Apparatus and Method for Testing Medicaments

Abstract

Apparatus for testing the solubility of a medical dosage form includes a chamber ( 12 ) for holding a solvent medium ( 18 ), in the preferred embodiment a bicarbonate based buffer system. The apparatus also includes a pH probe ( 66 ) which is connectable to a supply of carbon dioxide ( 32, 34 ),as well as to a supply of helium ( 40 ), the supplies being controlled by a control unit ( 50 ). The control unit ( 50 ) monitors changes in pH of the solvent medium ( 18 ) and, as appropriate, feeds pH increasing and/or pH reducing gas from the supplies( 32, 34, 40 ) into the chamber ( 12 ). The control unit ( 50 ) is able to maintain a uniform pH during testing or to provide a dynamically adjustable pH during testing, for example to three or more different pH levels in order to test the performance of a drug carrier at different levels of acidity or alkalinity for example, mimicking the conditions of the gastrointestinal tract. The apparatus( 20 ) and associated method are particularly suitable for testing and developing dosage forms for oral delivery of drugs.

1 . An apparatus for testing pH-induced changes in a test substance including:
 a chamber for holding a solvent medium and the test substance;   a sensing device for sensing a parameter derivable from the chamber, the parameter being indicative of a pH-dependent change in the test substance;   a pH probe disposable in the chamber for measuring the pH of solvent medium in the chamber;   a first valve coupling connectable to a supply of pH reducing fluid, the first valve coupling including a first conduit feeding into the chamber;   a second valve coupling connectable to a supply of pH increasing fluid, the second valve coupling including a second conduit feeding into the chamber;   a control device connected to the probe and to the first and second valve couplings and operable to control the supply of pH increasing and pH reducing fluid into the chamber on the basis of the determined pH within the chamber; and   a data logger operable to keep a log of data obtained during operation of the apparatus; and a bicarbonate based medium as the solvent medium for the chamber.   
     
     
         2 . The apparatus according to  claim 1 , including as a source of pH reducing fluid a source of carbon dioxide. 
     
     
         3 . The apparatus according to  claims 2 , wherein the source of carbon dioxide is one of:
 pure carbon dioxide;   a mixture of carbon dioxide and oxygen;   a mixture of carbon dioxide and medical oxygen gas; and   a mixture of carbon dioxide with compressed air or an inert gas.   
     
     
         4 . The apparatus according to  claim 2 , wherein the source of increasing fluid is one of:
 a source of helium;   an inert gas; and   compressed air.   
     
     
         5 . The apparatus according to  claim 1 , including a temperature sensor disposed to sense temperature in the chamber and coupled to the control device. 
     
     
         6 . The apparatus according to  claim 1 , wherein the sensing device includes one of: a spectrometer, a liquid chromatography device and an auto-sampling device for collecting samples for further analysis. 
     
     
         7 . The apparatus according to  claim 1 , wherein the chamber includes an upper portion and a lower portion, and wherein at least one of the first and second conduits terminates at the upper portion of the chamber. 
     
     
         8 . The apparatus according to  claim 1 , wherein the control device can be set to monitor a predetermined pH threshold and is operable to control the first and second valve couplings on the basis of the set threshold so as to change the pH of solution in the chamber. 
     
     
         9 - 10 . (canceled) 
     
     
         11 . The apparatus according to  claim 1 , wherein the control device is operable to measure change in pH in the chamber during the supply of pH increasing and/or reducing fluid into the chamber. 
     
     
         12 . The apparatus according to  claim 11 , wherein the control device is operable to determine change in pH on the basis of one or more of: rate of supply fluid, temperature and time.  13 , (canceled) 
     
     
         14 . The apparatus according to  claim 12 , wherein the control device is operable to determine said change in pH during a first control cycle and to control the supply of pH increasing and/or decreasing fluid in a subsequent cycle on the basis of the determined change of said first cycle. 
     
     
         15 . The apparatus according to  claim 14 , wherein the control device is operable to control the supply of pH increasing and/or decreasing fluid by controlling one or more of:
 a time of supply,   a rate of supply,   an amount of supply.   
     
     
         16 . The apparatus according to  claim 1 , comprising a plurality of chambers and a set of first and second valve couplings and conduits per chamber, wherein the control device is operable to control the supply of pH increasing and/or reducing fluid to each of the chambers. 
     
     
         17 . The apparatus according to  claim 16 , including one of:
 a single pH probe for the plurality of chambers, and   a plurality of pH probes for the chambers.   
     
     
         18 - 31 . (canceled) 
     
     
         32 . A method of testing the solubility and/or dissolution of a medical dosage form by means of apparatus which includes a chamber for holding a solvent medium and a dosage form for testing; a sensing device for sensing a parameter derivable from the chamber, the parameter being indicative of dissolution of a medical dosage form; a pH probe disposable in the chamber for measuring the pH of solvent medium in the chamber; a first valve coupling connectable to a supply of pH reducing fluid, the first valve coupling including a first conduit feeding into the chamber; a second valve coupling connectable to a supply of pH increasing fluid, the second valve coupling including a second conduit feeding into the chamber; and a control device connected to the probe and to the first and second valve couplings and operable to control the supply of pH increasing and pH reducing fluid into the chamber on the basis of the determined pH within the chamber; the method including the steps of:
 providing in the chamber a solvent, the solvent being a bicarbonate based medium;   providing in the chamber at least one dosage form to be tested;   monitoring for the dissolution of the dosage form; and   monitoring the pH of the solution and adjusting the pH of the solvent in the chamber by supplying one or both of the pH reducing and the pH increasing fluids.   
     
     
         33 . (canceled) 
     
     
         34 . A method according to  claim 32 , including the step of supplying as the pH reducing fluid carbon dioxide. 
     
     
         35 . A method according to  claim 34 , wherein one of the following is supplied:
 pure carbon dioxide;   a carbon dioxide and oxygen mixture; or   a mixture of 95% oxygen and 5% carbon dioxide   
     
     
         36 - 38 . (canceled) 
     
     
         39 . A method according to  claim 32 , including the step of supplying as the pH increasing fluid one of:
 helium;   compressed air; and   an inert gas.   
     
     
         40 - 42 . (canceled) 
     
     
         43 . A method according to any one of  claim 32 , wherein the medical dosage form comprises a pH-dependent carrier material capable of controlling the release of a drug or other substance. 
     
     
         44 . A method according to  claim 32 , wherein the pH-dependent change is release of a drug or other substance by disintegration of the medical dosage form. 
     
     
         45 - 47 . (canceled)