Description:FIELD OF THE INVENTION
[0001] The present disclosure pertains to a particulate co-processed self-lubricating excipient composition and methods for producing the same. In particular, the present disclosure provides a particulate co-processed self-lubricating excipient composition for oral solid dosage forms comprising a co-processed mixture of a binder and a lubricant, wherein the binder and the lubricant particles are in intimate association with each other.

BACKGROUND OF THE INVENTION
[0002] The 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 present invention, or that any publication specifically or implicitly referenced is prior art.
[0003] A list of excipients is used to manufacturing dosage forms. Generally, dosage forms divided into three types viz., solid, liquid, and semi-solid dosage forms. Solid dosage forms may be Tablet, Capsules, and powders. Tablet is most popular and better patient compliance, there are three basically methods are used to manufactured tablets, like wet granulation, dry granulation, and direct compression. In wet granulation method required to manufacture granules after that compress tablets, whereas manufacturing of granulations is time consuming process, and it is Costlier method. But direct compression method is fast method for tablet manufacturing. In this method no need to prepare granules only mix the binder and glidant, disintegrant and API mixed it properly after that add lubricant for lubrication. Addition of Lubricant in the mixture is very important because it helps to increase flow of the mixture and it reduces die-fraction during tableting. When die fraction is more, tablet got rejected in physical defects. Little quantity of Lubricant reduced die-frication and punch good quality of tablet.
[0004] As a result of their numerous advantages, such as the high physical and chemical stability, the precision of dosage, the ease of administration, portability, cheap mass production, and the ability to provide a variety of release patterns of active ingredients, tablets are the most commonly used form of delivering active pharmaceutical ingredients on site to cure disease. Tablet can be obtained by compressing powders formulated in an appropriate manner. Tablets are manufactured by three ways in the pharmaceutical industry: wet granulation, dry granulation, and direct compression (DC). Granulation techniques involve multiple steps and manufacturing challenges, leading to a substantial increase in the cost and time of production. Direct tableting is the preferred method.
[0005] DC tableting as a technique involves the compression of a dry blend of powders that comprises drugs and various excipients, which results in a number of benefits including time and cost savings. With this formulation procedure, granulation is no longer necessary before tableting. In a word, the simplicity and cost-effectiveness of DC have positioned it as a preferred alternative. However, DC process is highly influenced by powder characteristics such as flowability and compressibility. At the beginning, untreated excipients were applied for DC, such as powder cellulose or α-lactose-monohydrate. Then, the excipients were improved by using various manufacturing processes, such as spray drying (spray-dried lactose), or by using a special sieve fraction, but the improvement is limited and does not always provide the requisite performance for drugs in formulation and manufacture. Co-processed excipient is the next technological innovation for DC, which fulfils the increasing demand for multifunctional excipients for DC tableting. Co-processed excipients are prepared by incorporating one excipient into the particle structure of another excipient using processes such as co-drying, hot-melt extrusion, freeze thawing, and co-precipitation. Co-processing implies the combination of two or more established excipients in some common process (granulation, spray drying, milling, co-crystallization, etc.) in order to synergistically improve excipient functional properties and mask undesired properties. This concept is based on component interactions on the sub particle level, wherein particles of one excipient can be incorporated on the surface or within the core of particles of another excipient. Since no chemical changes occur during co-processing, the obtained product can be considered as a mixture of the existing excipient and thus is not subjected to extensive toxicological studies The co-processed multifunctional excipients are introduced to achieve better characteristics and tableting properties, including high compatibility, high intrinsic flow, good lubricating efficiency, improved blending properties and good binding properties, than a single substance or the physical mixtures.
[0006] Traditional compressible mixtures are made by combining an API with appropriate excipient components such as diluents, fillers/carriers, binders or adhesives, disintegrants, glidants or flow promoters, colours, and flavourings, among others. The powders have a glidant advance flowability into the tableting apparatus. Glidants can be blended or granulated in both a dry and a wet state. Once the material has been thoroughly mixed, a lubricating excipient is added, and the material is compacted into a tablet. The mixture would next be compacted into tablets and combined with an API and, if desired, a lubricant. Prior to compression, a lubricant is combined with the carrier and active substance, regardless of the tableting technique.
[0007] However, in the field, a lubricant is thought important to ensure that the compressed shape or tablet is released from the device. At the same time, the lubricant is thought to affect the necessary binding between the various carrier components, and, in the case of hydrophobic lubricants like magnesium stearate, tablet disintegration properties are thought to be negatively affected. The causes for the binding qualities would be due to lubricants' inclination to cover the excipient components, preventing them from attaching to one another. In addition, a hydrophobic lubricating coat repels water, which aids in disintegration. As a result, the application of lubricant is postponed until all components have been thoroughly mixed, in order to reduce the amount of time lubricant and other tablet components are in touch.
[0008] The API excipients and lubricant are mixed together as part of the process of providing ready-to-use co-processed tablet excipient components. However, in the field, a lubricant is thought to be required to enable the compressed form or tablet to be released from the device. Even so, it is also contended that the lubricant may coincide with the necessary binding between the various carrier components and, in the case of hydrophobic lubricants like magnesium stearate, adversely affect tablet disintegration properties. Lubricants have a tendency to coat excipient components, making it difficult for them to adhere to one another. Water plays a vital role in disintegration, so a hydrophobic lubricant coat resists it. As a result, the use of lubricant prior to the actual compression step helps to minimise contact time between lubricant and other tablet components.
[0009] However, there is a perpetual need to optimise the process for producing ready-to-use co-processed Self-lubricating excipient combinations in the art. Although the principal goal of lubricants and glidants is to enhance tableting and flowability into the tablet press, some lubricants can also promote flow. Lubricants are regularly used in several formulations to ease in the tableting step. A tablet must be ejected from the tablet press die after compression. Lubricants contribute to reduce friction between the tablet and the die metal surface, minimizing the ejection force and ensuring that the tablet is discharged cleanly and without breaking or fracture.
[00010] Lubricants can reduce friction in two ways: either one liquid lubricant forms a thin, uninterrupted fluid layer between the tablet and the metal die surface, or lubricant particles form a boundary layer on the formulation particles or metal die surfaces. Fluid lubricants are less widespread than solid lubricants. For pharmaceutical tableting, there are six different types of Solid lubricants (a) metallic salts of fatty acids; (b) fatty acids, hydrocarbons, and fatty alcohols; (c) fatty acid esters; (d) alkyl sulfates; (e) polymers; and (f) inorganic materials.
[00011] Magnesium stearate, a metallic salt boundary lubricant, is probably the most widely used lubricant for pharmaceutical tableting because it is inexpensive, provides better lubrication, has a high melting point, and is chemically stable. Another metallic salt Solid lubricant that can be used in place of magnesium stearate in a formulation is calcium stearate. Metallic salt lubricants are normally added in the range of 0.25 to 1.0 weight percent to formulations. The most prevalent fatty acid boundary lubricant is stearic acid. Fatty acids are more effective die lubricants than their alcohol counterparts, and alcohols are better than their hydrocarbon equivalents. Stearic acid is commonly added at a concentration of 2.5 percent by weight. Talc, also known as hydrous magnesium silicate, is an inorganic boundary lubricant which comes in handy when other lubricants aren't working.
[00012] Lubricants are crucial for tableting, although they might alter the tablet's properties in an undesired way. Tablet compression is influenced by lubricant type, concentration, lubrication method, and lubricant incorporation. Magnesium stearate is thought to have a detrimental effect on the hardness of tablets made of more malleable materials rather than brittle ones. When microcrystalline cellulose, a type of plastic, was combined with magnesium stearate, the tablet strength dropped dramatically as the amount of lubricant added increased. With different lubricants, similar results were observed. Other regularly used plastically deformable excipients, such as lactose and starch, were found to have a detrimental effect on magnesium stearate. Tablet disintegration and dissolving rates are frequently affected by the hydrophobic nature of various lubricants.
[00013] To determine the flow characteristics of powder, many methods have been devised. Static angle of repose, compressibility index, Hausner ratio, and shear cell testing are some of the most commonly used methods. Avalanche testing is a relatively new way of determining powder flowability. A revolving disc and a measurement system comprise the avalanche testing equipment. The powder sample is transported up the side of the drum as it rotates, eventually collapsing or avalanching due to the weight of the powder. To determine powder flowability, the properties of this powder avalanche are monitored and studied. Manufacturers use several measurement and analysis methods: an Aero-Flow Analyzer photocell array, a Revolution Analyzer sophisticated camera and imaging system, and a load cell to measure the change.
[00014] Powder flow is vital during tableting because it must flow freely and consistently into the tablet dies to ensure uniform tablet weight and consistent and repeatable tablet characteristics. The flow of powder is influenced by a number of factors. Physical factors governing powder flow involve particle size and size distribution, density, surface morphology, and particle shape. Smaller particles with low densities and an irregular surface and shape have less flow than large, smooth, and spherical particles with high densities. Particle shape and surface morphology influence particle–particle interaction, which can increase friction and reduce flowability if the contact area is expanded. Because boundary layer lubricants form a film surrounding particles, they might alter particle–particle interaction, which can have negative consequences.
[00015] Although lubricants are necessary and added to facilitate tableting, their significance on tablet characteristics and manufacture should not be disregarded. Lubricants' effects on tablet characteristics have been researched in a range of ways. Only a few people have examined the effect on flowability. The purpose of this invention was to see how lubricants affected the flowability of pharmaceuticals, as flowability is crucial in several procedures, including tableting.
[00016] Thus, the present invention relates to a co-processed self-lubricating excipient composition comprising a binder and a lubricant having superior lubrication and satisfactory tableting profile that are useful for the formulation of a wide variety of drugs.

OBJECTS OF THE INVENTION
[00017] An object of the present invention is to provide a particulate co-processed self-lubricating excipient composition for oral solid dosage forms.
[00018] An object of the present invention is to provide a particulate co-processed self-lubricating excipient composition that enhances final product tablet quality.
[00019] An object of the present invention is to provide a particulate co-processed self-lubricating excipient composition having superior lubrication profile.
[00020] An object of the present invention is to provide a particulate co-processed self-lubricating excipient composition having reduced die friction.
[00021] Another object of the present invention is to provide a method for producing a particulate co-processed self-lubricating excipient composition comprising a binder, and a lubricant for oral solid dosage forms.
[00022] Another object of the present invention is to provide a method for producing a particulate co-processed self-lubricating excipient composition comprising MCC as binder, and a lubricant for oral solid dosage forms.
[00023] Another object of the present invention is to provide a particulate co-processed self-lubricating excipient composition comprising MCC, and magnesium stearate as lubricant, which has superior lubrication profile.
[00024] Another object of the present invention is to provide a particulate co-processed self-lubricating excipient composition comprising MCC, and magnesium stearate that helps to increase flowability and tablet hardness.
[00025] Another object of the present invention is to provide a particulate co-processed self-lubricating excipient composition comprising MCC, and magnesium stearate suitable for tableting by wet granulation, direct compression and/or dry granulation.
[00026] Yet another object of the present invention is to provide a tablet formulation comprising a therapeutically active ingredient, the particulate co-processed self-lubricating excipient composition, and one or more excipients.

SUMMARY OF THE INVENTION
[00027] The present disclosure pertains to a particulate co-processed self-lubricating excipient composition and methods for producing the same. In particular, the present disclosure provides a particulate co-processed self-lubricating excipient composition for oral solid dosage forms comprising a co-processed mixture of a binder and a lubricant, wherein the binder and the lubricant particles are in intimate association with each other.
[00028] In some aspects, the present invention provides a particulate co-processed self-lubricating excipient composition for oral solid dosage forms.
[00029] In an aspect, the present invention provides a particulate co-processed self-lubricating excipient composition having reduced die friction.
[00030] In an aspect, the present invention provides a particulate co-processed self-lubricating excipient composition comprising a co-processed mixture of a binder and a lubricant.
[00031] In an aspect, the present invention provides a particulate co-processed self-lubricating excipient composition comprising a co-processed mixture of microcrystalline cellulose (MCC) as binder with a lubricant.
[00032] In some aspects, the present invention provides a method for the preparation of a particulate co-processed self-lubricating excipient composition comprising a co-processed mixture of microcrystalline cellulose (MCC) with magnesium stearate as lubricant.
[00033] In an aspect, the present invention provides particulate co-processed self-lubricating excipient composition for oral solid dosage forms comprising co-processed mixture of microcrystalline cellulose (MCC), and a lubricant; wherein said particulate co-processed self-lubricating excipient composition comprises based on total weight of the composition:
microcrystalline cellulose (MCC) in an amount ranging between 90% w/w and 99.90% w/w; and
the lubricant in an amount ranging between 0.1% w/w and 10% w/w.
[00034] In a preferred aspect, the present invention provides a particulate co-processed self-lubricating excipient composition comprising co-processed mixture of microcrystalline cellulose (MCC), and magnesium stearate; wherein said particulate co-processed self-lubricating excipient composition comprises based on total weight of the composition:
microcrystalline cellulose (MCC) in an amount ranging between 90% w/w and 99.90% w/w; and
magnesium stearate in an amount ranging between 0.1% w/w and 10% w/w.
[00035] In one aspect, the present invention provides a method for preparing the particulate co-processed self-lubricating excipient composition (FIG. 1A), the method comprising the steps of:
forming a homogeneous slurry of a binder using demineralized water;
blending of a lubricant powder to the homogeneous slurry of the binder to form a homogeneous mixed slurry; and
spray or flash drying the homogeneous mixed slurry to form the particulate co-processed self-lubricating excipient composition,
wherein, temperature during blending is maintained at 30 °C to 100 °C; and
wherein, pH during blending is maintained at 5 to 7.5.
[00036] In another aspect, the present invention provides a method for preparing the particulate co-processed self-lubricating excipient composition (FIG. 1B), the method comprising the steps of:
providing powders of a lubricant and a binder;
blending the powders of the binder and the lubricant to form a mixed powder;
forming a slurry of mixed powder using demineralized water; and
spray or flash drying the homogeneous mixed slurry to form the particulate co-processed self-lubricating excipient composition,
wherein, the blending is effected for 5 minutes at 25 rpm,
wherein, temperature during blending is maintained at 30 °C to 100 °C; and
wherein, pH during blending is maintained at 5 to 7.5
[00037] In a preferred aspect, the present invention provides a tablet formulation comprising:
the particulate co-processed self-lubricating excipient composition in an amount ranging between 30% w/w and 98% w/w;
a therapeutically active ingredient in an amount ranging between 1% w/w and 60% w/w; and
pharmaceutically acceptable excipient in an amount ranging between 1% w/w and 10% w/w.
[00038] In another aspect, the present invention provides a particulate co-processed self-lubricating excipient composition comprising MCC, and magnesium stearate suitable for tableting by wet granulation, direct compression and/or dry granulation.
[00039] In yet another aspect, the present invention provides a particulate co-processed self-lubricating excipient composition that enhances final product tablet quality.
[00040] In yet another aspect, the present invention provides a particulate co-processed self-lubricating excipient composition comprising MCC and magnesium stearate, which helps to protect pharmaceutical active ingredient form moisture.
[00041] In yet another aspect, the present invention provides a particulate co-processed self-lubricating excipient composition comprising MCC and magnesium stearate, which helps to increase flowability and tablet hardness.
[00042] In yet another aspect, the present invention provides a tablet formulation comprising a therapeutically active ingredient, particulate co-processed self-lubricating excipient composition, and one or more excipients.
[00043] Various objects, features, aspects and advantages of the inventive subject matter will become more apparent from the following detailed description of preferred embodiments.

BRIEF DESCRIPTION OF DRAWINGS
[00044] Characteristics and advantages of the subject matter as disclosed in the present disclosure will become clearer from the detailed description of an embodiment thereof, with reference to the attached drawing, given purely by way of an example, in which:
[00045] FIG. 1A relates to the flow diagram of a method for preparing co-processed excipient composition comprising Microcrystalline Cellulose (MCC) and Magnesium stearate
[00046] FIG. 1B relates to the flow diagram of another method for preparing co-processed excipient composition comprising MCC as binder and magnesium stearate as lubricant.
[00047] FIG. 2A and 2B relates to the scanning electron microscopic image co-processed excipient composition comprising MCC and Magnesium stearate.

DETAILED DESCRIPTION OF THE INVENTION
[00048] The following is a detailed description of embodiments of the disclosure. 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.
[00049] 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 and the definition of that term in the reference does not apply.
[00050] Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
[00051] In some embodiments, numbers have been used for quantifying weight percentages, angles, and so forth, to describe and claim certain embodiments of the invention and are to be understood as being modified in some instances by the term “about.” 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. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
[00052] 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.
[00053] As used in the description herein and throughout the claims that follow, the meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise.
[00054] Unless the context requires otherwise, throughout the specification which follows, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense that is as “including, but not limited to.”
[00055] 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.
[00056] 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.
[00057] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified.
[00058] The description that follows, and the embodiments described therein, is provided by way of illustration of an example, or examples, of particular embodiments of the principles and aspects of the present disclosure. These examples are provided for the purposes of explanation, and not of limitation, of those principles and of the disclosure.
[00059] The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.
[00060] The following discussion provides many example embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus if one embodiment comprises elements A, B, and C, and a second embodiment comprises elements B and D, then the inventive subject matter is also considered to include other remaining combinations of A, B, C, or D, even if not explicitly disclosed.
[00061] Various terms are used herein. 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.
[00062] The term “particulate co-processed self-lubricating excipient composition” as used herein, refers to a mixture of two or more components, i.e., a filler, a binder, a glidant and optionally lubricant and disintegrant, that have been co-processed using various means but not limited to co-milling, mechanical milling, spray drying, freeze-drying, and the like.
[00063] While a particular form of the invention has been illustrated and described, it will be apparent that various modifications can be made without departing from the spirit and scope of the invention.
[00064] The present disclosure pertains to a particulate co-processed self-lubricating excipient composition and methods for producing the same. In particular, the present disclosure provides a particulate co-processed self-lubricating excipient composition for oral solid dosage forms comprising a co-processed mixture of a binder and a lubricant, wherein the binder and the lubricant particles are in intimate association with each other.
[00065] In an embodiment of the present invention, the particulate co-processed self-lubricating excipient composition superior lubrication profile, flowability, compressibility and satisfactory tableting profile.
[00066] In some embodiments, the particulate co-processed self-lubricating excipient composition includes about 0.1 wt % to about 10 wt% of lubricant. In some embodiments about 0.1 wt % ; about 0.25 wt % ; about 0.5 wt % ; about 0.75 wt % ; about 1 wt %; about 1.1 wt % ; about 1.25 wt % ; about 1.5 wt % ; about 1.75 wt % ; about 2 wt %; about 2.5 wt % ; about 3 wt % ; about 3.5 wt % ; about 4 wt %; about 4.5 wt %; about 5 wt %; about 5.5 wt %; about 6 wt % about 6.5 wt % ; about 7 wt %; about 7.5 wt %; about 8 wt %; about 8.5 wt %; about 9 wt %; about 9.5 wt %; or about 10 wt %. More preferably 0.3 wt% - 3 wt% lubricant.
[00067] In some embodiments, the particulate co-processed self-lubricating excipient composition includes about 90 wt % to about 99.9 wt% of microcrystalline cellulose; In some embodiments, about 90 wt % ; about 90.5 wt % ; about 91 wt % ; about 91.5 wt % ; about 92 wt % ; about 92.5 wt % ; about 93 wt % ; about 93.5 wt % ; about 94 wt % ; about 94.5 wt % ; about 95 wt % ; about 95.5 wt % ; about 96 wt % ; about 96.5 wt % ; about 97 wt % ; about 97.5 wt % ; about 99 wt % ; about 99.5 wt % ; about 99.6 wt % ; about 99.7 wt % ; about 99.8 wt % ; or about 99.9 wt %.
[00068] In an embodiment of the present invention, the lubricant is selected from but not limited to magnesium stearate or sodium stearyl fumarate. Most preferably magnesium stearate.
[00069] In an embodiment, the present invention provides a a particulate co-processed self-lubricating excipient composition for oral solid dosage forms comprising co-processed mixture of microcrystalline cellulose (MCC), and a lubricant; wherein said co-processed excipient composition comprises based on total weight of the composition:
microcrystalline cellulose (MCC) in an amount ranging between 90% w/w and 99.90% w/w; and
the lubricant in an amount ranging between 0.1% w/w and 10% w/w.
[00070] In an embodiment, the present invention provides a particulate co-processed self-lubricating excipient composition for oral solid dosage forms comprising co-processed mixture of microcrystalline cellulose (MCC), and magnesium stearate; wherein said co-processed excipient composition comprises based on total weight of the composition:
microcrystalline cellulose (MCC) in an amount ranging between 90% w/w and 99.90% w/w; and
magnesium stearate in an amount ranging between 0.1% w/w and 10% w/w.
[00071] In an embodiment of the present invention, pH of the particulate co-processed self-lubricating excipient composition ranges between 5.0 and 7.5.
[00072] In an embodiment of the present invention, bulk density of the particulates of the particulate co-processed self-lubricating excipient composition ranges between 0.20 g/ml to 0.65 g/ml. Most preferably 0.28 g/ml to 0.55 g/ml.
[00073] In an embodiment of the present invention, moisture content of the particulates of the particulate co-processed self-lubricating excipient composition is below 30% and ranges between 0.1% and 15%. Most preferably 0.5% to 10%.
[00074] In an embodiment of the present invention, BET surface area of particulates of the particulate co-processed self-lubricating excipient composition ranges between 1 m2/g and 30 m2/g. Most preferably 2 m2/g and 8m2/g.
[00075] In an embodiment of the present invention, the particulate co-processed self-lubricating excipient composition has median particle size distribution of the composition ranging in the micometer scale. However, many microparticles have wider ranges of sizes. In some embodiments, the microparticles may have a diameter of at least about 1 micron, 10 micron, 50 micron, 100 micron, 200 µm, 300 µm, 400 µm, 500 µm, 600 µm, 700 µm, 800 µm, 900 µm, or 1000 µm. In some embodiments, the microparticles may have a diameter of less than 1000 µm, 900 µm, 800 µm, 700 µm, 600 µm, 500 µm, 250 µm, or less than 100 µm. The diameter of microparticles can range from any of the minimum values described above to any of the maximum values described above, for example from 1 µm to 1000 µm, 50 µm to 500 µm, 10 µm to 250 µm, 20 µm to 200 µm, or 50 µm to 100 µm. Preferably, the size of the microparticles ranges from about 25 µm to about 250 µm. Most preferably, the size of the microparticles ranges from about 50 µm to about 200 µm.
[00076] In an embodiment, the present invention provides a method for preparing the particulate co-processed self-lubricating excipient composition (FIG. 1A), the method comprising the steps of:
forming a homogeneous slurry of a binder using demineralized water;
blending of a lubricant powder to the homogeneous slurry of the binder to form a homogeneous mixed slurry; and
spray or flash drying the homogeneous mixed slurry to form the particulate co-processed self-lubricating excipient composition,
wherein, temperature during blending is maintained at 30 °C to 100 °C; and
wherein, pH during blending is maintained at 5 to 7.5.
[00077] In another embodiment, the present invention provides a method for preparing the particulate co-processed self-lubricating excipient composition (FIG. 1B), the method comprising the steps of:
providing powders of a lubricant and a binder;
blending the powders of the binder and the lubricant to form a mixed powder;
forming a slurry of mixed powder using demineralized water; and
spray or flash drying the homogeneous mixed slurry to form the particulate co-processed self-lubricating excipient composition,
wherein, the blending is effected for 5 minutes at 25 rpm,
wherein, temperature during blending is maintained at 30 °C to 100 °C; and
wherein, pH during blending is maintained at 5 to 7.5
[00078] In another embodiment of the present invention, solid content of the homogenous slurry is less than 50%. In preferred embodiment, the solid content of homogeneous slurry is 10%-50%.
[00079] In a preferred embodiment of the present invention, the moisture of homogeneous mixed slurry during the preparation is less than 5%.
[00080] In an embodiment of the present invention, the particulate co-processed self-lubricating excipient composition may further comprise one or more excipients selected from the group consisting of diluents, disintegrants, fillers, bulking agents, vehicles, pH adjusting agents, stabilizers, anti-oxidants, binders, buffers, lubricants, antiadherants, coating agents, preservatives, emulsifiers, suspending agents, release controlling agents, polymers, colorants, flavoring agents, plasticizers, solvents, preservatives, glidants, and chelating agents; used either alone or in combination.
[00081] In an embodiment of the present invention, the term “oral solid dosage formulation” shall be construed to include a particulate co-processed self-lubricating excipient composition plus a therapeutically active ingredient, optionally a disintegrant, optionally a glidant, optionally a sweetener, optionally a flavor, optionally a color, and optionally other excipients.
[00082] In an embodiment of the present invention, the oral solid dosage formulations are generally administered orally to patients, which include, but are not limited to, mammals, for example, humans, in the form of, for example, a tablet, a caplet, pills, capsules, granules or a suspension.
[00083] In an embodiment of the present invention, the oral solid dosage formulations are pharmaceutical, herbal, ayurvedic, or nutraceutical formulations.
[00084] In a preferred embodiment, the present invention provides a tablet formulation comprising:
the particulate co-processed self-lubricating excipient composition in an amount ranging between 30% w/w and 98% w/w;
a therapeutically active ingredient in an amount ranging between 1% w/w and 60% w/w; and
one or more excipients in an amount ranging between 1% w/w and 10% w/w..
[00085] In another embodiment of the present invention, the therapeutically active ingredient includes but not limited to an active pharmaceutical ingredient (For example, but not limited to Diclofenac sodium, Ondansetron HCl, Cetirizine Hydrochloride, Metformin Hydrochloride, Aceclofenac), a biosomilar, a biological, a nutraceutical, Vitamins (For example, but not limited to Ascorbic acid, Pyridoxine, Thiamine, Folic acid), Minerals (For example, but not limited to Iron, Calcium, Zinc, Magnesium, and the like) , an herbal active, (For example, but not limited to Ginseng, Curcumin , Garlic, Ginger, milk Thistel, and the like), and the like.
[00086] In an embodiment of the present invention, the tablet may be prepared by wet granulation, direct compression and/or dry granulation methods
[00087] In another aspect, the present invention provides a particulate co-processed self-lubricating excipient composition comprising MCC, and magnesium stearate suitable for tableting by wet granulation, direct compression and/or dry granulation.
[00088] In another embodiment of the present invention, the particulate co-processed self-lubricating excipient composition that enhances final product tablet quality.
[00089] In another embodiment of the present invention, the particulate co-processed self-lubricating excipient composition comprising MCC and magnesium stearate, which helps to protect pharmaceutical active ingredient form moisture.
[00090] In another embodiment of the present invention, the particulate co-processed self-lubricating excipient composition comprising MCC and magnesium stearate, which helps to increase flowability and tablet hardness.
[00091] While the foregoing description discloses various embodiments of the disclosure, other and further embodiments of the invention may be devised without departing from the basic scope of the disclosure. 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.
EXAMPLES
[00092] The present disclosure is further explained in the form of following examples. However, it is to be understood that the foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention.
Example:1 Particulate co-processed self-lubricating excipient composition 1
Table 1: Particulate co-processed self-lubricating excipient composition 1
Microcrystalline cellulose:99.9%/Magnesium stearate :0.1%
Parameters Result
pH 6.00
Bulk density, g/ml 0.30
Loss on Drying, % 4.5
Angle of Repose, ° 32
BET Surface Area, m2/g 1.83
Average PSD, µm 125

Example:2 Particulate co-processed self-lubricating excipient composition 2
Table 2: Particulate co-processed self-lubricating excipient composition 2
Microcrystalline cellulose:99.7%/Magnesium stearate :0.3%
Parameters Result
pH 6.32
Bulk density, g/ml 0.33
Loss on Drying, % 5.0
Angle of Repose, ° 30
BET Surface Area, m2/g 3.22
Average PSD, µm 120

Example:3 Particulate co-processed self-lubricating excipient composition 3
Table 3: Particulate co-processed self-lubricating excipient composition 3
Microcrystalline cellulose:99.4%/Magnesium stearate :0.6%
Parameters Result
pH 6.40
Bulk density, g/ml 0.38
Loss on Drying, % 4.80
Angle of Repose, ° 31
BET Surface Area, m2/g 5.82
Average PSD, µm 108

Example: 4 Particulate co-processed self-lubricating excipient composition 4
Table 4: Particulate co-processed self-lubricating excipient composition 4
Microcrystalline cellulose:99.2%/Magnesium stearate :0.8%
Parameters Result
pH 6.42
Bulk density, g/ml 0.43
Loss on Drying, % 5.0
Angle of Repose, ° 33
BET Surface Area, m2/g 7.14
Average PSD, µm 102

Example: 5 Particulate co-processed self-lubricating excipient composition 5
Table 5: Particulate co-processed self-lubricating excipient composition 5
Microcrystalline cellulose:99.0%/Magnesium stearate :1%
Parameters Result
pH 6.45
Bulk density, g/ml 0.40
Loss on Drying, % 5.5
Angle of Repose, ° 34
BET Surface Area, m2/g 10.23
Average PSD, µm 100

Example: 6 Particulate co-processed self-lubricating excipient composition 6
Table 6: Particulate co-processed self-lubricating excipient composition 6
Microcrystalline cellulose:98%/Magnesium stearate :2%
Parameters Result
pH 6.48
Bulk density, g/ml 0.48
Loss on Drying, % 5.80
Angle of Repose, ° 35
BET Surface Area, m2/g 13.14
Average PSD, µm 98

Example: 7 Particulate co-processed self-lubricating excipient composition 7
Table 7: Particulate co-processed self-lubricating excipient composition 7
Microcrystalline cellulose:96%/Magnesium stearate :4%
Parameters Result
pH 6.52
Bulk density, g/ml 0.59
Loss on Drying, % 6.00
Angle of Repose, ° 38
BET Surface Area, m2/g 15.24
Average PSD, µm 95

Example: 8 Particulate co-processed self-lubricating excipient composition 8
Table 8: Particulate co-processed self-lubricating excipient composition 8
Microcrystalline cellulose:94%/Magnesium stearate :6%
Parameters Result
pH 6.54
Bulk density, g/ml 0.61
Loss on Drying, % 6.5
Angle of Repose, ° 43
BET Surface Area, m2/g 18.30
Average PSD, µm 80

Example: 9 Particulate co-processed self-lubricating excipient composition 9
Table 9: Particulate co-processed self-lubricating excipient composition 9
Microcrystalline cellulose:92%/Magnesium stearate :8%
Parameters Result
pH 6.58
Bulk density, g/ml 0.61
Loss on Drying, % 6.50
Angle of Repose, ° 43
BET Surface Area, m2/g 20.51
Average PSD, µm 65

Example: 10 Particulate co-processed self-lubricating excipient composition 10
Table 10: Particulate co-processed self-lubricating excipient composition 10
Microcrystalline cellulose:90%/Magnesium stearate :10%
Parameters Result
pH 6.68
Bulk density, g/ml 0.65
Loss on Drying, % 7.00
Angle of Repose, ° 44
BET Surface Area, m2/g 30.14
Average PSD, µm 50
Example 11: Amino acids, L-Cysteine Tablet Composition
Table 11: Amino acids, L-Cysteine Tablet with particulate co-processed self-lubricating excipient composition:
Name of Iingredient mg/tablet
Active ingredient (L-Cysteine amino acid) 500
Croscarmellose Sodium 27
Co-processed self -Lubricating Excipient 373

Table 12: L-Cysteine Amino Acid Tablet Evaluation
Characteristic Result
Description Oval, Concave, White
Tablet weight (mg) 900.0
Diameter (mm) 18.00
Thickness (mm) 6.65
Hardness (N) 93.8
Friability (%) 00
Disintegration Time (Sec) 7

Example 12: Vitamin:Ascorbic acid (Vitamin C) Tablet with particulate co-processed self-lubricating excipient composition:
Table 13: Vitamin:Ascorbic acid (Vitamin C) Tablet with particulate co-processed self-lubricating excipient composition:
Name of Iingredient mg/tablet
Active Ingredient (Ascorbic acid) 500
HiLose Croscarmellose sodium C
Co-processed Self Lubricating Excipient 373

Table 14: Vitamin:Ascorbic acid (Vitamin C) Tablet Evaluation:
Characteristic Result
Description Round, Bevel, White
Tablet weight (mg) 900
Diameter (mm) 16.00
Thickness (mm) 3.53
Hardness (N) 56.7
Friability (%) 0.616
Disintegration (sec) 13

Example 13: Herbal extract, Ginseng tablet with particulate co-processed self-lubricating excipient composition:
Table 15: Herbal extract, Ginseng tablet with particulate co-processed self-lubricating excipient composition:
Name of ingredient mg/tablet
Active Ingredient (Ginseng) 200
HiLose Croscarmellose Sodium 22.5
Co-Processed Self -lubricating Excipient 277.5

Table 16: Herbal extract, Ginseng tablet Evaluation:
Characteristic Result
Tablet description Elongated off white color tablet
Average weight (mg) 500
Average Hardness, (N) 66.1
Thickness (mm) 4.50
Average Diameter (mm) 18.0
Friability (%) 00
Average Disintegration Time (Sec) 48.5
Example 14: Pharmaceutical Active Ondansetron HCl Tablet with particulate co-processed self-lubricating excipient composition:
Table 17: Pharmaceutical Active Ondansetron HCl Tablet with particulate co-processed self-lubricating excipient composition:
Name of Iingredient mg/tablet
Ondansetron HCl 8
CCS 2.8
BARETab Lub 119.2

Table 18: Pharmaceutical Active Ondansetron HCl Tablet tablet Evaluation:
Characteristic Result
Description Elongated, Concave, White
Tablet weight (mg) 130.0
Diameter (mm) 3.47
Thickness (mm) 3.47
Hardness (N) 64.9
Friability (%) 0.046
Disintegration Time (Sec) 8.33
Dissolution Time (Min) 100% released in 10 min

Example 15: Scanning electron microscopy (SEM) analysis of co-processed self-lubricating excipient
SEM data evaluated for the excipient composition prepared with 99.5% MCC and 0.5 % Magnesium stearate composition (Composition 11).
Table 19: Particulate co-processed self-lubricating excipient composition 11
Microcrystalline cellulose:99.5%/Magnesium stearate :0.5%
Parameters Result
pH 6.31
Bulk density, g/ml 0.32
Loss on Drying, % 4.5
Angle of Repose, ° 30
BET Surface Area, m2/g 3.25
Average PSD, µm 119

SEM images of composition 11 particles in Fig: 2A and 2B show that Magnesium stearate coated on MCC particles. After coating self -lubricating excipient particles are smoother and having bigger BET surface area, excellent flowability (Table 19).
[00093] Various modification and variation of the described assays, techniques and various means disclosed herein to implement the assays/methods in accordance with the present invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention that are obvious to those skilled in the relevant fields are intended to be within the scope of the following claims.
, Claims:1. A particulate co-processed self-lubricating excipient composition for oral solid dosage forms comprising a co-processed mixture of a binder, and a lubricant; wherein said composition comprises based on total weight of the composition:
the binder in an amount ranging between 90% w/w and 99.90% w/w; and
the lubricant in an amount ranging between 0.1% w/w and 10% w/w,
wherein, the MCC and lubricant being in intimate association with each other and the lubricant integrated with or partially coating on MCC.

2. The composition as claimed in claim 1, wherein the binder is microcrystalline cellulose (MCC)

3. The composition as claimed in claim 1, wherein the lubricant is magnesium stearate.

4. The composition as claimed in claim 3, wherein magnesium stearate is comprised in an amount ranging between 0.1% w/w and 5% w/w.

5. The composition as claimed in claim 3, wherein magnesium stearate is comprised in an amount ranging between 0.3% w/w and 3% w/w.

6. The composition as claimed in claim 1, wherein the average particle size of the particulates ranges between 1 µm to 1000 µm.

7. The composition as claimed in claim 1, wherein the average particle size of the particulates ranges between 10 µm to 800 µm.

8. The composition as claimed in claim 1, wherein the average particle size of the particulates ranges between 30 µm to 250 µm.
9. The composition as claimed in claim 1, wherein the average particle size of the particulates ranges between 25 µm to 100 µm.

10. The composition as claimed in claim 1, wherein the average particle size of the particulates ranges between 30 µm to 60 µm.

11. The composition as claimed in claim 1, wherein pH of the composition ranges between 5.0 and 7.5.

12. The composition as claimed in claim 1, wherein moisture content of the composition ranges between 0.5% and 10%.

13. The composition as claimed in claim 1, wherein the bulk density of the particulates ranges between 0.20 g/ml to 0.65 g/ml.

14. The composition as claimed in claim 1, wherein the bulk density of the particulates ranges between 0.28 g/ml to 0.55 g/ml.

15. The composition as claimed in claim 1, wherein the BET surface area of the particulates ranges between 1 m2/g and 30 m2/g.

16. The composition as claimed in claim 1, wherein the BET surface area of the particulates ranges between 2 m2/g and 8m2/g.

17. The composition as claimed in claim 1, wherein the oral solid dosage formulation is a tablet, a pill, or a capsule.

18. A pharmaceutical formulation comprising the composition as claimed in claim 1.

19. A nutraceutical formulation comprising the composition as claimed in claim 1.
20. A method for preparing the particulate co-processed self-lubricating excipient composition as claimed in claim 1, the method comprising the steps of:
forming a homogeneous slurry of a binder using demineralized water;
blending of a lubricant powder to the homogeneous slurry of the binder to form a homogeneous mixed slurry; and
spray or flash drying the homogeneous mixed slurry to form the particulate co-processed self-lubricating excipient composition,
wherein, temperature during blending is maintained at 30 °C to 100 °C; and
wherein, pH during blending is maintained at 5 to 7.5.

21. A method for preparing the particulate co-processed self-lubricating excipient composition as claimed in claim 1, the method comprising the steps of:
providing powders of a lubricant and a binder;
blending the powders of the binder and the lubricant to form a mixed powder;
forming a slurry of mixed powder using demineralized water; and
spray or flash drying the homogeneous mixed slurry to form the particulate co-processed self-lubricating excipient composition,
wherein, the blending is effected for 5 minutes at 25 rpm,
wherein, temperature during blending is maintained at 30 °C to 100 °C; and
wherein, pH during blending is maintained at 5 to 7.5

22. The method as claimed in claim 20 or 21, wherein the binder is microcrystalline cellulose (MCC).

23. The method as claimed in claim 20 or 21, wherein the lubricant is magnesium stearate.

24. A tablet formulation comprising:
the particulate co-processed self-lubricating excipient composition as claimed in claim 1 in an amount ranging between 30% w/w and 98% w/w;
a therapeutically active ingredient in an amount ranging between 1% w/w and 60% w/w; and
one or more excipients in an amount ranging between 1% w/w and 10% w/w.

25. The tablet formulation as claimed in claim 24, wherein the therapeutically active ingredient is selected from active pharmaceutical ingredient, a biosomilar, a biological, a nutraceutical, Vitamins, Minerals, an herbal active, and the like.

26. The tablet formulation as claimed in claim 24, wherein the one or more excipients is selected from the group consisting of diluents, disintegrants, fillers, bulking agents, vehicles, pH adjusting agents, stabilizers, anti-oxidants, binders, buffers, lubricants, antiadherants, coating agents, preservatives, emulsifiers, suspending agents, release controlling agents, polymers, colorants, flavoring agents, plasticizers, solvents, preservatives, glidants, and chelating agents; used either alone or in combination.

27. The tablet formulation as claimed in claim 24, wherein the tablet is prepared by wet granulation, direct compression and/or dry granulation methods.