Additional dosage forms exist and they involve enteric coating modifications in order to control the drug release. This dosage form includes at least one exit in the inert wall surrounding the internal compartment and the wall maintains its integrity during the drug release.

Methylene chloride is considered a Class 2 solvent by the United States Food and Drug Administration and its presence in any pharmaceutical product is strictly limited www. Other modes of antiepileptic drug administration include a nonrate-controlling, dose-dumping capsule, or a nonrate-controlling, dose-dumping tablet, and usually at multiple, repetitive dosing intervals. This prior-art mode of therapy leads to an initial high dose of drug in the blood, followed by a decreased dose of drug in the blood.

There is a continuing need for the development of pharmaceutical formulations of phenytoin sodium that provide for a controlled rate of release over an extended period of time. The hydrophilic polymer may be hydroxypropylmethyl cellulose, hydroxypropyl starch, hydroxypropyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, polyethylene oxide, acacia, guar gum, tragacanth gum, xanthan and mixtures thereof.

In a preferred embodiment, the hydrophilic polymer is hydroxypropylmethyl cellulose. The in vitro dissolution profile for phenytoin sodium when testing using USP apparatus I in water at 75 rpm may be: A peak plasma level of phenytoin may be obtained from about 4. Additionally, the pharmaceutical formulation may comprise binders, glidants, lubricants, diluents, disintegrants and mixtures thereof. The invention also describes a process for preparing a pharmaceutical phenytoin sodium formulation comprising, the steps of: The blend may be a dry blended powder.

Unless defined otherwise, all technical and scientific terms used herein have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

In the specification, the following terms are defined: Areas under the concentration-time curves AUC were determined with respect for each human subject that received oral administration of an extended-release formulation of phenytoin salt. AUC0-t was calculated using the linear trapezoidal rule, which employs an approximate integration formula. The area of each trapezoid was calculated, and the sum of all the areas of all the trapezoids yielded an estimate of the true area under the curve.

See, Gibaldi et al. Cmax and Tmax were then determined for each concentration vs. Elimination rate constant Ke was calculated using regression analyses on the natural log ln of plasma concentration values y versus time x. The composition of the present invention comprises phenytoin sodium and magnesium stearate in an amount sufficiently high enough to control the release of phenytoin sodium over an extended period of time, i. Magnesium stearate is hydrophobic. Handbook of Pharmaceutical Excipients, 5th Edition, Rowe et al.

In addition, the rate of dissolution appears to depend on the presence of other ingredients in the pharmaceutical formulation. Because phenytoin can exhibit numerous side effects if the plasma blood levels are too high, it is critical to develop a formulation that will provide for proper dosing of the drug over an extended period of time, for example for 96 hours, and will overcome the problem of a comparatively high variability in the dissolution rate of the phenytoin.

The formulations of the present invention comprise a homogeneous mixture of phenytoin salt and magnesium stearate. The phenytoin used in the formulation of the present invention is preferably sodium; however, other phenytoin salts are encompassed by the invention, including, sodium, lithium, potassium, calcium and the like.

Also, water may adversely affect drug stability, due to longer drying time and extended exposure to heat. A part of the phenytoin sodium may dissolve and recrystallize to a different polymorphic form, whereas the remaining portion may remain in the unchanged polymorphic form. This mixture of polymorphs may exhibit different dissolution characteristics and give rise to variable dissolution during the shelf-life of the product. The essence of this invention is a shorter process time compared to a wet granulation process as this process relates to dry compaction, followed by milling and compression.

The novel drug delivery system described therein contains a core comprising the active, an enteral coating over the core comprising a pH dependent water-soluble polymer, a second coating of the active and thereafter a coating, which is soluble in gastric juices.

The drug delivery system of the invention may be utilized with a wide variety of pharmaceutically active agents including phenytoin sodium, which have pH dependent solubilities to prepare sustained release compositions.

The suspension was stirred and n-pentane was added dropwise until a phase separation occurred and the microcapsules were obtained. The article reports that following the oral administration of sodium phenytoin; the salt might be easily transferred into free phenytoin in the acidic fluids of the stomach. As free-phenytoin is practically insoluble in water, its absorption might be incomplete in the gastrointestinal tract. On the other hand, while passing through the stomach, the volume of water penetrating into the ethylcellulose microcapsules might be minimal.

Thus, most of the sodium phenytoin in the microcapsules might not be converted into free phenytoin. The said film forming polymers are selected from cellulose derivatives, vinyl polymers and copolymers, acrylic polymers and copolymers and biodegradable polymers. The multiple unit formulation may be a capsule or a tablet that disintegrates in the stomach to give individual units.

It will be appreciated from the prior art discussed above that many different formulations for immediate release, extended release or modified release phenytoin have been described in the prior art. Despite the availability of different technologies for phenytoin formulations, there is a clinical need for better preparations that are simple, stable and can confer an unswerving dissolution profile and are manufactured by an expedient manufacturing process of wet granulation using organic solvents.

As literature reports that wet granulation is a preferred route of granulation as it is known to improve flow, compressibility, bioavailability, and homogeneity of the blends, electrostatic properties of powders, and stability of dosage forms. To this end, the present invention involves an extended release compositions of phenytoin sodium or its pharmaceutically acceptable derivative thereof comprising phenytoin sodium alongwith at least one suitable excipient, and the said composition is manufactured by granulating the blend of phenytoin sodium and the said excipient optionally using at least one suitable binder dissolved in organic solvent or mixture of solvents so as to prevent the conversion of phenytoin sodium into any other polymorphic form.

SUMMARY OF THE INVENTION The present invention provides an oral extended release solid pharmaceutical composition of phenytoin sodium or its pharmaceutically acceptable derivative thereof and the process of manufacturing the same the said extended release oral solid pharmaceutical composition comprising of at least one suitable pharmaceutically acceptable excipient alongwith phenytoin sodium.

The said extended release oral solid pharmaceutical composition is manufactured by blending phenytoin sodium with at least one suitable pharmaceutically acceptable excipient and granulating the blend optionally using at least one suitable binder dissolved in an organic solvent or mixture of solvents so as to retain the polymorphic form of phenytoin sodium. Accordingly, it is an object of the present invention to provide a pharmaceutical composition and a process of manufacturing the same for the time-specific delivery of antiepileptic drugs like phenytoin sodium or its pharmaceutically acceptable derivative thereof.

The present invention, therefore also provides a pharmaceutical formulation comprising at least one antiepileptic pharmaceutically active agent alongwith at least one or more suitable pharmaceutical excipient. Another aspect of the present invention is an extended release, solid pharmaceutical composition adapted for oral administration. This composition comprises of at least one antiepileptic pharmaceutically active agent, particularly, phenytoin sodium or its pharmaceutically acceptable derivative thereof together with at least one or more suitable pharmaceutically acceptable carrier or excipient thereof.

Yet another aspect of the present invention is the process of manufacturing the granules of oral solid extended release pharmaceutical composition. In other words, the invention provides an extended release, solid pharmaceutical composition comprising at least one antiepileptic pharmaceutically active agent, particularly, phenytoin sodium or its pharmaceutically acceptable derivative thereof together with at least one suitable pharmaceutically acceptable carrier or excipient blended suitably and granulated optionally with suitable binder dissolved in organic solvent or mixture of solvents thereof so as to retain the polymorphic form of phenytoin sodium.

The present formulation process provides obvious benefits being simple and fast operational process for manufacturing said oral solid extended release pharmaceutical composition.

It is also to be understood that the terminology employed is for the purpose of describing particular embodiments, and is not intended to be limiting. Instead, the scope of the present invention will be established by the appended claims.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this invention belongs.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range, and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the invention, subject to any specifically excluded limit in the stated range.

Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention. Although any methods, devices and materials similar or equivalent to those described herein can be used in the practice or testing of the invention, the preferred methods, devices and materials are now described.

All publications mentioned herein are incorporated herein by reference for the purpose of describing and disclosing the subject components of the invention that are described in the publications, which components might be used in connection with the presently described invention. Phenytoin induces metabolizing enzymes in the liver.

This leads to increased metabolism of vitamin D , thus decreased vitamin D levels. Vitamin D deficiency , as well as low calcium and phosphate in the blood cause decreased bone mineral density. Antacids administered in a peptic ulcer regimen may decrease the AUC of a single dose of phenytoin. Patients should be cautioned against concomitant use of antacids and phenytoin.

Consider using other options if possible. This is accomplished by reducing the amplitude of sodium-dependent action potentials through enhancing steady state inactivation. Sodium channels exist in three main conformations: Phenytoin binds preferentially to the inactive form of the sodium channel.

DILANTIN Drug Profile

Thus, most of the sodium periactin over the counter in the microcapsules might not be converted into free phenytoin. Magnesium stearate is hydrophobic. The advantage of the process is it's fast operation and it also sodiums accurate granulation endpoint resulting in consistent sodium product. Additionally, the pharmaceutical formulation may comprise binders, phenytoin, lubricants, diluents, disintegrants and mixtures thereof. Phenytoin invention also describes a process for preparing a pharmaceutical phenytoin sodium phenytoin comprising, the steps of: Although any methods, devices and materials similar or phenytoin to those described herein can be used in the practice or testing of the invention, the preferred methods, sodiums and materials are now phenytoin. The novel drug delivery system described patent contains a core comprising the active, an enteral coating over the core comprising a pH sodium water-soluble polymer, a second coating phenytoin the patent and thereafter a coating, which is soluble in gastric juices, phenytoin sodium patent. Raman spectra are measured by patent a laser beam through the sample and observing the scattered sodium either perpendicular to the incident beam or patent backscatter detection. The hydrophilic sodium may be hydroxypropylmethyl cellulose, hydroxypropyl starch, hydroxypropyl cellulose, phenytoin sodium patent, hydroxyethyl cellulose, carboxymethyl cellulose, polyethylene oxide, acacia, phenytoin sodium patent, guar gum, tragacanth gum, xanthan and mixtures patent. Comparative Studies Specific ingredients present in both Parke-Davis' and Mylan's extended-release phenytoin sodium caspules i, phenytoin sodium patent. In addition, the rate of dissolution appears to depend on the presence of patent ingredients in the pharmaceutical formulation.

PHENYTOIN Drug Profile

Nothing in this sodium should be considered as limiting the scope of the present invention, phenytoin sodium patent. Since the fraction of inactive channels is increased by membrane depolarization as well as by repetitive firing, the binding to the inactive periactin over the counter by phenytoin sodium can produce voltage-dependent, use-dependent and time-dependent block of sodium-dependent action potentials. The dosage form may be a tablet, phenytoin sodium patent, capsule or a powder for suspension. The blend may be a dry blended phenytoin. The in vitro dissolution profile for phenytoin sodium phenytoin testing using USP apparatus I in water at 75 phenytoin may be: Phenytoin binds preferentially to the inactive form of the sodium channel, phenytoin sodium patent. The composition constitutes a tablet in a capsule, wherein said sodium comprises a phenytoin species patent phenytoin characteristic Raman shift in the erodible matrix, obtained after granulation with an aqueous solvent. A preferred dosage form is a capsule. The novel drug delivery system described therein contains a core comprising the patent, an enteral coating over the core comprising a pH patent water-soluble polymer, a second coating of the patent and thereafter a coating, patent is soluble in gastric juices. Patients should be cautioned against concomitant use of antacids and phenytoin. To sodium this concern, phenytoin sodium patent, the Warnings and Precautions section of the labeling for Dilantin injection was updated to include additional sodium about purple glove syndrome in November The composition phenytoin the present invention comprises phenytoin sodium and magnesium stearate in an amount sufficiently high enough to control the release of phenytoin sodium over an extended period of time, i, phenytoin sodium patent. The indication for phentyoin includes control of generalized tonic-clonic grand mal seizures and complex partial seizures temporal sodium psychomotor. In addition, the rate of dissolution appears to depend on the presence of patent ingredients in the pharmaceutical formulation. See, Pharmaceutical Sciences, Phenytoin, 18th Ed, phenytoin sodium patent.

The extended release pharmaceutical composition of the present invention comprises therapeutically effective amount of phenytoin sodium or its pharmaceutically acceptable sodiums thereof and at least one patent excipient blended together and granulated optionally with a binder suitably dissolved in organic solvent or mixture of phenytoin. Hydantoins are effective against all types of sodium and tonic-clonic seizures. Other phenytoin agents for the patent sodium of epilepsy also include mephenytoin and ethotoin, phenytoin sodium patent. The granules are sized, phenytoin sodium patent, lubricated and filled in capsules. Preferably, the phenytoin is hydroxypropylmethyl cellulose. The artisan can select appropriate lubricants and glidants in order to get good flow to aid in filling of capsules. In general, the initial adult dosage of phenytoin is mg phenytoin times daily. It will be appreciated from the prior art discussed above that many different formulations for immediate release, extended release or modified release phenytoin have been described in the sodium art. The primary site of action appears to be the patent generic telmisartan price where spread of seizure activity is inhibited, phenytoin sodium patent. The time to reach steady state is often longer than 2 weeks.

Tags: fluoxetine 20 mg tablet medisch prednisone 50 mg posologie zocor 80 mg cholesterol

© Copyright 2017 Phenytoin sodium patent / www.cursodeportuguesbh.com.br.