Abstract: Non-crystalline, in particular amorphous, pharmaceutically acceptable atorvastatin salts, especially the calcium salt, are prepared from atorvastatin lactone or from a compound of formula (I) where A denotes a common protecting group or separate protecting groups for the two hydroxy groups, and B denotes a carboxylic acid protecting group, without the need of prior formation of atorvastatin lactone, the crystalline form of the atorvastatin salt, or a mixture of amorphous and crystalline forms of the atorvastatin salt. Pharmaceutical formulations are prepared from these salts.

Abstract: Atorvastatin calcium, the substance known by the chemical name (R—(R*,R*))-2-(4-fluorophenyl)-?, ?-dihydroxy-5-(1-methylethyl)-3-phenyl-((phenylamino)carbonyl)-1H-pyrrole-1-heptanoic acid hemi calcium salt is known as HMG-CoA reductase inhibitor and is used as an antihypercholesterolemic agent. Atorvastatin in the pharmaceutical compositions available in the market, is usually prepared as its calcium salt since it enables atorvastatin to be conveniently formulated in the pharmaceutical formulations, for example, in tablets, capsules, powders and the like for oral administration. Atorvastatin calcium can exist in an amorphous form or in one of the at least four known crystalline forms (Form I, Form II, Form III and Form IV). Atorvastatin calcium is the substance which is sparingly soluble in water, with pKa 4,5, and it has been found that the crystalline forms are less soluble than the amorphous form, which may cause problems in bioavailability of atorvastatin in the body.

Abstract: The present invention relates to a novel solid pharmaceutical formulation containing lovastatin and simvastatin, respectively, with a particle size D(0.9) between 15 and 100 ?m and a specific particle surface area between 1 and 4 m2/g, and to the process for its preparation. The present invention also relates to the method for production of lovastatin and simvastatin with the size of crystals which are suitable for the preparation of the pharmaceutical formulation of the present invention. The novel solid pharmaceutical formulation is useful for treating hypercholesterolemia and hyperlipidemia.

Abstract: Atorvastatin, the substance known by the chemical name [R-(R*,R*)]-2-(4-fluorophenyl)-?,? dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid hemi calcium salt, is readily available in one of its crystalline forms as it is known from the prior art. The present invention relates to a novel process for preparing atorvastatin in an amorphous form by precipitating the atorvastatin using a solvent of a second type from a solution of atorvastatin which is provided with a solvent of a first type. This process is useful for the conversion of atorvastatin in a crystalline form into atorvastatin in an amorphous form.

Abstract: Lovastatin, pravastatin, simvastatin, mevastatin, atorvastatin, and derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus, some are obtained by treating the fermentation products using the methods of chemical synthesis or they are the products of total chemical synthesis.

Abstract: A process for the isolation and purification of HMG-CoA reductase inhibitors from a mycelium biomass is described, which process comprises: clarifying a mycelium broth and concentrating the clarified broth to a lower volume, acidifying of the concentrate to a pH value in the range of 4.5 to 7.5, followed by extracting the HMG-CoA reductase inhibitor with ethyl acetate, crystallization of the HMG-CoA reductase inhibitor from a water-miscible or water-soluble organic solvent, and crystallization of the HMG-CoA reductase inhibitor from an organic solvent having limited miscibility or solubility with water. The crystallization steps may also be reverse. The concept of a combination of the specified crystallization steps can also be used for the purification of a crude HMG-CoA reductase inhibitor.

Abstract: Lovastatin, pravastatin, simvastatin, mevastatin, atorvastatin, and derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus, and some are obtained by treating the fermentation products using the methods of chemical synthesis or they are the products of total chemical synthesis. The aforementioned active substances may be destabilized by the environmental factors, their degradation may also be accelerated by interactions with other pharmaceutical ingredients, such as fillers, binders, lubricants, glidants and disintegrating agents, therefore the pharmaceutical ingredients and the process for preparation of the pharmaceutical formulation should be meticulously chosen to avoid the aforementioned undesired interactions and reactions.

Abstract: The present invention relates to a novel solid pharmaceutical formulation containing lovastatin and simvastatin, respectively, with a particle size D(0.9) between 15 and 100 &mgr;m and a specific particle surface area between 1 and 4 m2/g, and to the process for its preparation. The present invention also relates to the method for production of lovastatin and simvastatin with the size of crystals which are suitable for the preparation of the pharmaceutical formulation of the present invention. The novel solid pharmaceutical formulation is useful for treating hypercholesterolemia and hyperlipidemia.

Abstract: Non-crystalline, in particular amorphous, pharmaceutically acceptable atorvastatin salts, especially the calcium salt, are prepared from atorvastatin lactone or from a compound of formula (I) where A denotes a common protecting group or separate protecting groups for the two hydroxy groups, and B denotes a carboxylic acid protecting group, without the need of prior formation of atorvastatin lactone, the crystalline form of the atorvastatin salt, or a mixture of amorphous and crystalline forms of the atorvastatin salt. Pharmaceutical formulations are prepared from these salts.

Abstract: A crystalline form of the sodium salt of pravastatin, which is known by the chemical name 1-naphthaleneheptanoic acid, 1,2,6,7,8,8a-hexahydro-&bgr;, &dgr;,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-, mono sodium salt, which is useful as a pharmaceutical substance. A method for its preparation and isolation, a pharmaceutical formulation containing the sodium salt of pravastatin in the crystalline form and a pharmaceutically acceptable carrier, and the pharmaceutical method of treatment are also disclosed.

Abstract: Non-crystalline, in particular amorphous, pharmaceutically acceptable atorvastatin salts, especially the calcium salt, are prepared from atorvastatin lactone or from a compound of formula (I) 1

Abstract: Lovastatin, pravastatin, simvastatin, mevastatin, atorvastatin, and derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as and antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergilus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicilium genus, some are obtained by treating the fermentation products using the method of chemical synthesis or they are the products of total chemical synthesis. The purity of the active ingredient is an important factor for manufacturing the safe and effective pharmaceutical, especially if the pharmaceutical product must be taken on a longer term basis in the treatment or prevention of high plasma cholesterol. The accumulation of the impurities from the pharmaceuticals of lower purity may cause many side effects during the medical treatment.

Abstract: The present invention relates to a novel solid pharmaceutical formulation containing lovastatin and simvastatin, respectively, with a particle size D(0.9) between 15 and 100 &mgr;m and a specific particle surface area between 1 and 4 m2/g, and to the process for its preparation. The present invention also relates to the method for production of lovastatin and simvastatin with the size of crystals which are suitable for the preparation of the pharmaceutical formulation of the present invention. The novel solid pharmaceutical formulation is useful for treating hypercholesterolemia and hyperlipidemia.

Abstract: Atorvastatin and pravastatin may be destabilized by the environmental factors, their degradation may also be accelerated by interactions with other pharmaceutical ingredients, such as fillers, binders, lubricants, glidants and disintegrating agents, therefore the pharmaceutical ingredients and the process for preparation of the pharmaceutical formulation should be meticulously chosen to avoid the aforementioned undesired interactions and reactions. The present invention relates to a stable solid pharmaceutical formulation for the treatment of hypercholesterolemia and hyperlipidemia. More precisely, the present invention relates to the new stable solid pharmaceutical formulation containing as an active ingredient, an HMG-CoA reductase inhibitor, such as atorvastatin and pravastatin and pharmaceutically acceptable salts thereof.

Abstract: There is disclosed a method for stabilizing active substances that are unstable in acidic medium, unstable when stored for longer periods of time in the presence of water and at the same time sensitive to heating, by means of anhydrous granulation of active substances and dried pharmaceutically acceptable auxiliary substances for the preparation of pellet cores or granules. All pharmaceutically acceptable auxiliary substances employed are dried before use so that their weight loss at drying is less than 1.0% of the total weight of the pharmaceutically acceptable auxiliary substance, preferably less than 0.5%. Organic solvents used in process of anhydrous granulation should contain less than 0.2% of water. A novel pharmaceutical formulation with controlled release of active substances that are unstable in acidic medium, unstable when stored for longer periods of time in the presence of water and at the same time sensitive to heating, is disclosed as well.

Abstract: Atorvastatin, the substance known by the chemical name [R-(R*,R*)]-2-(4-fluorophenyl)-&bgr;,&dgr;-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid hemi calcium salt, is readily available in one of its crystalline forms as it is known from the prior art. The present invention relates to a novel process for preparing atorvastatin in an amorphous form by precipitating the atorvastatin using a solvent of a second type from a solution of atorvastatin which is provided with a solvent of a first type. This process is useful for the conversion of atorvastatin in a crystalline form into atorvastatin in an amorphous form.

Abstract: Lovastatin, pravastatin, simvastatin, mevastatin, atorvastatin, and derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus, some are obtained by treating the fermentation products using the methods of chemical synthesis or they are the products of total chemical synthesis.

Abstract: Lovastatin, pravastatin, simvastatin, mevastatin, atorvastatin, and derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus, some are obtained by treating the fermentation products using the methods of chemical synthesis or they are the products of total chemical synthesis.

Abstract: There is disclosed a method for stabilizing active substances that are unstable in acidic medium, unstable when stored for longer periods of time in the presence of water and at the same time sensitive to heating, by means of anhydrous granulation of active substances and dried pharmaceutically acceptable auxiliary substances for the preparation of pellet cores or granules. All pharmaceutically acceptable auxiliary substances employed are dried before use so that their weight loss at drying is less than 1.0% of the total weight of the pharmaceutically acceptable auxiliary substance, preferably less than 0.5%. Organic solvents used in process of anhydrous granulation should contain less than 0.2% of water. A novel pharmaceutical formulation with controlled release of active substances that are unstable in acidic medium, unstable when stored for longer periods of time in the presence of water and at the same time sensitive to heating, is disclosed as well.

Abstract: A process for the isolation of clavulanic acid and pharmaceutically acceptable salts thereof, such as potassium clavulanate, from the aqueous fermentation broth of a clavulanic acid-producing microorganism comprises the microfiltration of the broth without prior treatment.