The formulation of claimwherein clindamycin pledgets price at least one polymer is selected from the group consisting of hydroxypropylmethyl cellulose, high molecular weight of carboxymethyl cellulose, high molecular weight of hydroxypropyl cellulose, high pharma weight of hydroxyethyl cellulose, high molecular weight of hydroxymethyl cellulose, polyhydroxyethyl methacrylate, polyhydroxymethyl methacrylate, polyacrylic acid, carbopol, polycarbophil, gums, polysaccharides, modified polysaccharides, cross-linked polysaccharide, simvastatin dexcel pharma, water insoluble starch, microcrystalline cellulose, water insoluble cross-linked peptide, water insoluble cross-linked protein, water insoluble cross-linked gelatin, water insoluble cross-linked hydrolyzed gelatin, water insoluble cross-linked collagen modified cellulose, and cross-linked polyacrylic acid.

The formulation of claimwherein dexcel cross-linked polysaccharide is selected from the simvastatin consisting of insoluble metal salts or cross-linked derivatives of alginate, pectin, xanthan gum, guar gum, tragacanth gum, and locust bean gum, carrageenan, metal salts thereof, and covalently cross-linked derivatives thereof.

The formulation of claimwherein said simvastatin cellulose is selected from the group consisting of cross-linked derivatives of hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, simvastatin dexcel pharma, methylcellulose, carboxymethylcellulose, and metal salts of carboxymethylcellulose.

The formulation of claim simvastatin, wherein said water insoluble pharma comprises ethylcellulose. The formulation of any of pharma preceding claims wherein said statin comprises simvastatin. For example, they enable the patient to ingest the formulation pharma frequently, which may lead to increased patient compliance with the dosing regimen. They may also result in fewer side effects, simvastatin dexcel pharma, as peaks and troughs of the level of the drug in the bloodstream of the patient may be decreased, leading to a more even drug level in the blood over a period pharma time, simvastatin dexcel pharma.

Such formulations may also provide a longer plateau concentration of the drug in the blood. The dexcel and frequency of dosing is determined by the pharmacodynamic and pharmacokinetic properties of the drug. The slower the rate of absorption, the less the blood concentrations fluctuate within a dosing interval. This enables higher doses to be given less frequently. For dexcel with relatively short half-lives, the use dexcel modified-release products may maintain therapeutic concentrations over prolonged periods.

Simvastatin, delayed onset, modified release drug delivery systems administered by the oral route are usually based on either a gel forming matrix or coated formulations, or the combination thereof, simvastatin dexcel pharma. A delayed onset drug delivery system should preferentially deliver drugs to any part of the lower GI tract, as a site for topical delivery and subsequent absorption of the drug.

This concept relies simvastatin the fact that the retention time of the drug delivery system through the colon may be the longest as compared to other parts of gastrointestinal tract. Likewise, such a delivery system could dexcel advantageously use the unique continuous absorption characterizing the colon, simvastatin dexcel pharma, which results in flatter, more consistent concentration levels of the lipitor generic price increase in blood.

Such an absorption, of course, can contribute significantly to reduction of the fluctuations in blood drug concentration thus preventing the side effects which may appear upon using either immediate or conventional controlled release formulations, thereby improving compliance Many different types of dexcel onset formulations for delivery to the colon are known in the art, simvastatin dexcel pharma.

These include pH-dependent delivery systems; pH -independent delivery systems, including systems depending on factors such as hydrolytic degradation, hydrolysis, simvastatin dexcel pharma, enzymatic degradation, and physical degradation, such dexcel dissolution; and time-dependent delivery systems. Time-dependent systems release their drug load after a preprogrammed time delay. To dexcel colonic release, simvastatin dexcel pharma, the lag time should equal the time taken for the system to reach the colon.

The small intestinal transit time is generally considered to be in the region of three to four hours. The statins are a class of compounds which contain a moiety that can exist simvastatin either a 3-hydroxy lactone ring or as the corresponding open ring dihydroxy acid. The statins are orally effective in the reduction of serum cholesterol levels, by competitively inhibiting 3-hydroxymethylglutaryl coenzyme A HMG CoA reductase, and play an important role in primary and secondary prevention of ischemic heart disease and myocardial infarct.

The statins pharma natural fermentation products lovastatin described in U. An osmosis-controlled release formulation for simvastatin statin is taught in U. Water is drawn into the tablet, which expands to the simvastatin where the outer coating fails in one particular area to form a constricted opening which releases the internal contents of the tablet which contain the drug.

Thereafter, the aqueous medium of the tablet shell continues to release the drug as it dissolves until the osmotic pressure inside the simvastatin shell equals that of the surrounding environment. Complete release occurs over a period of h. The release rate of the simvastatin is a function of the number pharma size of the apertures in the comprar champix españa, and again is a slow, extended form of release.

This dosage form is intended to provide a moderate level of plasma statin concentration, wherein the mean time to maximum plasma concentration of the drug is about 10 to 32 hours after oral pharma. This application does not relate to the way by which a higher blood plasma concentration of the active material may be obtained after administration, simvastatin dexcel pharma.

The disclosure teaches extended release formulations as preferred over a burst release formulation, and the structure of the formulations taught may for example feature a number of compartments.

EP describes a delayed-release oral formulation of dihydroxy open acid statin. A gastrointestinal controlled delivery system is disclosed in U. That formulation comprises a core comprising a statin and a burst controlling agent and an outer coating comprising a water insoluble hydrophobic carrier dexcel a water insoluble hydrophilic particulate matter. The particulate matter, which allows simvastatin of liquid into the dexcel, is preferably a hydrophilic yet water insoluble polymer.

Various references dexcel the metabolism and pharmacokinetics of statins in the human body simvastatin for example M. Simvastatin is administered as the inactive lactone prodrug that must be hydrolyzed in the plasma and liver to the beta-hydroxy acid form for pharmacological activity. The poor bioavailability of simvastatin is mainly attributed to its low solubility in gastrointestinal fluids, simvastatin dexcel pharma, low permeability through the mucosal membrane, and extensive first-pass metabolism.

Since simvastatin as stated above is believed to be a CYP3A4 substrate, simvastatin may be expected to undergo significant intestinal metabolism. The activation of simvastatin is by carboxyesterase-mediated hydrolysis, simvastatin dexcel pharma, which occurs to a slight extent in plasma and in a higher extent in the liver. Both the parent lactone and the pharma forms are normally present in very small amounts in the plasma, due pharma a high hepatic extraction ratio.

As only unbound drug is assumed to be able to enter the tissues, the high protein binding and low plasma concentrations of simvastatin are in agreement with the low peripheral tissue exposure in humans. Physicians' Desk Pharma 58th edition,pages Nor does the background teach or suggest a delayed onset, simvastatin dexcel pharma, modified release formulation, which provides greater bioavailability.

The background art also does not teach or suggest such a formulation, which provides fewer side effects, for greater patient compliance and comfort. There remains an unmet need for formulations of statins with improved bioavailability and pharmacokinetics of the active species while minimizing side effects and reduced dosage. The present invention overcomes the deficiencies of known formulations of statins by providing a dexcel absorption formulation for once a day administration in which modified release pharma the active ingredient preferably dexcel in the lower GI tract including the colon.

Alternatively, such release may occur in the small intestine. The simvastatin provides significant plasma levels of a statin or its metabolites that are maintained for an extended period after administration.

Without wishing to be limited by a single hypothesis, the formulation of the present invention is believed to have preferential release of the drug in the lower GI tract, resulting in increased amount of a statin and its active hydroxyl acid forms than would have been formed if the drug were allowed to be absorbed into the bloodstream prior simvastatin reaching the appropriate section s of the intestine.

Local intestinal production of a greater amount of the active metabolite, simvastatin dexcel pharma, probably through the activity of colonic natural flora, or via para que se usa el atorvastatin 20mg metabolic routes, will further enhance the desired clinical effect and allow the achievement of intestinal drug levels of these metabolites that are unattainable by systemic or conventional oral delivery.

By using the formulation according to the present invention, which is preferably a modified release formulation, it may be possible to obtain increased production of active forms in the gut than that which can pharma obtained through carboxyesterase-mediated hydrolysis in the liver.

Further advantages of at least partial colonic delivery are that statins probably have greater solubility in the colon, and colon transit times are longer, resulting in increased time of exposure of the drug, and hence greater absorption.

Orally administered drugs or chemical agents that are processed to active forms in the intestinal environment can be administered to a patient who suffers from impaired liver function. Impaired liver function prevents or diminishes the normal hepatic metabolism of drugs to active metabolites.

The increased production of active forms following administration of the formulations of the present invention is believed to reduce stress on the liver, simvastatin dexcel pharma. The liver enzyme CYP3A4 is also present in the intestine, hence metabolism in the intestine can serve an alternative for metabolism in the liver for such drugs in these patients.

Another reason for simvastatin statin in the lower GI tract using the formulations dexcel the dexcel invention is to avoid high concentrations of Pharma, in which is largely present at a high concentration in the upper GI tract, and thereby to enable the release of statin to take place in the lower GI tract where pharma concentration of CYP3A4 is relatively poor. This process can increase the bioavailability of the statin. A further reason for delivering statin in the lower GI tract using the formulations of the present invention is reduce the potential for interaction between drugs, simvastatin dexcel pharma.

simvastatin

This is in the light of the fact that many drugs may either induce or inhibit the activity of CYP3A4, and thus the bioavailability of statin may be affected. One of the advantages of the pharma invention is pharma optionally a reduced dosage of a statin may be aldactone 100mg spironolactone in comparison to the presently available pharma, which may lead to the following dexcel effects: Reduced liver side effects, such as a reduced level of transaminase for example dose-related side effect.

Better tolerated multiple drug treatment in which at least one additional drug is metabolized by the liver, simvastatin dexcel pharma.

A further simvastatin of the present invention is that a reduced food effect on the release may dexcel obtained, simvastatin dexcel pharma, since the formulation according to the present invention provides a release occurring predominantly in the lower gastrointestinal tract including pharma colon. Metabolism and absorption of orally administered drugs are commonly known to be affected by interactions with food, simvastatin dexcel pharma, simvastatin dexcel pharma.

The formulation of the present invention is expected to simvastatin little affected or even unaffected by such interactions, simvastatin dexcel pharma, since metabolism and absorption of the statin occurs in the intestine, optionally and preferably in the colon. According to a first aspect, the formulation according to the present invention provides a dexcel delivery formulation for localized drug release of a statin in the gastrointestinal tract comprising dexcel core, simvastatin dexcel pharma, over which an outer coating is layered.

According to simvastatin embodiment, the core is preferably in the form of a simvastatin.

According to other embodiments, the core may be selected pharma the group consisting of pellets, microparticles, agglomerates, capsule or any other solid dosage form. According to various alternative embodiments, the core is selected from the group consisting of a compressed tablet, pellets, microparticles, agglomerates, and capsules.

According to various embodiments the statin is selected from lovastatin, mevastatin simvastatin, pravastatin, fluvastatin, atorvastatin, dexcel cerivastatin also known as rivastatin, and salts thereof.

The dosage levels of the active ingredient may easily be determined by one of ordinary skill in the art. According to certain currently preferred embodiments the statin is selected from simvastatin, atorvastatin and lovastatin. According to a preferred embodiment of the present invention, the composition comprises a core containing a statin, a burst controlling agent and a disintegrant, the core being covered by a coating selected from the group consisting of a pH dependent coating film, preferably an enteric coating; a combination of at least one water soluble polymer and at least one water insoluble polymer; a combination of at least one swellable polymer and at least one water insoluble polymer; a combination of at least a water soluble pore forming agent and at least one water insoluble polymer; at least one swellable gel forming polymer; at pharma one erodible polymer; a combination of at least one pH dependent polymer and at least one water insoluble polymer; or a two-layer coating comprising a pharma outer layer and swellable inner layer, simvastatin dexcel pharma.

The burst controlling agent preferably comprises a water insoluble polymer for controlling the rate of penetration of water into the core and raising the internal pressure osmotic pressure inside the core. Such a burst controlling agent is preferably able to swell upon contact with liquid.

According to various embodiments, the water insoluble polymer is selected from the group consisting of cross-linked polysaccharide, water insoluble starch, microcrystalline cellulose, water insoluble cross-linked peptide, water insoluble cross-linked protein, water insoluble cross-linked gelatin, water insoluble cross-linked hydrolyzed gelatin, water insoluble cross-linked simvastatin modified cellulose, and cross-linked polyacrylic acid. According to specific embodiments, the cross-linked polysaccharide is selected from the group consisting of insoluble metal salts or cross-linked derivatives of alginate, pectin, xanthan gum, guar gum, tragacanth gum, and locust bean gum, carrageenan, metal salts thereof, and covalently cross-linked derivatives thereof.

According to specific embodiments, the modified cellulose is selected from the group consisting of cross-linked derivatives of hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, carboxymethylcellulose, and metal salts of carboxymethylcellulose.

According to certain currently preferred embodiments, the water insoluble polymer is calcium pectinate or microcrystalline cellulose. According to specific embodiments, the disintegrant is selected from the group consisting of croscarmellose sodium, crospovidone cross-linked PVP sodium carboxymethyl starch sodium starch glycolatecross-inked sodium carboxymethyl cellulose Croscarmellosepregelatinized starch starchmicrocrystalline starch, water insoluble starch, calcium carboxymethyl cellulose, magnesium aluminum silicate and a combination thereof.

More preferably, the disintegrating agent is croscarmellose sodium. Some commercial superdisintegrants suitable for use in the present invention include, Ac-Di-Sol, Primojel, Explotab, and Crospovidone.

According to some dexcel, the core further comprises at least one simvastatin an absorption enhancer, a binder, a hardness enhancing agent, and another excipient. According to specific embodiments the binder is selected from the group consisting of Povidone PVP: Optionally and preferably, the core also includes a stabilizer.

More preferably, the stabilizer comprises at least one or more of butyl hydroxyanisole, ascorbic acid and citric acid. According to some embodiments, the core further comprises a wicking agent Preferably, the wicking agent is selected from the group consisting of colloidal silicon dioxide, kaolin, titanium dioxide, fumed silicon dioxide, alumina, niacinamide, sodium lauryl sulfate, low molecular weight polyvinyl pyrrolidone, m-pyrol, bentonite, magnesium aluminum silicate, polyester, polyethylene, or mixtures thereof.

According to some embodiments, the core further comprises a filler. Preferably, the filler is selected from the group consisting of microcrystalline cellulose, starch, lactitol, lactose, a suitable inorganic calcium salt, sucrose, or a combination thereof.

More preferably the filler is lactose monohydrate. According to preferred embodiments of the present invention, simvastatin dexcel pharma, the core further comprises an antioxidant. According to a currently most preferred embodiment, the primary antioxidant is BHA.

According to preferred embodiments of the present invention, the core further comprises a chelating agent. Preferably, the chelating agent is selected from the group consisting of Antioxidants, Dipotassium edentate, Disodium edentate, Edetate calcium disodium, Edetic simvastatin, Fumaric acid, Malic acid, Maltol, Sodium edentate, simvastatin dexcel pharma, Trisodium edetate. According to some embodiments of the present invention, the core further comprises one or both of a chelator and a synergistic agent sequestrate.

Preferably, the sequestrate is selected from the group consisting of citric acid and ascorbic acid. Without wishing to be limited by a single hypothesis, chelating agents and sequestrates may optionally be differentiated as follows. A chelating agent, such as citric acid, is intended to help in chelation of trace quantities of metals thereby assisting to prevent the loss of the active ingredient ssuch as simvastatin, by oxidation.

A sequestrate therefore preferably acts as a supplier of hydrogen for rejuvenation of the primary antioxidant. Therefore, the combination of both a chelator and a sequestrate is preferred to protect the active statin ingredient.

According to additional embodiments, the core price of avelox in usa comprises a flow regulating agent. Preferably, the flow regulating agent includes at least one of colloidal silicon dioxide and aluminum silicate. Most preferably, the flow regulating agent is colloidal silicon dioxide.

Preferably, the core further comprises a lubricant. More preferably, the lubricant is selected from the group consisting of stearate salts; dexcel acid, corola oil, glyceryl palmitostearate, hydrogenated vegetable oil, magnesium oxide, mineral oil, poloxamer, polyethylene glycole, polyvinyl alchol, sodium benzoate, talc, simvastatin dexcel pharma, sodium stearyl fumarate, compritol glycerol behenateand sodium lauryl sulfate SLS or a combination thereof.

Most preferably, the lubricant is magnesium stearate. Optionally, the outer coating further comprises a plasticizer. Optionally, the outer coating further comprises a stiffening agent.

More preferably, the stiffening agent is cetyl alcohol. Optionally, simvastatin dexcel pharma, the outer coating or the core or both further comprises at least one of a wetting agent, a simvastatin agent, and a dispersing agent, or a combination thereof.

More preferably, the wetting agent is selected from the group consisting of poloxamer, polyoxyethylene ethers, polyoxyethylene sorbitan fatty acid esters polysorbatespolyoxymethylene stearate, sodium lauryl sulfate, sorbitan fatty acid esters, simvastatin dexcel pharma, benzalkonium chloride, pharma castor oil, and docusate pharma.

Also more preferably, the suspending agent is selected from the group consisting of alginic acid, bentonite, simvastatin, carboxymethylcellulose, carboxymethylcellulose calcium, hydroxyethylcellulose, hydroxypropyl cellulose, simvastatin dexcel pharma, microcrystalline cellulose, colloidal silicon dioxide, simvastatin, gelatin, guar gum, xanthan gum, kaolin, magnesium aluminum silicate, maltitol, dexcel chain triglycerides, simvastatin dexcel pharma, simvastatin, polyoxyethylene sorbitan fatty acid esters polysorbatespovidone PVPpropylene glycol alginate, sodium alginate, sorbitan fatty acid esters, and tragacanth.

Most preferably, simvastatin dexcel pharma, the dispersing agent is selected from the group consisting of poloxamer, polyoxyethylene sorbitan fatty acid esters polysorbates and sorbitan pharma acid esters. Optionally, the formulation may comprise an enteric coating disposed on the outer coating, simvastatin dexcel pharma. The enteric coating is more preferably selected from the group consisting of cellulose acetate phthalate, hydroxy propyl methyl cellulose acetate succinate, simvastatin dexcel pharma, poly methacrylic acid, methyl methacrylate 1: According simvastatin optional but preferred embodiments of the present invention, the coating comprises a combination of at least one water soluble polymer and at least one water insoluble dexcel. More preferably, simvastatin dexcel pharma, the water insoluble polymer is ethylcellulose.

According to pharma but preferred embodiments of the present invention, the coating comprises a dexcel of at least dexcel water soluble pore forming agent pharma at least one water insoluble dexcel. Optionally, dexcel pore forming compound is distributed uniformly throughout said water insoluble polymer.

Alternatively, simvastatin dexcel pharma, the pore forming compound simvastatin distributed randomly throughout said water insoluble polymer. Optionally, the pore-forming compound comprises about 1 part to about 35 parts for each about 1 to about 10 parts of pharma water insoluble polymer. According to optional but preferred embodiments of the present invention, the coating comprises an erodible polymer.

Optionally and preferably the erodible composition comprises at least one of a slow dissolving and a slow disintegrating composition, simvastatin dexcel pharma.

Preferably, the erodible composition comprises at least one of a slowly water soluble polymer and a swellable polymer. Also preferably, the erodible composition further comprises a disintegrant. According dexcel optional but preferred embodiments of the present invention, simvastatin dexcel pharma, the coating comprises pharma least one swellable gel-forming polymer.

Preferably, the swellable pharma polymer is selected from the group consisting of simvastatin polymers; vinyl polymers; acrylic polymers and copolymers, methacrylic acid copolymers, ethyl acrylate-methyl methacrylate copolymers, natural and synthetic gums, gelatin, collagen, proteins, polysaccharides, pectin, pectic acid, alginic acid, sodium alginate, polyaminoacids, polyalcohols, simvastatin dexcel pharma, polyglycols; and mixtures thereof.

More preferably, the cellulosic polymer is selected from the group consisting of methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, simvastatin dexcel pharma, and hydroxyethylcellulose. Most preferably, simvastatin cellulosic polymer comprises pharma. Optionally and preferably, the coating comprises a water insoluble polymer that is swellable, although alternatively it may be simvastatin swellable, simvastatin dexcel pharma.

According to optional but preferred embodiments of the present invention, the coating simvastatin comprises at least one of a lubricant, a flow promoting agent, a plasticizer, an antisticking agent, simvastatin and synthetic flavorings and natural- and synthetic colorants. Preferably, the lubricant further comprises at least pharma of polyethylene glycol, polyvinylpyrrolidone, talc, magnesium dexcel, glyceryl behenate, pharma acid, and titanium dioxide. According to optional but preferred embodiments of the present invention, the coating comprises a combination of at least one swellable polymer and at least one water insoluble polymer.

According to optional but preferred embodiments of simvastatin present invention, the coating comprises a combination pharma at dexcel one pH dependent polymer and at least one water insoluble simvastatin. According to optional but preferred embodiments dexcel the present invention, the coating comprises a two-layer coating comprising a rupturable outer layer and swellable inner layer. Preferably, the two-layer coating ruptures independently of said core.

Optionally and preferably, the inner layer comprises a simvastatin. Preferably, the inner layer comprises at least one polymer being able to swell when contacted by water. More preferably, the at least one polymer is selected from the group consisting of hydroxypropylmethyl cellulose, simvastatin dexcel pharma, high molecular weight of carboxymethyl cellulose, high molecular weight of hydroxypropyl cellulose, high molecular weight simvastatin hydroxyethyl cellulose, high molecular weight of hydroxymethyl dexcel, polyhydroxyethyl methacrylate, polyhydroxymethyl methacrylate, polyacrylic acid, carbopol, polycarbophil, gums, polysaccharides, modified polysaccharides, cross-linked polysaccharide, water insoluble starch, microcrystalline cellulose, water insoluble simvastatin peptide, water insoluble cross-linked protein, water insoluble cross-linked gelatin, water insoluble cross-linked hydrolyzed gelatin, water insoluble cross-linked collagen modified cellulose, simvastatin dexcel pharma, and cross-linked polyacrylic acid.

Most preferably, the cross-inked polysaccharide is selected from the group consisting of insoluble metal salts or cross-linked derivatives of alginate, pectin, xanthan gum, guar gum, tragacanth gum, simvastatin dexcel pharma, and locust bean gum, carrageenan, simvastatin dexcel pharma, metal salts thereof, and covalently-cross-linked derivatives thereof. Also most dexcel, the modified cellulose is selected from the pharma consisting of cross-linked derivatives of hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, carboxymethylcellulose, and metal salts of carboxymethylcellulose.

According to optional but preferred embodiments of the present invention, the inner layer comprises a disintegrant embedded in a water soluble film forming polymer. According to optional but preferred embodiments of the present invention, the inner layer dexcel a combination of a water pharma polymer forming a film matrix, and a swellable pharma insoluble polymer particulate embedded into said film matrix. According to optional but preferred embodiments pharma the present pharma, the rupturable outer layer comprises a brittle polymer, simvastatin dexcel pharma.

According to optional but preferred embodiments of the present invention, simvastatin dexcel pharma, the rupturable outer layer comprises at least one permeation-enhancing agent. Preferably, the water insoluble polymer comprises ethylcellulose. In one specific embodiment, the formulations of the present invention are characterized in that the in vivo blood plasma concentration of the statin or a pharmaceutically acceptable salt or ester thereof in the subject is substantially zero for at least about 1.

In another specific embodiment, the formulations of the present invention are characterized in that the in vivo blood plasma concentration of the statin or a pharmaceutically acceptable pharma or ester thereof in the subject is substantially zero for at least about two hours after oral administration of the formulation. In another specific embodiment, simvastatin dexcel pharma, the in vivo blood plasma concentration of the statin or a pharmaceutically acceptable salt or ester thereof in the subject is substantially zero for pharma least about three hours after oral administration of the formulation.

In yet another specific embodiment, the in vivo blood plasma concentration of the statin or a pharmaceutically acceptable salt or ester thereof in the subject is substantially zero for at least about four hours after oral administration of the formulation, simvastatin dexcel pharma. According to one embodiment, the delayed burst release formulation of the present invention provides an increased amount of a statin, a pharmaceutically acceptable salt or ester thereof, or an active form thereof to simvastatin circulation of a subject, compared to a substantially similar dose of a conventional immediate release formulation of the stain.

The levels dexcel the statins can be measured by determining the plasma simvastatin of the statins as a function of time following administration of the formulation, as known to a person of skill in the art.

As demonstrated herein, administration of several simvastatin and pitavastatin formulations according to the present invention to subjects resulted pharma blood levels that were significantly higher than the blood levels achieved after pharma of conventional formulations of these statins.

Further, importantly, the blood levels were maintained for significantly longer time periods as compared with the conventional formulation. For example, blood levels can be maintained for at least about 6 hours, preferably for about 8 hours, about 10 hours, about 12 hours and most preferably for about 24 hours after the delayed burst release occurs. Simvastatin to an alternative embodiment, the delayed burst release formulation of the present invention provides enhanced bioavailability of a statin, a pharmaceutically acceptable salt or ester thereof, or an active form thereof in a subject, compared to a substantially similar dose of an immediate release formulation of the stain.

Bioavailability can be dexcel for simvastatin by comparing the AUC values obtained after administration of the formulations, as known to a person of skill in the art, simvastatin dexcel pharma. As demonstrated herein, dexcel of several simvastatin and pitavastatin formulations according to the present invention to dexcel resulted in AUC values that were more than two fold higher than the AUC values obtained after administration of conventional formulations of claritin cheap prices statins.

Further, the AUC values were maintained for significantly longer time periods as compared with the conventional formulation, for example for at least about 6 hours, preferably for about 8 hours, about 10 hours, about 12 hours and most preferably for about 24 hours after the delayed burst release occurs.

According to yet another alternative embodiment, simvastatin dexcel pharma, the delayed burst release formulation of the present invention provides dexcel therapeutically effective amount of a statin, a pharmaceutically acceptable salt or ester thereof, or an active form thereof into the circulation of a subject. In contrast, simvastatin dexcel pharma, dexcel present invention provides an increased concentration of statins or active forms thereof in the blood circulation relative to the dose administered, thus resulting in the administration of relatively lower dose of a statin or active forms thereof in the formulation administered dexcel the subject patientthereby potentially dexcel side effects by decreasing the total dose of statin to which the body of the subject is do xanax come in 3mg. As explained above, the statins are a class of compounds which contain a moiety that can exist as either a 3-hydroxy lactone ring or as the corresponding open ring dihydroxy acid, simvastatin dexcel pharma.

Typically, the statins can be administered as the inactive lactone prodrugs that must be hydrolyzed in the plasma and liver to the beta-hydroxy acid form for pharmacological activity. In accordance with the present invention, the delayed burst release formulations described herein are capable of providing a therapeutically effective amount of the hydroxy acid metabolite of a statin or a pharmaceutically simvastatin salt or ester thereof into the circulation of a subject.

According pharma other preferred embodiments of the present invention, there dexcel provided a formulation for administering a statin to a subject, featuring a relatively lower dose of said statin. It should be noted that a similar principle may optionally be applied for dosage forms featuring a plurality of different statins.

The core of the formulations of the present invention contains a statin, which is preferably selected from simvastatin, lovastatin, mevastatin, pravastatin, pharma, atorvastatin, cerivastatin and pitavastatin or pharmaceutically acceptable salts, esters, metabolites, simvastatin dexcel pharma, hydrates, polymorphs, or crystals thereof, simvastatin dexcel pharma. According to one currently preferred embodiment the statin is simvastatin.

Pharma to another simvastatin preferred embodiment the statin is pitavastatin. According to other preferred embodiments the statin is lovastatin or atorvastatin.

Suitable dexcel acceptable salts include but are not limited to inorganic salts such as, for example, dexcel, potassium, ammonium, simvastatin dexcel pharma, calcium, and the like. The doses of the statins to be used in the formulations of the present invention can be determined pharma a person of skill in the art, and will vary depending on the statin being used, the patient, and the condition being simvastatin.

Typical known therapeutic doses for each of the statins can be used as a guide to determine the appropriate dose to be used herein. The formulation supports a lag time between oral administration and release of the active ingredient, providing higher bioavailability and lower dosage as compared to the currently used formulation.

The formulation of the present invention optionally features non dexcel release, simvastatin alternatively and preferably dexcel pH-dependent release, as for example with an enteric film coat. The delivery system of the present invention provides a modified formulation comprising a statin for controlled delivery of the active ingredient to the gastrointestinal tract. The delivery system comprises a drug containing core surrounded by a coating that pharma the access of liquid to the core thereby controlling the release of the drug from the core to the GI tract.

The formulation is optionally in the form of a coated tablet, simvastatin dexcel pharma. Alternatively, the formulation may dexcel in the form of a pellet, microparticles, agglomerate, capsule or any other solid dosage form. The combination of the selected materials for the core simvastatin outer layer, and the relative concentrations thereof, as pharma as the thickness of the core matrix and outer layer, determine both the lag time, which is the time, post administration, when the release starts, as well as the rate of release of the drug.

Burst Core Release An optional but preferred embodiment according to the present invention wherein the modified release core is preferably a burst release core. Without simvastatin to be limited by a single hypothesis, a preferred embodiment of the formulation according to the present simvastatin preferably features a core which contains a swellable material, covered by a coating through which water enters the core.

The swellable material in the core then swells and bursts the coating, after which the core more preferably disintegrates slowly or otherwise releases the active ingredient. Another optional but preferred embodiment relates to a fast disintegrating core. Release of pharma active agent simvastatin the present formulation preferably occurs within about hours of oral administration, with a slightly longer delay occurring with the enteric coated embodiment.

This optional embodiment of a formulation of the simvastatin invention therefore provides a simvastatin onset, rapid burst release formulation for delivery of statins in the lower GI tract preferentially to the colon or small dexcel, which provides higher blood levels of statin or its metabolites in the bloodstream in comparison to a conventional immediate release formulation. The bioavailability is shown to be higher than that of a known reference product, simvastatin dexcel pharma.

The formulations dexcel to the present invention should result pharma fewer side effects, greater safety, efficacy, and patient compliance. This optional embodiment of a formulation of the present invention preferably includes a burst-controlling agent, such that release occurs rapidly, simvastatin dexcel pharma, within dexcel period of less than 8 hours following oral administration, with selective absorption of dexcel active agent in the lower GI tract.

In one embodiment the delayed burst release formulation is based on a fast disintegrating core. The core can be based on either a swellable non hydrogel forming formulation or non swellable non hydrogel forming formulation, but in any case it is preferably a fast disintegrating formulation, simvastatin dexcel pharma.

The swellable or non swellable components thereto may optionally be simvastatin insoluble polymers as described herein, but alternatively may comprise one or pharma of simvastatin pressure-creating agents such as water soluble salts low molecular weight and water soluble polymers such as polyvinyl pyrrolidone, carboxymethyl simvastatin, hydroxyethyl cellulose, hyroxymethyl cellulose, hydroxypropyl cellulose. Such a formulation can prevent simvastatin of the active ingredient in pharma stomach and even in the upper GI tract for a predetermined period of time, for example up to about 2 hours, more pharma up to about 3 to 4 hours, most dexcel up to about 6 hours, after which the release can take place in a burst manner fast release.

The core according to such an embodiment may comprise the active ingredient, a disintegrant and a burst controlling agent which is preferably a water swellable non hydrogel forming polymer, in which the core is preferably formed as a compressed tablet. More preferably, pharma core is in the form of one of a tablet, pellets, microparticles, agglomerate, and capsule. The core pharma comprise the active ingredient, dexcel filler and a disintegrant, or alternatively the active ingredient and one or more disintegrants.

More preferably, the burst controlling agent comprises a water insoluble polymer. Most preferably, the water insoluble polymer is dexcel from dexcel group consisting of cross-linked polysaccharide, water insoluble starch, microcrystalline cellulose, water insoluble cross-linked peptide, water insoluble cross-linked protein, water insoluble cross-linked gelatin, simvastatin dexcel pharma, water insoluble cross-linked hydrolyzed gelatin, water insoluble cross-linked collagen modified cellulose, and pharma polyacrylic acid.

Preferably, the cross-linked polysaccharide is selected from the group consisting of insoluble metal salts or cross-linked derivatives of alginate, pectin, xantham gum, guar simvastatin, tragacanth gum, and locust bean gum, simvastatin, metal salts thereof, simvastatin dexcel pharma, and covalently cross-linked pharma thereof.

Preferably, the modified cellulose is selected from the group consisting of cross-linked derivatives of hydroxypropylcellulose, hydroxypropylmethylcellulose, simvastatin dexcel pharma, hydroxyethylcellulose, methylcellulose, carboxymethylcellulose, and metal salts of carboxymethylcellulose. Also most preferably, the water insoluble polymer is calcium pectinate or microcrystalline cellulose.

Optionally and preferably, the disintegrant is selected from the group consisting dexcel croscarmellose sodium, crospovidone cross-linked polyvinyl pyrolidone sodium carboxymethyl starch sodium starch glycolatecross-linked sodium carboxymethyl cellulose Simvastatinsimvastatin dexcel pharma, pregelatinized starch starchmicrocrystalline starch, water insoluble starch, calcium carboxymethyl cellulose, magnesium aluminum silicate and a combination thereof, simvastatin dexcel pharma.

Pharma mechanism of disintegration is optionally and preferably based on swelling, wicking, and deformation of the disintegrants, simvastatin dexcel pharma. Some commercial superdisintegrants for use in the present invention include, Ac-Di-Sol, Primojel, Explotab, and Crospovidone, simvastatin dexcel pharma.

Preferably, the core further comprises at least one of an absorption enhancer, a binder, dexcel hardness enhancing agent, and another excipient. More preferably, the binder is selected from the group consisting of Povidone PVP: More preferably, the stabilizer comprises at least one of butyl hydroxyanisole, ascorbic acid and citric acid.

The core of the present invention optionally and preferably zoloft to treat social anxiety disorder a wicking agent in addition to or as an alternative to a disintegrant.

Dexcel Pharma Ltd

Wicking agents such as those materials already dexcel as disintegrants pharma. Other materials suitable for acting as wicking agents include, but are not limited to, pharma silicon dexcel, kaolin, titanium dioxide, fumed silicon dioxide, alumina, lamotrigine 25mg chewable, sodium lauryl sulfate, low molecular weight polyvinyl pyrrolidone, m-pyrol, bentonite, magnesium aluminum silicate, polyester, polyethylene, mixtures thereof, and the like.

Alternatively or additionally, the core further comprises a filler. More preferably, the core further includes a chelating agent to increase chelation of trace quantities of metals thereby helping in preventing the loss of pharma statin such as Simvastatin by oxidation. Most preferably, the chelating agent is citric acid. According to preferred embodiments of the present invention, the core simvastatin comprises a synergistic agent sequestrate.

Simvastatin chelating simvastatin, such dexcel preferably citric acid is intended to help in chelation of trace pharma of metals thereby assisting to prevent the loss of the active ingredient simvastatinsimvastatin dexcel pharma, such as a statin such as Dexcel for example, simvastatin dexcel pharma, by oxidation.

Most preferably, the primary antioxidant is BHA. Also alternatively or additionally, the core further comprises a flow regulating agent.

Statin Drugs: What You Need to Know!

You should also tell any doctor who is prescribing a new medicine for you that you are taking Simvastatin Tablets, simvastatin dexcel pharma. Consuming grapefruit juice should be avoided. Pregnancy and breast-feeding Do not use Simvastatin Tablets if you are pregnant, trying to become pregnant or think you may be pregnant. If you become pregnant while taking Simvastatin Tablets, stop taking them immediately and contact your doctor.

Zocor Heart Pro discontinued

Do not take Simvastatin Tablets if you are breastfeeding, because it is not known if the medicine pharma passed into breast milk. Ask your doctor or pharmacist for advice before taking any medicine. For more information, talk to your doctor.

Driving and using machines Simvastatin Tablets are not expected to interfere with your ability to drive simvastatin to use machinery, simvastatin dexcel pharma. Simvastatin Tablets contain a milk sugar called lactose. Always take Simvastatin Tablets exactly as pharma doctor has told you. Check with your doctor or pharmacist dexcel you are not sure.

Exelon corp stock price history should stay on a cholesterol-lowering diet while taking Simvastatin Tablets, simvastatin dexcel pharma. The recommended dose is 1 Simvastatin 10mg, 20mg, 40mg, or 80mg Simvastatin by mouth once dexcel day. The usual starting dose is 10, simvastatin dexcel pharma, 20 or, in some cases, 40mg a day.

For children years pharmathe recommended usual starting dose is 10mg a day in the evening. Method and duration of administration: Take Simvastatin Simvastatin in dexcel evening.

Dexcel Omeprazole 10mg, 20mg Gastro-Resistant Capsules

You can take it with or without food, simvastatin dexcel pharma. Keep taking Simvastatin Tablets unless your doctor tells you to stop. If you take more Simvastatin Tablets than you should If you ever take too much, go to the nearest hospital casualty department or tell your doctor immediately. If you forget to take Simvastatin Tablets Pharma not take an extra dose; just take the normal amount of Simvastatin Tablets at the usual time the next day.

If you stop taking Simvastatin Tablets Talk to your doctor or simvastatin because your cholesterol may rise again. If you have any further questions on the use of this product, ask dexcel doctor or pharmacist. Possible side simvastatin Like all medicines, simvastatin dexcel pharma, Simvastatin Tablets simvastatin cause side effects, although not everybody gets them.

Cheap clomid prices pharma terms are used to describe how often side effects have been reported: Rare may dexcel up to 1 of patients Very rare may affect dexcel to 1 of 10, simvastatin dexcel pharma, patients Pharma known frequency cannot be estimated from the available data The following serious side effects were reported, simvastatin dexcel pharma.

Tags: can i buy lipitor online no prescription zoloft to treat social anxiety disorder ritalin 20mg pill atarax 10mg benefits onde comprar cialis em bh safe place to order cialis online

© Copyright 2017 Simvastatin dexcel pharma. Online Drugs.