WO2019198109A1

WO2019198109A1 - Novel pharmaceutical composition of essential oil

Info

Publication number: WO2019198109A1
Application number: PCT/IN2019/050305
Authority: WO
Inventors: Anwar Siraj DAUD; Shamsuddin JAMALUDDIN; Swapnil PANDE; Girish Achliya; Shajahan Abdul; Abdul JAWED
Original assignee: Zim Laboratories Limited
Priority date: 2018-04-13
Filing date: 2019-04-15
Publication date: 2019-10-17

Abstract

of the Invention The present invention relates to a pharmaceutical composition of an essential oil with pharmaceutically acceptable carriers. More particularly the present invention relates to a capsule 5 dosage form comprising Peppermint Oil and a process for manufacturing the same. 10

Description

NOVEL PHARMACEUTICAL COMPOSITION OF ESSENTIAL OIL

FIELD OF THE INVENTION

The present invention relates to a pharmaceutical composition of an essential oil with pharmaceutically acceptable carriers. More particularly the present invention relates to a pharmaceutical composition comprising Peppermint Oil, Caraway oil, and alike or combination thereof, and a process for manufacturing the same.

BACKGROUND OF THE INVENTION

An essential oil is a concentrated hydrophobic liquid containing volatile chemical compounds which is obtained from plants. Essential oils are also known as volatile oils, ethereal oils, aetherolea, or simply as the oil of the plant from which they were extracted, such as Peppermint oil, oil of clove and alike. An essential oil is“essential” in the sense that it contains the“essence of’ the plant’s fragrance -the characteristic fragrance of the plant from which it is derived. Most commonly used essential oils are lavender oil, peppermint oil, tea tree oil, patchouli, and eucalyptus oil. Peppermint is Mentha x piperita, also known as Mentha balsamea Wild. Peppermint oil is obtained from plant source Mentha piperita L. The main active constituents of peppermint oil is menthol and menthone, additionally it also contains (±)-menthyl acetate, l,8-cineole, limonene, beta-pinene and beta-caryophyllene.

Peppermint oil is indicated for the relief of the symptoms of Irritable Bowel Syndrome

(IBS).

Peppermint oil is approved in different forms such as Capsules, vapour drops, mixture and peppermint water in UK market. Further Peppermint oil enteric coated gelatin capsule had been approved in UK as Colpermin on May 01, 2005. Additionally IBgard hard gelatin capsules is also marketed which contain individually triple-coated, sustained-release microspheres of Ultramen®, an ultrapurified peppermint oil, along with fiber and amino acids (from gelatin protein). Further peppermint oil is also available in enteric coated soft gelatin capsules such as Peppermint Gels Softgels, Pepogest.

Current marketed products are quite complex, required specialized machinery, and expensive like microspheres, soft gelatin capsules. Soft gelatin capsules are not easily prepared which required costly specialized equipment, an expensive dosage form which require special precautionary packaging and storage condition. In soft gelatin capsule, more intimate contact between the shell and its liquid contents than exists with dry-filled hard gelatin capsules, which increases the possibility of interactions. These are not adaptable to incorporation of more than one kind of fill into the same capsule as compare with hard shell capsules. The physical strength of the soft gelatin shell could become weaker under high temperature and moisture which might stick together or break the seam-line or deform the shape of the capsule which may hamper the quality of product.

The PCT application WO2014175852A1 discloses a multiparticulate composition where individual core comprises a hydrophobic phase containing Peppermint Oil dispersed in a microcrystalline cellulose-based gel and a hydrophilic phase containing a hydrogel. An enteric coating is over the individual cores. Below enteric coating, there is a proteinaceous subcoating layer of Gelatin covering the individual cores and separating the individual cores from their respective enteric coatings.

US patent publication US2012/0207842 discloses making of enteric coated multiparticulate L-menthol compositions. To prevent the L-menthol from sublimating as the cores were being processed, low temperature processing techniques were used.

However there is still a need to provide alternative formulations of essential oils, which is easy to manufacturing, cost effective, and avoid the drawbacks associated with existing marketed compositions or formulations of essential oils, specifically peppermint oil, caraway oil, and alike or combination thereof.

OBJECT OF THE INVENTION

It is an objective of the invention to provide suitable oral solid dosage forms of essential oils, which are convenient for administration.

It is also an objective of the invention to provide oral solid dosage forms of peppermint oil, Caraway oil, and alike or combination thereof.

Another objective of the present invention is to provide capsule or tablet dosage form of multiparticulate(s) comprising peppermint oil, Caraway oil, and alike or combination thereof. Yet another objective of the present invention is to provide capsule or tablet dosage form of multiparticulate(s) comprising peppermint oil, Caraway oil, and alike or combination thereof optionally coated with suitable pharmaceutically acceptable delayed release polymeric excipient.

SUMMARY OF THE INVENTION

In a primary aspect, the present invention is providing a solid dosage form comprising peppermint oil, Caraway oil, and alike or combination thereof.

Another aspect of the present invention is to provide solid dosage form of multiparticulate(s) comprising peppermint oil, Caraway oil, and alike or combination thereof.

Yet another aspect of the present invention is to provide solid dosage form of multiparticulate(s) comprising peppermint oil Caraway oil, and alike or combination thereof adsorbed on/in substrate(s), more significantly on substrate, optionally coated with suitable pharmaceutically acceptable delayed release using enteric coating polymeric excipient.

Another aspect of the present invention is to provide a process for manufacture of capsule or tablet dosage form comprising peppermint oil, Caraway oil, and alike or combination thereof.

Specifically, present invention is related to solid dosage form comprising delayed release layer coated multiparticulate(s) of peppermint oil or Caraway oil, and alike or combination thereof.

Another aspect of the present invention is to provide capsule or tablet dosage form of multiparticulate(s) comprising peppermint oil, Caraway oil, and alike or combination thereof, wherein particulate(s) comprise a core of peppermint oil, Caraway oil, and alike or combination thereof adsorbed on a substrate, optionally with solvent, or/ cosolvent, mixture(s) of solvent /cosolvent along with one or more pharmaceutical ingredient(s) or combination thereof.

Another aspect of the present invention is to provide capsule or tablet dosage form of multiparticulate(s) comprising peppermint oil Caraway oil, and alike or combination thereof optionally coated with suitable pharmaceutically acceptable delayed release polymeric excipient.

DETAILED DESCRIPTION OF THE INVENTION

While the invention has been described and illustrated with reference to certain particular embodiments thereof, those skilled in the art will appreciate that various adaptations, changes, modifications, substitutions, deletions, or additions of procedures and protocols may be made without departing from the spirit and scope of the invention. It is intended, therefore, that the invention be defined by the scope of the claims which follow and that such claims be interpreted as broadly as is reasonable.

In addition to the active or therapeutic ingredients, capsules may contain a number of inert materials known as excipients. They may be classified according to the role they play in the final composition or capsule. The primary composition includes filler, binder, lubricant and glidant or other essential pharmace u ticall y acceptable ingredient(s) or combination thereof.

Multiparticulate(s) or pellet(s) or particle(s) have a significant role in delivering optimal quantity of active ingredient to get a maximum therapeutic effect due to their morphology. Pellet(s) disperse freely in Gastro Intestinal Tract (GIT), maximize drug absorption, and minimize local irritation in stomach of the mucosa by peppermint oil. Development of a formulation for peppermint oil which is simple and stable is need of researchers.

Inventors of present invention developed a capsule dosage form containing pellet(s) of peppermint oil.

Peppermint oil containing pellet(s) are prepared using peppermint oil and suitable pharmaceutically acceptable polymeric excipient(s). Said peppermint oil pellets may optionally be coated with separating layer comprising suitable pharmaceutically acceptable polymeric or non-polymeric excipient(s) or combination thereof. Peppermint oil containing pellet(s) may further be coated with suitable pharmaceutically acceptable delayed release polymeric excipient(s). Said coated pellet(s) are filled in capsule.

In one feature, the present invention provides a pharmaceutical composition comprising an essential oil, a substrate for adsorption of essential oil, and one or more pharmaceutically acceptable excipient(s). In a preferred feature, the essential oil is peppermint oil, Caraway oil, and alike or combination thereof.

In another feature, the present invention provides compositions of essential oil, wherein the substrate is selected from silicon dioxide, aluminium magnesium silicate, microcrystalline cellulose, powdered cellulose, silicified microcrystalline cellulose, tribasic calcium phosphate, dibasic calcium phosphate, maltodextrin, precipitated silica, colloidal silica, starch, pregelatinized starch, hydroxypropyl cellulose, magnesium oxide, magnesium hydroxide and alike or a combination thereof, on which the essential oil is adsorbed. In another feature of the invention, the composition of the present invention is further coated with a seal coating or barrier coating as a separating layer.

In yet another feature, the composition of the present invention is further coated with an enteric coating or delayed release coating.

In yet another feature, the present invention provides a pharmaceutical composition comprising enteric coated pellets, wherein the pellets comprise an essential oil adsorbed on a substrate. In preferred features, the pellets are optionally coated with a seal coating before enteric coating. The seal coating is performed by a coating composition comprising polymeric and/or non-polymeric material which is selected from but not limited to acacia, polyvinyl acetate, povidone, gelatin, cellulosic polymers like Hydroxy Propyl Cellulose, Hydroxy Propyl methyl Cellulose, methacrylic acid copolymer, acrylate copolymer, and alike(s) or combination thereof with other essential one or more pharmaceutically acceptable excipients required for seal coating. The enteric coating is performed by a coating composition comprising, polymeric and non-polymeric enteric material preferably selected from but not limited to methacrylic acid co polymer, acrylate polymer, hydroxyl propyl methyl phthalate, Cellulose acetate phthalate, cellulose acetate succinate and alike or combination thereof. In yet another feature, the pellets so prepared are filled in a capsule, preferably hard gelatin capsule or/ tableting in tablet form.

In another feature, the present invention provides a pharmaceutical composition of an essential oil or a combination of essential oils, comprising: a substrate containing neutral or active ingredient(s), one or more pharmaceutically acceptable excipient(s); essential oil(s) and/or one or more pharmaceutical ingredient(s), adsorbed on the substrate; optionally, an outer film coat on the essential oil adsorbed substrate. In preferred feature, said composition is in the form of pellets or particulates or particles or granules, filled in capsule or/ tableting in tablet form.

In another feature, the present invention provides a process for preparing a composition of essential oil adsorbed on a substrate, the process comprising:

(a) mixing essential oil with substrate and adding other pharmaceutically acceptable excipients to obtain a dough,

(b) granulating and/or extruding the dough to obtain granules or extrudes and spheronizing and drying the same to obtain spheroid particles or pellets or granules,

(c) optionally seal coating said particles or pellets or granules to obtain seal coated particles or pellets, (d) enteric coating on said particles or pellets or granules of step (b) or seal coated particles or pellets of step (c), to obtain enteric coated particles or pellets or granules,

(e) optionally filling the enteric coated particles or pellets or granules in capsules or tableting in tablet form.

In a preferred feature, in the process of the present invention, the essential oil is selected from but not limited to peppermint oil, caraway oil, lavender oil, tea tree oil, patchouli, eucalyptus oil or combination thereof. Further substrate is selected from but not limited to silicon dioxide, aluminium magnesium silicate, microcrystalline cellulose, powdered cellulose, silicified microcrystalline cellulose, tribasic calcium phosphate, dibasic calcium phosphate, maltodextrin, precipitated silica, colloidal silica, starch, pregelatinized starch, hydroxypropyl cellulose, magnesium oxide, and magnesium hydroxide or a combination thereof. Further additionally pharmaceutically acceptable excipients are selected from diluents, preferably but not limited to one or more microcrystalline cellulose, sugar alcohols, starch, lactose or combination thereof, disintegrants, lubricants, binders, glidant, preferably talc, and the alike or mixture thereof. In another preferred feature, in the process of the present invention, the seal coating is performed with a composition comprising polymeric and/or non-polymeric material which is selected from but not limited to acacia, polyvinyl acetate, povidone, gelatin, cellulosic polymers like Hydroxy propyl cellulose, Hydroxy propyl methyl cellulose, methacrylic acid copolymer, acrylate copolymer, and alike(s) or combination thereof with other essential one or more pharmaceutically acceptable excipients required for seal coating and the enteric coating is performed with a composition comprising polymeric and non-polymeric enteric material preferably selected from but not limited to methacrylic acid co-polymer, acrylate polymer, hydroxyl propyl methyl phthalate, Cellulose acetate phthalate, cellulose acetate succinate and alike or combination thereof.

EXAMPLES

The following examples are set forth below to illustrate the composition and methods according to the present invention. These examples are not intended to be inclusive of all aspects of the subject matter disclosed herein, but rather to illustrate representative methods, compositions, and results. These examples are not intended to exclude equivalents and variations of the present invention, which are apparent to one skilled in the art. Example 1

Manufacturing procedure:

Granulation and extrusion:

1) Peppermint oil is mixed with silicon dioxide in RMG, add crospovidone, Microcrystalline Cellulose, aluminium magnesium silicate and talc in it and granulate. 2) Above granules are extruded through pore plate.

Spheronization:

3) Extrude prepared as above are spheronized in spheronizer to form pellets. During spheronization, blend of magnesium oxide and purified talc is dusted.

Seal coating:

4) Pellets prepared as above are sealed coated with Acacia using Ethyl acrylate and methyl methacrylate copolymer as binder in CFG.

Enteric coating:

5) Methacrylic acid co-polymer are dissolved in a mixture of Methyl alcohol and Methylene chloride, Further triethyl citrate is added in it followed by addition purified talc. With this solution, above prepared sealed coated pellets are further coated in Fluid bed coater. After coating pellets are dried.

Optional coat:

6) Hydroxypropyl methyl cellulose and triethyl citrate is dissolved in methyl alcohol and methylene chloride. Using this solution above enteric coated pellets may be coated and dried.

Capsule filling or Tableting in Tablet form:

7) Pellets prepared as above are filled into hard gelatin capsules or tableting in tablet form according to dose of peppermint oil.

Example 2:

Manufacturing Procedure:

Stage I: Drug pellets preparation:

Sift Microcrystalline Cellulose and silicon dioxide through 40#, dry mix in RMG for 10 min. Mix and granulate with peppermint oil and arachis oil followed by copovidone solution in water and mix. Dry the blend in FBD, again regranulate the blend with Ethyl acrylate and Methyl methacrylate Copolymer dispersion and PEG previously dissolved in water. Granules are extruded and pelletized in spheronizer followed by drying of pellets.

Stage II: Seal coated pellets preparation

Pellets prepared in stage I is subjected to seal coat with the solution of Hypromellose E6 + Talc in FBC, followed by drying.

Stage III: Enteric coating of pellets

After drying of seal coated pellets, enteric coating is carried out with solution of Hypromellose HP-55, Dibutyl sebacate, methyl alcohol and Methylene chloride, followed by drying.

Stage IV: Lubrication

Above dried enteric coated pellets are lubricated with talc.

Stage V : Capsule filling or tableting in tablet

Above prepared pellets are filled in capsules or tableting in tablet form according to the dose of peppermint oil. Example 3

Manufacturing procedure:

Granulation and extrusion:

1) Peppermint oil is mixed with silicon dioxide in RMG, add crospovidone,

Microcrystalline Cellulose, and talc in it and granulate.

2) Above granules are extruded through pore plate.

Spheronization:

3) Extrude prepared as above are spheronized in spheronizer to form pellets. During spheronization purified talc is dusted.

Seal coating:

4) Pellets prepared as above are sealed coated with Acacia using Hydroxypropyl Methyl Cellulose as binder in CFG.

Enteric coating: 5) Methacrylic acid co-polymer type A is dissolved in a mixture of Methyl alcohol and Methylene chloride, Further triethyl citrate is added in it followed by addition purified talc. With this solution, above prepared sealed coated pellets are further coated in Fluid bed coater. After coating pellets are dried.

Optional coat:

Capsule filling:

7) Pellets prepared as above are filled into hard gelatin capsules according to dose of peppermint oil.

Example 4:

Manufacturing procedure:

Granulation and extrusion:

1) Peppermint oil is mixed with silicon dioxide and Di-Calcium Phosphate in RMG and granulate. 2) Above granules are extruded through pore plate.

Spheronization:

Seal coating:

4) Pellets prepared as above are sealed coated with Ethyl acrylate and Methyl methacrylate Copolymer Dispersion in CFG.

Enteric coating:

5) Hypromellose phthalate is dissolved in a mixture of Methyl alcohol and Methylene chloride, Further DibutylSebacate is added in it followed by addition purified talc. With this solution, above prepared sealed coated pellets are further coated in Fluid bed coater. After coating pellets are dried.

Optional coat:

6) Hydroxypropyl methyl cellulose and DibutylSebacate is dissolved in methyl alcohol and methylene chloride. Using this solution above enteric coated pellets may be coated and dried.

Capsule filling:

Claims

We Claim:

1. A pharmaceutical composition comprising an essential oil, a substrate for adsorption of essential oil, and one or more pharmaceutically acceptable excipient(s).

2. The composition as claimed in claim 1 , wherein the composition is further coated with a seal coating.

3. The composition as claimed in any of the preceding claims, wherein the composition is further coated with an enteric coating.

4. A pharmaceutical composition comprising enteric coated pellets, wherein the pellets comprise an essential oil adsorbed on a substrate.

5. The composition as claimed in any of the preceding claims, wherein the essential oil is selected from peppermint oil, caraway oil, lavender oil, tea tree oil, patchouli, eucalyptus oil or combination thereof.

6. The composition as claimed in any of the preceding claims, wherein the substrate is selected from silicon dioxide, aluminium magnesium silicate, powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, tribasic calcium phosphate, dibasic calcium phosphate, maltodextrin, precipitated silica, colloidal silica, starch, pregelatinized starch, hydroxypropyl cellulose, magnesium oxide, magnesium hydroxide and alike or a combination thereof.

7. The composition as claimed in any of the preceding claims 4 to 6, wherein the pellets are further coated with a seal coating before enteric coating.

8. The composition as claimed in any of the preceding claims, wherein the seal coating is performed by a coating composition comprising polymeric and non-polymeric material preferably selected from acacia, polyvinyl acetate, povidone, cellulosic polymers like Hydroxy propyl Cellulose, Hydroxy propyl methyl Cellulose, methacrylic acid copolymer, acrylic acid copolymer, and alike or combination thereof.

9. The composition as claimed in any of the preceding claims, wherein the enteric coating is performed by a coating composition comprising polymeric and non-polymeric enteric material, selected from methacrylic acid-methacrylate copolymer, methacrylic acid copolymers, acrylic acid copolymers, hydroxyl propyl methyl phthalate, Cellulose acetate phthalate, cellulose acetate succinate and alike or combination thereof which are preferably soluble above pH 5 to 5.5..

10. The composition as claimed in any of the preceding claims 4 to 9, wherein the pellets are filled in a capsule or tableting in tablet form.

11. A pharmaceutical composition of an essential oil or a combination of essential oils, comprising:

(a) a substrate containing neutral or active ingredient(s), one or more pharmaceutically acceptable excipient(s),

(b) essential oil(s) and/or one or more pharmaceutical ingredient(s), adsorbed on the substrate,

(c) optionally, an outer film coat on the essential oil adsorbed substrate or particles or pellets or granules

(d) enteric coating said adsorbed substrates or particles or pellets or granules of step (b) or seal coated particles or pellets or granules of step (c), to obtain enteric coated particles or pellets.

12. The composition as claimed in claim 11, wherein the composition is in the form of particles or pellets, filled in capsule.

13. A process for preparing a composition of essential oil adsorbed on a substrate, the process comprising:

(b) granulating and/or extruding the dough to obtain granules and spheronizing and drying the same to obtain spheroid particles or pellets,

(c) optionally seal coating said particles or pellets to obtain seal coated particles or pellets,

(d) enteric coating said particles or pellets of step (b) or seal coated particles or pellets of step (c), to obtain enteric coated particles or pellets,

(e) optionally filling the enteric coated particles or pellets in capsules or tableting in tablet form.

14. The process as claimed in claim 13,

wherein in step (a), the essential oil is peppermint oil, substrate is selected from silicon dioxide, aluminium magnesium silicate, microcrystalline cellulose, powdered cellulose, silicified microcrystalline cellulose, tribasic calcium phosphate, dibasic calcium phosphate, maltodextrin, precipitated silica, colloidal silica, starch, pregelatinized starch, hydroxypropyl cellulose, magnesium oxide, magnesium hydroxide and alike or a combination thereof, and pharmaceutically acceptable excipients are selected from diluents, binders, disintegrants, lubricants, and combination thereof;

in step (c) seal coating is performed with a composition comprising polymeric and non-polymeric material preferably selected from acacia, polyvinyl acetate, povidone, gelatin, cellulosic polymers like Hydroxy Propyl Cellulose, Hydroxy Propyl Methyl Cellulose, and alike or combination thereof, plasticizer, and other essential ingredients ; in step (d) enteric coating is performed with a composition comprising polymeric and non-polymeric enteric material preferably Methacrylic acid co-polymer, methacrylic acid-methacrylate copolymer, acrylic acid copolymers, hydroxyl propyl methyl phthalate, Cellulose acetate phthalate, cellulose acetate succinate and alike or combination thereof, plasticizer and other essential ingredients.