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Department of Pharmacy (Pharmaceutics) | Sagar savale

CONTENTS INTRODUCTION TYPES OF INTERACTION MECHANISM OF INTERACTION PHYSICAL INTERACTION CHEMICAL INTERACTION PHYSIOLOGICAL INTERACTION METHOD OF EVALUATION FOR EXCIPIENTS DSC XRD FTIR DRUG-CONTAINER INTERACTION

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INTRODUCTION

Excipients are one of the three components that in combination produce the medicine that the patient will take.

In therapeutic terms, the API is of primary importance because without it there is no treatment and no product.

In term of drug manufacturing all three of them are equally important so we cannot neglect anyone of them.

The interactions between excipients and the other two components (the API and the manufacturing process), and/or between two or more excipients, are fundamental to the transformation of an API into a medicinal product.

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TYPES OF INTERACTION

DRUG - EXCIPIENT INTERACTION DRUG – DRUG INTERACTION

EXCIPIENT – EXCIPIENT INTERACTION

DRUG – CONTAINER INTERACTION

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MECHANISM OF INTERACTION

PHYSICAL INTERACTION

CHEMICAL INTERACTION PHYSIOLOGICAL/BIOPHARMACEUTICAL INTERACTION

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PHYSICAL INTERACTIONPhysical interactions do not involve chemical change. The

components retain their molecular structure.

For example, silicified microcrystalline cellulose after processing cannot be separated entirely into its two separate components. But by investigation they shows different spectra.

Physical interaction evaluated by using DSC,TGA,HPTLC,XRD and TLC method

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CHEMICAL INTERACTION

Chemical interactions involve chemical reactions; i.e., a different molecule (or molecules) is (are) created.

Some example of chemical interaction are; Maillard reaction. Lactone formation. Oxidation. Hydrolysis

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PHYSIOLOGICAL INTERACTION

Physiological interactions are the interactions between the excipient(s) and the body fluids.

One physiological interaction that can potentially cause serious problems for the patient is the interaction between enteric coatings and antacids.

A classic biopharmaceutical incompatibility is the interaction between tetracycline antibiotics and calcium and magnesium ions.

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METHOD OF EVALUATION FOR EXCIPIENTS

Thermal Analysis DSC, DTA, DTG & Isothermal calorimetry

Chromatography HPLC, TLC

IR, XRD

LC-MS/MS,NMR

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DIFFERENTIAL SCANNING CALORIMETRY

Calorimeter Measures the heat into or out of the sample

Differential Calorimeter Measures the heat of the sample relative to the

reference

Differential Scanning Calorimeter Dose all the above and heat the sample and

reference with linear temperature range.10

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Differential Scanning Calorimetry (DSC) measures the temperatures and heat flow associated with the transitions in the material as a function of time and temperature in a controlled atmosphere These measurements provides qualitative and quantitative information about the physical and chemical changes that involve endothermic and exothermic processes or changes in the heat capacity Cover the temperature range from -60°to 1600°C with variable atmospheres

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WORKING PRINCIPLE OF DSC

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DSC INSTRUMENTATION

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Power Compensated DSC Heat Flux DSC

THE DSC THERMOGRAPH

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IBUPROFEN-Mg OXIDE INTERACTION BY DSC

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APPLICATION OF DSC

Accurate determination of melting point Determination of the purity without knowing type of impurityFor quantifying the crystallinity of lyophilized or spray dried

productFor identification of polymorphism in formulationFor stability determination To study the decomposition and degradation kineticsFor determination of the glass transition temperatureTo check the drug excipient compatibilityDetermination of the molecular environment of water in crystals

and hydrates

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PRINCIPLE OF XRD

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X-ray of known wavelength is focused onto a crystal that can be aligned until a diffraction pattern is created.

X-RAY POWDER DIFFRACTION (XRPD)

One of the most powerful techniques for analyzing the crystalline nature of solids.

The sample is usually in a powdery form

In this method the crystal is reduced to a fine powder and is placed in a beam of monochromatic x-rays.

Powder methods - fixed, vari

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XRPD PROVIDES FOLLOWING INFORMATION

Type and nature of crystalline phase present

Degree of crystallnity

Degree of amorphous content

Microstrain & size and preferred orientation of crystallites Also used for studying particles in liquid Suspensions or polycrystalline solids (bulk or thin film materials).

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X-RAY DIFFRACTION PATTERN

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PRINCIPLE

When sample comes to exposure of IR radiation it shows vibrations (either stretching or bending) depending on characteristic of the sample. When the frequencies of these vibrations becomes same as that of IR radiation it shows characteristic peak on IR spectrum.

Vibrations

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Stretching Bending

IR SAMPLING METHODS

Salt disks (NaCl): for liquids (a drop) and small amounts of solids. Sample is held between two plates or is squeezed onto a single plate.

KBr/CsI pellet: a dilute (~1%) amount of sample in the halide matrix is pressed at >10000 psi to form a transparent disk. Disadvantages: dilution required, can cause changes in sample

Mulls: Solid dispersion of sample in a heavy oil (Nujol) Disadvantages: big interferences

Cells: For liquids or dissolved samples. Includes internal reflectance cells (CIRCLE cells)

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INTERPRETATION OF IR SPECTRA

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DRUG-CONTAINER INTERACTION

Most probably the pharmaceutical container are: Glass Plastic Rubber MetalThe main interaction between drug-container are: Leaching Sorption Permeation Flaking Chemical reactivity

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REFERENCES

1. Blecher L. The formation of the International Pharmaceutical Excipients Council. Pharm Technol 1991; 15(6):54, 56.

2. Blecher L. Excipients–the important components. Pharm Process 1995; 12(1):6–7.3. Chrzanowski FA, Ulissi LA, Fegely BJ, Newman AC. Preformulation excipient

compatibility testing: application of a differential scanning calorimetric method versus a wet granulation simulating, isothermal stress method. Drug Devel Ind Pharm 1986; 12(6):783–800.

4. Botha SA, Lotter AP. Compatibility study between Naproxen and tablet excipients using differential scanning calorimetry. Drug Dev Ind Pharm 1990; 16(4):673–683.

5. Foda NH. Compatibility study between Fluvoxamine Maleate, mebeverine hydrochloride and tablet excipients using differential scanning calorimetry. Egypt J Pharm Sci 1992; 33(1–2):73–81.

6. Wilson RJ, Beezer AE, Mitchell JC. Determination of thermodynamic and kinetic parameters from isothermal heat conduction microcalorimetry: applications to long term reaction studies. J Phys Chem 1996; 99:7108–7113.

7. Guillory JK, Soon CH, Lach JL. Interactions between pharmaceutical compounds by thermal methods. J Pharm Sci 1969; 58(3):301–308.

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8. S. Class et al.; Differential Scanning Calorimetry: Applications in Drug Development, PSTT Vol. 2, No.8, Aug 1999,1-10

9. J.Luypaert et al.; Near-infra red spectroscopy applications in pharmaceutical analysis, Talanta, 72(2007), 865-883

10. J. Connolly et al.; Introduction to X ray powder diffraction, Spring 2007;1-911.Kratos; Analytical Applications Note "X-Ray Diffraction for Solid State

Pharaceutical Products", NY Office, August 199812.http://www.kratos.com/XRD/Apps/index.html

13.http://www.assainternational.com/workshops/iwpcps_1/exhibitors.cfm

14.http://www.ptli.com/testlopedia/tests/DSC- d3417.asp

15.http://www.psrc.usm.edu/macrog/dsc.htm