ATORVASTATIN CALCIUM IN PHARMACEUTICAL FORM, COMPOSITION THEREOF, AND PHARMACEUTICAL FORMULATION COMPRISING ATORVASTATION CALCIUM

The invention herewith described refers to the atorvastatin calcium, a substance known by the chemical name (R-(R*,R*))-2-(4- fluorophenyl) )-ß,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-((phenylamino) carbonyl)-1H-pyrrole-1- -heptanoic acid, hemicalcium salt which is known as an inhibitor of HMG-CoA reductase and is used as antihypercholesterolemic agent. Atorvastatin in the pharmaceutical mixtures, available on the market, is generally prepared in the form of its calcium salt since it enables atorvastatin to be conveniently formulated in pharmaceutical formulations, for example, tablets, capsules, powders and similar formulations for oral use. Atorvastatin calcium can exist in an amorphous form or in one of at least four known crystalline forms (Form I, Form II, Form III and Form IV). Atorvastatin calcium is the substance which is moderately soluble in water, with pKa 4,5, and it is determined that the crystalline forms are less soluble than the amorphous form, and that it can cause problems in the bioavailability of atorvastatin in the body. The invention solves the problem of providing therapeutic equivalence of atorvastatin pharmaceutical formulation, regardless of the form (crystalline, amorphous or a mixture of both) of atorvastatin calcium, which is used for its creating. Atorvastatin kalcijum, supstanca, poznata po hemijskom imenu (R-(R*,R*))-2-(4-fluorofenii)-(β,δ-dihidroksi-5-(1-metiletil)-3-fenil-((fenilamino) karbonil)-1H-pirol-1-heptanoična kiselina, hemi kalcijumova so, poznat je kao inhibitor HMG-CoA reduktaze i koristi se kao antihiper-holesterolemijski agens. Atorvastatin u farmaceutskim smešama, raspoloživim na tržištu, uglavnom se priprema u vidu svoje kalcijumove soli, s obzirom na to da ona omogućava da atorvastatin bude pogodno formulisan u farmaceutskim formulacijama, na primer, u tabletama, kapsulama, praškovima i sličnim formulacijama za oralnu primenu. Atorvastatin kalcijum može postojati u amorfnom obliku ili u jednom od najmanje četiri poznata kristalna oblika (Oblik I, Oblik II, Oblik III i Oblik IV). Atorvastatin kalcijum je supstanca, koja je umereno slabo rastvorljiva u vodi, sa pKa 4,5, a utvrđeno je da su kristalni oblici manje rastvorljivi od amorfnog oblika, što može izazvati probleme u bioraspoloživosti atorvastatina u organizmu. Ovaj pronalazak razrešava problem obezbeđivanja terapeutske ekvivalentnosti farmaceutske formulacije atorvastatina, bez obzira na oblik (kristalni, amorfni ili smeša jednog i drugog) atorvastatin