WO2009153654A1 - Formes pharmaceutiques solides d’anti-rétroviraux - Google Patents
Formes pharmaceutiques solides d’anti-rétroviraux Download PDFInfo
- Publication number
- WO2009153654A1 WO2009153654A1 PCT/IB2009/006008 IB2009006008W WO2009153654A1 WO 2009153654 A1 WO2009153654 A1 WO 2009153654A1 IB 2009006008 W IB2009006008 W IB 2009006008W WO 2009153654 A1 WO2009153654 A1 WO 2009153654A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- ritonavir
- lopinavir
- surfactant
- blend
- blending
- Prior art date
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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Definitions
- the present invention relates to solid oral dosage forms comprising lopinavir and ritonavir prepared by an improved process.
- AIDS Acquired Immunodeficiency Syndrome
- HBV human immunodeficiency virus
- NRTI' nucleoside/nucleotide reverse transcriptase inhibitors
- NRTFs non-nucleoside reverse transcriptase inhibitors
- Lopinavir and ritonavir belongs to the class of protease inhibitors.
- Lopinavir is chemically known as [lS-[lR*,(R*),3R*,4R*]]-N-[4-[[2,6- dimethylphenoxy)acetyl]amino]-3-hydroxy-5-phenyl-l-(phenylmethyl)pentyl] tetrahydro- ⁇ -(l-methylethyl)-2-oxo-l(2H)-pyrimidineacetamide and ritonavir is chemically known as 10-hydroxy-2-methyl-5-(l-methylethyl)-l-[2-(l- methylethyl)-4-thiazolyl]-3,6-dioxo-8, 1 l-bis(phenylmethyl)-2,4,7, 12-tetraazatri decan-13-oic acid, 5-thiazolylmethyl ester,[5S-(5R*,8R*,10R
- Ritonavir is marketed under trade name Norvir® in United States in the form of oral solution and capsule as well as in combination with lopinavir under the trade name Kaletra® in the form of oral solution, capsule and tablet.
- protease inhibitors such as lopinavir, ritonavir, nelfmavir and indinavir are less bioavailable due to poor water solubility and hence difficult to formulate.
- Dosage forms for these products are prepared by dissolving the drug in a solvent and further processed into liquid formulation or liquid filled soft gelatin capsule in which the drug is properly dissolved.
- hard gelatin capsule and tablet formulations have been developed. Even though lopinavir and ritonavir are low soluble and permeable, the particle size reduction or crystal form will not have a significant impact on the dissolution or bioavailability of the tablet dosage form.
- the currently available tablet dosage form is formulated using hot melt extrusion (Meltrex) technology, which helps in increasing the bioavailability by dispersing the active ingredient in molecular level. Moreover, this technology is advantageous over conventional technologies by suspending the drug particles to deaggregate in the polymer melt due to intense mixing and agitation and also by allowing high drug loading.
- Meltrex hot melt extrusion
- composition comprises lopinavir and ritonavir, water soluble polymer and surfactant, comprising the steps of (a) preparing a mixture of combination of HIV protease inhibitors, a water soluble polymer and a surfactant, (b) feeding the mixture in a twin screw extruder while maintaining a high temperature to form a homogenous melt and (c) finally compressing the dried melt to form a tablet.
- US 7,364,752 discloses a solid dispersion comprising HIV protease inhibiting compound prepared by dissolving or dispersing the HIV protease inhibiting compound in a sufficient amount of an organic solvent followed by dispersion into a suitable water soluble carrier. The solvent is then evaporated followed by cooling, leaving the drug dispersed or dissolved in the molten matrix.
- WO 2006/037827 discloses a composition comprising ritonavir and a compound enabling gastrointestinal fluid to penetrate that composition which is selected from the group comprising silicates and silica oxide and further discloses a process, which comprises a kneading step in which the speed and the time of addition of the solvent is thoroughly controlled.
- WO 2008/009689 discloses a composition comprising active ingredients including lopinavir and ritonavir along with at least one pharmaceutically acceptable polymer and a solubilizing composition comprising at least one tocopheryl compound having a polyalkylene glycol and at least one alkylene glycol fatty acid monoester, wherein the composition is prepared by homogeneous melting of active ingredients, polymers and solubilizing composition and allowing the melt to solidify to obtain a solid dispersion.
- WO 2008/017867 discloses a composition comprising one or more antiretroviral drugs including lopinavir and ritonavir or their pharmaceutically acceptable salts, solvates or hydrates and at least one water insoluble polymer prepared by various methods such as melt granulation, melt extrusion, spray drying and solution evaporation, wherein the melt extrusion process comprises the steps of a) preparing a homogeneous melt of each drug; water insoluble polymer and excipients; (b) cooling the melt obtained in step (a); (c) allowing the cooled melt to solidify to obtain extrudates; and (d) processing the extrudates into a desired shape.
- WO 2008/029417 discloses a formulation prepared by a process devoid of hot melt extrusion, comprising the steps of: a) mixing at least one antiretroviral drug with at least one pharmaceutical additive in an organic solvent; b) drying said mixture; c) milling said mixture to form milled product; d) compressing said milled product into tablets or filling said milled product into capsules.
- WO 2008/067164 discloses a dosage form comprising solid dispersion or solid solution of ritonavir in a matrix of water soluble polymer and surfactant and further discloses a melt extrusion process comprising the steps of (a) preparing a mixture of ritonavir or a combination of ritonavir and another therapeutic agent(s), water soluble polymer and surfactant (b) feeding the mixture in a twin screw extruder to form a homogenous melt and (c) finally compressing the dried melt to form a tablet.
- the above prior art references disclose various formulations and its preparation for solid oral dosage form comprising lopinavir and ritonavir.
- the main objective of the present invention is to provide a solid oral dosage form comprising lopinavir and ritonavir prepared by an improved process.
- Yet another objective of the present invention is to provide a solid oral dosage form comprising lopinavir and ritonavir prepared by an improved process in such a way that it will comply with the reference product in terms of in vivo parameters like bioequivalence such as C max , AUC, T max and in vitro parameters like tablet erosion pattern in dissolution media, disintegration time and dissolution etc.
- the present invention provides a solid oral dosage form comprising lopinavir, ritonavir, water soluble polymer and surfactant prepared by a process comprising the steps of: a) blending lopinavir, ritonavir and one or more excipients, b) heating a surfactant to about 50-80 0 C to form a clear transparent solution, c) spraying the surfactant solution of step (b) on the blend of step (a), d) blending the material of step (c) with water soluble polymer and e) processing the blend of step (d) into a solid dosage form.
- a process comprising the steps of: a) blending lopinavir, ritonavir and one or more excipients, b) heating a surfactant to about 50-80 0 C to form a clear transparent solution, c) spraying the surfactant solution of step (b) on the blend of step (a), d) blending the material of step (c) with
- the surfactant is heated to about 50-80 0 C and the resulting solution is sprayed on to the blend of lopinavir and ritonavir, which results in uniform mixing of the surfactant with lopinavir and ritonavir blend.
- the blend obtained in step (d) is further processed into a solid dosage form using processes selected from melt extrusion, melt granulation, wet granulation, dry granulation, direct compression and solvent evaporation, preferably using melt extrusion process.
- the melt extrusion process involves preparation of extrudates and is carried out in hot melt extrusion equipment.
- Various parameters of the hot melt extruder are feed rate, screw speed, zone temperatures, die temperature, melt temperature, chiller temperature and chill roll speed in order to achieve the end product in the form of a solid dispersion with all desirable dosage form and stability characteristics.
- the processing conditions involved in making the extrudates help in uniform distribution of the drugs throughout the blend and also improve the bioavailability.
- zone temperature plays an important role as it affects the product stability and dissolution.
- An improper setting of zone temperature has certain disadvantages such as:
- the zone temperature of the melt extruder is preset to a gradual increase in temperature ranging from about I 0 C to about 13O 0 C. Most preferably, the melting occurs at the temperature ranging from about 115 0 C to 125 0 C.
- excipients in the formulation are the most important factor as it ultimately affects the bioavailability.
- surfactants have low pourability due to viscous nature, it is difficult to properly mix with other excipients and the drug. Moreover, they may form small lumps due to uneven distribution. However, their pourability increases when melted, which can be easily sprayed, to form homogeneous blend. This process also helps in maintaining less temperature in the extruder, which ultimately helps in reduction of hard lumps and also prevents the drug from decomposition.
- the solid oral dosage form of the present invention comprising lopinavir and ritonavir may be in the form of tablet, capsule, powder, dispersible granules or cachet.
- the prepared extrudates were further mixed with excipients and compressed into tablets or filled into capsules.
- Suitable surfactants according to the present invention are selected from the group comprising polyoxyethylene alkylaryl ethers such as polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether; polyethylene glycol fatty acid esters such as PEG monolaurate, PEG dilaurate, PEG distearate, PEG dioleate; polyoxyethylene sorbitan fatty acid ester such as polysorbate 40, polysorbate 60, polysorbate 80; sorbitan fatty acid mono esters such as sorbitan monolaurate, sorbitan monooleate, sorbitan sesquioleate, sorbitan trioleate, polyoxyethylene castor oil derivates such as polyoxyl castor oil, polyoxyl hydrogenated castor oil, copolymers of polyoxyethylene and polyoxypropylene such as poloxamer and the like or combinations thereof.
- the amount of surfactant used is in the range of about 2 to 20% by weight of the composition.
- the pharmaceutically acceptable water soluble polymers according to the present invention include photopolymers and copolymers of N- vinyl lactase, especially photopolymers and copolymers of N-vinyl pyrrolidone, e.g. polyvinylpyrrolidone, copolymers of N-vinyl pyrrolidone and vinyl acetate e.g. copovidone, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, cellulose phthalates or succinates, cellulose acetate phthalate hydroxypropyl methylcellulose phthalate, polyethylene oxide, polyacrylates, methyl methacrylate, butyl methacrylate and the like or combinations thereof.
- the amount of water soluble polymer used is in the range of about 40 to 80% by weight of the composition.
- the excipients comprise one or more diluents, surfactants, flow regulators, lubricants and the like.
- Suitable diluents used according to the present invention are selected from lactose, sucrose, dextrose, mannitol, sorbitol, starch and the like or combinations thereof.
- Suitable flow regulators include highly dispersed silica or colloidal silicon dioxide, talc and the like.
- Suitable lubricants used according to the present invention are selected from magnesium stearate, calcium stearate, sodium stearyl fumarate, stearic acid, fumaric acid and the like or combinations thereof.
- the tablets may be uncoated or optionally coated with film coating composition.
- the film coat may be an aqueous moisture barrier.
- the coating solution mainly comprises of film forming polymers and one or more of plasticizers, opacifier, surfactant, anti tacking agents, coloring agent and the like.
- the coating according to the present invention is applied by solubilising or suspending the excipients in solvents such as isopropyl alcohol, water, acetone, ethanol, methylenechloride and the like or mixtures thereof.
- solvents such as isopropyl alcohol, water, acetone, ethanol, methylenechloride and the like or mixtures thereof.
- the present invention provides a solid oral dosage form comprising lopinavir, ritonavir, water soluble polymer and surfactant prepared by a process comprising the steps of: a) blending lopinavir, ritonavir and one or more excipients, b) heating about 2 to 20 % w/w of surfactant to about 50-80 0 C to form a clear transparent solution, c) spraying the surfactant solution of step (b) on the blend of step (a), d) blending the material of step (c) with 40 to 80% w/w of water soluble polymer, and e) processing the blend of step (d) into a solid dosage form.
- the present invention provides a solid oral dosage form comprising lopinavir, ritonavir, water soluble polymer and surfactant prepared by a process comprising the steps of: a) blending lopinavir, ritonavir and one or more excipients such as flow regulators selected from colloidal silicon dioxide or talc, b) heating a surfactant selected from sorbitan monolaurate, polyoxyl hydrogenated castor oil to about 50-80 0 C to form a clear transparent solution, c) spraying the surfactant solution of step (b) on the blend of step (a), d) blending the material of step (c) with water soluble polymer such as polyvinylpyrrolidone, copovidone, methyl cellulose and hydroxypropyl methylcellulose and e) processing the blend of step (d) into a solid dosage form.
- excipients such as flow regulators selected from colloidal silicon dioxide or talc
- a surfactant selected from sorbitan
- the present invention provides a solid oral dosage form comprising lopinavir, ritonavir, water soluble polymer and surfactant prepared by a process comprising the steps of: a) blending lopinavir, ritonavir and one or more excipients, b) heating about 2 to 20 % w/w of surfactant to about 50-80 0 C to form a clear transparent solution, c) spraying the surfactant solution of step (b) on the blend of step (a), d) blending the material of step (c) with 40 to 80% w/w of water soluble polymer, and e) loading the blend of step (d) to hot melt extruder and maintaining a gradual increase in zone temperature ranging from about I 0 C to about 13O 0 C to get extrudates, f) milling the extrudates obtained in step (e), g) blending the extrudates of step (f) with one or more excipients and h) compressing
- the present invention provides a solid oral dosage form comprising lopinavir, ritonavir, water soluble polymer and surfactant prepared by a process comprising the steps of: a) blending lopinavir, ritonavir and one or more excipients such as flow regulators selected from colloidal silicon dioxide or talc, b) heating a surfactant selected from sorbitan monolaurate, polyoxyl hydrogenated castor oil to about 50-80 0 C to form a clear transparent solution, c) spraying the surfactant solution of step (b) on the blend of step (a), d) blending the material of step (c) with water soluble polymer such as polyvinylpyrrolidone, copovidone, methyl cellulose and hydroxypropyl methylcellulose, e) loading the blend of step (d) to hot melt extruder and maintaining a gradual increase in zone temperature ranging from about I 0 C to about 13O 0 C to get extrudates,
- lopinavir and ritonavir are present in the ratio from about 8:1 to about 3:1.
- the dosage form comprising lopinavir and ritonavir prepared according to the present invention is used for the treatment of HIV infection in an infected individual.
- step (i) lopinavir, ritonavir and colloidal silicon dioxide were sifted and blended using rapid mixer granulator, ii) sorbitan monolaurate was heated to about 60-70 0 C to form a clear transparent solution, iii) the solution of step (ii) was sprayed on to the blend of step (i) by means of spray gun under air pressure, iv) copovidone was mixed with the product obtained in step (iii) using rapid mixer granulator, v) the material obtained in step (iv) was loaded to a hot melt extruder to get extrudates, vi) the extrudates of step (v) was milled and blended with the extragranular colloidal silicon dioxide and sodium stearyl fumarate, vii) compressed the blend of step (vi) to form tablet, viii) prepared the film coating solution and coated tablets to obtain film-coated
- compositions given in examples 2 to 8 were prepared using similar procedure described in example 1.
- Example 8 Dissolution profile of lopinavir and ritonavir tablets prepared according to the present invention was carried out in water with 0.06M polyoxyethylene 10 lauryl ether as dissolution medium using USP Apparatus II with 900 ml at 75 rpm speed.
- the release profile (% drug released in min) is given in Table 1.
- the tablets of lopinavir and ritonavir prepared according to example 2 of the present invention were found to be stable.
- the stability data obtained after 3 months at 4O 0 C/ 75% RH is shown in Table 2.
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Abstract
La présente invention concerne une forme pharmaceutique orale solide comportant du lopinavir, du ritonavir, un polymère hydrosoluble et un tensioactif préparée par un procédé comprenant les étapes suivantes : a) le mélange de lopinavir, de ritonavir et un ou des excipients ; b) le chauffage d’un tensioactif jusqu’à environ 50 à 80°C pour former une solution transparente incolore ; c) la pulvérisation de la solution de tensioactif de l’étape (b) sur le mélange de l’étape (a) ; d) le mélange de l’étape (c) avec le polymère hydrosoluble ; et e) la préparation du mélange de l’étape (d) en une forme pharmaceutique solide.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN1469/CHE/2008 | 2008-06-17 | ||
IN1469CH2008 | 2008-06-17 |
Publications (1)
Publication Number | Publication Date |
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WO2009153654A1 true WO2009153654A1 (fr) | 2009-12-23 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/IB2009/006008 WO2009153654A1 (fr) | 2008-06-17 | 2009-06-15 | Formes pharmaceutiques solides d’anti-rétroviraux |
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013128467A1 (fr) * | 2012-03-01 | 2013-09-06 | Hetero Research Foundation | Compositions de ritonavir |
WO2013164559A1 (fr) * | 2012-05-03 | 2013-11-07 | Cipla Limited | Composition antirétrovirale |
US9096556B2 (en) | 2011-05-27 | 2015-08-04 | Hetero Research Foundation | Amorphous ritonavir co-precipitated |
US9532979B2 (en) | 2011-09-09 | 2017-01-03 | The University Of Liverpool | Compositions of lopinavir and ritonavir |
US10603279B2 (en) | 2011-09-09 | 2020-03-31 | The University Of Liverpool | Compositions of lopinavir |
CN112263554A (zh) * | 2020-10-22 | 2021-01-26 | 安徽贝克生物制药有限公司 | 一种洛匹那韦利托那韦复方片剂及其制备方法 |
US11576861B2 (en) * | 2011-12-12 | 2023-02-14 | Adare Pharmaceuticals Usa, Inc. | Sustained release particle formulations |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB970462A (en) * | 1962-05-02 | 1964-09-23 | Monsanto Co | Free-flowing acid compositions |
US20010006650A1 (en) * | 1997-09-19 | 2001-07-05 | Beth A. Burnside | Solid solution beadlet |
US20050048112A1 (en) * | 2003-08-28 | 2005-03-03 | Jorg Breitenbach | Solid pharmaceutical dosage form |
WO2008017867A2 (fr) * | 2006-08-10 | 2008-02-14 | Cipla Limited | Composition orale solide antirétrovirale |
WO2008029417A2 (fr) * | 2006-09-04 | 2008-03-13 | Matrix Laboratories Limited | Formulation pharmaceutique employée dans la thérapie du vih |
-
2009
- 2009-06-15 WO PCT/IB2009/006008 patent/WO2009153654A1/fr active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB970462A (en) * | 1962-05-02 | 1964-09-23 | Monsanto Co | Free-flowing acid compositions |
US20010006650A1 (en) * | 1997-09-19 | 2001-07-05 | Beth A. Burnside | Solid solution beadlet |
US20050048112A1 (en) * | 2003-08-28 | 2005-03-03 | Jorg Breitenbach | Solid pharmaceutical dosage form |
WO2008017867A2 (fr) * | 2006-08-10 | 2008-02-14 | Cipla Limited | Composition orale solide antirétrovirale |
WO2008029417A2 (fr) * | 2006-09-04 | 2008-03-13 | Matrix Laboratories Limited | Formulation pharmaceutique employée dans la thérapie du vih |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9096556B2 (en) | 2011-05-27 | 2015-08-04 | Hetero Research Foundation | Amorphous ritonavir co-precipitated |
US9532979B2 (en) | 2011-09-09 | 2017-01-03 | The University Of Liverpool | Compositions of lopinavir and ritonavir |
US10603279B2 (en) | 2011-09-09 | 2020-03-31 | The University Of Liverpool | Compositions of lopinavir |
US11576861B2 (en) * | 2011-12-12 | 2023-02-14 | Adare Pharmaceuticals Usa, Inc. | Sustained release particle formulations |
WO2013128467A1 (fr) * | 2012-03-01 | 2013-09-06 | Hetero Research Foundation | Compositions de ritonavir |
EP2819668A4 (fr) * | 2012-03-01 | 2015-07-29 | Hetero Research Foundation | Compositions de ritonavir |
WO2013164559A1 (fr) * | 2012-05-03 | 2013-11-07 | Cipla Limited | Composition antirétrovirale |
CN104411300A (zh) * | 2012-05-03 | 2015-03-11 | 希普拉有限公司 | 抗逆转录病毒组合物 |
JP2015519326A (ja) * | 2012-05-03 | 2015-07-09 | シプラ・リミテッド | 抗レトロウイルス組成物 |
CN112263554A (zh) * | 2020-10-22 | 2021-01-26 | 安徽贝克生物制药有限公司 | 一种洛匹那韦利托那韦复方片剂及其制备方法 |
CN112263554B (zh) * | 2020-10-22 | 2022-09-30 | 安徽贝克生物制药有限公司 | 一种洛匹那韦利托那韦复方片剂及其制备方法 |
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