DOSAGE FORM DESIGN PARAMETERS

SOLID-STATE CHARACTERIZATION AND PHYSICAL BEHAVIOR

Prof Nalini Shastri SVCP,HYD

THERMAL METHODS
Differential thermal analysis - DTA
Differential Scanning Calorimetry - DSC Thermogravimetric analysis -TGA

THERMAL ANALYSIS
DEFINITION Group of techniques in which a physical property of a substance is measured while the substance is subjected to a controlled temperature program Change in property of material when heated or cooled Smaller sample size Correlation of higher temperature activity with ambient temperature

FUSION CURVE FOR MELTING

DTA-THEORY
Sample and Reference heated simultaneously Subjected to controlled temperature Temperature differences Changes during recrystallization, glass transition (exothermic) or Melting (endothermic)

DTA PHENYBUTAZONE
Spray drying temperatures a=30oC; b=40oC; c=70oC; d=80oC; e=100oC

CASE STUDY
DTA of a drug studied under different pressure conditions

DTA FOR CEPHALEXIN

50 100 150 200 g

a) monohydrate, b) ground for 3min c) ground for 5 min d) ground for 30min e) ground for 60min f) ground for 90min g) Amorphous drug

(a) (b) (c) (d) (e) (f) (g) 50 100 150 200 Temperature (

f
e d c b a

DSC-THEORY
Sample and Reference heated simultaneously Maintaining both a same temperature Amount of energy required to heat both is monitored DCp of sample remains relatively constant Changes during recrystallization, glass transition (exothermic) or Melting (endothermic)

DSC PARAMETERS

DSC

DSC - POLYMORPHS
Form II

Form I

diflunisal

DSC SOLVATES
DMF

i-propanol

n-propanol

t-butanol

Diuretic piretanide

DRUG EXCIPIENT INTERACTION

a=Famotidine b=Famotidine + talc c=Famotidine + DCP

DSC PURITY ANALYSIS

Broadening effect of the melting curve of b-hydroxypropyltheophylline due to impurities. PSA = phase solubility analysis. All batches have the same TLC purity results.

CASE STUDY

TGA
Thermally induced weight loss/gain Measurement as function of temperature Loss of solvent Decomposition reaction Determination of volatile components Selection of proper polymorphs based on higher decomposition temperture

TGA

Ca-oxalate dehydration CaCO3 CaO

THERMAL ANALYSIS - ADVANCES

MODULATED DSC Differentiate between energy associated with reversible and non reversible transitions RAPID SCAN/HIGH SPEED/HYPER DSC More sensitive to specific transitions Enables lower LOD HIGH SENSITIVITY DSC Detect signals + 0.5mW Slow scan rates Study small changes in enthapy proteins

THERMAL ANALYSIS - ADVANCES

ISOTHERMAL MICROCALORIMETRY Sample kept at constant temperature Changes induced in sample crystallization/polymorphism Amount of heat gained or lost monitored Sample not heated so change observed at ambient temperature Sensitive to small changes in heat Not discriminative, exact nature of transition must be known to interpret the data HYPENATED SYSTEMS

DSC & MTDSC

DSC DIFFERENT SCAN SPEEDS

DSC traces for gepirone hydrochloride run at a range of scanning speeds.

HYPER-DSC

High-speed DSC curves for carbamazepine Form III

HSDSC

Beef blood hemoglobin at different pH

DSC - TGA

Mgst dihydrate

DSC-GEA &TGA
chloramphenicol pyridinate

SEM-XRD

loratadine particles (a) as received, (b) precipitated water ethanol solution (c) formed by vacuum evaporation of ethanol from solution of the drug in alcohol/water mixture

CASE STUDY
code Content A B C D E Rofecoxib Rofecoxib:PVP:talc (1:3:1) Rofecoxib:PVP:talc (1:3:1) Method No processing Spray dried PM Dissolution X 3X X 2X X

Rofecoxib:HPMC:talc (4:4:1) Spray dried Rofecoxib:HPMC:talc (4:4:1) PM

Suggest suitable analytical techniques to explain the findings. What type of results do you anticipate?

DSC-TGA-VT-XRD,HSM

ambient temperature. 45C

65C

160C

170C

175C

180C

190C

OTHER THERMAL ANALYSIS

Microthermal analysis TSC-Thermally stimulated current Thermoptometry Thermomechanical analysis Dielectric thermal analysis