FIELD: medicine; pharmaceutics.
SUBSTANCE: group of inventions relates to pharmaceutics, namely, to pellets of ilaprazole with enteric coating, a method of producing pellets, a pharmaceutical composition for treating and/or preventing gastrointestinal diseases, a method of treating and/or preventing gastrointestinal diseases and using an enteric coated pellet for preparing a drug. Pellet with an enteric coating for treating and/or preventing gastrointestinal diseases, comprising a pellet core, a first insulating layer, a second insulating layer and an enteric coating layer successively from the inside out, wherein the pellet core contains ilaprazole and/or a pharmaceutically acceptable salt of ilaprazole and a water-insoluble basic compound as a first auxiliary substance, wherein the enteric coated pellet is characterized by that the first insulating layer contains a water-insoluble basic compound; wherein the enteric coated ilaprazole pellet contains the following components in the specified ranges in weight parts: 1) pellet core: empty pellet core 5–15, drug loading layer containing: ilaprazole (or its pharmaceutically acceptable salt) 5–15, water-insoluble basic compound 5–15, surfactant 0.2–0.6, binder 8–24; 2) first insulating layer: binder, 5–36, water-insoluble basic compound 5–36; 3) second insulating layer: 4) binder 4–26; 5) anti-adhesive 7–44; 6) enteric coating layer:enteric coating materials 30–100 (content of solid substance), anti-adhesive 1–5, plasticizer 9–30; 7) protective layer: 8) binder 0.5–4; 9) anti-adhesion agent 0.5–5; wherein the water-insoluble basic compound is selected from one or more of magnesium hydroxide, magnesium oxide, magnesium carbonate, calcium carbonate and calcium hydroxide; wherein the binder is selected from one or more of hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose and polyethylene glycol; wherein the anti-adhesion agent isselected from one or more of talc, magnesium stearate, titanium dioxide and silicon dioxide. Weight ratio of the first excipient to ilaprazole and/or the pharmaceutically acceptable salt of ilaprazole is 0.2:1–5:1; wherein the water-insoluble basic compound contained in the first insulating layer and the water-insoluble basic compound of the first auxiliary substance can be the same or different; wherein the enteric coated pellet is characterized by that the particle size D90 of ilaprazole and/or the pharmaceutically acceptable salt of ilaprazole is less than or equal to 100 mcm, and the second insulating layer does not contain basic substances. Method of producing a pellet with an enteric coating involves the following steps: 1) obtaining a pellet core containing ilaprazole and/or a pharmaceutically acceptable salt of ilaprazole and a first excipient; 2) applying a first insulating layer and then applying a second insulating layer; 3) applying a layer of enteric coating; and 4) applying a protective layer. Pharmaceutical composition for treating and/or preventing gastrointestinal diseases, selected from an enteric coated pellet comprising an enteric coated pellet and a second excipient and optionally a film coating; capsule containing enteric coated pellets with protective layer, and a dry suspension containing enteric coated pellets and dry suspended particles. Method of treating and/or preventing gastrointestinal diseases includes a step of administering to a patient in need of such treatment and/or prevention, a therapeutic and/or prophylactic effective amount of an enteric coated pellet, or a pharmaceutical composition. Use of an enteric coated pellet or a pharmaceutical composition for preparing a drug for treating and/or preventing gastrointestinal diseases, wherein said gastrointestinal diseases are selected from heartburn, inflammatory bowel disease, Crohn's disease, irritable bowel syndrome, ulcerative colitis, peptic ulcer, stress ulcer, bleeding peptic ulcer, duodenal ulcer and recurrent duodenal ulcer, NSAID-associated gastric ulcer, active benign gastric ulcer in adults, infectious enteritis, colitis, gastric acidity, dyspepsia, gastroparesis, Zollinger-Ellison syndrome, gastroesophageal reflux disease (GERD), associated with Helicobacter pylori disease or elimination of helicobacter pylori, all degrees of erosive esophagitis, short bowel syndrome, gastric ulcer, peptic ulcer caused by non-steroidal anti-inflammatory compounds, and gastrointestinal bleeding and associated ulcers caused by antiplatelet preparations, as well as any combination of the above diseases.
EFFECT: said group of solutions enables to obtain pellets which have good stability, good acid resistance, high solubility and/or improved drug loading and bioavailability.
14 cl, 6 dwg, 18 tbl, 5 ex
