Pharmaceutical dosage forms and methods of use
AssigneeEmalex Biosciences, Inc.
InventorsStephen P. Wanaski, Virginia D. Schmith, Jay A. White, Timothy M. Cunniff
Life of this patent
Estimating the term…
Abstract
Pharmaceutical dosage forms of D1/D5 receptor antagonists, and related methods of their use, are disclosed.
Claims48
A pharmaceutical dosage form for intra-oral absorption of ecopipam, comprising ecopipam or a pharmaceutically acceptable salt thereof and a pH modifier, the pH modifier being present in amount such that the pharmaceutical dosage form has a pH of about 2 to about 4, wherein when the dosage form is in solid form, the pH is as measured after dissolving the dosage form in 30 g of artificial saliva having a pH of 6.72.
The pharmaceutical dosage form of any one of the preceding claims, wherein the pharmaceutical dosage form comprises about 0.01 to about 0.8 wt % pH modifier based on the total weight of the formulation.
The pharmaceutical dosage form of any one of the preceding claims, wherein the pharmaceutical dosage form has a pH of about 2 to about 3.5.
The pharmaceutical dosage form of any one of the preceding claims, wherein the pharmaceutical dosage form is a tablet, powder, sachet, film, gel, gum, aerosol, oral lyophilizate, oravescent, sprayable liquid, wafer, mouthwash, or lozenge.
The pharmaceutical dosage form of any one of the preceding claims, wherein the pharmaceutical dosage form comprise one or more excipients selected from the group an absorption enhancer (also called permeation enhancer), an antioxidant, a binder, a carrier, a colorant, a diluent, a disintegrant, a flavor, a lubricant, a pH modifier, a plasticizer, a preservative, a sweetener, a taste masking agent, a taste modulating agent, a viscosity modifier, a lyophilization agent, and nitrosamine scavengers, and including one or more from each group of excipients.
The pharmaceutical dosage form of any one of the preceding aspects, wherein the pharmaceutical dosage form comprises an absorption enhancer selected from one or more in the group of chelators (e.g., citric acid, EDTA, EGTA, methoxy salicylates, sodium salicylate);
- surfactants, including nonionic, e.g., polyoxyethylene vegetable-based fatty ethers derived from lauryl, cetyl, stearyl or oleyl alcohols (e.g., Brij), dodecylmaltoside, laureth-9, ethoxylated fatty acids (e.g. Myrj), poloxamer, polysorbate 80, span, sucrose esters, Tween, cationic (e.g., benzalkonium chloride, cetylmethylammonium bromide, Cetyl pyridinium chloride), and anionic (e.g., sodium dodecyl glycocholate, sodium lauryl sulfate, laureth-9 sodium dodecylsulfate);
- bile salts and other steroidal detergents (e.g., sodium glycocholate, sodium taurocholate, saponins, sodium taurodeoxycholate, sodium taurodihydrofusidate, and sodium glycodihydrofusidate);
- fatty acids (e.g., Oleic acid, Caprylic acid, Lauric acid, Lyso phosphatidyl choline, Phosphatidyl choline, sodium myristate);
- non-surfactants (e.g., 1-dodecylazacycloheptane-2-one (Azone), salicylates, and sulfoxides);
- enzymes (e.g., phospholipases, hyaluronidases, neuraminidase, and chondroitinase ABC);
- and Cyclodextrins (e.g., a, B, y, Cyclodextrin, methylated β-cyclodextrins, hydroxypropyl beta-cyclodextrin), chitosan, trimethyl chitosan, poly-l-arginine, l-lysine, chondroitinase ABC, 1-dodecylazacycloheptan-2-one, and quillajasaponin.
The pharmaceutical dosage form of any one of the preceding claims, wherein upon administration, the pharmaceutical dosage form reduces a pH of saliva of a subject by at least 1 pH unit.
The pharmaceutical dosage form of any one of the preceding claims, wherein upon administration, the pharmaceutical dosage form reduces a pH of saliva of a subject to 6.5 or less, 6 or less, 5.5 or less, 5 or less, 4.5 or less, or 4 or less.
The pharmaceutical dosage form of any one of the preceding claims, wherein the pharmaceutical dosage form comprises one or more compounds selected from AB block copolymers of oligo(methyl methacrylate) and PAA, acacia, and polyvinyl alcohol, anionic types, Carbopol e.g. 934P, cationic types, chitosan (e.g. free or cross-linked by an anionic polymer), copolymers of PAA and PEG monoethylether monomethacrylate, epoxy resins, Eudragit polymers (e.g. Eudragit L-100, an anionic copolymer based on methacrylic acid and methyl methacrylate), gelatin, gellan gum, glycol, guar gum, hyaluronic acid, hydrogels of poly(N N-dimethylaminoethyl methacrylate-co-methyl methacrylate) e.g., poly(DMA/MMA) cross-linked with DVB, hydrophilic pressure-sensitive adhesives (PSAs), hydroxyethyl cellulose, hydroxyethyl methacrylate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, a modified starch-polyacrylic acid mixture, monomeric alpha-cyanoacrylate, PAA complexed with PEGylated drug conjugate, pectin, poly(acrylic acid/divinyl benzene), polyacrylates, polymethacrylates, polycarbophil, polyethylene carboxymethyl cellulose, polymers with thiol groups, polymethyl vinyl ether-maleic anhydride, polystyrenes, polyurethanes, polyvinyl pyrrolidone, psyllium amberlite-200 resin, sodium alginate, sodium alginate, tamarind gum, thermally modified starch, tragacanth, and xanthan gum.
The pharmaceutical dosage form of any one of the preceding aspects, wherein the pharmaceutical dosage form comprises an amount of ecopipam or a pharmaceutically acceptable salt thereof, of about 1 wt % to about 40 wt % based on the total weight of the pharmaceutical dosage form.
The pharmaceutical dosage form of any one of the preceding aspects, wherein the pharmaceutical dosage form comprises an amount of ecopipam or a pharmaceutically acceptable salt thereof, of about 1 mg to about 200 mg.
A method of improving a safety profile of ecopipam, comprising administering to a subject in need thereof the pharmaceutical dosage form of any one of the preceding claims, wherein the ecopipam is intraorally absorbed, wherein the safety profile is improved as compared to an oral dosage form of ecopipam or pharmaceutically acceptable salt in which ecopipam is absorbed in the GI tract.
The pharmaceutical dosage form of any one of claims 36 to 47, wherein the pharmaceutical dosage form is administered to achieve a total daily dose of less than 2 mg/kg, 1.5 mg/kg or less, 1 mg/kg or less, or 0.5 mg/kg or less.
- The pharmaceutical dosage form of any one of claims 36 to 48, wherein the pharmaceutical dosage form is administered to achieve a total daily dose of at least 25% less, or at least 50% less, or at least 75% less than a total daily dose needed for an oral dosage form which provides for absorption of ecopipam in the GI tract.
Dependencies are inferred from the claim text.