WO2006090350A1 - A method for sieving pharmaceutical substances - Google Patents
A method for sieving pharmaceutical substances Download PDFInfo
- Publication number
- WO2006090350A1 WO2006090350A1 PCT/IB2006/050627 IB2006050627W WO2006090350A1 WO 2006090350 A1 WO2006090350 A1 WO 2006090350A1 IB 2006050627 W IB2006050627 W IB 2006050627W WO 2006090350 A1 WO2006090350 A1 WO 2006090350A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pharmaceutical substance
- sieve
- pharmaceutical
- ultrasonic
- substance
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 48
- 238000007873 sieving Methods 0.000 title claims description 14
- 239000000126 substance Substances 0.000 title abstract description 31
- 239000002245 particle Substances 0.000 claims abstract description 14
- 238000002844 melting Methods 0.000 claims abstract description 9
- 230000008018 melting Effects 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims description 41
- 239000000463 material Substances 0.000 claims description 18
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims description 16
- 229960001243 orlistat Drugs 0.000 claims description 16
- 239000002552 dosage form Substances 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 5
- 239000002947 C09CA04 - Irbesartan Substances 0.000 claims description 4
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 claims description 4
- NGBFQHCMQULJNZ-UHFFFAOYSA-N Torsemide Chemical compound CC(C)NC(=O)NS(=O)(=O)C1=CN=CC=C1NC1=CC=CC(C)=C1 NGBFQHCMQULJNZ-UHFFFAOYSA-N 0.000 claims description 4
- OGQICQVSFDPSEI-UHFFFAOYSA-N Zorac Chemical compound N1=CC(C(=O)OCC)=CC=C1C#CC1=CC=C(SCCC2(C)C)C2=C1 OGQICQVSFDPSEI-UHFFFAOYSA-N 0.000 claims description 4
- -1 antiadherants Substances 0.000 claims description 4
- RRGUKTPIGVIEKM-UHFFFAOYSA-N cilostazol Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCCC1=NN=NN1C1CCCCC1 RRGUKTPIGVIEKM-UHFFFAOYSA-N 0.000 claims description 4
- 229960004588 cilostazol Drugs 0.000 claims description 4
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 claims description 4
- 229960003804 efavirenz Drugs 0.000 claims description 4
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 4
- 229960003592 fexofenadine Drugs 0.000 claims description 4
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 claims description 4
- 229960002198 irbesartan Drugs 0.000 claims description 4
- 229960000565 tazarotene Drugs 0.000 claims description 4
- 229960005461 torasemide Drugs 0.000 claims description 4
- 102000019280 Pancreatic lipases Human genes 0.000 claims description 3
- 108050006759 Pancreatic lipases Proteins 0.000 claims description 3
- 230000001780 adrenocortical effect Effects 0.000 claims description 3
- 230000000507 anthelmentic effect Effects 0.000 claims description 3
- 230000003288 anthiarrhythmic effect Effects 0.000 claims description 3
- 230000000844 anti-bacterial effect Effects 0.000 claims description 3
- 230000001387 anti-histamine Effects 0.000 claims description 3
- 230000001315 anti-hyperlipaemic effect Effects 0.000 claims description 3
- 230000002924 anti-infective effect Effects 0.000 claims description 3
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 3
- 230000000842 anti-protozoal effect Effects 0.000 claims description 3
- 230000000767 anti-ulcer Effects 0.000 claims description 3
- 239000003416 antiarrhythmic agent Substances 0.000 claims description 3
- 229940121375 antifungal agent Drugs 0.000 claims description 3
- 239000000739 antihistaminic agent Substances 0.000 claims description 3
- 239000003963 antioxidant agent Substances 0.000 claims description 3
- 239000002249 anxiolytic agent Substances 0.000 claims description 3
- 230000000949 anxiolytic effect Effects 0.000 claims description 3
- 239000002876 beta blocker Substances 0.000 claims description 3
- 229940097320 beta blocking agent Drugs 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 3
- 239000004067 bulking agent Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000011248 coating agent Substances 0.000 claims description 3
- 238000000576 coating method Methods 0.000 claims description 3
- 239000003086 colorant Substances 0.000 claims description 3
- 230000003291 dopaminomimetic effect Effects 0.000 claims description 3
- 230000002439 hemostatic effect Effects 0.000 claims description 3
- 229940088597 hormone Drugs 0.000 claims description 3
- 239000005556 hormone Substances 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 230000000510 mucolytic effect Effects 0.000 claims description 3
- 229940116369 pancreatic lipase Drugs 0.000 claims description 3
- 238000012545 processing Methods 0.000 claims description 3
- 229940088594 vitamin Drugs 0.000 claims description 3
- 239000011782 vitamin Substances 0.000 claims description 3
- 229930003231 vitamin Natural products 0.000 claims description 3
- 235000013343 vitamin Nutrition 0.000 claims description 3
- 239000005541 ACE inhibitor Substances 0.000 claims description 2
- FWKQNCXZGNBPFD-UHFFFAOYSA-N Guaiazulene Chemical compound CC(C)C1=CC=C(C)C2=CC=C(C)C2=C1 FWKQNCXZGNBPFD-UHFFFAOYSA-N 0.000 claims description 2
- 239000002269 analeptic agent Substances 0.000 claims description 2
- 230000000202 analgesic effect Effects 0.000 claims description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 2
- 230000002456 anti-arthritic effect Effects 0.000 claims description 2
- 230000001078 anti-cholinergic effect Effects 0.000 claims description 2
- 230000000843 anti-fungal effect Effects 0.000 claims description 2
- 230000000561 anti-psychotic effect Effects 0.000 claims description 2
- 230000000840 anti-viral effect Effects 0.000 claims description 2
- 230000003078 antioxidant effect Effects 0.000 claims description 2
- 239000003904 antiprotozoal agent Substances 0.000 claims description 2
- 239000002899 monoamine oxidase inhibitor Substances 0.000 claims description 2
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 2
- 238000012216 screening Methods 0.000 abstract description 13
- 238000001914 filtration Methods 0.000 abstract description 4
- 238000005516 engineering process Methods 0.000 abstract description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- 102000010909 Monoamine Oxidase Human genes 0.000 description 2
- 108010062431 Monoamine oxidase Proteins 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000002525 ultrasonication Methods 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940124339 anthelmintic agent Drugs 0.000 description 1
- 239000000921 anthelmintic agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000003173 antianemic agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- 229940030225 antihemorrhagics Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 229940036589 antiprotozoals Drugs 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000002874 hemostatic agent Substances 0.000 description 1
- 239000012770 industrial material Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229940066491 mucolytics Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B07—SEPARATING SOLIDS FROM SOLIDS; SORTING
- B07B—SEPARATING SOLIDS FROM SOLIDS BY SIEVING, SCREENING, SIFTING OR BY USING GAS CURRENTS; SEPARATING BY OTHER DRY METHODS APPLICABLE TO BULK MATERIAL, e.g. LOOSE ARTICLES FIT TO BE HANDLED LIKE BULK MATERIAL
- B07B1/00—Sieving, screening, sifting, or sorting solid materials using networks, gratings, grids, or the like
- B07B1/42—Drive mechanisms, regulating or controlling devices, or balancing devices, specially adapted for screens
Definitions
- the present invention relates to a method for clarifying, screening, sifting, separating, and sorting substances of pharmaceutical interest using ultrasonic vi- brosifter technology.
- the present invention provides an excellent process that includes applying an ultrasonic frequency to a mechanical sieve for clarifying, screening, sifting, separating, filtering, grading or sorting the substances of pharmaceutical interest which are difficult to sift, excessively dry, waxy, low melting, electrostatically charged, fluffy or have an uneven particle size distribution.
- sieving is an ubiquitous process step.
- the sieving of pharmaceutical materials is a principal factor in achieving a desired particle size, which in turn impacts on various pharmacokinetic and pharmacodynamic parameters.
- the sieving process also plays a vital role in determining the rheological properties of raw materials and excipients involved in pharmaceutical manufacturing. It has been observed that sieving becomes challenging when the material to be sieved is excessively dry, waxy, low melting, electrostatically charged, fluffy or has an uneven particle size distribution.
- references do not extend up to the application of ultrasonic vi- brosifting for sieving substances of pharmaceutical interest; instead the references are related to metallurgical and inorganic substances.
- Pharmaceutical substances unlike many other industrial materials, are highly sensitive to temperature, humidity and other process parameters.
- the crystallinity and polymorphic states of active medicaments are also affected by the sieving process. Practicing an incompetent sieving method may negatively affect the critical characteristics of the active medicament and may yield unwanted results.
- Our search reveals that no efficient method is so far available for sieving of such substances of pharmaceutical interest especially those which are excessively dry, waxy, low melting, electrostatically charged, fluffy or having an uneven particle size distribution. As a consequence, pharmaceutical chemists must compensate either on the particle size or on the yield.
- a method of processing a pharmaceutical substance includes applying an ultrasonic frequency to a mechanical sieve containing a pharmaceutical substance.
- Embodiments of the method may include one or more of the following features.
- the pharmaceutical substance may be characterized by one or more of being difficult to sift, excessively dry, waxy, low melting, electrostatically charged, fluffy or having uneven particle size distribution.
- the application of an ultrasonic frequency to the mechanical sieve may clarify, screen, sift, separate, filter, grade, and/or sort the pharmaceutical substance.
- the pharmaceutical substance may be one or more of an ACE inhibitor, a pancreatic lipase inhibitor, a CNS stimulant, a MAO inhibitor, a beta blocker, an adrenocortical suppressant, an analgesic, an anti-inflammatory, an antihistaminic, an anthelmintic, an antiarrhythmic, an antiinfective, an antiarthritic, an antibacterial, an antiprotozoal, an antiviral, an anxiolytic, an antiulcerative, a dopaminergic, an antipsychotic, an anticholinergic, a mucolytic, an antihyperlipidemic, an antioxidant, an antifungal, a hormone, a vitamin, a hemostatic, a hematinic and a hepatoprotectant.
- the pharmaceutical substance may be one or more of orlistat, cilostazol, irbesartan, efavirenz, fexofenadine, torsemide and tazarotene
- the pharmaceutical substance may be one or more of bulking agents, disintegrating agents, antiadherants, lubricants, binding agents, colorants and coating materials.
- the method may further include incorporating the pharmaceutical substance into a pharmaceutical dosage form.
- a method of sieving a pharmaceutical substance includes charging the pharmaceutical substance onto a sieve, ultrasonicating the sieve with an ultrasonic unit while optionally applying a mechanical vibration simultaneously, and collecting the sieved pharmaceutical substance.
- Embodiments of the method may include one or more of the following features or those described above.
- the sieve may be equipped with an ultrasonic device.
- the method may further include incorporating the sieved pharmaceutical substance into a pharmaceutical dosage form.
- a pharmaceutical substance prepared by a method that includes charging the pharmaceutical substance onto a sieve, ultra- sonicating the sieve with an ultrasonic unit while optionally applying a mechanical vibration simultaneously, and collecting the sieved pharmaceutical substance.
- Embodiments of the pharmaceutical substance may include one or more of the following features or those described above.
- the sieve may be equipped with an ultrasonic device.
- the pharmaceutical substance may be incorporated into a dosage form.
- the present inventors decided to explore an efficient method to overcome the processing problems described above.
- the present inventors have now developed an effective, highly productive, consistent and less time consuming method that includes applying an ultrasonic frequency to a mechanical sieve for clarifying, screening, sifting, separating, filtering, grading and/or sorting substances of pharmaceutical interest which are difficult to sift, excessively dry, waxy, low melting, electrostatically charged, fluffy or having an uneven particle size distribution.
- a first aspect of the present invention provides a method that includes applying an ultrasonic frequency to a mechanical sieve for clarifying, screening, sifting, separating, filtering, grading or sorting the substances of pharmaceutical interest which are difficult to sift, excessively dry, waxy, low melting, electrostatically charged, fluffy or having uneven particle size distribution.
- the substance of pharmaceutical interest may be selected from, for example, pharmaceutical substances such as Angiotensin Converting Enzyme (ACE) inhibitors, pancreatic lipase inhibitors, Central Nervous System (CNS) stimulants, Monoamine Oxidase (MAO) inhibitors, beta blockers, adrenocortical suppressants, analgesics, antiinflammatories, antihistaminics, anthelmintics, antiarrhythmics, antiinfectives, an- tiarthritics, antibacterials, antiprotozoals, antivirals, anxiolytics, antiulceratives, dopaminergics, antipsychotics, anticholinergics, mucolytics, antihyperlipidemics, antioxidants, antifungals, hormones, vitamins, hemostatics, hematinics, and hepato- protectants.
- ACE Angiotensin Converting Enzyme
- CNS Central Nervous System
- MAO Monoamine Oxidase
- the substance of pharmaceutical interest may specifically include substances selected from, for example, orlistat, cilostazol, irbesartan, efavirenz, fexofenadine, torsemide, tazarotene, and the like.
- the substance of pharmaceutical interest may further include substances selected from, for example, bulking agents, disintegrating agents, antiadherants, lubricants, binding agents, colorants and coating materials.
- a second aspect of the present invention provides a method of clarifying, screening, sifting, separating, and/or sorting of a substance of pharmaceutical interest by using ultrasonic vibrosifter technology whereby the blinding or clogging of the screen are significantly reduced or eliminated.
- a third aspect of the present invention provides a method of clarifying, screening, sifting, separating, and/or sorting a substance of pharmaceutical interest in a process that includes: [26] a) charging a substance of pharmaceutical interest onto a sieve equipped with an ultrasonic device, [27] b) ultrasonicating the sieve charged with the substance of pharmaceutical interest, and optionally applying mechanical vibration simultaneously, and [28] c) collecting the pharmaceutical substance obtained from step b).
- a fourth aspect of the present invention provides a method of obtaining a substance of pharmaceutical interest having a desired particle size in a process that includes: [31] a) charging a substance of pharmaceutical interest onto a sieve,
- the substance of pharmaceutical interest is charged onto a sieve of appropriate mesh size.
- the sieve then is ultrasonicated with an ultrasonic unit and a mechanical vibration is applied to accompany the ultrasonication.
- the sifted pharmaceutical substance is collected.
- the substance of pharmaceutical interest of the above aspects should be selected from any material of pharmaceutical use which is difficult to sift, excessively dry, waxy, low melting, electrostatically charged, fluffy or having uneven particle size distribution. Nonetheless, materials that are not characterized by having these properties will benefit from the ultrasonic sieving process described herein.
- the following experiments were carried out using various equipment such as locally fabricated and assembled vibrosifters having an 8 inch diameter and ultrasonic unit, a vibrosifter from M/s Sweco India, and a locally available ultrasonic unit, C400
- Example 1 Screening of Orlistat Using Ultrasonic Vibrosifter
- a vibrosifter from M/s Sweco India and locally available ultrasonic unit
Abstract
The present invention relates to a method for clarifying, screening, sifting, separating, and sorting pharmaceutical substances using ultrasonic vibrosifter technology. The present invention provides an excellent process that includes applying an ultrasonic frequency to a mechanical sieve for clarifying, screening, sifting, separating, filtering, grading or sorting the pharmaceutical substances which are difficult to sift, excessively dry, waxy, low melting, electrostatically charged, fluffy or having uneven particle size distribution.
Description
Description A METHOD FOR SIEVING PHARMACEUTICAL SUBSTANCES
[1] Field of the Invention
[2] The present invention relates to a method for clarifying, screening, sifting, separating, and sorting substances of pharmaceutical interest using ultrasonic vi- brosifter technology. The present invention provides an excellent process that includes applying an ultrasonic frequency to a mechanical sieve for clarifying, screening, sifting, separating, filtering, grading or sorting the substances of pharmaceutical interest which are difficult to sift, excessively dry, waxy, low melting, electrostatically charged, fluffy or have an uneven particle size distribution.
[3] Background of the Invention
[4] In manufacturing pharmaceutical formulations, sieving is an ubiquitous process step. The sieving of pharmaceutical materials is a principal factor in achieving a desired particle size, which in turn impacts on various pharmacokinetic and pharmacodynamic parameters. The sieving process also plays a vital role in determining the rheological properties of raw materials and excipients involved in pharmaceutical manufacturing. It has been observed that sieving becomes challenging when the material to be sieved is excessively dry, waxy, low melting, electrostatically charged, fluffy or has an uneven particle size distribution. Several pharmaceutical substances typically exhibiting at least one of the above discussed characters include orlistat, cilostazol, irbesartan, efavirenz, fexofenadine, torsemide, tazarotene, and the like. It is very difficult to sieve such materials using conventional vibrosifters because the material binds to the sieve during sifting and subsequently cannot pass through even a coarser screen. It ultimately affects particle size, bulk density and other rheological properties making the manufacturing process complicated, unyielding and time consuming.
[5] There are several published literature and patent references available on the application of ultrasonics in the field of screening powder materials. Japanese Patent Nos. 57-048317, 11-128842 and 11-207262, PCT Patent Application No. 02/20182 and U.S. Patent No. 5,653,346 describe the apparatuses and their use in sifting solid and liquid substances using ultrasonic vibration.
[6] However, these references do not extend up to the application of ultrasonic vi- brosifting for sieving substances of pharmaceutical interest; instead the references are related to metallurgical and inorganic substances. Pharmaceutical substances, unlike many other industrial materials, are highly sensitive to temperature, humidity and other process parameters. The crystallinity and polymorphic states of active medicaments are also affected by the sieving process. Practicing an incompetent sieving method may negatively affect the critical characteristics of the active medicament and may yield
unwanted results. Our search reveals that no efficient method is so far available for sieving of such substances of pharmaceutical interest especially those which are excessively dry, waxy, low melting, electrostatically charged, fluffy or having an uneven particle size distribution. As a consequence, pharmaceutical chemists must compensate either on the particle size or on the yield.
[7] Summary of the Invention
[8] In one general aspect there is provided a method of processing a pharmaceutical substance. The method includes applying an ultrasonic frequency to a mechanical sieve containing a pharmaceutical substance.
[9] Embodiments of the method may include one or more of the following features. For example, the pharmaceutical substance may be characterized by one or more of being difficult to sift, excessively dry, waxy, low melting, electrostatically charged, fluffy or having uneven particle size distribution. The application of an ultrasonic frequency to the mechanical sieve may clarify, screen, sift, separate, filter, grade, and/or sort the pharmaceutical substance.
[10] The pharmaceutical substance may be one or more of an ACE inhibitor, a pancreatic lipase inhibitor, a CNS stimulant, a MAO inhibitor, a beta blocker, an adrenocortical suppressant, an analgesic, an anti-inflammatory, an antihistaminic, an anthelmintic, an antiarrhythmic, an antiinfective, an antiarthritic, an antibacterial, an antiprotozoal, an antiviral, an anxiolytic, an antiulcerative, a dopaminergic, an antipsychotic, an anticholinergic, a mucolytic, an antihyperlipidemic, an antioxidant, an antifungal, a hormone, a vitamin, a hemostatic, a hematinic and a hepatoprotectant. The pharmaceutical substance may be one or more of orlistat, cilostazol, irbesartan, efavirenz, fexofenadine, torsemide and tazarotene.
[11] The pharmaceutical substance may be one or more of bulking agents, disintegrating agents, antiadherants, lubricants, binding agents, colorants and coating materials.
[12] Applying the ultrasonic frequency to the mechanical sieve may result in reducing or eliminating screen blinding or clogging.
[13] The method may further include incorporating the pharmaceutical substance into a pharmaceutical dosage form.
[14] In another general aspect there is provided a method of sieving a pharmaceutical substance. The method includes charging the pharmaceutical substance onto a sieve, ultrasonicating the sieve with an ultrasonic unit while optionally applying a mechanical vibration simultaneously, and collecting the sieved pharmaceutical substance.
[15] Embodiments of the method may include one or more of the following features or those described above. For example, the sieve may be equipped with an ultrasonic device. The method may further include incorporating the sieved pharmaceutical substance into a pharmaceutical dosage form.
[16] In another general aspect there is provided a pharmaceutical substance prepared by a method that includes charging the pharmaceutical substance onto a sieve, ultra- sonicating the sieve with an ultrasonic unit while optionally applying a mechanical vibration simultaneously, and collecting the sieved pharmaceutical substance.
[17] Embodiments of the pharmaceutical substance may include one or more of the following features or those described above. For example, the sieve may be equipped with an ultrasonic device. The pharmaceutical substance may be incorporated into a dosage form.
[18] The details of one or more embodiments of the invention are set forth in the description below. Other features, objects and advantages of the invention will be apparent from the description and claims.
[19] Detailed Description of the Invention
[20] The present inventors decided to explore an efficient method to overcome the processing problems described above. By their ingenious effort, the present inventors have now developed an effective, highly productive, consistent and less time consuming method that includes applying an ultrasonic frequency to a mechanical sieve for clarifying, screening, sifting, separating, filtering, grading and/or sorting substances of pharmaceutical interest which are difficult to sift, excessively dry, waxy, low melting, electrostatically charged, fluffy or having an uneven particle size distribution.
[21] A first aspect of the present invention provides a method that includes applying an ultrasonic frequency to a mechanical sieve for clarifying, screening, sifting, separating, filtering, grading or sorting the substances of pharmaceutical interest which are difficult to sift, excessively dry, waxy, low melting, electrostatically charged, fluffy or having uneven particle size distribution.
[22] The substance of pharmaceutical interest may be selected from, for example, pharmaceutical substances such as Angiotensin Converting Enzyme (ACE) inhibitors, pancreatic lipase inhibitors, Central Nervous System (CNS) stimulants, Monoamine Oxidase (MAO) inhibitors, beta blockers, adrenocortical suppressants, analgesics, antiinflammatories, antihistaminics, anthelmintics, antiarrhythmics, antiinfectives, an- tiarthritics, antibacterials, antiprotozoals, antivirals, anxiolytics, antiulceratives, dopaminergics, antipsychotics, anticholinergics, mucolytics, antihyperlipidemics, antioxidants, antifungals, hormones, vitamins, hemostatics, hematinics, and hepato- protectants. The substance of pharmaceutical interest may specifically include substances selected from, for example, orlistat, cilostazol, irbesartan, efavirenz, fexofenadine, torsemide, tazarotene, and the like.
[23] The substance of pharmaceutical interest may further include substances selected from, for example, bulking agents, disintegrating agents, antiadherants, lubricants,
binding agents, colorants and coating materials. [24] A second aspect of the present invention provides a method of clarifying, screening, sifting, separating, and/or sorting of a substance of pharmaceutical interest by using ultrasonic vibrosifter technology whereby the blinding or clogging of the screen are significantly reduced or eliminated. [25] A third aspect of the present invention provides a method of clarifying, screening, sifting, separating, and/or sorting a substance of pharmaceutical interest in a process that includes: [26] a) charging a substance of pharmaceutical interest onto a sieve equipped with an ultrasonic device, [27] b) ultrasonicating the sieve charged with the substance of pharmaceutical interest, and optionally applying mechanical vibration simultaneously, and [28] c) collecting the pharmaceutical substance obtained from step b).
[29] In this method, a substance of pharmaceutical interest is charged onto a sieve having the appropriate mesh size and equipped with an ultrasonic device. The sieve is ultrasonicated and a mechanical vibration is applied to accompany the ultrasonication.
When the sifting process is complete, the sifted pharmaceutical substance is collected. [30] A fourth aspect of the present invention provides a method of obtaining a substance of pharmaceutical interest having a desired particle size in a process that includes: [31] a) charging a substance of pharmaceutical interest onto a sieve,
[32] b) ultrasonicating the sieve charged with the substance of pharmaceutical interest with an ultrasonic unit, and optionally applying mechanical vibration simultaneously, and
[33] c) collecting the pharmaceutical substance obtained from step b).
[34] The substance of pharmaceutical interest is charged onto a sieve of appropriate mesh size. The sieve then is ultrasonicated with an ultrasonic unit and a mechanical vibration is applied to accompany the ultrasonication. When the sifting process is complete, the sifted pharmaceutical substance is collected. [35] To enjoy the full benefits of these processes, the substance of pharmaceutical interest of the above aspects should be selected from any material of pharmaceutical use which is difficult to sift, excessively dry, waxy, low melting, electrostatically charged, fluffy or having uneven particle size distribution. Nonetheless, materials that are not characterized by having these properties will benefit from the ultrasonic sieving process described herein. [36] The following experiments were carried out using various equipment such as locally fabricated and assembled vibrosifters having an 8 inch diameter and ultrasonic unit, a vibrosifter from M/s Sweco India, and a locally available ultrasonic unit, C400
Vibrosifter fitted with VDS 2000 ultrasonic unit of M/s Russel Finex, UK, and
ZS30S66 SWECO Vibro-Energy Separator with ultrasonic system. Although there are examples given below and the invention is further explained with these examples, it is not intended that the invention be limited by the disclosure of these examples as it is expected that one of ordinary skill in the art can apply the invention to other pharmaceutical aspects
[37] Example 1 : Screening of Orlistat Using Ultrasonic Vibrosifter
[38] Orlistat (10 g) having an initial particle size distribution (PSD) in which d was about 400 μm was fed onto a vibrosifter (locally fabricated and assembled) with a 310 μm sieve opening. The room temperature was maintained at about 30°C and the vibrosifter was turned on to its mechanical mode. No material was observed to pass through the sieve. The ultrasonic unit then was turned on to its continuous mode. The material started passing through the sieve and approximately 9 g of orlistat were collected in a collection tray at the end of the sifting operation. [39] Example 2: Screening of Orlistat Using Ultrasonic Vibrosifter
[40] Orlistat (50 g) having an initial PSD in which the d 0.8 was about 400 μm was fed onto a vibrosifter (from M/s Sweco India and locally available ultrasonic unit) with a 250 μm sieve opening. The room temperature was maintained at about 30°C and the vibrosifter was turned on to its mechanical mode. No material was observed to pass through the sieve. The ultrasonic unit then was turned on to its continuous mode. The material started passing through the sieve and about 35 g of orlistat were collected in a collection tray at the end of the sifting operation.
[41] Example 3: Screening of Orlistat Using Ultrasonic Vibrosifter:
[42] Orlistat (100 g) having an initial PSD in which the d was about 400 μm was fed onto a vibrosifter (C400 Vibrosifter fitted with VDS 2000 ultrasonic unit of M/s Russel Finex, UK) with 150 μm sieve opening. The room temperature was maintained at about 15°C and the vibrosifter was turned on to its mechanical mode. No material was observed to pass through the sieve. The ultrasonic unit then was turned on to its continuous mode. The material started passing through the sieve and about 99 g of orlistat were collected in a collection tray at the end of the sifting operation. [43] Example 4: Screening of Orlistat Using Ultrasonic Vibrosifter:
[44] Orlistat (100 g) having a d of about 400 μm was fed onto a vibrosifter (ZS30S66
0.8
SWECO Vibro-Energy Separator with ultrasonic system) with a 120 μm sieve opening. The room temperature was maintained at about 18° to 20°C and the vibrosifter was turned on to its mechanical mode. No material was observed to pass through the sieve. The ultrasonic unit then was turned on to its continuous mode. The material started passing through the sieve and about 75 g of orlistat was collected in a collection tray at the end of the sifting operation. [45] While the present invention has been described in terms of its specific em-
bodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention. For example, the pharmaceutical substances prepared by the sieving operations described above may be incorporated into a pharmaceutical dosage form.
Claims
[I] A method of processing a pharmaceutical substance, the method comprising applying an ultrasonic frequency to a mechanical sieve containing a pharmaceutical substance.
[2] The method of claim 1, wherein the pharmaceutical substance is characterized by one or more of being difficult to sift, excessively dry, waxy, low melting, electrostatically charged, fluffy or having uneven particle size distribution.
[3] The method of claim 1, wherein the application of an ultrasonic frequency to the mechanical sieve clarifies, screens, sifts, separates, filters, grades, and/or sorts the pharmaceutical substance.
[4] The method of claim 1, wherein the pharmaceutical substance comprises one or more of an ACE inhibitor, a pancreatic lipase inhibitor, a CNS stimulant, a MAO inhibitor, a beta blocker, an adrenocortical supressant, an analgesic, an antiinflammatory, an antihistaminic, an anthelmintic, an antiarrhythmic, an anti- infective, an antiarthritic, an antibacterial, an antiprotozoal, an antiviral, an anxiolytic, an antiulcerative, a dopaminergic, an antipsychotic, an anticholinergic, a mucolytic, an antihyperlipidemic, an antioxidant, an antifungal, a hormone, a vitamin, a hemostatic, a hematinic and a hepatoprotectant.
[5] The method of claim 1, wherein the pharmaceutical substance comprises one or more of bulking agents, disintegrating agents, antiadherants, lubricants, binding agents, colorants and coating materials.
[6] The method of claim 1, wherein the pharmaceutical substance comprises one or more of orlistat, cilostazol, irbesartan, efavirenz, fexofenadine, torsemide and tazarotene.
[7] The method of claim 1, wherein applying the ultrasonic frequency to the mechanical sieve results in reducing or eliminating screen blinding or clogging.
[8] The method of claim 1, further comprising incorporating the pharmaceutical substance into a pharmaceutical dosage form.
[9] A method of sieving a pharmaceutical substance, the method comprising: a) charging the pharmaceutical substance onto a sieve; b) ultrasonicating the sieve with an ultrasonic unit while optionally applying a mechanical vibration simultaneously; and c) collecting the sieved pharmaceutical substance.
[10] The method of claim 9, wherein the sieve is equipped with an ultrasonic device.
[II] The method of claim 9, further comprising incorporating the sieved pharmaceutical substance into a pharmaceutical dosage form.
[12] A pharmaceutical substance prepared by a method comprising:
a) charging the pharmaceutical substance onto a sieve; b) ultrasonicating the sieve with an ultrasonic unit while optionally applying a mechanical vibration simultaneously; and c) collecting the sieved pharmaceutical substance.
[13] The pharmaceutical substance of claim 12, wherein the sieve is equipped with an ultrasonic device. [14] The pharmaceutical substance of claim 12, wherein the pharmaceutical substance is incorporated into a dosage form.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN432/DEL/2005 | 2005-02-28 | ||
| IN432DE2005 | 2005-02-28 |
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| Publication Number | Publication Date |
|---|---|
| WO2006090350A1 true WO2006090350A1 (en) | 2006-08-31 |
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ID=36570952
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2006/050627 WO2006090350A1 (en) | 2005-02-28 | 2006-02-28 | A method for sieving pharmaceutical substances |
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| Country | Link |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009039157A2 (en) * | 2007-09-17 | 2009-03-26 | Dr. Reddy's Laboratories Ltd. | Orlistat pharmaceutical formulations |
| WO2011048412A1 (en) * | 2009-10-21 | 2011-04-28 | Prosonix Limited | Process for improving crystallinity |
| WO2021080531A1 (en) * | 2019-10-23 | 2021-04-29 | Arven Ilac Sanayi Ve Ticaret Anonim Sirketi | A process for the preparation of dry powder compositions for inhalation |
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| US20020120147A1 (en) * | 2000-08-14 | 2002-08-29 | Marco Kordova | Micronized torsemide |
| US20040033266A1 (en) * | 2002-08-19 | 2004-02-19 | Thassu Deepak K. | Pharmaceutically active particles of a monomodal particle size distribution and method |
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2006
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020120147A1 (en) * | 2000-08-14 | 2002-08-29 | Marco Kordova | Micronized torsemide |
| US20040033266A1 (en) * | 2002-08-19 | 2004-02-19 | Thassu Deepak K. | Pharmaceutically active particles of a monomodal particle size distribution and method |
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| Title |
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| ZÜST: "ULTRASCHALLUNTERSTÜTZTES SIEBEN DURCHSATZLEISTUNG UND QUALITÄT SIGNIFIKANT STEIGERN", TECHNISCHE RUNDSCHAU, EDITION COLIBRI AG., WABERN, CH, vol. 88, no. 33, 16 August 1996 (1996-08-16), pages 26 - 27, XP000622145, ISSN: 1023-0823 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009039157A2 (en) * | 2007-09-17 | 2009-03-26 | Dr. Reddy's Laboratories Ltd. | Orlistat pharmaceutical formulations |
| WO2009039157A3 (en) * | 2007-09-17 | 2009-05-07 | Reddys Lab Ltd Dr | Orlistat pharmaceutical formulations |
| WO2011048412A1 (en) * | 2009-10-21 | 2011-04-28 | Prosonix Limited | Process for improving crystallinity |
| US8771744B2 (en) | 2009-10-21 | 2014-07-08 | Prosonix Limited | Barrier composition |
| EP2998007A1 (en) * | 2009-10-21 | 2016-03-23 | Prosonix Limited | Process for improving crystallinity |
| WO2021080531A1 (en) * | 2019-10-23 | 2021-04-29 | Arven Ilac Sanayi Ve Ticaret Anonim Sirketi | A process for the preparation of dry powder compositions for inhalation |
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