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Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
Effect Of Hydrate Formation (A Common Problem In Wet Granulation)
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Effect Of Hydrate Formation (A Common Problem In Wet Granulation)

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  • Nice slide Show!Prediktor a Norwegian Company makes an excellent On-Line NIR Spectrometer
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    • 1. <ul><li>NAME: SHASHANK JAIN </li></ul><ul><li>INSTUCTOR: </li></ul><ul><li>DR. E.SQUILANTE </li></ul>Effect of hydrate formation on dissolution profile of theophylline (A common problem in wet granulation) Theophylline (TP)
    • 2. PRE-TEST <ul><li>Q.Do you know how hydrate formation effect the dissolution profile of a drug. </li></ul><ul><li>a] Yes </li></ul><ul><li>b] No </li></ul><ul><li>Response : 34 responses </li></ul><ul><li>Yes:3 </li></ul><ul><li>No :31 </li></ul>
    • 3. THESIS STATEMENT <ul><li>To know the effect of hydrate formation on dissolution rate of theophylline and propose a best available method to detect these hydrate by analysing two current PAT techniques i.e NIR and Raman. </li></ul>
    • 4. Hydrates-A PIT <ul><li>Process-induced transformations (PIT) occur as a result of mechanical or thermal stress imposed upon a system during processing or after exposure to solvent. </li></ul><ul><li>PIT’s are important because they may alter the properties of the final dosage form such as </li></ul><ul><li>Solubility </li></ul><ul><li>Dissolution rate </li></ul><ul><li>Hygroscopicity </li></ul><ul><li>Stability </li></ul><ul><li>Bioavailability. </li></ul>
    • 5.  
    • 6. Hydrate Formation in Theophylline
    • 7. SEM ANALYSIS ( MORPHOLOGICAL CHANGE DURING ANHYDRATE MONOHYDRATE ) (Anhydrate theophylline) (Monohydrate theophylline)
    • 8. “ EXPECTED ” DISSOLUTION PROFILE OF THEOPHYLLINE <ul><li>Step1(stable anhydrate) Step2(Hydrate) Step3(metastable anhydrate) </li></ul><ul><li>Least dissolution : Step 2( by affecting thermodynamic property of theophyllline) </li></ul><ul><li>Step3>Step1 </li></ul><ul><li>the expected rank order of dissolution rates was as follows: Step 3 > Step 1 > Step 2. </li></ul>
    • 9. FIGURE 1. DISSOLUTION PROFILES OF UNPROCESSED AND PROCESSED ANHYDROUS THEOPHYLLINE SAMPLES: STEP 1 ( ● ), STEP 2 ( ♦ ), AND STEP 3 ( ■ ). THESE ARE DESCRIBED IN SCHEME 1. ( REF :DEBNATH S, SURYANARAYANAN R. INFLUENCE OF PROCESSING-INDUCED PHASE TRANSFORMATIONS ON THE DISSOLUTION OF THEOPHYLLINE TABLETS. AAPS PHARMSCITECH. 2004; 5(1) Step 1 Step 2 Step 3
    • 10. ACTUAL DISSOLUTION PROFILE <ul><li>Actual dissolution profile of theophylline follows: </li></ul><ul><li>step 1(Stable) > Step 2(hydrate) ≈ Step 3(metastable) </li></ul><ul><li>Why ??? </li></ul><ul><li>Rapid metastable anhydrate(Step3) -> theophylline monohydrate during dissolution. </li></ul>
    • 11. CASE STUDY <ul><li>“ FDA issued a warning letter to XX company due to failure of dissolution test in four batches of theophylline” </li></ul><ul><li>--Problem of hydrate formation was found to the major reason . </li></ul>
    • 12. How we can determine the Hydrate formation in theophylline? <ul><li>Current approach- </li></ul><ul><li>NIR(Near Infra-Red) spectroscopy </li></ul><ul><li>Raman Spectroscopy </li></ul>
    • 13. NIR SPECTROSCOPY METHOD <ul><li>The absorption bands in NIR spectra are sensitive to changes in hydrogen bonding and packing in the crystal lattice. </li></ul><ul><li>We can detect the hydrate formation by observing the energy distribution of OH vibration. </li></ul><ul><li>How ? </li></ul>
    • 14. <ul><li>NIR spectra of theophylline -microcrystalline cellulose (1:1, w/w) wet granules. Absorbance maxima are observed as troughs. Free water: 1905 nm, hydrate water: 1970 nm. Arrows indicate changes taking place with increasing water content. </li></ul><ul><li>( Ref- Reseach based study of university of Helsinki ) </li></ul>
    • 15. CRITICAL ISSUES <ul><li>The NIR spectroscopy enables the determination of the state of water and has also been used for quantitative determination of moisture (Osborne et al., 1993). </li></ul><ul><li>However the changes in other vibration originating from other constituents are obscured. </li></ul><ul><li>In addition, if the water content is high, the free water absorbance may overlap the hydrate water absorbance </li></ul><ul><li>This problem is not encountered using Raman spectroscopy, Why? </li></ul>
    • 16. RAMAN SPECTROSCOPY <ul><li>Raman spectroscopy is based on measurement </li></ul><ul><li>of frequency shifts of scattered light. </li></ul><ul><li>Raman spectrometers can be coupled with fibre optic probing which enables on-line and </li></ul><ul><li>non-invasive measurements. </li></ul>
    • 17. Comparision of NIR and Raman spectra AT has distinct peaks at 1664 and 1707 cm -1 and MT has a distinct peak at 1686 cm -1 , NIR spectra of AT and MT from 1100 to 1850 nm.
    • 18. Waterfall Plot of NIR and Raman Effect
    • 19. Summary : Advantage of Raman Over NIR Spectroscopy <ul><li>In NIR, the free water absorbance may overlap the hydrate water absorbance. Water is a weak Raman scatter </li></ul><ul><li>In contrast to NIR, the Raman bands are well resolved. </li></ul><ul><li>Raman instruments can also measure lattice vibrations (Bugay, 2001), so called phonons, which occur at low frequencies (400-50 cm -1 ). </li></ul>
    • 20. CONCLUSION <ul><li>NIR spectroscopy could not be used to monitor the phase transformation in this system because of the large absorbance of bulk water . However In-line Raman spectroscopy was successfully interfaced to high-shear wet granulation for detection of hydrates in theophylline as water is the poor raman scatter. </li></ul>
    • 21. POST SEMINAR QUESTION <ul><li>Q. How hydrate formation may effect the End Point Determination in theophylline during wet granulation process? </li></ul>
    • 22.  
    • 23. THANK YOU

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