Pharmaceutical compositions for direct systemic introduction
The invention relates to pharmaceutical compositions for direct systemic introduction, are also known as DSI pharmaceutical compositions, for used as human veterinary pharmaceutical compositions. In one embodiment, the invention relates to a pharmaceutical composition for direct system introduction comprising bovine gelatin, mannitol, an optional surfactant, an optional flavorant, and an active pharmaceutical ingredient. A DSI pharmaceutical composition of the invention has a disintegration time of 7 seconds or less in deionized water maintained at 37.0° C.±0.5° C. The invention also relates to a method of delivering an active pharmaceutical ingredient to an animal comprising the step of placing a DSI pharmaceutical composition of the invention into a mucosal cavity of an animal to be treated with the active pharmaceutical ingredient and to the corresponding methods of treatment.
1. A method of making a pharmaceutical composition for direct system introduction, the composition comprising:
about 10-17 dry mass % bovine gelatin,
about 10-17 dry mass % mannitol,
about 0-1 dry mass % of a surfactant,
about 0-0.5 dry mass % of a flavorant, and
about 65-80 dry mass % of an active pharmaceutical ingredient which is a proton pump inhibitor;
wherein the method comprises:
combining the active pharmaceutical ingredient with one or more pharmacologically inactive compound(s) to form a pre-formulation;
freezing the pre-formulation;
reducing the pressure surrounding the pre-formulation; and
lyophilizing the pre-formulation.
2. The method according to claim 1 , wherein the method comprises combining the pharmaceutically active ingredient with bovine gelatin and water and adding at least one compound selected from mannitol, flavorant, and surfactant.
3. The method according to claim 1 , wherein the method further comprises adjusting the pH of the pre-formulation.
4. The method according to claim 1 , wherein the method further comprises adjusting the pH of the pre-formulation to a basic pH value.
5. The method according to claim 4 , wherein the pH is adjusted to between about 8 to 9; between about 9 to 10; between about 10 to 11; between about 8 to 8.5; or about 8.3.
6. The method according to claim 1 , wherein the pre-formulation comprises the surfactant, flavorant, and/or other excipients.
7. The method according to claim 1 , wherein the components of the pre-formulation are dissolved together in a single solution.
8. The method according to claim 1 , wherein the components of the pre-formulation are prepared as separate solutions that are combined to make the pre-formulation.
9. The method according to claim 1 , wherein the pre-formulation comprises:
about 1-10 mass % bovine gelatin;
about 1-10 mass % mannitol;
about 0-0.5 mass % surfactant;
about 0-0.2 mass % flavorant;
about 10-30 mass % of the proton pump inhibitor; and
about 45-90 mass % water.
10. The method according to claim 1 , wherein the pre-formulation comprises:
about 3-5 mass % bovine gelatin;
about 3-5 mass % mannitol;
about 0.1-0.3 mass % surfactant;
about 0.05-0.15 mass % flavorant;
about 15-25 mass % of the pharmaceutically active ingredient; and
about 55-75 mass % water.
11. The method according to claim 1 , wherein the pharmaceutical composition comprises:
about 10-17 dry mass % bovine gelatin,
about 10-17 dry mass % mannitol, and
about 0-0.5 dry mass % of a surfactant.
12. The method according to claim 1 , wherein the pharmaceutical composition comprises:
about 10-13 dry mass % bovine gelatin,
about 12-15 dry mass % mannitol, and
about 0.1-0.3 dry mass % of a surfactant.
13. The method according to claim 1 , wherein the active pharmaceutical ingredient is omeprazole or esomeprazole.
14. The method according to claim 1 , wherein the pharmaceutical composition has a disintegration time of 7 seconds or less in deionized water maintained at 37.0° C.±0.5° C.
15. The method according to claim 1 , wherein the pharmaceutical composition has a disintegration time of 4 seconds or less in deionized water maintained at 37.0° C.±0.5° C.
16. A method of delivering an active pharmaceutical ingredient which is omeprazole or esomeprazole to an animal via the animal's non-keratinous tissues comprising the step of placing the pharmaceutical composition prepared according to claim 1 into a mucosal cavity of an animal to be treated with the active pharmaceutical ingredient.
17. The method according to claim 16 , wherein the animal is equine.
18. The method according to claim 16 , wherein the animal is human.
19. The method according to claim 16 , wherein the mucosal cavity is selected from an oral cavity, an anal cavity, a vaginal cavity, a nasal cavity, a gingival mucosa, a lingual mucosa, a palatal mucosa, a pharyngeal mucosa, a sublingual mucosa, and a non-gastric mucosa.
20. The method according to claim 16 , wherein the mucosal cavity is an oral cavity.
21. A method of treating a disease selected from the group consisting of gastric ulcers, duodenal ulcers, Zollinger-Ellison syndrome, laryngopharyngeal reflux, dyspepsia, peptic ulcer disease, gastritis, and gastroesophageal reflux in an animal, the method comprising administering an effective amount of the pharmaceutical composition prepared according to claim 1 to the animal.
22. The method according to claim 21 , wherein administering comprises placing the pharmaceutical composition into a mucosal cavity of the animal.
23. The method according to claim 22 , wherein the mucosal cavity is selected from an oral cavity, an anal cavity, a vaginal cavity, a nasal cavity, a gingival mucosa, a lingual mucosa, a palatal mucosa, a pharyngeal mucosa, a sublingual mucosa, and a non-gastric mucosa.
24. The method according to claim 21 , wherein the animal is equine.
25. The method according to claim 21 , wherein the animal is human.