7/29/2019 Applications of XRPD

1/21

LAXMAN BATHINI

7/29/2019 Applications of XRPD

2/21

AdvantagesIts capacity for:

Nondestructive testing

Analysis of final dosage form

Detection of Crystalline Impurities

Detection of changes in morphology duringproduction

7/29/2019 Applications of XRPD

3/21

X-Ray Diffraction

7/29/2019 Applications of XRPD

4/21

Schematic Diagram

7/29/2019 Applications of XRPD

5/21

New Generation XRD system

7/29/2019 Applications of XRPD

6/21

Applications Drug discovery: Determining whether a drug issuitable as drug through HTS

Drug Development:o Phase Identification

o Analyzing the of Effects of Processing on crystal form

oAnalyzing the Forensic Samples

o Reverse Engineering of the Drug Productso Quantitative Phase Analysis

Identify Counterfeit Medicines:

7/29/2019 Applications of XRPD

7/21

High throughput Screening

7/29/2019 Applications of XRPD

8/21

Polymorphic Forms

7/29/2019 Applications of XRPD

9/21

Different API Phases & Conc.

7/29/2019 Applications of XRPD

10/21

Effects of Processing Monitoring of Crystallization Process

Monitoring Drying of Active Pharmaceutical Ingredient

Monitoring the Influence of Milling of ActivePharmaceutical Ingredient

Monitoring Wet Granulation Processes

Effects of Freeze Drying Processes

7/29/2019 Applications of XRPD

11/21

Monitoring Crystallization Process

7/29/2019 Applications of XRPD

12/21

Monitoring the Milling Process

7/29/2019 Applications of XRPD

13/21

Monitoring Tablet Pressure

7/29/2019 Applications of XRPD

14/21

Stability Studies Nonambient Conditions X-ray Powder Diffractiono Phase transitions are directly monitored during

analysis

o temperature controlled XRPD (TC-XRPD)-Gives fruitful

information in combination with Differential Scanning

Calorimetry (DSC) on phase diagram of substance

o

humidity controlled XRPD (HC-XRPD)-Hydration orDehydration processes are analyzed. By correlating

Dynamic Vapor sorption (DVS) analysis and HC-XRPD

weight changes are assigned to polymorphic phase trans.

7/29/2019 Applications of XRPD

15/21

Drug Regulation PANalytical- Quick & Reliable screening of tablets

without removing blister packing.

The typical measurement time for this technique takesbetween 10 and 30 minutes, depending upon thickness and

properties of the tablets/capsules

Scattering from the mainly amorphous polymer used for

the blister material produces only a slightly increasedbackground

Aluminum lidding is evidenced by just two characteristic

Bragg reflections at higher angles

7/29/2019 Applications of XRPD

16/21

Counterfeit Medicines

7/29/2019 Applications of XRPD

17/21

Blister with & without Al lidding

7/29/2019 Applications of XRPD

18/21

Blister with & without Tablet

7/29/2019 Applications of XRPD

19/21

Summary Compatibility Studies

Control of ingredients- limit of detection 0.05%

Crystallography and crystal structure determination

Crystallintiy determination

R&D application

Phase analysis and polymorph screening

Batch and dosage uniformity

7/29/2019 Applications of XRPD

20/21

References Groen, H.; Mougin, P.; Thomas, A.; White, G.; Wilkinson,

D.; Hammond, R. B.; Lai, X.; Roberts, K.J. Ind. Eng.

Chem.Res. 2003, 42, 4888.

Cameron, M.; Zhou, G. X.; Hicks, M. B.; Antonucci, V.;Ge, Z.; Lieberman, D. R.; Lynch, J. E.; Shi, Y. J.J.Pharm.Biomed. Anal.2002, 28, 137.

Chan, H. K.; Doelker, E. Drug Dev. Ind. Pharm. 1985,11,315.

Otsuka, M.; Matsuda, Y. Drug Dev. Ind. Pharm. 1993,19,2241.

7/29/2019 Applications of XRPD

21/21