FORMULATIONS OF ATORVASTATIN STABILIZED WITH ALKALI METAL ADDITIONS

• Main Authors: ROMI BHARAT SINGH, RAJIV MALIK, PANANCHUKUNNATH MANOJ KUMAR
• Format: Patent
• Language: English
• Published: 31.07.2006
• Subjects: HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Farmaceutska formulacija koja poboljšava biološkudostupnost i biološku ujednačenost, podrazumijevačestice amorfnog i/ili kristaličnog atorvastatina, čija veličina (d90) ne prelazi 150 µm, a prosječna veličina čestica (d50) varira unutar raspona od5-50 µm. Atorvastatin može biti kalcij atorvastatin, magnezij atorvastatin, aluminij atorvastatin, željezo atorvastatin, cink atorvastatin, ili njihova kombinacija. Formulacije atorvastatina mogu se stabilizirati miješanjem atorvastatina s aditivom soli alkalnog metala koji je u ukupnoj težini formulacije zastupljen s 1.2% do manje od 5%. Aditiv soli alkalnog metala može biti natrijev karbonat, natrijev bikarbonat, natrijev hidroksid, natrijev silikat, dinatrij hidrogen ortofosfat, natrijev dihidrogen fosfat, dinatrijev hidrogen fosfat, natrijev fosfat, natrijev aluminat, kalcijev karbonat, kalcijev hidroksid, magnezijev karbonat, magnezijevhidroksid, magnezijev silikat, magnezijev aluminat, aluminij magnezijev hidroksid, odnosno jedna odnjihovih kombinacija. Formulacije atorvastatina koriste se u liječenju bolesti kao što je primarna hiperkolesterolemija, disbetalipoproteinemija te homozigotična familijama hiperkolesterolemija. A pharmaceutical formulation having improved bioavailability and bioequivalence includes particles of amorphous and/or crystalline atorvastatin that have a particle size (d90) less than 150 mu m and a mean particle size (d50) of the atorvastatin particles that is between approximately 5 and 50 mu m. The atorvastatin can be one or more of atorvastatin calcium, atorvastatin magnesium, atorvastatin aluminum, atorvastatin iron, and atorvastatin zinc. The formulations of atorvastatin can be stabilized by mixing atorvastatin with an alkali metal salt additive at between approximately 1.2% and less than 5% w/w of the formulation. The alkali metal salt additive may be one or more of sodium carbonate, sodium bicarbonate, sodium hydroxide, sodium silicate, disodium hydrogen orthophosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, sodium aluminate, calcium carbonate, calcium hydroxide, magnesium carbonate, magnesium hydroxide, magnesium silicate, magnesium aluminate, and aluminum magnesium hydroxide. The atorvastatin formulations can be used to treat medical conditions, including primary hypercholesterolemia, dysbetalipoproteinemia, and homozygous familial hypercholesterolemia.