity inhalable insulin material, used for preparing a pulmonary pharmaceutical product, includes insulin particles having a particle size at the micrometer level and having the following characteristics: (i) the purity of insulin is not less than 96% on the dried basis; (ii) the total amount of insulin-related impurities is not more than 2%; (iii) the total amount of solvent impurities, which is not a co-solvent formulation component for a pulmonary product, is not more than 0.03%; and (iv) the total amount of non-solvent impurities is not more than 0.3%. Up to 99% by volume of the insulin particles in the inhalable insulin have a particle size of less than 5 ?m, based on the total volume of the insulin particles. A high-efficiency method prepares high-purity inhalable insulin material. The yield rate for the high-efficiency method is 75 to 85% or more.

Abstract: A method of preparing an inhalable insulin suitable for pulmonary delivery includes: dissolving an insulin raw material in an acidic solution to form a dissolved insulin solution; titrating the dissolved insulin solution with a buffer solution to form a suspension comprising micronized insulin particles; and stabilizing the micronized insulin particles.

Abstract: Pharmaceutical compositions for long-term sustained release of bisphosphonate drugs are provided. In one embodiment, the composition includes an aqueous suspension of a solid which includes a salt of a bisphosphonate drug and a salt of pentavalent phosphorus oxoacid. The compositions can be used to treat a variety of bone diseases, including osteoporosis.