WO2008059522A2

WO2008059522A2 - Herbal gastrointenstinal controlled drug delivery dosage forms including pellets and process for their preparation

Info

Publication number: WO2008059522A2
Application number: PCT/IN2007/000455
Authority: WO
Inventors: Anwar Siraj Daud; Jamaluddin Shamsuddin; Faiz Zakir Vali; Shakera Hussain; Mohammed Saleh Vali
Original assignee: Unijules Life Sciences Ltd
Priority date: 2006-09-28
Filing date: 2007-09-26
Publication date: 2008-05-22
Also published as: WO2008059522A3; WO2008059522B1

Abstract

Described is novel oral dosage form for administration of one or more of an herbal extract and process for preparing the same wherein a herbal extract is coated on pellets and the said pellets are either filled into a capsule or compressed into a tablet, the said capsule may contain pellets coated with one or more of a herbal extract and the said tablet is compressed from pellets coated with at least two or more of a herbal extract. Process for preparation of the said dosage form is also described. The said pellets coated with herbal extract are finally coated with a controlled release coat of a polymer that shall result in controlled release of the herbal extract/s in the gastrointestinal tract.

Description

HERBAL GASTROINTENSTINAL CONTROLLED DRUG DELIVERY DOSAGE FORMS INCLUDING PELLETS AND PROCESS FOR THEIR PREPARATION;

TECHNICAL FIELD

The present invention relates to a controlled release herbal gastrointestinal drug delivery dosage forms including pellets, tablets and capsules and process for their preparation.

BACKGROUND OF INVENTION

Herbal medicines are largely traditional. Solid dosage forms of products from medicinal plants and their extracts available in the market are restricted to the traditional dosage forms of powders, tablets and powders filled in capsules.

Process of preparation of a powder, a tablet or a capsule comprises use of crude herbal materials and extracts prepared from crude herbs. The crude herbs are washed, dried, crushed, pulverized, and sifted through a suitable sieve and. finally this powder is used as such, or converted into a tablet or filled up in capsule shells, usually made of hard gelatin or any other suitable material. The prior art dosage forms, thus, effectively delivered the plant material or its extract in a powder form, and its bioavailability and efficacy was limited by the efficacy with which the active principles of powder got released and absorbed in the digestive tract of the patient.

Further, when two or more herbal extracts were aimed at being administered in a single dosage form, they will have to be invariably in a direct physical contact with each other in a tablet or a capsule form in a prior art process, exposing them to unknown interactions with complex components of each other right from stage of mixing together for processing purpose, through compressing together in a tablet or filling together in a capsule, and continuing the physical contact all through storage up to actual administration to the patient. Traditional systems of medicine based on herbal extracts, such as Ayurveda are regarded as authentic on account of practices followed for generations with known effects on pathological problems for which they are applied. The authenticity of these practices is considered to be maintained so long as they conform to the books of ancient scriptures in spirit. In Ayurvedic system, when more than one extracts are intended to be used for a treatment, they are either taken sequentially and separately or mixed immediately prior to oral administration.

Thus, when it comes to administration of crude herbal extracts for any reason, because of their complex and substantially unknown composition, and because in intimate physical contact for a long time, interactions of two or more crude herbal extracts and their effect on their pharmaceutical efficacy and bioavailability will be largely unknown, there is a reason to state that such intimate physical mixing be avoided altogether. The need to evolve an appropriate method by which it would also be possible to formulate, store and administer a mixture of crude herbal extracts in a single dosage form without giving a scope for their coming in intimate contact or allowing least possible contact with each other before oral administration so that treatments involving more than one crude herbal extract can be made available in one and the same dosage form.

Further, odor / flavour of some herbal extracts, Garlic extract for example, is so strong that it induces belching of Garlic odor which is highly discomforting.

Similarly, Sennosides present in extract of Cassia angustifolia Vahl are meant for laxative action in colon, induces a gripping action in upper gastrointestinal region. In yet another instance, Boswellic acid extracted from Boswellia serrata Roxb. ex Colebr. Boswellic acid has analgesic and anti-inflammatory action and therefore very useful in arthritis. However due to its rapid absorption & short duration of action, drug is required to administered frequently in large quantities. In another example of special problems of application of problematic applications in some herbal extracts, Curcumin in pure form extracted from Turmeric (Curcuma longa Linn.) also has fast absorption and short life.

PRIOR ART

Jiang and Wang (2005) in a patent application no. CN1682966A have disclosed a product oral disintegrating tablet containing Yunnan Manyleaf paris Rhizome extract and its preparing process. Said application discloses orally disintegrating Gongxuening tablet as a kind of medicine preparation for treating menorrhagia, metrorrhagia and chronic pelvic inflammation. The medicine preparation has the functions of cooling blood, arresting bleeding, clearing away heat, eliminating wetness, dispersing blood clots and relieving pain. The application also relates to the preparation process of orally disintegrated Gongxuening tablet, and the preparation process includes preparing pellet, coating powder and tablet pressing. The patent does not disclose a capsule containing the pellets.

Debregeas et al (2004) in US patent application no. 20040081691 has disclosed granules containing at least one plant substance, comprising a neutral core having a particle size of between 200 and 1600 .mμm coated with a layer containing the plant substance combined with a pharmaceutically acceptable excipient, wherein the layer containing the plant substance further comprises polyvinylpyrrolidone as a binder. The composition disclosed by Debregeas et al is also claimed as a controlled release composition. SUMMARY OF THE INVENTION

This invention embodies a process of delivering the herbal extracts, including a herbal drug, in a form of a coat over pellets, optionally applying a finishing coat and an optional color over the coated pellets, and filling the said coated pellets of one or more of an extract in the same capsule optionally with color coated nonpareil seeds. The invention also describes a process of preparation of such pellets, a process of filling such pellets in capsule of hard gelatin or other material or pressing these pellets into tablets.

The invention is also embodied in the benefits it imparts to a herbal extract in general and a crude herbal extract in particular, of increase in the surface area of the extract several-fold resulting from applying and coating on inert beads of a suitable size made of an inert material, to facilitate improvement in bioavailability of the active ingredients.

This invention is also embodied in the products in the form of herbal pellets, herbal pellet filled capsules, the said capsules being transparent or otherwise. This invention also embodies a method of preparing a dosage form in which physical contact between individual particles in a crude herbal extract with each other or between particles of two or more crude herbal extracts with each other is substantially limited or practically prevented. A further embodiment of the invention relates to treating the pellets after their formation with one or more of a_. polymer in such a way that the active principle is released in a controlled manner, as per the requirement, in small intestine, large intestine or sustained release over a longer period of time such as for about 12 hours. Release in small intestine overcomes strong odors that lead to belching. Release in large intestine shall ensure contact of the herbal drug with the body does not occur in upper gastro-intestinal tract, in stomach or small intestine that is critical for avoiding a "gripping action "in stomach. A sustained release over a long period such as 12 hours or so shall help in avoiding fast absorption for drugs like purified curcumin.

DETAILS OF INVENTION

The process essentially involves applying extract layer on a core of pellets of a suitable size consisting of an inert material available in the form of beads. Such inert beads are conventionally used in pharmaceutical science, and are readily available in market in all industrial countries. The advantages of a process of coating of an extract on pellets are that the coating usually gives a uniform and continuous product coating. Aqueous or organic coatings can be applied. Coating and drying take place in one machine. In terms of containment, the coating process and the filling and emptying of the machine can be carried out in complete isolation and without product spreading into the environment. Acquiring herbal raw material is always a big problem. Loss of material can be avoided due to this isolation process. The most preferred bead is one prepared from starch and sucrose, for use in confectionary as well as in pharmaceutical manufacturing. However, beads of any pharmaceutically acceptable excipient may be used, including, for example, microcrystalline cellulose, vegetable gums, waxes, and the like. The primary characteristic of the inert bead is to be inert, with regard both to extract and the other excipients in the pellet and with regard to the patient who will ultimately ingest the pellets. But at the same time the bead material should be easily excretable and / or digestible.

The size of the beads depends, of course, on the desired size of the pellets to be manufactured. In general, pellets can be as small as 0.1 mm, or as large as 2 mm. Preferred beads are from about 0.3 to about 0.8 mm, in order to provide finished pellets in the desired preferred size range of from about 0.5 to about 1.5 mm in diameter. It is always prudent to select beads with a reasonably narrow particle size distribution, in order to improve the uniformity of various coatings desired to be added and the homogeneity of the final product. For example, the beads may be specified as being of particle size ranges such as from 14 to 20 U.S. mesh, from 20 to 25 U.S. mesh or from 25 to 35 U.S. mesh to obtain acceptable size distributions of various sizes.

The amount of beads to be used obviously depends on the weight and thickness of the added layers; in general, the beads comprise from about 15 to about 90 percent of the product. More preferably, the charge of beads should represent from about 20 to 65 percent of the product.

When manufacture of the pellets begins with inert beads, the extract is coated on the beads to yield a final drug concentration of about 1 to about 50 percent of the product, in general. The amount of extract, of course, depends on the desired dose of the drug and the quantity of pellets, which it is desired to administer. The usual amount of pellets is that amount which is conveniently held in gelatin, capsules.

Historically, this process has . been conducted in conventional coating- pans similar to those employed in sugar coating processes. This process can be used to prepare pellets, but this equipment has less efficient air flow and drying capabilities which limits application rates and can result in longer processing times in order to minimize agglomerations.

Alternately the present product could be made in fluidized bed equipment (using a rotary processor), or in rotating plate equipment. The rotating plate equipment typically consists of a cylinder, the bottom of which is a rotatable plate. Motion of the mass of particles to be coated is provided by friction of the mass between the stationary wall of the cylinder and the rotating bottom of it. Means can be provided to apply warm air to dry the mass, and liquids can be sprayed on the mass and balanced against the drying rate as in the fluidized bed case.

Extract may be built up on the cores by spraying a slurry comprising extract suspended in a solution of the excipients, dissolved or suspended in sufficient water and lsopropyl alcohol (IPA) to make the slurry sprayable. Such slurry may be milled through a machine adapted for grinding suspension in order to reduce the particle size of extract. Grinding in suspension form is desirable because it avoids dust generation and containment problems, which arise in grinding dry powder drugs. A preferred method for applying this suspension is in the classic pharmaceutical fluidized bed coating device, which consists simply of a vertical cylinder with an air-permeable bottom and an upward spraying nozzle close above the bottom, or a downward-spraying nozzle mounted above the product mass. The cylinder is charged with particles to be coated, sufficient volume of air is drawn through the bottom of the cylinder to suspend the mass of particles, and the liquid to be applied is sprayed onto the mass. The temperature of the fluidizing air is balanced against the spray rate to maintain the mass of pellets at the desired level of moisture and stickiness while the coating is built up.

A finishing layer over the extract layer is not necessary in every case, but frequently improves the elegance of the product and its handling, storage and machinability and may provide further benefits as well. The simplest finishing layer is simply a small amount, about less than 1% of an anti-static ingredient such as talc or silicon dioxide, simply dusted on the surface of the pellets. Another simple finishing layer is a small amount, about 1%, of a wax such as beeswax melted onto the circulating mass of pellets to further smooth the pellets, reduce static charge, prevent any tendency for pellets to stick together, and increase the hydrophobicity of the surface. More complex finishing layers may constitute a final sprayed-on layer of ingredients. For example, a thin layer of polymeric material such as Hydroxy Propyl Methyl Cellulose (HPMC), Polyvinylpyrrolidone (PVP) and the like, in an amount such as from about 2% up to about 10%, may be applied. The polymeric material may also carry a suspension of an opacifier, a bulking agent such as talc, or a coloring material, particularly an opaque finely divided color agent such as red or yellow iron oxide. Such a layer quickly dissolves away in the stomach, but provides an added measure of pharmaceutical elegance and protection from mechanical damage to the product. Finishing layers to be applied to the present product are of essentially the same types commonly used in pharmaceutical science to make the surface smooth and shining, and color the products, and may be formulated and applied in the manners commonly known to a person skilled in the art of manufacture of pharmaceutical dosage forms.

The pellets coated with herbal extracts by process of this invention are dust free, round in shape, free flowing, with good dispersibility, decreased hygroscopicity, better uniformity in grain size distribution, with even distribution of drugs, and heavy metal content is also within recommended limits of W.H.O. and US F.D.A. i.e. for Lead, less than 10 ppm, for Cadmium less than 0.3 ppm, for Arsenic less than 10 ppm, and for Mercury less than 1 ppm. The tests for heavy metals are carried out as per US Pharmacopoea methods; for Lead - as per USP 23< 251>,for Arsenic as per USP 24 <211>, Mercury as per USP 25 <261>, and Cadmium is estimated as per the method given in the book 'Quality control methods for medicinal plant material' WHO Geneva 1998 page 61 This invention, in general, is applicable to all herbal extracts that can be palletized in the way described in this invention. This invention embodies capsules as an oral dosage form containing pellets coated with a herbal extract. The pellets may be coated with only one extract or, when the extracts have no incompatibility with each other either for chemical reasons or when the extracts pertains to a pharmaceutical system where mixing extracts from two or more plants is not barred during preparation and storage of the product, the pellets may also be coated with more than one extract on the same batch. The pellets may or may not be coated with a finishing layer. The pellets containing a finishing layer may or may not contain a color or they may or may not be additionally colored. The capsules may be filled with pellets of only one extract, or of more than one extract prepared in independent batches, with or without additional colored non-pareil seeds. Thus, it is possible to envisage several variations of embodiments covered by this invention.

However, a special application lies in its application for improvement of Ayurvedic drug treatment on account of coating of an extract on herbal pellets, surface area available for action and absorption increases tremendously and further particle- to-particle contact within the same extract or two different extracts existing in a same packing / storage space such as a capsule, gets minimized. Such a contact can get further minimized when coated pellets are further applied a finishing coat, which practically eliminates such a possibility. This makes it possible to make. . mixtures of extracts for improving efficacy of Ayurvedic preparation without prejudicing the basic practices of Ayurveda wherein interaction of two different extracts before they are inside stomach is required to be avoided. The increase in surface area leads to improvement in their bioefficacy and bioavailability without resorting to purification of an active ingredient, a method not complaint with Ayurveda, and without changing relative content of other ingredients in the crude extract prepared adhering to the recommended Ayurvedic practice.

Ayurvedic drug treatment is a traditional system of medicine in India based predominantly on use of extracts of medicinal plants prepared by ways scrupulously recommended by Ayurveda and validated for their medicinal effect by observations over several generations. The medicinal plant extracts used in this system, although crude, are highly specific for their efficacy only when prepared in the recommended way. Multiple components present in crude plants behave like a polytherapy. The different components of the extract modulate the activity of each other and are relatively nontoxic as they are present in naturally well balanced ratios (Saxena, R.C., World Congress on Biotechnological Developments in Medicinal Substances of Plant and Marine Origin, Lucknow. (India), Feb.19-22 (1995) For example, of the various components present in Glycyrrhiza glabra Linn., glycyrrhezinic acid in its pure isolated form has shorter life as compared to when it is a part of unpurified crude extract of the same plant. . Similarly reserpine from Rauwolfia serpentina Benth. is more toxic, morphine from Papaver somniferum Linn, is more addictive and bioavailability of curcumin from Curcuma longa Linn. is poor when purified

Therefore it can be said that isolation of an active principle from among different components of natural substances alters its pharmacokinetic as well as pharmacodynamic profile. An attempt of improvement In Ayurvedic drug therapy, the age old traditional system of medicine in India based predominantly on use of crude extracts of medicinal plants, through isolation of chief active principle is not considered advisable. The Ayurvedic extracts are best when their composition in crude form is not altered by way of a purification step in anticipation that this will lead to improvement in efficacy. Thus, improvement in Aurvedic drug therapy has formidable constraints for further improvement and achievement of improvement without purifying a crude extract is a challenge.

Invention described in this specification makes no change in crude forms of the extract; it only changes the surface area available for absorption and bio-activity. Relative content of individual components in the extract remains unaltered, which ensures the same medicinal properties but with more efficacious pharmacokinetic and pharmacodynamic action of its ingredients. Thus, the requirement that the crude extract should not be purified to an extent not recommended in Ayurveda is also complied and an improvement in efficacy inherent from improved surface area available for absorption and action is also achieved. Thus this invention provides a feasible route / tool to improve efficacy of Ayurvedic treatments by pelletizing Ayurvedic drugs. This is a very important achievement of this invention. The established practice of self manufacturing and dispensing by the Ayurved practitioner after formulation as per Ayurvedic methodology and dispensing small quantities at a time also have important merits. What they achieve is that the components of the Ayurvedic drug treatment remain separate from each other until administered orally; they are not exposed to interaction with each other during preparation or in storage. This invention helps to achieve the effect of this principle even for formulations which aim at administering two or more ayurvedic extracts in one and the same dosage form. Here too the individual plant extracts remain distinctly separate from each other even in storage in a single capsule and they come in contact with each other, within the same plant extract as well as between two or more different plant extracts, only after ingestion. This becomes clear from the manufacturing process in which, crude extract ingredients are first deposited on inert spherical beads, which are further individually coated with a finishing coat, which helps in preventing the coat of the extract with coat of extract of other individual pellet particle, whether of the same extract or another extract. They are then dried, mixed and offered as attractive capsules. It has been noted that attractive and elegant capsules add to the acceptance and compliance to the products by patients, facilitating the success of the therapy. The coating as well as spherical shape of beads ensures that the individual ingredients come in minimal contact of each other during their storage until their actual use by the patient. When the spherical beads are not coated with a finishing coat, of course, some contact between medicinal coat of two beads shall inevitably occur, however, such contact shall be very minimal and hence, even in uncoated beads, this invention provides a way to minimize a contact between particles of a crude extract with another particle of same or different extract packed and stored in same dosage form.

The coating is formulated with such ingredients which dissolve in the stomach, thus making available all the ingredients in original Ayurvedic intended form as it made fresh and delivered at the time of administration itself.

Thus a herbal pellet formulation of this invention is in true spirit of Ayurveda with the following advantages:

Spherical shape of pellets enables them to flow freely and pack uniformly, thereby alleviating handling and packaging problems

The drug coated pellets can be given an outer coating of different colour that distinguish one drug from the other and these can be blended and filled into transparent hard gelatin capsules. This improved elegance facilitated better acceptability and compliance to the product by the patient. It has better bioavailability due to larger area in comparison with conventional dosage form.

It is economical, feasible and viable.

The list of extracts of herbs known traditionally for their medicinal properties is very long. Some of them are illustrated in this specification, literature references on medicinal properties of which are given below. Zingiber officinale Roxb. (Yamahara J, Rong HQ, Iwamoto M, Kobayashi G, Mastuda H, Fujimura H, Active components of ginger exhibiting antiserotonergic action. Phytotherapy Research 1989;3:70-1), Piper longum Linn. (Neogi, N. C. et al.: J. Res. Med. 6:1 (1971), Boswellia serrata Roxb. ex Colebr. (Safayhi, H. et al. (1992) Boswellic acids: novel, specific, non-redox inhibitors of 5-lipoxygenase. J. Pharmacol. Exp. Ther. 261 :1143-6.), Vitex negundo Linn. (Jain, P.K. and T.N.Pande : J. Res. Ind. Med. Yoga Homeo. 11 :2 (1976)), Tinospora cordifolia (WiIId.) Miers ex Hook. f. & Thorns. (Pendse V.K. et al., Ind. J. Pharmacol. 9:221 (1977), Curcuma longa Linn. (Deodhar SD, Sathi R, Srimal RC. Preliminary clinical study of anti-arthritic activity of Curcumin. Ind J Med Res 1902:71 :632-4.), Centella asiatca Linn. (Bhargava R. K. and Soni V. Rajasthan Med. J. 1980, 19,23), Bacopa monnieri Linn. (Appa Rao MVR, Koteswara Rao, TJ. Res. Indian Med. 1973, 8(4), 9), Momordica charantia Linn. (Khanna P. et al, (1981), J. Natl. Prod.44, 648.), Azadirachta indica A. Juss. (Indrayani C. Apte, Ph. D. Thesis (1983), Effect of indigenous preparations on certain important enzymes of pathways involved in Diabetes Mellitus. Nagpur University.), Ocimum sanctum Linn. (Verma P. et al. (1991), Ind. J. Pharmacol. 23,99-103), Zingiber officinale Roxb. (Giri JJnd.J.Nutr. Diet.21 , 433(1984).), Picrorhiza kurroa Royle ex Benth. (Simons J. M., (1989), J Ethnopharmacol. 26(2) 169-182), Withania somnifera Dunal. J. Ethnopharmacol 1994 Dec.;44(3): 131-5.), Bacopa monnieri Linn. (Bhattacharya SK, Ghosal S, Phtomedicine 1998; 5:77-82.), Nardostachys jatamansi DC. (Chopra, I. C, et.al. Indian J. of Med. Res. 42:385(1954).), Boerhavia diffusa Linn. Pharmacopoeia of India, Ministry of Health and Family Welfare, Govt. of India, 605 (1966)), Tribulus terristris Linn. (Sangeeta D, Sidhu H., Thind S.K. and Nath R., J. Ethnopharmacol '.44, 61(1994)), Picrorhiza kurroa Royle ex Benth (Pandey, V.N., M. D. (Ay.)Thesis, Clinical exerimental studies on certain liver diseases with special reference to indigenous drug Kutki (Picrorrhiza kurroa) in the treatment of jaundice (Kamala Roga), Banaras Hindu University, Varanasi (1966).), Phyllanthus niruri Linn. (Umarani, D.et al.: Ancient Sci. L/fe.4:174 (1984).), Cassia angustifolia Vahl. (Brittain R.T., Grimshaw.J.J. J. Pharma, Pharmacol., 1962, 14, 715), Holarrhena antidysenterica (Roth) A. DC. (Singh, KP. : Ancient Science Life 5:228 (1986)), Euphorbia hirta Linn. (Vijaya, K.et al., J. Ethanopharmacology 49, 2-1 , 115-118 (1995).), Asparagus racemosus WiIId. (Anjaria, J.V., Varia, M. R., Janakiraman, K. and Gulati, O.D., Indian J. Exp. Biol. 13, 448 (1975).), Allium sativum Linn. (Velasquez, B. L. and Rodriguez, J. M. O. Arch. Inst. Farmacol. Exp. (Madrid) 8, 10-12 (1955)), Euphorbia hirta Linn. (Blanc P., Bertrand, P.De Saqui-Sannes, G. and Lescure, R. Ann. Biol. Clin, 21 , 829 (1963)), Pueraria tuberosa DC. (Indian J. Chem., 7, 210(1969)), Leptadenia reticulata Wight and Arn. (Anjaria, J.V.and Gupta, I., Indian Vet. J., 44,967(1967).), Trigonella foenum-graecum Linn. (Scarpa, A. Fitoterapia 21 ,143(1950)), Withania somnifera Dunal. (Singh, R.H.and Malviya, P.C. J.Res.lndian Med.Yoga and Homeo. 13,17-24 (1978).), Tribulus terristris Linn. (Gauthaman K.Ganesh AP., Prasad R.N. J.AItern complement Med. 2003 Apr. 9(2) L 257-65.), Mucuna prureins Baker. (Bell,E.A.et al: Phytochemistry 10 : 2191 (1971)), Tribulus terristris Linn. (Seth S. D and Jagadesh, G. Cardiac action of T. terrestris L. Indian J Med. Res., 64[12]: 1821-25,1976.), Terminalia arjuna W. and A.

(Vaidya AB: Terminalia arjuna in cardiovascular therapy. J Assoc Physi lnd 1994, 42:281-282)

Specific plant parts used for making extracts of the above mentioned plants are given in the following Table no.1. In all the cases where a specific plant part is mentioned, whole plant may also be used for making the extract. Table No. 1:

Herbal extracts mentioned above are prepared with any of the method known to the pharmaceutical art as per methods indicated in the related literature, mainly based on soxhlet extraction. Solvent or a mixture of solvent may be used to get total extracts. Solvent may be water, hydroalcoholic, acetone, hexane or any solvent reported in the literature for preparing herbal extracts.

In addition to the preferred solvents mentioned above for the preferred plant part, a herbal extract for the purpose of application of this invention can also be prepared by using any other plant part by using a solvent not mentioned herein or by a method not mentioned herein. Methods of preparation extract mentioned here are only illustrative in nature.

A herbal extract for the purpose of application of this invention may also be prepared by any of the other methods as long as it can be coated on the pellets by one or the other methods.

The said process of coating could be any of the process of applying a coat known in the art of pharmacy or a novel method. A process of imparting a property of controlled release includes one or more of a method including but not limited to use of a polymer or a like material for facilitating a controlled release of the drug at the desired site of its release. The said controlled release pellets may be immediate release, enteric coated, and colon targeted or sustained release and the like. Such pellets may be filled into Gelatin or HPMC capsules or are pressed in to form a tablet. A controlled release dosage form of herbal pellets may also include treating a capsule or a tablet in a way that exposes the pellets for release of the drug and its absorption in a manner that is controlled.

Wherever delayed release or sustained release is desired, the pellets described above could be coated with polymers to control release as per requirement. Thus, compositions of this invention combine delayed release mechanism with the advantages of large surface area for achieving better efficacy as well as avoiding contact of two herbal extracts before they are available for absorption, when administered as part of a same composition.

Controlled drug release pellets are prepared by film coating process that has become widely used in the pharmaceutical industry. This process provides a great deal of flexibility to the formulator when designing high quality pharmaceutical dosage form concurrent with the emergence of newer types of coating system has been the evolution in design of coating equipment. Previous emphasis on the use of conventional pans is gradually being replaced by the adaption of side vented coating pans and fluidized bed coating equipment as the process methodologies of choice. Fluidised bed technologies have gained a position of significant importance when coating multiparticulates. Basic approaches to film coating process involve the use of: 1. .film forming materials dissolved in an appropriate solvent (Usually organic in nature).

2. Aqueous polymer dispersion.

3. .hot Melt.

In one experiment, enteric-coated Garlic pellets are prepared which releases the medicaments in small intestine to avoid belching of Garlic odor by avoiding the release of medicaments in stomach. Garlic pellets are enteric coated with polymer Cellulose Acetate Pthalate, which releases the Garlic only in intestine not in stomach therefore belching of Garlic odor is avoided.

In another experiment on Colon delivery sennosides pellets the medicament is released in colon to avoid gripping action of sennosides in upper gastrointestinal region. Site of action of sennosides is in colon. The pellets are so designed to release sennosides in colon. Sennosides are presents in Cassia angustifolia

Vahl., and is extracted from it. The action of Sennosides is mainly upon the large intestine and is, therefore, especially suitable in habitual constipation. The glycosides are absorbed from the intestinal tract and the active anthraquinones are excreted into the colon, where they stimulate and increase the peristaltic movements of the colon, decrease absorption of water from colon and produce a bulky softer fecal mass. This suggests their action is in lower bowel and have no effect in stomach and small intestine (Leng-Peschlow E. Dual effect of orally administered Sennosides on large intestine transit and fluid absorption in the rat.

J Pharm parmacol, 38: 606-610, 1986). In the light of this information Sennosides colon targeting pellets is developed to provide effective safe therapy of taxation. In this experiment Sennosides is loaded over NP seeds and coated with Eύdragit S100, which provides a coat which disintegrates only in colonic pH.

In yet another experiment Boswellic acid sustained release pellets releases Boswellic acid from the pellets for 12 hrs after oral administration. Boswellic acid is extracted from Boswellia serrata Roxb. ex Colebr. Boswellic acid has analgesic and anti-inflammatory action and therefore very useful in arthritis (Safayhi, H. et al. (1992) Boswellic acids: novel, specific, non-redox inhibitors of 5-lipoxygenase. J. Pharmaacol. Exp. Ther. 261:1143-6). In this experiment Boswellic acid pellets are prepared and coated with Eudragit RS RL 100 polymer or by any other polymer known in field of pharmacy, which releases the Boswellic acid from the pellets for 12 hrs. Therefore drug is available for more span of time and less dosage is required.

In yet another experiment on Turmeric (Curcuma tonga Linn.) sustained release pellets which are designed to prolong the release of curcumin present in turmeric, so as to maintain the therapeutic effect for long time. Bioavailability of curcumin from Curcuma longa Linn, is poor when purified Saxena, R.C., World Congress on Biotechnological Developments in Medicinal Substances of Plant and Marine Origin, Lucknow. (India), Feb. 19-22(1995). To make more bioavailable curcumin pellets is coated with suitable polymer known to field of pharmaceutical art.

It is also possible to make multi-coated pellets which have controlled release herbal extract in the inner coats and immediate release coats (untreated with polymers) as outer core or cores.

The combinations in which the uncoated pellets can be used as such a or filled in a capsule or pressed into a tablet can be applied in same way to polymer coated slow release / controlled release pellets too. The following examples set out the preparation of a number of different pellets within the concept of the present invention. The examples are not to be construed as limiting the scope of invention but are to be construed as illustrative only in nature, intended further to enlighten the reader about the pellets and their methods of manufacture claimed in this specification; additional variations within the concept of the invention will be clear to the pharmaceutical scientist ordinarily skilled in the art and such a preparation shall also be embodiment of invention claimed in this specification. Further, mention of singular is also construed to include pleural, unless the context does not permit so. Thus, "a method of peptization" includes "one or more methods of peptization". Mention of "an extract" includes one or more than one extract. Mention of a generic word is construed to include all members of its own kind, singly or in combination which can perform the claimed function in the alternative. Thus "a solvent" includes mention of all solvents, individually as well a collectively which can be used in the alternative to serve the same function as described.

"Non-pareil seeds" mentioned in the examples are inert beads as mentioned above, which are easily available in market and are commonly known in production of Pharmaceutical dosage forms based on peptization.

EXAMPLE 1

PREPARATION OF ANTIEMETIC PELLETS

Materials taken per 150 kg batch of antiemetic pellets Non-pareil seeds (NP. seeds 18-20#) 62 kg

Zingiber officinale Roxb. extract 5 kg Piper longum Linn. extract 4 kg

Demineralised water 25 litres lsopropyf alcohol (IPA) 12.5 litres

HPMC-5cps 0.15 kg

Zingiber officinale Roxb. extract and Piper longum Linn, extract were dispersed in separate batches of hot demineralised water to which was added isopropyl alcohol in which HPMC-5cps (Hdroxy Propyl Methyl Cellulose) was dispersed.

Each mixture was mixed thoroughly. Non-pareil seeds are put in Fluidized Bed equipment and above extract dispersions were sprayed on two separate batches through peristaltic pump at 50 rpm, over NP seeds, keeping bed temperature at

60⁰C. After extract layer was fully formed, finishing layer was applied over each batch of the pellets as described in the follows.

FINISHING LAYER APPLICATION

Ingredients:

HPMC-5cps 1.4 kg

Talc 2.8 kg Titanium Dioxide 2.8 kg

IPA 1 1 litres

Demineralised water 22 litres

HPMC-5cps was dispersed in IPA, water was added slowly while stirring, further

Talc and Titanium were added. This dispersion was sprayed in a fluidized bed equipment through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C.

APPLICATION OF COLORED COAT OVER THE PELLETS

Ingredients:

HPMC-5cps 0.75 kg PEG-6000 0.15 kg

Brilliant Blue colour 0.05 kg

Erythrosine colour 0.20 kg Talc 0.15 kg

Titanium Dioxide 0.15 kg

IPA 6 litres

Demineralised water 12 litres HPMC was dispersed in IPA, PEG-6000 (Poly Ethylene Glycol) was added in it, water was gradually added to make solution, permitted colour was added, and talc and titanium dioxide was suspended in it. In one solution Brilliant Blue was used as permitted color and in second solution, erythrosine was used as permitted color. These dispersions with one color were sprayed in a fluidized bed equipment, through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C, over talc-titanium layer of the herbal pellets of the extract of plant to which that colour was designated. When the addition was complete, airflow was continued for 15 minutes to dry the batch. Prior to filling into capsules, herbal pellets were mixed with each other in desired proportion and then with N. P. seeds to match the net desired content.

Herbal extracts finished and colored pellets as prepared above can also be compressed into tablets as follows.

Composition per tablet

Herbal extract pellets 250 mg Microcrystalline cellulose spray dried 180 mg Lactose directly compressible 180 mg

Magnesium stearate 6 mg

Talc 3 mg

Herbal extracts pellets are mixed with Microcrystalline cellulose spray dried and Lactose directly compressible. Further this mixture is lubricated with magnesium stearate and talc. This mixture is compressed into tablet as per the procedure known to the art of pharmacy. EXAMPLE 2

PREPARATION OF ANTIARTHRITIC PELLETS

Ingredients for 100 kg batch size:

Non-pareil seeds (N. P. seeds 18-20#) 45 kg Boswellia serrata Roxb. ex Colebr. Extract 26 kg

Vitex negundo Linn, extract 3 kg

Tinospora cordifolia (WiIId.) Miers ex Hook. f. & Thorns.

Extract 1.7 kg

Curcuma longa Linn, extract 2.6 kg PEG-6000 0.2 kg

Demineralised water 50 litres lsopropyl alcohol 25 litres

Four different preparations of pellets coated with Boswellia sp., Vitex sp.,

Tinospora sp. and Curcuma sp. were prepared by the same process as done with the product of Example-1 , without finishing layer.

Finally, the prepared herbal pellets were filled into capsules in desired proportions and with N. P. seeds

EXAMPLE 3

PREPARATION OF MEMORY SUPPORT PELLETS Ingredients for 250 kg batch size

Non-pareil seeds (N. P. seeds 18-20#) 100 kg

Bacopa monnieri Linn, extract 7.2 kg

Centella asiatica Linn, extract 7.2 kg

PEG-6000 0.1 kg Demineralised water 50 litres lsopropyl alcohol 25 litres

HPMC-5cps 2.5 kg Talc 3 kg

Titanium Dioxide 3 kg

Demineralised water 15 litres lsopropyl alcohol 10 litres The product was made in substantially the same manner, as was the product of.

Example-1in separate two batches with each herbal extract without colouring the pellets. Finally the prepared herbal pellets were filled into capsules with coloured

N. P. seed. Colouring of NP. seed was done as follows.

N. P. seed 16-20# 100 kg HPMC-5cps 0.5 kg

PEG-6000 0.5 kg

Sunset Yellow colour 0.5 kg

Talc 0.5 kg

Titanium Dioxide 0.5 kg IPA (isopropyl alcohol) 5.0 liters

Demineralised water 25.0 litres

HPMC was dispersed in IPA₁ add water slowly to make solution, dissolve colour & PEG and suspend titanium and talc. Put N. P. seed in Fluid Bed Coater and proceeded with the coating operation as in Example-1 by spraying the colour suspension and finally continuing air for further 15 minutes to dry the pellets.

EXAMPLE 4

PREPARATION OF ANTIDIABETIC PELLETS

Materials taken per 250 kg batch of antidiabetic pellets Non-pareil seeds (N. P. seeds 18-20#) 65 kg

Momordica charantia Linn, extract 47.9 kg

Azadirachta indica A. Juss. extract 3,25 kg Ocimum sanctum Linn, extract 1.25 kg

Zingiber officinale Roxb. extract 4.3 kg

Picrorhiza kυrroa Royle ex Benth. extract 5.3 kg Demineralised water 120 litres lsopropyl alcohol 60 litres

HPMC-5cps 1.25 kg

Momordica charantia Linn, extract, Azadirachta indica A. Juss. extract, Ocimum sanctum Linn, extract Zingiber officinale Roxb. extract Picrorhiza kurroa Royle ex Benth. extract were dispersed in separate batches of hot demineralised water to which was added isopropyl alcohol in which HPMC-5cps was dispersed. Each mixture was mixed thoroughly. Non-pareil seeds are put in Fluidized Bed equipment and above extract dispersions were sprayed on two separate batches through peristaltic pump at 50 rpm, over NP seeds, keeping bed temperature at 60⁰C. After extract layer was fully formed, finishing layer was applied over each batch of the pellets as described in the follows.

FINISHING LAYER APPLICATION

Ingredients:

HPMC-5cps 1.25 kg Talc 2.5 kg

Titanium Dioxide 2.5 kg

IPA 15 litres

Demineralised water 30 litres

HPMC-5cps was dispersed in IPA; water was added slowly while stirring, and further Talc and Titanium were added. This dispersion was sprayed in fluidized bed equipment through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C. APPLICATION OF COLORED COAT OVER THE PELLETS

Ingredients:

HPMC-5cps 0.75 kg

PEG-6000 0.15 kg Sunset yellow colour 0.3 kg Talc 0.1 kg

Titanium Dioxide 0.1 kg

IPA 10 litres

Demineralised water 20 litres HPMC was dispersed in IPA, PEG-6000 was added in it, water was gradually added to make solution, permitted colour was added, and talc and titanium dioxide was suspended in it. Sunset yellow was used as permitted color. These dispersions with one color were sprayed in a fluidized bed equipment, through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C, over talc-titanium. layer of the herbal pellets of the extract of plant to which that colour was designated. When the addition was complete, airflow was continued for 15 minutes to dry the batch. Prior to filling into capsules, herbal pellets were mixed with N. P. seeds with green colour utilizing Brilliant Blue & Tartrazine colour to match the net desired content.

EXAMPLE 5

PREPARATION OF ANTISTRESS PELLETS

Materials taken per 250 kg batch of antistress pellets

Non-pareil seeds (N. P. seeds 18-20#) 150 kg

Withania somnifera Dunal. extract 4.0 kg Bacopa monnieri Linn, extract 6.6 kg

Nardostachys jatamansi DC. extract 2.6 kg

Demineralised water 40 litres lsopropyl alcohol 20 litres

Withania somnifera Dunal. extract, Bacopa monnieri Linn, extract, and

Nardostachys jatamansi DC. extract were dispersed in separate batches of hot demineralised water to which was added isopropyl alcohol. Each mixture was mixed thoroughly. Non-pareil seeds are put in Fluidized Bed equipment and above extract dispersions were sprayed on two separate batches through peristaltic pump at 50 rpm , over NP seeds, keeping bed temperature at 60⁰C.

After extract layer was fully formed, finishing layer was applied over each batch of the pellets as described in the follows.

FINISHING LAYER APPLICATION

Ingredients:

HPMC-5cps 1.5 kg

Talc 2.0 kg Titanium Dioxide 2.0 kg

IPA 10 litres

Demineralised water 20 litres

HPMC-5cps was dispersed in IPA; water was added slowly while stirring, and further Talc and Titanium were added. This dispersion was sprayed in fluidized bed equipment through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C.

APPLICATION OF COLORED COAT OVER THE PELLETS

Ingredients:

HPMC-5cps 1.0 kg PEG-6000 1.0 kg

Erythrosine colour 0.2 kg

Talc 0.2 kg Titanium Dioxide 0.2 kg

IPA 10 litres

Demineralised water 20 litres

HPMC was dispersed in IPA, PEG-6000 was added in it, water was gradually added to make solution, permitted colour was added, and talc and titanium dioxide was suspended in it. Sunset yellow was used as permitted color. These dispersions with one color were sprayed in a fluidized bed equipment, through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C, over talc-titanium layer of the herbal pellets of the extract of plant to which that colour was designated. When the addition was complete, airflow was continued for 15 minutes to dry the batch. Prior to filling into capsules, herbal pellets were mixed with N. P. seeds with blue colour utilizing Brilliant Blue colour to match the net desired content.

EXAMPLE 6

PREPARATION OF DIURETICS PELLETS

Materials taken per 250 kg batch of diuretics pellets

Non-pareil seeds (N. P. seeds 18-20#) 150 kg

Boerhavia diffusa Linn, extract 22.9 kg

Tribulus terrestris Linn, extract 11.5 kg Demineralised water 80 litres lsopropyl alcohol 40 litres

HPMC 5cps 0.2 kg

Boerhavia diffusa Linn, extract, and Tribulus terrestris Linn, extract were dispersed in separate batches of hot demineralised water to which was added isopropyl alcohol in which HPMC was added. Each mixture was mixed thoroughly. Non-pareil seeds are put in Fluidized Bed equipment and above extract dispersions were sprayed on two separate batches through peristaltic pump at 50 rpm, over NP seeds, keeping bed temperature at 60⁰C. After extract layer was fully formed, finishing layer was applied over each batch of the pellets as described in the follows.

FINISHING LAYER APPLICATION Ingredients:

HPMC-5cps 1.0 kg

Talc 1.0 kg

Titanium Dioxide 10 kg

IPA 10 litres Demineralised water 20 litres

Ingredients:

HPMC-5cps 0.5 kg

PEG-6000 0.25 kg

Brilliant Blue 0.1 kg Talc 0.5 kg

Titanium Dioxide 1.0 kg

IPA 10 litres

Demineralised water 20 litres

HPMC was dispersed in IPA, PEG-6000 was added in it, water was gradually added to make solution, permitted colour was added, and talc and titanium dioxide was suspended in it. Brilliant blue was used as permitted color. These dispersions with one color were sprayed in a fluidized bed equipment, through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C, over talc-titanium layer of the herbal pellets of the extract of plant to which that colour was designated. When the addition was complete, airflow was continued for 15 minutes to dry the batch. Prior to filling into capsules, herbal pellets were mixed with NP. seeds to match the net desired content.

EXAMPLE 7

PREPARATION OF HEPATOPROTECTIVE PELLETS

Materials taken per 250 kg batch of hepatoprotective pellets

Non-pareil seeds (N. P. seeds 18-20#) 150 kg Picrorhiza kurroa Royle ex Benth. extract 2.95 kg

Phyllanthus niruri Linn, extract 5.9 kg

Demineralised water 100 litres lsopropyl alcohol 50 litres

HPMC 5cps 0.5 kg Picrorhiza kurroa Royle ex Benth. extract, and Phyllanthus niruri Linn, extract were dispersed in separate batches of hot demineralised water to which was added isopropyl alcohol in which HPMC was added. Each mixture was mixed thoroughly. Non-pareil seeds are put in Fluidized Bed equipment and above extract dispersions were sprayed on two separate batches through peristaltic pump at 50 rpm, over NP seeds, keeping bed temperature at 60⁰C. After extract layer was fully formed, finishing layer was applied over each batch of the pellets as described in the follows.

FINISHING LAYER APPLICATION

Ingredients: HPMC-5cps 1.25 kg

Talc 1.25 kg

Titanium Dioxide 1.0 kg IPA 15 litres

Demineralised water 30 litres

APPLICATION OF COLORED COAT OVER THE PELLETS Ingredients: HPMC-5cps 0.5 kg PEG-6000 0.25 kg

Tartrazine colour 0.3 kg

Talc 0.5 kg

Titanium Dioxide 1.0 kg

IPA 10 litres Demineralised water 20 litres

HPMC was dispersed in IPA, PEG-6000 was added in it, water was gradually added to make solution, permitted colour was added, and talc and titanium dioxide was suspended in it. Tartrazine was used as permitted color. These dispersions with one color were sprayed in a fluidized bed equipment, through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C, over talc-titanium layer of the herbal pellets of the extract of plant to which that colour was designated. When the addition was complete, airflow was continued for 15 minutes to dry the batch. Prior to filling into capsules, herbal pellets were mixed with brown N. P. seeds utilizing caramel colour to match the net desired content. EXAMPLE 8

PREPARATION OF LAXATIVE PELLETS

Materials taken per 250 kg batch of laxative pellets

Non-pareil seeds (N. P. seeds 18-20#) 150 kg Cassia angustifolia Vahl. extract 8.6 kg

Glycyrrhiza glabra Linn, extract 2.9 kg

Zingiber officinale Roxb. extract 2.3 kg

Demineralised water 80 litres lsopropyl alcohol 40 litres HPMC 5cps 0.3 kg

Cassia angustifolia Vahl. extract, Glycyrrhiza glabra Linn, extract and Zingiber officinale Roxb. were dispersed in separate batches of hot demineralised water to which was added isopropyl alcohol in which HPMC was added. Each mixture was mixed thoroughly. Non-pareil seeds are put in Fluidized Bed equipment and above extract dispersions were sprayed on two separate batches through peristaltic pump at 50 rpm, over NP seeds, keeping bed temperature at 60⁰C.

FINISHING LAYER APPLICATION Ingredients:

HPMC-5cps 1.1 kg

Talc 1.0 kg

Titanium Dioxide 1.0 kg

IPA 10 litres Demineralised water 20 litres

APPLICATION OF COLORED COAT OVER THE PELLETS Ingredients:

HPMC-5cps 0.5 kg

PEG-6000 0.25 kg

Tartrazine colour 0.3 kg

Brilliant Blue colour 0.2 kg Talc 0.5 kg

Titanium Dioxide 1.0 kg

IPA 10 litres

Demineralised water 20 litres

HPMC was dispersed in IPA, PEG-6000 was added in it, water was gradually added to make solution, permitted colour was added, and talc and titanium dioxide was suspended in it. Tartrazine and Brilliant Blue were used as permitted color. These dispersions of color were sprayed in a fluidized bed equipment, through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C, over talc-titanium layer of the herbal pellets of the extract of plant to which that colour was designated. When the addition was complete, airflow was continued for 15 minutes to dry the batch. Prior to filling into capsules, herbal pellets were mixed with pink colour N. P. seeds utilizing erythrosine colour to match the net desired content.

EXAMPLE 9

PREPARATION OF ANTIDIARRHEAL PELLETS

Materials taken per 250 kg batch of antidiarrheal pellets Non-pareil seeds (N. P. seeds 18-20#) 150 kg

Holarrhena antidysenterica (Roth) A. DC. extract 24 kg

Euphorbia hirta Linn, extract 6.6 kg

Demineralised water 100 litres lsopropyl alcohol 50 litres

HPMC 5cps 0.4 kg

Holarrhena antidysenterica (Roth) A. DC. extract and Euphorbia hirta Linn. extract were dispersed in separate batches of hot demineralised water to which was added isopropyl alcohol in which HPMC was added. Each mixture was mixed thoroughly. Non-pareil seeds are put in Fluidized Bed equipment and above extract dispersions were sprayed on two separate batches through peristaltic pump at 50 rpm, over NP seeds, keeping bed temperature at 60⁰C.

After extract layer was fully formed, finishing layer was applied over each batch of the pellets as described in the follows. FINISHING LAYER APPLICATION

Ingredients:

HPMC-5cps 1.3 kg

Talc 1.0 kg

Titanium Dioxide 1.0 kg IPA 10 litres

Demineralised water 20 litres

Ingredients:

HPMC-5cps 0.6 kg

PEG-6000 0.3 kg Brilliant Blue colour 0.3 kg

Talc 0.5 kg

Titanium Dioxide 1.0 kg

IPA 15 litres

Demineralised water 30 litres HPMC was dispersed in IPA, PEG-6000 was added in it, water was gradually added to make solution, permitted colour was added, and talc and titanium dioxide was suspended in it. Brilliant BJue was used as permitted color. These dispersions with one color were sprayed in a fluidized bed equipment, through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C, over talc-titanium layer of the herbal pellets of the extract of plant to which that colour was designated. When the addition was complete, airflow was continued for 15 minutes to dry the batch. Prior to filling into capsules, herbal pellets were mixed with N. P. seeds to match the net desired content.

EXAMPLE 10

PREPARATION OF GALACTAGOGUE PELLETS

Materials taken per 250 kg batch of galactagogue pellets

Non-pareil seeds (N. P. seeds 18-20#) 100 kg

Asparagus racemosus WiIId. extract 8.5 kg

Allium sativum Linn, extract 1.325 kg Euphorbia hirta Linn, extract 2.65 kg

Pueraria tuberosa DC.extract 7.0 kg

Leptadenia raticulata Wight and Arn. extract 4.18 kg Trigonella foenum-graecum Linn, extract 7.0 kg

Withania somnifera Dunal. extract 1.7 kg

Demineralised water 120 litres lsopropyl alcohol 60 litres

HPMC-5cps 1.25 kg

Asparagus racemosus WiIId. extract, Allium sativum Linn, extract, Euphorbia hirta Linn, extract Pueraria tuherosa DC. extract Leptadenia raticulata Wight and Arn. extract, Trigonella foenum-graecum Linn, extract and Withania somnifera Dunal. extract were dispersed in separate batches of hot demineralised water to which was added isopropyl alcohol in which HPMC-5cps was dispersed. Each mixture was mixed thoroughly. Non-pareil seeds are put in Fluidized Bed equipment and above extract dispersions were sprayed on two separate batches through peristaltic pump at 50 rpm, over NP seeds, keeping bed temperature at 60⁰C. After extract layer was fully formed, finishing layer was applied over each batch of the pellets as described in the follows. FINISHING LAYER APPLICATION Ingredients:

HPMC-5cps 1.25 kg

Talc 2.5 kg Titanium Dioxide 2.5 kg

IPA 20 litres

Demineralised water 40 litres

Ingredients:

HPMC-5cps 0.75 kg

PEG-6000 0.15 kg Brilliant Blue 0.3 kg

Tartrazine colour 0.2 kg

Talc 0.1 kg

Titanium Dioxide 0.1 kg

IPA 10 litres Demineralised water 20 litres

HPMC was dispersed in IPA, PEG-6000 was added in it, water was gradually added to make solution, permitted colour was added, and talc and titanium dioxide was suspended in it. Brilliant Blue and Tartrazine was used as permitted color. These dispersions with one color were sprayed in a fluidized bed equipment, through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C, over talc-titanium layer of the herbal pellets of the extract of plant to which that colour was designated. When the addition was complete, airflow was continued for 15 minutes to dry the batch. Prior to filling into capsules, herbal pellets were mixed with N. P. seeds with green colour utilizing Brilliant Blue & Tartrazine colour to match the net desired content.

EXAMPLE 11

PREPARATION OF APHRODISIAC PELLETS

Material taken per 250 kg aphrodisiac pellets.

Non-pareil seeds (N. P. seeds 18-20#) 150 kg

Tribulus terrestris Linn, extract 4.0 kg Mucuna prureins Baker, extract 6.6 kg HPMC 5cps 0.5 kg

Talc 1.0 kg lsopropyl alcohol 100 litres Put NP seeds in coating pan. Disperse the extract in a mixture of Talc, HPMC &

IPA separately and for both the extracts and separately pour in 5 litres instalments. The extract mixture over NP seeds put in coating pan with 15 rpm.

Dry the pellets in current of hot air in pan itself. In this way pour all the extract mixtures and dry the pellets. Temperature of incoming air is kept 90 ° C. FINISHING LAYER APPLICATION

Ingredients:

HPMC-5cps 0.5 kg

PEG 6000 0.1 kg

Talc 2.0 kg Titanium Dioxide 2.0 kg

IPA 25 litres

Demineralised water 10 litres

Disperse HPMC in IPA, melt PEG 6000 and mix. Add water and mix talc and titanium dioxide, mix thoroughly. Spray this mixture over dried herbal pellets to form a finishing layer.

APPLICATION OF COLORED COAT OVER THE PELLETS

Ingredients:

HPMC-5cps 0.5 kg PEG-6000 0.1 kg

Candurin silver luster 5 kg

Methylene chloride 40 litres

IPA 20 litres Dispers HPMC in IPA, dissolve PEG 6000 in it, add methylene chloride to make solution. Disperse Candurin silver luster in this and colour the pellet in rotating coating pan by spraying the above mixture. Dry the pellets in tray drier at 60° C. mix NP seeds and fill in capsule.

EXAMPLE 12

PREPARATION OF CARDIOTONIC PELLETS Material taken for 100 kg cardiotonic pellets

Non-pareil seeds (N. P. seeds 18-20#) 30 kg

Dry extract Tribulus terrestήs Linn. 21.25 kg

Dry extract Terminalia arjuna W. and A. 42.5 kg HPMC 5cps 1.0 kg

Talc 2.0 kg lsopropyl alcohol 40 litres

Deminarilized water 10 litres

Disperse HPMC in IPA, add water to it and make solution, disperse talc in it.

Take NP seed in rotating pan at 12 rpm, wet the NP seed with above dispersion of talc and HPMC by spray gun and dust the herbal dry extract over wetted NP seed. In this way dust complete individual dry herbal extract separately and dry at 60° C in oven for 12 hrs.

FINISHING LAYER APPLICATION

Ingredients:

HPMC-5cps 2.5 kg

PEG 6000 0.5 kg Talc 0.5 kg

Titanium Dioxide 1.0 kg

IPA 33 litres

Methylene chloride 66 litres Dissolve PEG in IPA, and disperse HPMC in it, add methylene chloride to make solution. Add talc and titanium dioxide in this and mix well. Spray this solution in rotating coating pan at 20 rpm over herbal dried pellets. APPLICATION OF COLORED COAT OVER THE PELLETS Ingredients:

HPMC-5cps 2.5 kg

PEG-6000 0.5 kg

Tatrazine colour 2.0 kg Talc 0.5 kg litres

IPA 20 litres

Deminaralized water 80 litres

Dissolve PEG in IPA, disperse HPMC in it add water in which tartrazine colour was previously dissolved. Mix thoroughly to make solution. Add in this solution titanium and talc. Spray this solution in rotating pan at 20 rpm over above finished layered pellets to get coloured pellets. This pellets are to be filled in capsules.

EXAMPLE 13:

PREPARATION OF MEMORY SUPPORT PELLETS

Ingredients for 250 kg batch size

Non-pareil seeds (N. P. seeds 18-20#) 100 kg Bacopa monnieri Linn, extract 7.2 kg

Centella asiatica Linn, extract 7.2 kg

PEG-6000 0.1 kg

Demineralised water 50 litres lsopropyl alcohol . 25 litres HPMC-5cps 2.5 kg

Talc 3 kg

Titanium Dioxide 3 kg

Demineralised water 15 litres lsopropyl alcohol 10 litres

The extracts of the both herbs are combined and disperse in hot demineralized water, to which added isopropyl alcohol, PEG 6000, HPMC, talc and titanium dioxide. Non-pareil seeds are put in Fluidized Bed equipment and above extract dispersions were sprayed through peristaltic pump at 50 rpm, over NP seeds, keeping bed temperature at 60⁰C. After extract layer was fully formed, colouring of N. P. seed was done as follows.

N. P. seed 16-20# 100 kg

HPMC-5cps 0.5 kg

PEG-6000 0.5 kg Sunset Yellow colour 0.5 kg

Talc 0.5 kg

Titanium Dioxide 0.5 kg

IPA (isopropyl alcohol) 5.0 liters

Demineralised water 25.0 litres HPMC was dispersed in IPA, add water slowly to make solution, dissolve colour.

& PEG and suspend titanium and talc. Put N. P. seed in Fluid Bed Coater and proceeded with the coating operation as in Example-1 by spraying the colour suspension and finally continuing air for further 15 minutes to dry the pellets. This pellets are to be filled in capsules

EXAMPLE 14

PREPARATION OF DELAYED RELEASE GARLIC PELLETS

Materials taken per 160 kg batch of enteric coated garlic pellets Non-pareil seeds (N. P. seeds 18-20#) 120 kg

Allium Sativum Linn extract 17.02 kg

Demineralised water 34 litres lsopropyl alcohol 17 litres

HPMC-δcps 0.340kg

Allium Sativum Linn extract was dispersed in cold demineralised water to which was added isopropyl alcohol in which HPMG-5cps was dispersed. The solution was mixed thoroughly. Non-pareil seeds are put in Fluidized Bed equipment and above extract dispersions were sprayed through peristaltic pump at 50 rpm, over NP seeds, keeping bed temperature at 60⁰C. After extract layer was fully formed, finishing layer was applied the pellets as described below . Delayed release coating Ingredients: Methacrylic Acid Copolymer dispersion 20 kg Demineralised water 90 litres

Methacrylic Acid Copolymer dispersion was dispersed in Demineralised water slowly while stirring,. This dispersion was sprayed in a fluidized bed equipment through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C. The composition was subjected to the dissolution by USPXXVIII apparatus for dissolution with paddle at IOOrpm at 33°c using simulated gastric fluid without digestive enzymes for 2hrs and using simulated intestinal fluid having pH 6.8 without digestive enzymes for one hour. While using simulated gastric fluid, pellets do not break or rupture and remain intact as it is, while using simulated intestinal fluid pellets disintegrate. EXAMPLE 15

PREPARATION OF SENNOSIDES EXTENDED RELEASE PELLETS

Materials taken per 165 kg batch of sennosides extended release pellets. Non-pareil seeds (N. P. seeds 18-20#) 125 kg Cassia angustifolia Vahl extract 11.7 kg lsopropyl alcohol 15 litres

HPMC-5cps 0.25kg

Methylene Chlorode 30litres

In lsopropyl alcohol disperse HPMC -5Cps under stirring to it add Methylene Chloride after that add Cassia angustifolia Vahl extract under stirring.. Non-pareil seeds are put in Fluidized Bed equipment and above extract dispersions were sprayed through peristaltic pump at 50 rpm, over NP seeds, keeping bed temperature at 60⁰C. After extract layer was fully formed, finishing layer was applied the pellets as described below .

Extended release coating

Ingredients:

Methacrylic Acid Copolymer type B(Eudragit S100) 15 kg Aetone 100 litres

IPA IOOLitres

Methacrylic Acid Copolymer type B(Eudragit S100) was dissolved in mixture of Acetone & IPA slowly while stirring,. This solution was sprayed in a fluidized bed equipment through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C.

Composition is subjected to drug release of sennosides by USPXXVII dissolution test apparatus with paddle at IOOrpm using simulated gastric fluid without digestive enzyme and temperature 37⁰C The dosage form releases not more than 10% of labeled claim of sennosides.further the above procedure is followed again using simulated intestinal fluid again using simulated intestinal fluid at7.4 pH with enzyme. The dosage form releases sennoside not less than 70% of the labeled claim.

EXAMPLE 16

PREPARATION OF EXTENDED RELEASE BOSWELLIC ACID PELLETS AND TABLETS.

Materials taken per 400 kg batch of extended release Boswellic Acid pellets Non- pareil seeds (N. P. seeds 25-30#) 137 kg

Boswellia serrata Roxb extract 250 kg

Demineralised water 20 litres lsopropyl alcohol 100 litres

HPMC-5cps 0.5kg Boswellia serrata Roxb extract was dispersed in cold demineralised water to which was added isopropyl alcohol in which HPMC-5cps was dispersed. The solution was mixed thoroughly. Non-pareil seeds are put in Fluidized Bed equipment and above extract dispersions were sprayed through peristaltic pump at 50 rpm, over NP seeds, keeping bed temperature at 60⁰C. After extract layer was fully formed, extended release layer was applied the pellets as described below .

Extended release coating

Ingredients: Poly ethyl acrylate & methyl methacrylate (2:1) aqueous dispersion 30kg Water 170 litres Poly ethyl acrylate & methyl methacrylate (2:1) aqueous dispersion was dispersed in Demineralised water slowly while stirring,. This dispersion was sprayed in a fluidized bed equipment through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C. After extended release coating was fully formed, the pellets was taken for Compression to Tablets as described below .

Tablet compression

Boswellia serrata Roxb extended release pellets 200kg Lactose compressible 150Kg Microcrystalline Cellulose spray dried 149.25Kg

Talc 0.75kg

The above material are mixed and are compressed to 1gm tablets by conventional tablet compression machine known to the art of pharmacy.

Tablet so prepared is subjected to dissolution test in USPXXVII dissolution test apparatus with paddle at IOOrpm using simulated gastric fluid without enzyme for 2hrs and temperature 37⁰C . an din simulated intestinal fluid without enzyme at 6.8 pHat 37°C.Active ingredient releases at least 60-100% of the active ingredients available from the said dosage form after 5-15 minutes.

EXAMPLE 17

PREPARATION OF EXTENDED RELEASE TURMERIC PELLETS

Materials taken per 160 kg batch of extended release turmeric pellets

Non-pareil seeds (N. P. seeds 25-30#) 75 kg Curcuma longa Linn, extract 68.09 kg

Demineralised water 34 litres lsopropyl alcohol 50 litres Methylene chloride 10OIitres Hydroxypropyl cellulose (HPC) 15kg

Curcuma longa extract was dispersed in isopropyl alcohol to which HPC was add & dispersed under stirring After that Methylene chloride was added. The solution was mixed thoroughly. Non-pareil seeds are put in Fluidized Bed equipment and above extract dispersions were sprayed through peristaltic pump at 50 rpm, over NP seeds, keeping bed temperature at 60⁰C. Extended release coating Ingredients:

Ethyl cellulose 1 kg Diethylpthalate 0.2kg

IPA 10litres

Methylene chloride 10litres

Ethyl cellulose & Diethylpthalate was dissolved in IPA slowly while stirring to this was added methylene chloride while stirring This solution was sprayed in a fluidized bed equipment through peristaltic pump at 50 rpm over the extract layer keeping bed temperature at 60⁰C.

Pellets so prepared is subjected to dissolution test in USPXXVII dissolution test apparatus with paddle at IOOrpm using simulated gastric fluid without enzyme for 2hrs and temperature 37⁰C . an din simulated intestinal fluid without enzyme at

6.8 pH at 37⁰C. Active ingredient releases at least 60-100% of the active ingredients available from the said dosage form after 5-15 minutes.

Claims

1. A pharmaceutical composition of pellets made by coating a composition of one or more of a herbal extract on a core of a material that is inert towards one or more of the said herbal extract where the said coat of herbal extract does not contain polyvinylpyrrolidone as binder and the said coat of herbal extract is in its turn coated externally with at least one layer of a controlled release coat, that controls release of the herbal extract in the gastrointestinal tract.

2. A pharmaceutical composition of an oral dosage form comprising pellets as one or more of an ingredient, the said pellets being made by coating a composition of one or more of a herbal extract on a core of a material that is inert towards one or more of the said herbal extract and a finishing coat; wherein (a) the said oral dosage form comprises a capsule containing pellets coated with one or more of a herbal extract or a tablet containing pellets coated with at least two or more of a herbal extract, (b) the said coat of herbal extract does not contain polyvinylpyrrolidone as binder, and ( c) the said core of pellets coated with said coat of herbal extract is coated further with at least one layer of a _, controlled release coat that controls release of the herbal extract in the gastrointestinal tract.

3. A pharmaceutical composition of pellets or of a capsule containing pellets coated with two or more of a herbal extract that are coated in two or more successive coats, each coat comprising one or more of a herbal extract and successive coats being applied with or without an intervening coat of material inert towards the herbal extract in contact; wherein the outermost coat is coated further with at least one layer of a controlled release coat that controls release of the herbal extract in gastrointestinal tract.

4. A composition of pellets of claim 1 or claim 2 wherein two or more ingredients of the said composition of herba! extract are coated as a mixture or coated as two or more successive coats, each coat comprising one or more of a herbal extract and successive coats being applied with or without an intervening coat of material inert towards the herbal extract- in contact.

5. A process of making pellets of two or more of a herbal extract comprising steps of : a. applying a coat of a herbal extract or a: mixture of herbal extracts from two or more than two herbs on a core of aggregates of particulate matter that is inert towards the herbal extract and one or more of an excipient used in the process and having no therapeutic activity of its own, the said herbal extract being preferably a crude extract, further preferably an extract from a medicinal plant, and the said core of aggregates including non-pareil seeds, b. if desired, applying a further coat of one or more of a herbal extract over the coated cores of step (a.) after applying at least one intervening coat of a material between two successive coats, the said intervening coat being inert towards the plant material in contact, c. applying a finishing coat over the said coated pellets of step (a.) or step (b.), if desired, d. optionally applying a permitted colour to non-pareil. seeds , e. optionally adding a permitted color to the said finishing coat of step (C), f. coating the outermost coat of coated pellets further with at least one layer of a controlled release coat that controls release of the herbal extract in gastrointestinal tract, g. and filling in a capsule shell or pressing into a tablet the pellets after the step f along with other optional ingredients including colored or non-colored non-pareil seeds.

6. A process of making products of claim 1 , claim 2 or claim3 or claim 4 comprising steps of, selected as per requirement of the product : a. applying one or more of a coat of a herbal extract or a mixture of herbal extracts from two or more than two herbs on a core of aggregates of particulate matter that is inert towards the herbal extract and excipients used in the process and having no therapeutic activity of its own, the said herbal extract being preferably a crude extract, further preferably from a medicinal plant, and the said core of aggregates including non-pareil seeds, b. applying a finishing coat over the said coated pellets of step (a.), if desired, c. optionally applying a further coat of one or more of a herbal extract over the coated cores of step (a.) or step (b.), after or without applying an intervening coat between ^ι two successive coats of herbal extract, the said intervening coat being of a material inert towards the plant material in contact, d. optionally applying a permitted colour to non-pareil seeds , e. optionally adding a permitted color to the said finishing coat of step (b.), f. coating the outermost coat coated pellets further at 40 - 70 ^{0 υ}CC preferably at about 60 degrees Celsius, with at least one layer of a controlled release coat, g. and filling in a capsule shell or pressing into a tablet the pellets of step (f.) along with other optional ingredients including colored or non-colored non-pareil seeds.

7. A process of claim 5 or claim 6 wherein, a. the said herbal extract comprises a selective component in solid or fluid form, composed of one or more individual chemical ingredients, of a part of or whole of a plant body, the said extract being prepared by selective segregation of components of the plant

) body by a physical method or by a method of extracting in a solvent, b. the said cores are preferably made of starch or sucrose or may also be made from one or more of a microcrystalline cellulose, a vegetable gum, an edible wax, and the like, c. the said finishing coat comprises of chemicals applied for purpose of achieving one or more effects which include achieving reduction in static charge, to add smoothness to pellets, to prevent tendency for pellets to stick together, increase hydrophobicity of the surface and further includes use of materials including one or more of talc, silicon dioxide, wax, thin polymeric material further including Hydroxy Propyl Methyl Cellulose (HPMC), Polyvinylpyrrolidone (PVP) and the like, d. the said coloring matter comprising one or more of a permitted colors including one or more of an opaque finely divided color agent further including a red iron oxide, a yellow iron oxide, sunset yellow, Brilliant Blue, Erythrosine and the like, e. the said capsule shell, being hard comprising of one or more of a material, preferably gelatin, being either opaque or preferably a transparent one, f. the said controlled release coat is preferably selected from one or more of a polymer that is inert towards the herbal extract, dissolves slowly in gastrointestinal tract permitting release of substantial quantity of a herbal extract at desired locations of action; the said polymer comprising one or more of a Hydroxy Propyl Methyl

Cellulose Pthalate(HPMCP), Hydroxy Propyl Methyl Pthalate Cellulose Acetate Succinate(HPMPCAS), Cellulose Acetate Pthalate(CAP), , EUDRAGIT L 100 [Poly (Methacrylic acid; Methyl Methacrylate) 1 :1] EUDRAGIT L 100-55 [ Poly (Methacrylic acid; Ethylacrylate) 1 :1], EUDRAGIT L 30 D [30% aqueous dispersion of

Poly (Methacrylic acid; Methyl Methacrylate)], EUDRAGIT NE 30 D [Poly (Ethylacrylate; Methyl Methacrylate) 2:1] EUDRAGIT RS 100 Poly (Ethylacrylate; Methyl Ethacrylate, Xrimethyl Amino Ethyl Methacrylate Chloride) 1 :2:0.1], EUDRAGIT RL 100 [ Poly (Ethylacrylate; Methyl Ethacrylate, Trimethyl Amino Ethyl

Methacrylate Chloride) 1 :2:0.2], EUDRAGIT S 100 [ Poly

(Methacrylic acid; Methyl Methacrylate) 1:2], Ethyl cellulose and the like.

8. A process of claim 5 or claim 6 or claim 7 comprising one or more of a following steps wherein: a. the said coat of one or more of a herbal extract is applied by a process which comprises one or more of a process of peptization including a method preferably consisting of (i) dispersing a herbal extract to be coated in water, (ii) adding to it a solvent , preferably lsopropyl alcohol (IPA) in which Hydroxy Propyl Methyl Cellulose (HPMC) is dispersed and mixing thoroughly, (iii) putting Non-pareil seeds in a Fluidized Bed equipment and spraying the mixture of the preceding step (ii), preferably with a peristaltic pump, over Nonpareil seeds keeping bed temperature preferably at about 60 degrees centigrade , followed by drying in oven at 60 degrees centigrade, b. the said coat of one or more of a herb is applied as a dry powder by a process which comprises dusting of a dry extract over Non pareil seeds in rotating pan by wetting the non pareil seeds with a binder comprising solution of one or more of HPMC, HPC (Hydroxy propyl cellulose) and the like, followed by drying of pellets in oven at 60 degrees centigrade, c. the said finishing layer is applied to pellets of preceding steps (a) or (b) of this claim by one or more of a process comprising: i. dusting on the coated pellets an anti-static powder including one or more of talc, silicon dioxide and like, 0.5 to 2% preferably at. about 1 %, or ii. melting over the circulating pellets, a wax, including a bees wax, preferably in about 0.5 to 2% preferably 1 % proportion of the pellets, or iii. dispersing a polymeric .material comprising one or more of hydroxypropylmethylcellulose, or polyvinylpyrrolidone and the like, preferably in a proportion of 0. 50% to 10 % of the bulk in lsopropyl alcohol to which water is slowly added accompanied by stirring, optionally adding an opacifier including talc or titanium, optionally adding an opaque permitted colours including red or yellow iron oxide and spraying the dispersion obtained through a peristaltic pump, over Non-pareil seeds or herbal extract coated pellets, keeping bed temperature preferably at about 60 degrees centigrade, - d. the said process of coloring non-pareil seeds or herbal extract coated pellets having finishing layer applied to them comprising dispersing polymeric material comprising one or more of a Hydroxy

Propyl Methyl Cellulose (HPMC), Polyvinylpyrrolidone (PVP) and the like, adding Polyethylene glycol, adding permitted colors comprising Brilliant blue, erythrosine, sunset yellow, red iron oxide, yellow iron oxide and the like, adding talc and titanium dioxide and spraying this dispersion over talc-titanium layer on the said non-pareil seeds or the said herbal extract coated pellets, and the said capsule in which the pellets are filled comprises an opaque or transparent hard gelatin capsule, more preferably a transparent gelatin capsule.

9. A product of claim 2, claim 3 or claim 4 wherein a dosage form for oral consumption, comprising one or more of a capsule, a tablet and the like where the said tablet contains herbal extract coated pellets of two or more herbs.

10. A composition of claim 1 or claim 2 or claim 3 or claim 4 comprising one or more of following herbal extract compositions comprising at least: a. an extract of Allium Sativum Linn ^"preferably taken, as percentage by weight of total final composition, in a range of about 3 to 15% more preferably to about 3.88%, b. an extract of Cassia angustifolia Vahl preferably taken, as percentage by weight of total final composition, in a range of about

0.5 to 15% more preferably to about 3.44%, c. an extract of Boswellia serrata Roxb preferably taken, as percentage by weight of total final composition, in a range of about 5 to 50% more preferably to about 26%, d. an extract of Curcuma longa Linn, preferably taken, as percentage by weight of total final composition, in a range of about 0.1 to 15% more preferably to about 2.6%, where the said core comprising a material that is inert towards the said plant material.

11. A process of any one of claim 5 or claim 6 or claim 7 or claim 8 for preparing pellets wherein the said composition of a herbal extract is selected from any one of Allium Sativum Linn, Cassia angustifolia Vahl, Boswellia serrata Roxb,, Curcuma longa Linn.; where the said core.

12. A process of any one of claim 5 or claim 6 or claim 7 or claim 8 of making a dosage form comprising pellets made by coating a composition of said plant material wherein the said composition of a herbal extract is selected from one of the following compositions comprising at least : a. an extract of Allium Sativum Linn preferably taken, as percentage by weight of total final composition, in a range of about 3 to15% more preferably to about 3.88%, b. an extract of Cassia angustifolia Vahl preferably taken, as percentage by weight of total final composition, in a range of about 0.5 to 15% more preferably to about 3.44%, c. an extract of Boswellia serrata Rόxb preferably taken, as percentage by weight of total final composition, in a range of about 5 to 50% more preferably to about 26%, d. an extract of Curcuma longa Linn, preferably taken, as percentage by weight of total final composition, in a range of about 0.1 to 15% more preferably to about 2.6%, where the said core comprising a material that is inert towards the said plant material.

13. A pharmaceutical composition of claim 1, or claim 2,,-claim 3 or claim 4 wherein delayed release dosage form require for release of not more than 10% of the active ingredients available from the dosage after 2 hourss as determined by USP XXVII paddle method at a paddle speed of 100 revolutions per minute using simulated gastric , fluid without digestive enzyme and temperature at 37 degrees Celsius.

14. A pharmaceutical composition of claim 1, or claim 2, claim 3 or claim 4 wherein delayed release dosage form require the pellets to remain intact and do not break or rupture within 2 hours as performed procedure of USP XXVII dissolution test apparatus with^* paddle at a paddle speed of 100 revolutions per minute using simulated gastric fluid without digestive enzymes and temperature of 37 degrees Celsius.

15. A pharmaceutical composition of claim 1 , or claim 2, claim 3 or claim 4 wherein delayed dosage form require the pellets to disintegrate within one hour as performed by USP XXVII dissolution test apparatus with simulated intestinal fluid having pH6.8 without digestive enzymes, with paddle at 100 revolutions per minute and at temperature of 37 degrees Celsius.

16. A pharmaceutical composition of claim 1, or claim 2, claim 3 or claim 4 wherein extended release dosage form require for release not more than 10% of the active ingredients available from the said dosage after 2 hours as determined by USP XXVII dissolution test apparatus with paddle at a paddle speed of 100 revolutions per minute using simulated gastric fluid without digestive enzyme and temperature of 37 degrees Celsius and require for release of not less than 70% of the active ingredients available from the said dosage form after one hr as determined by USP XXVII dissolution test apparatus with paddle having speed 100 revolutions per minute using simulated intestinal fluid having pH 7.4 without digestive enzymes and temperature of 37 degrees Celsius. .

17. A pharmaceutical composition of claim 1, or claim 2, claim 3 or claim 4 wherein delayed release dosage form require for release of at least 70% of the active ingredients available from the said dosage form after one hr as determined by the USP XXVII dissolution test apparatus with paddle having speed 100 revolutions per minute using simulated intestinal fluid without digestive enzymes with pH 6.8 and temperature of 37 degrees

Celsius.

18. A pharmaceutical composition of claim 1 , or claim 2, claim 3 or claim 4 wherein extended release dosage form required for release of at least 60 - 100% of the active ingredients available from the said dosage form after 5 to 15 hours as determined by the USP XXVII dissolution test apparatus with paddle having speed 100 revolutions per minute using simulated gastric fluid with pH 1.2 without digestive enzymes and temperature of 37 degrees Celsius for 2 hours and simulated intestinal fluid without digestive enzymes at pH 6.8 for further remaining hours.

19. A pharmaceutical composition of claim 1 or claim 2, claim 3 or claim 4 may be immediate release without final coating with any polymeric material.

20. A composition of claim 1 or claim 2 claim 3 or claim 4 wherein the said controlled release coat is preferably selected from one or more of a polymer that is inert towards the herbal extract, dissolves slowly in gastrointestinal tract permitting release of substantial quantity of a herbal extract at desired locations of action; the said polymer comprising one or more of a Hydroxy Propyl Methyl Cellulose Pthalate(HPMCP), Hydroxy Propyl Methyl Pthalate Cellulose Acetate Succinate(HPMPCAS),

Cellulose Acetate Pthalate(CAP), , EUDRAGIT L 100 [Poly (Methacrylic acid; Methyl Methacrylate) 1 :1] EUDRAGIT L 100-55 [ Poly (Methacrylic acid; Ethylacrylate) 1 :1], EUDRAGIT L 30 D [30% aqueous dispersion of Poly (Methacrylic acid; Methyl Methacrylate)], EUDRAGIT NE 30 D [Poly (Ethylacrylate; Methyl Methacrylate) 2:1] EUDRAGIT RS 100 Poly

(Ethylacrylate; Methyl Ethacrylate, Trimethyl Amino Ethyl Methacrylate Chloride) 1 :2:0.1], EUDRAGIT RL 100 [ Poly (Ethylacrylate; Methyl Ethacrylate, Trimethyl Amino Ethyl Methacrylate Chloride) 1 :2:0.2], EUDRAGIT S 100 [ Poly (Methacrylic acid; Methyl Methacrylate) 1 :2], Ethyl cellulose and the like.