EP0937247A1 - Verfahren zur prüfung des auflösens von feste steroidale pharmazeutische formulierungen - Google Patents

Verfahren zur prüfung des auflösens von feste steroidale pharmazeutische formulierungen

Info

Publication number
EP0937247A1
EP0937247A1 EP97946599A EP97946599A EP0937247A1 EP 0937247 A1 EP0937247 A1 EP 0937247A1 EP 97946599 A EP97946599 A EP 97946599A EP 97946599 A EP97946599 A EP 97946599A EP 0937247 A1 EP0937247 A1 EP 0937247A1
Authority
EP
European Patent Office
Prior art keywords
polysorbate
concentration
dissolution
measuring
solid
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP97946599A
Other languages
English (en)
French (fr)
Inventor
Michael Corbo
Paul Kevin Deghetto
Thomas William Schultz
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Janssen Pharmaceuticals Inc
Original Assignee
Ortho Pharmaceutical Corp
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 Ortho Pharmaceutical Corp filed Critical Ortho Pharmaceutical Corp
Publication of EP0937247A1 publication Critical patent/EP0937247A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/15—Medicinal preparations ; Physical properties thereof, e.g. dissolubility
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N13/00—Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects
    • G01N2013/006—Dissolution of tablets or the like

Definitions

  • the present invention relates to a method for measuring the dissolution rate of a solid steroidal pharmaceutical formulation. More particularly, the invention relates to a method for determining the dissolution rate of the steroids, norgestimate and ethinyl estradiol from tablet formulations.
  • a pharmaceutical agent is useless if it cannot be delivered to a biological system at a controlled rate sufficient to elicit and maintain a physiological effect for a desired period of time. Therefore is it imperative to the quality control of drug substances that a pharmaceutical manufacturer reproducibly and reliably test the rate at which a drug substance is released from its formulation.
  • the rate at which a drug is released from capsules or tablets to liquid media can be established by in vitro dissolution testing. In this type of test, solid formulations are added to a liquid medium and over time samples are withdrawn then analyzed for the percentage of dissolved drug substance. Studies have shown that in vitro dissolution rates are directly related to efficacy and bioavailability of many pharmaceutical formulations. Due to these results, drug manufacturers routinely use dissolution testing to assure the lot to lot consistency of their product.
  • dissolution medium The major component of dissolution medium is water, but often other components are added to increase the comparability of the in vitro dissolution test with a biological system.
  • Aqueous HCI, alcohols and surfactants (polysorbate 80) have been added to dissolution media for this purpose.
  • in vitro dissolution tests have used isopropanol and water as the dissolution medium. However, for such formulations, these tests have not satisfactorily replicated gastric conditions and have not proven sufficient to reproducibly discern between pharmaceutical formulations whose steroidal dissolution rates decline over time.
  • the object of the present invention is to measure the dissolution rate of steroids from their pharmaceutical formulations in a reproducible manner. Where said method distinguishes variations in dissolution behavior between different batches of formulations.
  • the invention provides for a method of determining the dissolution rate of a steroid from its solid pharmaceutical formulation. Said method comprises: adding a steroidal formulation to a paddle assembly containing an aqueous solution of polysorbate 20, where the concentration of polysorbate 20 is about 0.025 to about 0.15% weight/volume and the temperature of the assembly is about 37 °C; removing aliquots and measuring the percentage of steroid dissolved in each aliquot.
  • the present invention finds that the dissolution medium is critical and controls the composition of the medium, namely the type of water, the surfactant and the solution's concentration.
  • the method of preparing the dissolution medium can be critical with some surfactants.
  • the surfactant employed is polysorbate 20, a partially esterified cyclic derivative of sorbitol, a natural sugar.
  • the surfactant's most popular use is in the preparation of pharmaceutical formulations it may have other uses.
  • Polysorbate 20 is commercially available from a number of suppliers and due to the surfactant's susceptibility to degradation over time, USP (23/NF 18) has published standards for determining the suitability of the surfactant. However the published values (hydroxyl, saponification, water, residue on ignition, arsenic, heavy metals and acid content values) do not guarantee suitability of polysorbate 20 for this dissolution test. ( See Donbrow, M. et al Journal of Pharmaceutical Sciences, 67, 12, pgs. 1676-81 1978). Although polysorbate 20 produced by a variety of manufacturers can be used, the preferred surfactant is "fresh" polysorbate 20 as described hereinafter.
  • fresh polysorbate 20 polysorbate that is less than 2 years old, which has been stored in the absence of light and has been stored under an inert atmosphere. It is possible to obtain reliable and reproducible dissolution test results using polysorbate 20 that does not meet all three criteria. However, the preferred polysorbate 20 is material that meets all three criteria.
  • the type of water, temperature of the dissolution medium and concentration of the surfactant affect dissolution testing.
  • the preferred water is helium sparged deionized water, but bottled water may be substituted.
  • the preferred temperature of the dissolution medium is about 37 °C. However in vitro dissolution tests may be run from about 34 -42 °C.
  • the type of paddle assembly used in the invention's in vitro test may vary, and those skilled in the art of dissolution testing may use apparatuses suitable to their needs. However a USP Paddle Assembly II (Volume 23) is the preferred assembly.
  • Table A illustrates that dissolution rates increase with increasing surfactant concentration.
  • the data in this table was generated by testing a single lot of steroid with different concentrations of polysorbate 20 in the following manner. Deionized water was premixed with the sufficient polysorbate 20 to give the indicated concentration over 16 h. This solution (600 mL) was placed in each of the reaction vessels of a USP Paddle Assembly II (vol 23/18), stirred at 75 r.p.m. and equilibrated to 37 °C. A norgestimate and ethinyl estradiol formulation was added to each vessel, samples were removed at 20 min and analyzed by routine HPLC methods for the percentage of dissolved norgestimate.
  • the first four runs used fresh polysorbate and the last run (*) used 4 year old surfactant.
  • the data is represented as both the average % and the range of values obtained. As shown, the concentration of polysorbate 20 which give the narrowest range of values is 0.05% of fresh polysorbate 20. Therefore the preferred concentration of polysorbate 20 is 0.05%.
  • the data below was obtained for norgestimate, similar results are expected for ethinyl estradiol, the other steriodal component of the formulation.
  • Deionized water was sparged with helium for at least 12 min.
  • Fresh polysorbate 20 (3.0 g; Tween ® 20) was placed in a 400 mL beaker and dissolved in sparged water (200 mL) at room temperature with the aid of mechanical stirring. The resulting solution was diluted with sparged water to 6L and stirred overnight at room temperature.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biophysics (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Medicinal Preparation (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
EP97946599A 1996-11-07 1997-11-07 Verfahren zur prüfung des auflösens von feste steroidale pharmazeutische formulierungen Withdrawn EP0937247A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US2988596P 1996-11-07 1996-11-07
US29885P 1996-11-07
PCT/US1997/020395 WO1998020340A1 (en) 1996-11-07 1997-11-07 A dissolution test method for solid steroidal pharmaceutical formulations

Publications (1)

Publication Number Publication Date
EP0937247A1 true EP0937247A1 (de) 1999-08-25

Family

ID=21851397

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97946599A Withdrawn EP0937247A1 (de) 1996-11-07 1997-11-07 Verfahren zur prüfung des auflösens von feste steroidale pharmazeutische formulierungen

Country Status (7)

Country Link
EP (1) EP0937247A1 (de)
JP (1) JP2001503867A (de)
CN (1) CN1236435A (de)
AU (1) AU721983B2 (de)
CA (1) CA2270951A1 (de)
IL (1) IL129769A0 (de)
WO (1) WO1998020340A1 (de)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040115837A1 (en) * 2002-11-27 2004-06-17 Schapaugh Randal Lee Methods of measuring the dissolution rate of an analyte in a non-aqueous liquid composition

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4151273A (en) * 1974-10-31 1979-04-24 The Regents Of The University Of California Increasing the absorption rate of insoluble drugs
KR960000235A (ko) * 1994-06-30 1996-01-25 공용조 생체 이용율이 우수한 지용성 약물 조성물
US5759577A (en) * 1995-01-17 1998-06-02 American Home Products Corporation Controlled release of steroids from sugar coatings

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9820340A1 *

Also Published As

Publication number Publication date
JP2001503867A (ja) 2001-03-21
CN1236435A (zh) 1999-11-24
AU5173798A (en) 1998-05-29
AU721983B2 (en) 2000-07-20
WO1998020340A1 (en) 1998-05-14
CA2270951A1 (en) 1998-05-14
IL129769A0 (en) 2000-02-29

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