|Title of Invention||
EXTENDED RELEASE TABLET FORMULATION OF SERRATIOPEPTIDASE
|Abstract||The present invention provides a tablet containing serratiopeptidase which provides sustained release of the active material there by reducing the dosing frequency.|
|Full Text|| FORM 2THE PATENT ACT 1970(39 of 1970)&The Patents Rules, 2003PROVISIONAL SPECIFICATION(See section 10 and rule 13)
1. TITLE OF THE INVENTION:Extended Release Tablet Formulation Of Serratiopeptidase
(a) NAME: Corned Chemicals Limited(b) NATIONALITY: An Indian Company(c) ADDRESS: 3rd Floor, Orient Business Centre, Sayajigunj, Baroda- 390005, Gujarat, India.
3. PREMABLE TO THE DESCRIPTION
0 PROVISIONAL COMPLETE
The following specification describes the invention. The following specification particularly describes the invention and the manner in which it is to be performed.
The object of the present invention is to provide a tablet containing serratiopeptidase which provides sustained release of the active material there by reducing the dosing frequency.
Controlled-release drug delivery systems, particularly sustained-release preparations, are advantageous in that they help to reduce the frequency of administration of a drug without detracting from the effect of medication, prevent any sudden elevation of the blood concentration of the drug to reduce the risk of side effects, and maintain a therapeutically effective blood concentration for an extended period of time. Therefore, much research has been undertaken in the field of controlled release technology from the aspects of active drug, formulation and dosage form. By way of illustration, there are known an encapsulated preparation such that a core containing an active ingredient is covered with a shell, and a matrix type preparation such that an active ingredient has been dispersed in a release-controlling layer. These preparations are generally provided in such dosage forms as tablets, capsules and granules. Meanwhile, many drug substances are absorbed mostly from the small intestine and, to a lesser extent, from the large intestine. Moreover, in humans, reportedly it
takes about 5 to 6 hours for an orally administered drug to reach the large intestine
Serrapeptase, also known as Serratia Peptidase, is a proteolytic enzyme isolated from the non-pathogenic enterobacteria Serratia El5. Serrapeptase is found in negligible amounts in the urine, suggesting that it is transported directly from the intestine into the bloodstream. Clinical studies show that Serrapeptase induces fibrinolytic, anti-inflammatory and anti-edemic (prevents swelling and fluid retention) activity in a number of tissues, and that its anti-inflammatory effects are superior to other proteolytic enzymes.
It binds to alpha-2-macroglobulin in the blood in the ratio of 1:1 which helps to mask its antigenicity but retain its enzymatic activity. Levels of serratiopeptidase are slowly transferred to the exudate at the site of inflammation and gradually the blood level decline. By hydrolysing bradykinin, histamine and serotonin, it indirectly reduces dilatation of blood capillaries and controls permeability. Serratiopeptidase blocks plasmin inhibitors thus helping the fibrinolytic activity of plasmin. Degradation of 'extra-fibrin' to small fragment prevents clogging of
microcapillaries, helps clearance of exudate, reduces swelling and improves microcirculation. It treats inflammatory disorders by not only fighting inflammation, but also by relieving pain and swelling, improving recovery time and stimulating the immune system. Serrapeptase has a "scavenging" effect. It helps remove the heavy metals through which the body releases toxins and hence modulates the immune system, addresses hormonal imbalances and speeds wound and tissue repair time.
However, the enzyme is destroyed by acid in the stomach. Hence, it is given in the form of enteric coated tablets. Also the dosing regimen involves 5-10mg three times a day. This necessitates the extended release dosage form of serratiopeptidase to ensure patient compliance.
The present invention is directed to extended release pharmaceutical preparations.
The present invention is also directed to methods for producing extended release pharmaceutical preparations. The present invention is also directed to controlled release pharmaceutical preparations having desired dissolution rates that can be obtained in a diffusion controlled tablet. The invention provides an extended release tablet with the core
containing serratiopeptidase, a rate controlling extended release agent and enteric coating the tablet to protect it from the acidic degradation in stomach. The rate controlling agent can be a hydrophilic polymer like hypromellose, hydrophobic polymer like ethylcellulose or lipidic susbstances like stearic acid, glyceryl behenate, etc.
The objective of the current invention is to provide serratiopeptidase in a controlled and sustained manner, so as to reduce the crest and trough in the plasma levels and to reduce the dosing frequency.
The present invention relates to pharmaceutical compositions which can be administered orally, allowing the controlled release of pharmaceutically active substances, and to methods of preparing these pharmaceutical compositions.
One of the objectives currently sought in the development of pharmaceutical compositions which can be administered orally is to control the release of pharmaceutically active substances so that they can be administered in a few daily doses, ideally in a single daily dose. The release of active substances during oral administration can be controlled by means of matrix-type pharmaceutical compositions. The present
invention primarily concentrates on the hydrophilic matrices. The hydrophilic matrices comprise gelling excipients which can be divided into three classes: the cellulose derivatives (hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methylcellulose and the like), the noncellulose polysaccharides (galactomannans, guar gum, carob gum, gum arabic, sterculia gum, agar, alginates and the like) and the acrylic acid polymers (carbopols 934P and 974P and the like).
In an embodiment of the present invention, the extended release tablet comprises of active ingredient and water soluble rate controlling polymer and optionally conventional excipients including a binder. These tablets are coated with enteric coating polymers suitable for prohibiting the release in the stomach.
The embodiment in the current invention relates to a pharmaceutical composition which can be administered orally and allowing controlled release of serratiopeptidase as the active ingredient. The active is present in concentration of 5-40%, more preferably in the concentration of 10-20%w/w. The rate controlling hydrophilic polymer comprises about 10-50%w/w of weight, more preferably in the range of 25-35%w/w. The rate
controlling polymers can a combination of different grades of hypromellose viz. HPMC K4M & HPMC K15M.
Examples of lipid matrices which can be used according to the present invention are: glycerides (mono-, di- or triglycerides: stearin, palmitin, laurin, myristin, hydrogenated castor or cottonseed oils, precirol and the like), fatty acids and alcohols (stearic acid, palmitic acid, lauric acid; stearyl alcohol, cetyl alcohol, glycol and of sucrose, sucrose distearate and the like) and waxes (white wax, cachalot wax and the like).
The formulation also contains binder selected from polyvinyl pyrrolidone, Hydroxypropyl cellulose, Hydroxypropyl Methylcellulose (low viscosity grade), methyl cellulose, starch, pregelatinized starch, modified corn starch in a range of 1% to 10%, more preferably in range of 2.5% to 5% w/w of the extended release tablet. The composition also contains diluent selected from amongst microcrystalline cellulose, dibasic calcium phosphate.
In addition to the above-mentioned components, the pharmaceutical compositions according to the present invention may also contain other excipients such as diluents (example: emcompress, lactose and the like),
binders (avicel, starches, polyvinylpyrrolidone and the like), disintegrants (starches and modified starches, cellulose derivatives, alginic derivatives, pectins and the like), lubricants (talc, magnesium stearate, colloidal silica and the like)
The extended release tablet formulation prepared is optionally coated with enteric coated coating polymers. The enteric coating polymers may include Eudragit L30D, cellulose acetate phthalate, cellulose acetate butyrate.
According to the embodiment in the present invention, the tablet formulation is prepared by wet granulation process. The process of wet granulation includes aqueous or non aqueous granulation. The wet granulation process comprises the admixing of the active ingredient with 'diluent' or mixture of 'diluent' and rate controlling hydrophilic polymer, and granulation of the blend with the binder mass to form the wet mass followed by drying and sizing. The binder may optionally be admixed with the dry blend and granulation performed with aqueous or non aqueous solvent. The solvent for the non aqueous granulation is selected from ethanol, isopropyl alcohol and dichloromethane.
It should be understood, that compounds used in the art of pharmaceutical formulation generally serve a variety of functions or purposes. Thus, if a compound named herein is mentioned only once or is used to define more than one term herein, its purpose or function should not be construed as being limited solely to that named purpose(s) or function(s).
The present invention can be illustrated by the following example:
Sl.No Ingredients Mg/tablet
1 Serratiopeptidase 30
2 Microcrystalline cellulose 111
3 PVP K-30 5
4 Isopropyl alcohol q.s
5 HPMC K4 M 50.0
6 Magnesium stearate 4.0
Total 200.0 mg
1. Serratiopeptidase and diluents were properly in RMG.
2. The above blend was granulated with the PVP binder solution and wed milled through 16# sieve
3. The granules were dried in FBD until moisture content between 2-4 %w/w, and then granules sized through 20# sieve.
4. HPMC Magnesium Stearate and Aerosil were added to the above formed granules and mixed it properly in suitable mixer.
5. The lubricated granules were compressed in suitable punch with target weight of 200 mg with hardness range of 5-7 kg.
The tablets were evaluated for dissolution in USP type 1 apparatus, at l00rpm, 900ml phosphate buffer pH 6.8, 37°C. The samples were analyzed by UV spectrophotometer at Amax 278.5 ran. The dissolution are tabulated as under:
Time in Hrs %drug dissolved
01 14.13 ± 5
02 33.5 ± 10
04 45.4 ± 10
06 64.6 ± 10
08 NLT 75%
Dated this 3rd day of August 2007
|Indian Patent Application Number||1515/MUM/2007|
|PG Journal Number||11/2013|
|Date of Filing||06-Aug-2007|
|Name of Patentee||COMED CHEMICALS LIMITED|
|Applicant Address||3rd FLOOR, ORIENT BUSINESS CENTRE,' SAYAJIGUNJ, BARODA.|
|PCT International Classification Number||A61K9/00; C12N9/00|
|PCT International Application Number||N/A|
|PCT International Filing date|