Claims:I/We Claim:
1. A method of formulation of mucoadhesive gastroretentive tablet, wherein the method comprises the steps of:
creating the powdered mixture containing the drug, excipients and polymers;
molding the powdered mixture into tablet molds; and
compressing the mixture into tablet using a press.
2. The powdered mixture as claimed in Claim 1, wherein the powdered mixture comprises of the following ingredients:
the drug such a metoprolol succinate, in dry powdered form;
the lubricant magnesium stearate;
the excipient Talc;
the polymer Polyacrylic acid (Carbopol 934P); and
any one of the polymers Hydroxypropyl methylcellulose (HPMC K4M) and Sodium carboxymethyl cellulose (Na CMC).
3. The powdered mixture as claimed in Claim 1, where the component weight and percentage by weight of the dry ingredients in the final tablet are as follows:
Metoprolol succinate – 100mg – 14.28%;
Mg Stearate – 14mg – 2%;
Talc – 21mg – 3%;
HPMC K4M – (141 to 424) mg – (20.14 to 60.57) %;
Carbopol 934P – (141 to 424) mg – (20.14 to 60.57) %;
Na CMC – (141 to 424) mg – (20.14 to 60.57) %.
4. The creation of the powdered mixture as claimed in Claim 1, wherein the process comprises the following steps:
passing the drug and polymers separately through size 40 & 60 sieves respectively;
mixing for 5 min with mortar and pestle; and
adding Mg stearate and mixing at a slow speed for 5 min.
5. The molding step as claimed in Claim 1, where the mold is a 12.5 mm flat punch tablet dye.
6. The compression step as claimed in Claim 1, where the compressed tablet has final weight of 700mg.
7. A method of testing the properties of tablet made using the method claimed in Claim 1, where the testing comprises tests for:
physiochemical analysis;
water uptake and swelling;
in vitro bioadhesion;
in vitro dissolution; and
in vitro residence time.

, Description:MUCOADHESIVE DOSAGE FORM FOR GASTRORETENTIVE DRUG DELIVERY SYSTEM
TECHNICAL FIELD
The present disclosure relates to a drug delivery system and particularly it relates to a mucoadhesive dosage form for gastroretentive drug delivery system.
BACKGROUND
Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
Sustained release, sustained action, prolonged action, controlled release, extended action, timed release, depot dosage forms are terms used to identify drug delivery systems that are designed to achieve prolonged therapeutic effects by continuously releasing medication over an extended period of time after administration of single dose.
Oral administration is the most preferable route of administration for majority of drugs. Oral bioavailability of certain drugs can be limited by the residence time of the pharmaceutical formulations in the upper gastrointestinal tract. The ability to maintain an oral delivery system at the target absorption location for an extended period of time has great appeal for treatment of both local conditions, as well as for sustained systemic absorption. One of the most feasible approaches for achieving a prolonged and predictable drug delivery profile in the GI tract is to control the gastric residence time (GRT).
Mucoadhesive polymers are synthetic or natural polymers, which interact with the mucus layer covering the mucosal epithelial surface and mucins molecules constituting a major part of mucus. The concept of mucoadhesive has alerted many investigations to be possibility that these polymers can be used to overcome physiological barriers in long-term delivery. When mucoadhesive polymers are utilized, the residence time of dosage forms on the mucosa can be significantly prolonged, allowing a sustained drug release at a given target site. Furthermore, mucoadhesive polymers can guarantee an intimate contact with the absorption membrane, providing the basis for a high concentration gradient as a driving force for passive drug uptake. Moreover, due to this intimate contact, pre-systemic metabolism, such as the degradation of orally administered peptide drugs by luminal secreted intestinal enzymes can be avoided. They render the treatment more effective and safer not only for topical disorders but also for systemic problems.
Efforts have been made in the related prior art to provide different processes of preparation of gastroretentive dosage forms. PCT patent WO2013018031A1 describes controlled release pharmaceutical formulations of active principle(s) like tetracycline-class antibiotics for providing increased residence time in the gastrointestinal tract and the process of preparing them. Another patent US9433582B2 discloses extended-release pharmaceutical compositions comprising an opioid and an additional active pharmaceutical ingredient, wherein the composition exhibits gastric retentive properties which are achieved by a combination of a physical property of the composition and release of the opioid.
Academic paper by C. Narendra et al. (2006) presented a method to develop an optimized gastric floating drug delivery system (GFDDS) containing of hydroxypropyl methyl cellulose (HPMC). Another paper Kast Ce, et al. (2002) described polymer-cysteamine conjugates as new mucoadhesive excipients for drug delivery. Mahesh D. Chavanpatil et al. (2006) describes a new gastro retentive sustained release delivery system with floating, swellable and bioadhesive properties. Chowdary KPR, Suresh B, et al. (2003) describes design and development of diltiazem mucoadhesive tablets for oral controlled release. These disclosures indicate the need for a simple and cost-effective method for manufacture of gastroretentive mucoadhesive medications.
Therefore, the present disclosure overcomes the above-mentioned problem associated with the traditionally available method or system, any of the above-mentioned inventions can be used with the presented disclosed technique with or without modification. All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies. Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment.
The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.
OBJECTS OF THE INVENTION
It is an object of the present disclosure is to provide a method for formulation and evaluation of mucoadhesive gastroretentive drug dosage form.

SUMMARY
The present disclosure relates to a method for formulation and evaluation of mucoadhesive gastroretentive drug dosage form.
In this method, the formulation consists of the drug such as metoprolol succinate, excipient talc, lubricant magnesium stearate, the polymers Hydroxypropyl methylcellulose (HPMC K4M), Polyacrylic acid (Carbopol 934P) and Sodium carboxymethyl cellulose (Na CMC).
Further, In this method, the drug that is required is taken in powdered form and mixed with the dry excipients and polymers to generate a powered mixture. This powdered mixture is compressed by wet direct compression to generate flat circular tablets.
In the present invention, the tablets generated are evaluated for their properties such as appearance, thickness, hardness, friability, weight variation, drug content uniformity, water uptake, in vitro bioadhesion, in vitro dissolution and in vitro residence time.
One should appreciate that although the present disclosure has been explained with respect to a defined set of functional modules, any other module or set of modules can be added/deleted/modified/combined, and any such changes in architecture/construction of the proposed system are completely within the scope of the present disclosure. Each module can also be fragmented into one or more functional sub-modules, all of which also completely within the scope of the present disclosure.
Various objects, features, aspects and advantages of the inventive subject matter will become more apparent from the following detailed description of preferred embodiments, along with the accompanying drawing figures in which like numerals represent like components.
 

BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings are included to provide a further understanding of the present disclosure and are incorporated in and constitute a part of this specification. The drawings illustrate exemplary embodiments of the present disclosure and, together with the description, serve to explain the principles of the present disclosure.
FIG. 1 illustrates a flowchart method for formulation & evaluation of mucoadhesive gastro retentive tablet.
DETAILED DESCRITION
In the following description, numerous specific details are set forth in order to provide a thorough understanding of embodiments of the present invention. It will be apparent to one skilled in the art that embodiments of the present invention may be practiced without some of these specific details. As the detailed description is concerned various stages are included in embodiments of the present invention, which will be detailed below. The stages can be carried out along with statistical data and by machine-executable instructions, which can be used to direct a general-purpose or special-purpose processor to carry out the procedures. If the specification states a component or feature "may", "can", "could", or "might" be included or have a characteristic, that particular component or feature is not required to be included or have the characteristic.
Aspects of the present disclosure relate to method of preparing mucoadhesive gastroretentive oral dosage forms. It is inferred that the foregoing description is only illustrative of the present invention, and it is not intended that invention be limited or restrictive thereto. Many other specific embodiments of the present invention will be apparent to one skilled in the art from the foregoing disclosure. All substitutions, alterations and modifications of the present invention which comes within the scope of the following claims are to which the present invention is readily susceptible without departing from the spirit of the invention. The scope of the invention should therefore be determined not with reference to appended claims along with the full scope of equivalents to which such claims are entitled.
Thus, for example, it will be appreciated by those of ordinary skill in the art that the diagrams, schematics, illustrations, and the like represent conceptual views or processes illustrating systems and method embodying this invention. Those of ordinary skill in the art further understand that the exemplary processes, method, and/or pharmaceutical components described herein are for illustrative purposes and, thus, are not intended to be limited to any particular named.
The following is a detailed description of embodiments of the disclosure depicted in the accompanying drawings. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.
Various terms as used herein are shown below. To the extent a term used in a claim is not defined below, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing.
In an embodiment of the present disclosure, FIG. 1 illustrates a flowchart method of preparation of mucoadhesive gastro retentive tablet containing metoprolol succinate.
An aspect of the present invention, consists of drug selection and profile matching. This is carried out in pre-formulation stage by analyzing the IR absorbance spectra of a drug such as metoprolol succinate in pure solution and the drug after mixing with the polymers and other excipients. These should be identical, indicating no chemical change in the drug due to the formulation process.
Another aspect of the present invention is the method for preparation of the powdered drug excipient mixture, which comprises of, firstly, sieving the drug through size 40 sieve, sieving Polyacrylic acid (Carbopol 934P) and any one of the polymers Hydroxypropyl methylcellulose (HPMC K4M) & Sodium carboxymethyl cellulose (Na CMC) through size 60 sieve; secondly, mixing the drug and polymers for 5 mins with mortar and pestle; thirdly, addition of Mg stearate and other excipients and mixing slowly for 5 mins.
Another aspect of the present invention is the composition of the formulation which contains specified amounts of individual component – drug such as metoprolol succinate 100mg (14.28%), Talc 21mg (3%), Mg stearate 14 mg (2%), HPMC K4M between 141 to 424mg (20.14 to 60.57%), Carbopol 934P between 141 to 424mg (20.14 to 60.57%) and Na CMC between 141 to 424mg (20.14 to 60.57%). The prepared powdered mixture is molded into 12.5mm flat dye press and compressed to pressure of 6.5 ± 0.5 kg/cm2 using tablet press to thickness of 4.5 ± 0.5 mm and total weight of 700 ± 35mg.
Another aspect of the present invention is the methods of evaluation of the finished tablet comprising of the following tests –
Physicochemical evaluation: The product should appear white and odorless in appearance when inspected visually, with weight between 700 ± 35mg and thickness of 4.5 ± 0.5 mm.
Swelling study: The water uptake and swelling of the tablet is measured USP dissolution apparatus with 900ml distilled water rotated at 50 rpm at 37±0.5 ℃. Swelling characteristics of the tablets were expressed in terms of water uptake (WU) as
WU (%)=(Weight of the swollen tablet - Initial weight of the tablet)/(Initial weight of the tablet) ×100

In vitro bioadhesion: Bioadhesion analysis is performed using apparatus containing two platforms & Rat stomach mucosa was used as a model mucosal surface for bioadhesion testing. The upper stationary platform is linked to a digital balance of 0.01 gm sensitivity, measuring the force needed to break contact between the tablet and mucosa. The test cell is filled with pH 1.2 hydrochloric acid buffer maintained at 37℃, and the sections of rat stomach placed and fixed in place over the lower platform with cyanoacrylate adhesive and allowed to equilibrate in this solution for 2 min. Similarly, the tablets of the formulation are glued to the upper platform. The lower platform is elevated until the mucosal surface comes in contact with the surface of tablet attached to the upper platform and it is allowed to remain in contact for 3 min. Then a constantly increasing force is applied on the adhesive joint formed between mucosa and the test tablet by gradually lowering the lower platform. This process is continued until the contact between the test tablet and mucosa was broken and the maximum detachment force measured was recorded. The mean of 3 evaluations is taken as Bioadhesive strength. Force of bioadhesion (N) is calculated by
Force of bioadhesion (N)= (bioadhesive strength)/1000 ×9.81
Bond strength (N/m2) is calculated by
Bond strength (N⁄m^2 )= (Force of bioadhesion )/(Surface area of the tablet)
In vitro dissolution: Dissolution of the tablet was carried out using USP dissolution type II apparatus using paddle, fixing the tablet to the paddle. 900 ml of pH 1.2 hydrochloric acid dissolution medium was filled in a dissolution vessel and the temperature of the medium was set at 37 ± 0.5 ℃ The rotation speed of the paddle was set at 100 rpm. 5 ml of sample was withdrawn at predetermined time interval of 1 hour for 24 hours and same volume of fresh medium was replaced. The withdrawn samples were diluted to 10 ml in 10 ml volumetric flask with 0.1 N HCL analyzed by an UV spectrophotometer at 222nm against standard curve for the drug.

In vitro residence time: In vitro residence time was determined using modified USP disintegration apparatus. The disintegration medium was composed of 800 ml pH 1.2 hydrochloric acid buffer maintained at 37 ℃. A segment of rat stomach mucosa was glued to the surface of a glass slab, vertically attached to the apparatus. The mucoadhesive tablet was hydrated from one surface using 15 µl pH 1.2 HCl buffer and then the hydrated surface was brought into contact with the mucosal membrane. The glass slab was vertically fixed to the apparatus and allowed to move up and down so that the tablet was completely immersed in the buffer solution at the lowest point and was out at the highest point. The time necessary for complete erosion or detachment of the tablet from the mucosal surface was recorded.
While the foregoing describes various embodiments of the invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof. The scope of the invention is determined by the claims that follow. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person having ordinary skill in the art.
Thus, the scope of the present disclosure is defined by the appended claims and includes both combinations and sub-combinations of the various features described hereinabove as well as variations and modifications thereof, which would occur to persons skilled in the art upon reading the foregoing description.
For