SHAMSUDDIN JAMALUDDIN (IN)
VALI FAIZ ZAKIR (IN)
HUSSAIN SHAKERA (IN)
VALI MOHAMMED SALEH (IN)
DAUD ANWAR SIRAJ (IN)
SHAMSUDDIN JAMALUDDIN (IN)
VALI FAIZ ZAKIR (IN)
HUSSAIN SHAKERA (IN)
VALI MOHAMMED SALEH (IN)
| WO2003047551A1 | 2003-06-12 |
| US20040081691A1 | 2004-04-29 | |||
| US20030206978A1 | 2003-11-06 |
| CLAIMS
1. An oral dosage form comprising pellets coated with a herbal extract as one of the ingredients, wherein 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,
2. A process of preparation of an oral dosage form of claim 1 comprising steps of: a. applying one or more of a coat of an extract of a herb or a mixture of extract from two or more than two herbs, the said extract being ' preferably a crude extract, further preferably from a medicinal plant on a core of aggregates of particulate matter that is inert towards the extract, inert towards the excipients used in the process and having no pharmaceutical activity of its own, including non-pareil seeds, b. optionally applying a finishing coat over the said coated pellets of step (a.), c. optionally applying a permitted colour to non-pareil seeds , d. optionally adding a permitted color to the said finishing coat of step (b.), e. and filling in a capsule shell or pressing into a tablet the pellets of one more of a step (a.), (b.), (c.) or (d.) along with other optional ingredients including colored or non-colored non-pareil seeds.
3. A process of claim 2 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 inert aggregates 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 hydroxypropylmethylcellulose, polyvinylpyrrolidone 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 or soft, comprising of one or more of a material, preferably gelatin, being either opaque or preferably a transparent one. 4. A process of claim 2 or claim 3 comprising one or more of a following steps wherein: a. the said coat of one or more of an extract of a herb is applied by a process which comprises one or more of a process of peptization including a ' method preferably consisting of (i) dispersing an extract of a herb to be coated in water, (ii) adding to it a solvent , preferably isopropyl alcohol in which hydroxypropylmethylcellulose or polyvinylpyrrolidone 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 Non-pareil seeds keeping bed temperature preferably at about 60 0 C, followed by drying in oven at 60 0 C, b. the said coat of one or more of a herb is applied as a dry powder by a process which comprises dusting of dry extracts over Non pareil seeds in rotating pan by wetting the non pareil seeds with a binder comprising solution of one or more of HPMC, PVP and the like, followed by drying of pellets in oven at 60 0 C , 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, preferably at about 1 % or, ii. melting over the circulating pellets, a wax, including a bees wax, preferably in about 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 0 C, 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 hydroxypropylmethylcellulose, polyvinylpyrrolidone 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, e. A product of process 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, f. A product of claim 5 comprising one of more of following compositions: a. an extract of (i) Zingiber officinale Roxb., preferably taken, as percentage of total final composition, in a range of about 0.2 to 8% more preferably to about 3.33% %, and (ii) Piper longum Linn., preferably taken in a range of about 0.5 to 15 %, more preferably to about 2.66% % , b. an extract of (i) Boswellia serrata Roxb. ex Colebr., preferably taken, as percentage of total final composition, in a range of about 5 to 50%, more preferably to about 26%, (ii) Vitex negundo Linn, preferably taken, as percentage of total final composition, in a range of about 0.5 to 25% about 3% %, (iii) Tinospora cordifolia (Wilid.) Miers ex. Hook, f & Thorns, preferably taken, as percentage of total final composition, in a range of about 0.1 to 20%, more preferably to about 1.7%, and (iv) Curcuma lonαa Linn. preferably taken, as percentage of total final composition, in a range of 0.1 % to 15%, more preferably to 2.6%, c. an extract of (i) Bacopa monnieri Linnpreferably taken, as percentage of total final composition, in a range of 0.1 to
10%, more preferably to 2.88%, and (ii) Centella asiatica Linn, preferably taken, as percentage of total final composition, in a range of 0.1 to 20%, more preferably to 2.88%, d. an extract of (i) Momordica charantia Linn, extract preferably taken as percentage of total final composition in the range of 5% to 30% more preferably to 19%, (ii) Azadirachta indica A. Juss. extract preferably taken as percentage of total final composition in the range of 0.5% to 10% more preferably to 1.3%, (iii) Ocimum sanctum Linn, extract preferably taken as percentage of total final composition in the range of 0.1 % to 15% more preferably to 0.5%, (iv) Picrorhiza kurroa Royle ex Benth. extract preferably taken as percentage of total final composition in the range of 0.2% to 10% more preferably to 2.12%, (v) Zingiber officinale Roxb. extract preferably taken as percentage of total final composition in the range of 0.1 % to 10% more preferably to 1.72%, e. an extract of (i) Withania somnifera Dunal. extract preferably taken as percentage of total final composition in the range of 0.1 % to 10% more preferably to 1.6%, (ii) Bacopa monnieri Linn, extract preferably taken as percentage of total final composition in the range of 0.2% to 8% more preferably to
2.64%, (iii) Nardostachys jatamansi DC. extract preferably taken as percentage of total final composition in the range of 0.1% to 10% more preferably to 1.04%, f. an extract of (i) Boerhavia diffusa Linn, extract preferably taken as percentage of total final composition in the range of
2% to 20% more preferably to 9.16%, (v) Trihulus terrestris Linn, extract preferably taken as percentage of total final composition in the range of 1% to 15% more preferably to 4.6%, g. an extract of (i) Picrorhiza kurroa Royle ex Benth. extract preferably taken as percentage of total final composition in the range of 0.1 % to 10% more preferably to 1.11 %, (ii) Phyllanthus niruri Linn, extract preferably taken as percentage of total final composition in the range of 0.2% to 20% more preferably to 2.36%, h. an extract of (i) Cassia angustifolia Vahl. extract preferably taken as percentage of total final composition in the range of 0.5% to 15% more preferably to 3.44%, (ii) Glycyrrhiza glabra Linn, extract preferably taken as percentage of total final composition in the range of 0.1 % to 10% more preferably to 1.16%, (iii) Zingiber officinale Roxb. extract preferably taken as percentage of total final composition in the range of 0.1 % to 9% more preferably to 0.92%, i. an extract of (i) Holarrhena antidysenterica (Roth) A. DC. extract preferably taken as percentage of total final composition in the range of 2% to 20% more preferably to
9.6%, (ii) Euphorbia hirta Linn, extract preferably taken as percentage of total final composition in the range of 0.2% to 10% more preferably to 2.64%, j. an extract of (i) Asparagus racemosus WiIId. extract preferably taken as percentage of total final composition in the range of 0.5% to 15% more preferably to 3.4%, (ii) Allium sativum Linn, extract preferably taken as percentage of total final composition in the range of 0.1 % to 5% more preferably to 0.53%, (iii) Euphorbia hirta Linn, extract preferably taken as percentage of total final composition in the range of 0.1 % to 10% more preferably to 1.06%, (iv) Pueraria tuberosa DC. extract preferably taken as percentage of total final composition in the range of 0.2% to 20% more preferably to 2.8%. (v) Trigonella foenum-graecum Linn, extract preferably taken as percentage of total final composition in the range of
0.2% to 15% more preferably to 2.8%, (vi) Withania somnifera Dunal. extract preferably taken as percentage of total final composition in the range of 0.1% to 10% more preferably to 0.68%, k an extract of (i) Tribulus terrestris Linn, extract preferably taken as percentage of total final composition in the range of 0.1% to 10% more preferably to 1.6%, (ii) Mucuna prureins Baker, extract preferably taken as percentage of total final composition in the range of 0.2% to 20% more preferably to 2.64%, I. an extract of (i) An extract of Trihulus terrestris Linn, extract preferably taken as percentage of total final composition in the range of 5% to 30% more preferably to 21.25%, (ii) Terminalia arjuna W. and A. extract preferably taken as percentage of total final composition in the range of 15% to 70% more preferably to 42.5%, m. an extract of (i) Bacopa monnieri Linn, preferably taken, as percentage of total final composition, in a range of 0.1 to 10%, more preferably to 2.88%, and (ii) Cθntella asiatica Linn, preferably taken, as percentage of total final composition, in a range of 0.1 to 20%, more preferably to 2.88%. |
TITLE
PELLETS OF HERBAL EXTRACTS AND PROCESS FOR PREPARING THE SAME.
TECHNICAL FIELD
This invention relates to a process and a product of coating herbal extracts on the surface of pellets or aggregates of inert particulate matter and optionally filling such pellets in capsules.
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.
Thus, there is a 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.
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.
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 non-pareil 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.
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 is 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.
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.
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 hydroxypropyl methylcellulose, polyvinylpyrrolidone 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 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:
1. Spherical shape of pellets enable them to flow freely and pack uniformly, thereby alleviating handling and packaging problems
2. 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.
3. It has better bioavailability due to larger area in comparison with conventional dosage form.
4. 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 1 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. Then 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 monnieή Linn. (Appa Rao MVR, Koteswara Rao, T.J. 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. Life.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., passed 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 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 pelletization". 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 pelletization. EXAMPLE 1 PREPARATION OF ANTIEMETIC PELLETS Materials taken per 150 kg batch of antiemetic pellets Non-pareil seeds (N. P. seeds 18-20#) 62 kg
Zingiber officinale Roxb. extract 5 kg
Piper longum Linn. extract 4 kg
Demineralised water 25 litres lsopropyl alcohol 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 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 60 0 C. 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 11 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 60 0 C.
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 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
60 0 C, 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 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.
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 kurroa 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
60 0 C. 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 60 0 C.
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 60 0 C, 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 60 0 C.
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 60 0 C.
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
60 0 C, 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 60 0 C. 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 1.0 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 60 0 C.
APPLICATION OF COLORED COAT OVER THE PELLETS:
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 60 0 C, 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 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 60 0 C. 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
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 60 0 C. 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 60 0 C, 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 NP. 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 60 0 C.
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 1.1 kg
Talc 1.0 kg
Titanium Dioxide 1.0 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 60 0 C.
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 60 0 C, 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 NP. 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 60 0 C.
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
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 60 0 C. APPLICATION OF COLORED COAT OVER THE PELLETS:
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 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
60 0 C, 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 reticulata Wight and Am. 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 tuberosa 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 60 0 C. 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
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 60 0 C. APPLICATION OF COLORED COAT OVER THE PELLETS:
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 60 0 C, 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 (NP. 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 terrestris 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 1 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, PEG6000, 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 60 0 C. 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