WO2008059522A2 - Formes posologiques d'administration contrôlée de médicament gastro-intestinale à base d'herbe comprenant des pastilles et leur procédé de préparation - Google Patents

Formes posologiques d'administration contrôlée de médicament gastro-intestinale à base d'herbe comprenant des pastilles et leur procédé de préparation Download PDF

Info

Publication number
WO2008059522A2
WO2008059522A2 PCT/IN2007/000455 IN2007000455W WO2008059522A2 WO 2008059522 A2 WO2008059522 A2 WO 2008059522A2 IN 2007000455 W IN2007000455 W IN 2007000455W WO 2008059522 A2 WO2008059522 A2 WO 2008059522A2
Authority
WO
WIPO (PCT)
Prior art keywords
pellets
extract
herbal extract
coat
coated
Prior art date
Application number
PCT/IN2007/000455
Other languages
English (en)
Other versions
WO2008059522B1 (fr
WO2008059522A3 (fr
Inventor
Anwar Siraj Daud
Jamaluddin Shamsuddin
Faiz Zakir Vali
Shakera Hussain
Mohammed Saleh Vali
Original Assignee
Unijules Life Sciences Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Unijules Life Sciences Ltd filed Critical Unijules Life Sciences Ltd
Publication of WO2008059522A2 publication Critical patent/WO2008059522A2/fr
Publication of WO2008059522A3 publication Critical patent/WO2008059522A3/fr
Publication of WO2008059522B1 publication Critical patent/WO2008059522B1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/32—Burseraceae (Frankincense family)
    • A61K36/324—Boswellia, e.g. frankincense
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/482—Cassia, e.g. golden shower tree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8962—Allium, e.g. garden onion, leek, garlic or chives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger

Definitions

  • the present invention relates to a controlled release herbal gastrointestinal drug delivery dosage forms including pellets, tablets and capsules and process for their preparation.
  • 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.
  • odor / flavour of some herbal extracts Garlic extract for example, is so strong that it induces belching of Garlic odor which is highly discomforting.
  • Sennosides present in extract of Cassia angustifolia Vahl are meant for laxative action in colon, induces a gripping action in upper gastrointestinal region.
  • Boswellic acid extracted from Boswellia serrata Roxb. ex Colebr. Boswellic acid has analgesic and anti-inflammatory action and therefore very useful in arthritis.
  • drug is required to administered frequently in large quantities.
  • Curcumin in pure form extracted from Turmeric also has fast absorption and short life.
  • 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 .m ⁇ m 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the extract 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 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.
  • 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.
  • 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.
  • IPA lsopropyl alcohol
  • 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.
  • 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.
  • 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 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.
  • 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.
  • 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.
  • improvement in Aurvedic drug therapy has daunting constraints for further improvement and achievement of improvement without purifying a crude extract is a challenge.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • Non-pareil seeds (NP. seeds 18-20#) 62 kg
  • Demineralised water 25 litres lsopropyf alcohol (IPA) 12.5 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.
  • PEG-6000 Poly Ethylene Glycol
  • Herbal extracts finished and colored pellets as prepared above can also be compressed into tablets as follows.
  • Herbal extract pellets 250 mg Microcrystalline cellulose spray dried 180 mg Lactose directly compressible 180 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.
  • Non-pareil seeds N. P. seeds 18-20# 45 kg Boswellia serrata Roxb. ex Colebr. Extract 26 kg
  • Tinospora cordifolia (WiIId.) Miers ex Hook. f. & Thorns.
  • Tinospora sp. and Curcuma sp. were prepared by the same process as done with the product of Example-1 , without finishing layer.
  • Non-pareil seeds (N. P. seeds 18-20#) 100 kg
  • Centella asiatica Linn extract 7.2 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.
  • Titanium Dioxide 0.5 kg IPA (isopropyl alcohol) 5.0 liters
  • HPMC HPMC was dispersed in IPA 1 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.
  • Non-pareil seeds (N. P. seeds 18-20#) 65 kg
  • 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.
  • 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.
  • Non-pareil seeds N. P. seeds 18-20# 150 kg
  • 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.
  • 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.
  • HPMC 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.
  • Non-pareil seeds N. P. seeds 18-20# 150 kg
  • Tribulus terrestris Linn extract 11.5 kg Demineralised water 80 litres lsopropyl alcohol 40 litres
  • 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.
  • 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.
  • HPMC 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 NP. seeds to match the net desired content.
  • Non-pareil seeds N. P. seeds 18-20# 150 kg Picrorhiza kurroa Royle ex Benth. extract 2.95 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.
  • Titanium Dioxide 1.0 kg IPA 15 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.
  • HPMC 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 N. P. seeds utilizing caramel colour to match the net desired content.
  • Non-pareil seeds (N. P. seeds 18-20#) 150 kg Cassia angustifolia Vahl. extract 8.6 kg
  • 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.
  • HPMC 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 N. P. seeds utilizing erythrosine colour to match the net desired content.
  • Non-pareil seeds (N. P. seeds 18-20#) 150 kg
  • Demineralised water 100 litres lsopropyl alcohol 50 litres
  • Titanium Dioxide 1.0 kg IPA 10 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.
  • Non-pareil seeds (N. P. seeds 18-20#) 100 kg
  • 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.
  • HPMC 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.
  • 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 &
  • Non-pareil seeds N. P. seeds 18-20# 30 kg
  • Disperse HPMC in IPA add water to it and make solution, disperse talc in it.
  • Tatrazine colour 2.0 kg Talc 0.5 kg litres
  • Non-pareil seeds (N. P. seeds 18-20#) 100 kg Bacopa monnieri Linn, extract 7.2 kg
  • Centella asiatica Linn extract 7.2 kg
  • Demineralised water 50 litres lsopropyl alcohol . 25 litres HPMC-5cps 2.5 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 60 0 C. After extract layer was fully formed, colouring of N. P. seed was done as follows.
  • Demineralised water 25.0 litres HPMC was dispersed in IPA, add water slowly to make solution, dissolve colour.
  • 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 60 0 C.
  • 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 EXAMPLE 15
  • Non-pareil seeds N. P. seeds 18-20#
  • Cassia angustifolia Vahl extract 11.7 kg lsopropyl alcohol 15 litres
  • Methacrylic Acid Copolymer type B (Eudragit S100) 15 kg Aetone 100 litres
  • 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 60 0 C.
  • 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 37 0 C
  • 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.
  • 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 60 0 C. After extract layer was fully formed, extended release layer was applied the pellets as described below .
  • Boswellia serrata Roxb extended release pellets 200kg Lactose compressible 150Kg Microcrystalline Cellulose spray dried 149.25Kg
  • 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 37 0 C . 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.
  • 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
  • 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 60 0 C.
  • 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 37 0 C . an din simulated intestinal fluid without enzyme at
  • Active ingredient releases at least 60-100% of the active ingredients available from the said dosage form after 5-15 minutes.

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

L'invention porte sur une nouvelle forme posologique orale pour l'administration d'un ou de plusieurs extraits à base d'herbe et sur un procédé pour la préparation de celle-ci, le procédé comportant l'étape d'enrobage d'un extrait à base d'herbe sur des pastilles qui sont soit introduites dans une capsule, soit comprimées en un comprimé, la capsule pouvant contenir des pastilles enrobées d'un ou plusieurs extraits à base d'herbe et le comprimé étant comprimé à partir de pastilles enrobées par au moins deux extraits à base d'herbe ou plus. L'invention concerne également un procédé de préparation de la forme posologique en question. Les pastilles susmentionnées revêtues d'un extrait à base d'herbe sont finalement revêtues d'un revêtement à libération contrôlée composé d'un polymère qui devrait conduire à une libération contrôlée du ou des extraits à base d'herbe dans le tractus gastro-intestinal.
PCT/IN2007/000455 2006-09-28 2007-09-26 Formes posologiques d'administration contrôlée de médicament gastro-intestinale à base d'herbe comprenant des pastilles et leur procédé de préparation WO2008059522A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1576MU2006 2006-09-28
IN1576/MUM/2006 2006-09-28

Publications (3)

Publication Number Publication Date
WO2008059522A2 true WO2008059522A2 (fr) 2008-05-22
WO2008059522A3 WO2008059522A3 (fr) 2008-07-10
WO2008059522B1 WO2008059522B1 (fr) 2008-09-12

Family

ID=39402101

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2007/000455 WO2008059522A2 (fr) 2006-09-28 2007-09-26 Formes posologiques d'administration contrôlée de médicament gastro-intestinale à base d'herbe comprenant des pastilles et leur procédé de préparation

Country Status (1)

Country Link
WO (1) WO2008059522A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20132065A1 (it) * 2013-12-11 2015-06-12 Farmatron Ltd Sistemi terapeutici a rilascio modificato per la somministrazione orale di curcumina nel trattamento delle malattie intestinali
EP3031456A4 (fr) * 2013-08-06 2016-12-28 Tasly Pharmaceutical Group Co Application d'andrographolide dans la préparation d'un produit pharmaceutique pour le traitement d'affection inflammatoire du tube digestif, microgranule d'andrographolide pour la vectorisation de médicaments gastro-résistants et leur procédé de préparation

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003047551A1 (fr) * 2001-11-29 2003-06-12 Penwest Pharmaceutical Company Particules agglomerees comprenant un principe actif cotraite avec de la cellulose microcristalline silicifiee
US20030206978A1 (en) * 2001-11-29 2003-11-06 Bob Sherwood Agglomerated particles including an active agent coprocessed with silicified microcrystalline cellulose
US20040081691A1 (en) * 1999-03-12 2004-04-29 D B F Granules containing a plant substance and process for preparing them

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040081691A1 (en) * 1999-03-12 2004-04-29 D B F Granules containing a plant substance and process for preparing them
WO2003047551A1 (fr) * 2001-11-29 2003-06-12 Penwest Pharmaceutical Company Particules agglomerees comprenant un principe actif cotraite avec de la cellulose microcristalline silicifiee
US20030206978A1 (en) * 2001-11-29 2003-11-06 Bob Sherwood Agglomerated particles including an active agent coprocessed with silicified microcrystalline cellulose

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MEUNIER J.P. ET AL.: 'Use of rotary fluidized-bed technology for development of sustained-release plant extracts pellets: Potential application for feed additive delivery' J. ANIMAL SCIENCE vol. 84, 2006, pages 1850 - 1859 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3031456A4 (fr) * 2013-08-06 2016-12-28 Tasly Pharmaceutical Group Co Application d'andrographolide dans la préparation d'un produit pharmaceutique pour le traitement d'affection inflammatoire du tube digestif, microgranule d'andrographolide pour la vectorisation de médicaments gastro-résistants et leur procédé de préparation
ITMI20132065A1 (it) * 2013-12-11 2015-06-12 Farmatron Ltd Sistemi terapeutici a rilascio modificato per la somministrazione orale di curcumina nel trattamento delle malattie intestinali
WO2015087259A1 (fr) 2013-12-11 2015-06-18 Mogon Pharmaceuticals Sagl Systèmes thérapeutiques à libération modifiée pour l'administration par voie orale de curcumine dans le traitement de troubles intestinaux

Also Published As

Publication number Publication date
WO2008059522B1 (fr) 2008-09-12
WO2008059522A3 (fr) 2008-07-10

Similar Documents

Publication Publication Date Title
TWI481410B (zh) 克羅非莫(crofelemer)用於治療與腹瀉型腸躁症(d-IBS)相關聯之腹痛及腹部不適的醫藥用途
JP4779082B2 (ja) 減少された乱用潜在性を有する薬物製剤
CA2291796C (fr) Compositions therapeutiquement actives
US4948581A (en) Long acting diclofenac sodium preparation
AU2020280997B2 (en) A process to enhance the bioactivity of Ashwagandha extracts
EP0052075A1 (fr) Granule pharmaceutique à action retardée
KR101380507B1 (ko) 다중 미립자를 함유하고 이중 방출 프로파일을 갖는 고체 경구용 제형
CN108888670B (zh) 一种治疗溃疡性结肠炎的结肠靶向胶囊剂及其制备工艺
CN105377247B (zh) 用于治疗溃疡性结肠炎含磷脂酰胆碱的药物制剂
US9987323B2 (en) Process to enhance the bioactivity of Ashwagandha extracts
WO2008035354A1 (fr) Pastilles d'extraits d'herbes et son procédé de préparation
WO2008059522A2 (fr) Formes posologiques d'administration contrôlée de médicament gastro-intestinale à base d'herbe comprenant des pastilles et leur procédé de préparation
Brendler et al. Devil’s Claw (Harpagophytum procumbens DC) an evidence-based systematic review by the natural standard research collaboration
WO2021001860A1 (fr) Compositions pharmaceutiques de boswellia serrata
WO2014111956A2 (fr) Formulations à libération prolongée de curcuminoïdes et leur procédé de préparation
Hermenean et al. Plant-derived biomolecules and drug delivery systems in the treatment of liver and kidney diseases
WO2001054673A1 (fr) Procede de preparation et d'administration de materiau a base de plante medicinale
CN101496903B (zh) 一种减少药物对胃刺激的药物包衣液
CN1048897C (zh) 治疗冠心病、心绞痛、心肌梗塞的中成药及其制备方法
Mishra et al. Characterization of nanophytopharmaceuticals
CN109432082A (zh) 一种防治化学性肝损伤的药物组合物
Bakshi et al. Herbal Bioactive-Based Drug Delivery Systems: Challenges and Opportunities
Bolourchian et al. Development and evaluation of taste-masked pellets loaded with Matricaria chamomilla L. extract
WO2022162649A1 (fr) Composition à libération retardée comprenant un médicament entérosoluble chargé dans une matrice d'enveloppe de psyllium
Huang et al. Film-Controlled Synchronized Release Multicomponent Preparations of Chinese Materia Medica for Oral Administration

Legal Events

Date Code Title Description
NENP Non-entry into the national phase in:

Ref country code: DE

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07866716

Country of ref document: EP

Kind code of ref document: A2

122 Ep: pct application non-entry in european phase

Ref document number: 07866716

Country of ref document: EP

Kind code of ref document: A2