Академический Документы
Профессиональный Документы
Культура Документы
STUDIES:
PHYSICOCHEMICAL
CHARACTERIZATION
Muhammad Dzakwan OF
APIS
1
CONTENTS
INTRODUCTION
OBJECTIVES
PREFORMULATION STUDIES
PHYSICOCHEMICAL CHARACTERISATIONS
ANALYTICAL MEASURES
CONCLUSION
REFERENCES
6/8/17 2
INTRODUCTION
Preformulation testing is the first step in the rational
development of dosage forms.
6/8/17 3
OBJECTIVES
6/8/17 4
Why is Preformulation Important ?
It describes the process of optimizing the delivery of
drug thorough determination of physical, chemical
properties of new drug molecule that affect drug
performance and development of an efficacious,
quality, stable and safe dosage form.
Preformulation studies on a new drug molecule
provide useful information for subsequent formulation
of a physicochemically stable and biopharmaceutically
suitable dosage form.
6/8/17 5
PHYSICOCHEMICAL PROPERTIES
1. BULK PROPERTIES
Bulk properties of the solid form such as crystallinity,
polymorphism, particle size, powder flow property, and surface
characteristics are likely to change during process development.
Crystallinity
The crystal habit describes the outer appearance of crystals
( platy, equant, needle, bladed, etc.) and internal structure
arrangement.
6/8/17 6
Polymorphism
polymorphism is the ability of the compound to crystallize as
more than one distinct crystalline species with different internal
structure.
6/8/17 7
Particle size
Study of particle size give an information about solubility,
dissolution rate, absorption, etc.
particle size and surface area of a solid drug are inversely related
to each other.
eg: Griseofulvin
6/8/17 9
SOLUBILITY ANALYSIS
1. AQUEOUS SOLUBILITY
Important goal of the preformulation effort is to devise a
method for making solutions of the drug
6/8/17 10
2. Drug pKa / Ionization at physiological pH
6/8/17 11
The percentage of ionization can be calculated as
K=Co/Cw
Intrinsic dissolution
Paricular dissolution
6/8/17 15
STABILITY ANALYSIS
DRUG STABILITY
In this study includes both solutions and solid-state experiments
under various conditions for handling, formulation, storage, and in
vivo administration.
6/8/17 16
COMPATIBILITY
Compatibility test play a very important role in the
preformulation studies of oral dosage forms.
6/8/17 17
ANALYTICAL MEASURES
These includes:
1. Microscopy
2. Spectroscopy
3. Chromatography
6/8/17 18
A. MICROSCOPY:
6/8/17 19
B. SPECTROSCOPY
UV and Visible Spectrophotometry
6/8/17 21
X-RAY DIFFRACTION
Single Crystal X-ray provides the most complete information about the
solid state.
This method is tedious, time consuming & hence unsuitable for routine
use.
6/8/17 22
Thermal Analysis
Differential scanning calorimetry (DSC) and differential
thermal analysis(DTA) are particularly useful in
preformulation studies including purity, polymorphism,
solvation, degradation, and excipient compatibility.
Thermigravimetric analysis
Used to detect the existange and stability of solvated
drug molecule.
6/8/17 23
C. CHROMATOGRAPHY
6/8/17 25
REFERENCES
1) Banker GS, Rhodes CT., Modern pharmaceutics, 4th ed. New
York: Marcel Dekker; 2002. p.167-184
6/8/17 26
KARAKTERISASI STUDI PREFORMULASI
No Uji Metode, fungsi dan karakterisasi
1 Kelarutan
Larutan Fase kelarutan, kemurnian, kelarutan intrinsik
pKa Efek pH, kontrol kelarutan
Garam Pembentukan garam
Pelarut Stabilitas, ekstra
Koefisien partisi (log P) Lipofilisitas, struktur aktivitas
Disolusi Biofarmasetika
2 Titik leleh DSC, polimorfisme, hidrat, solvate
3. Metode Analisi UV, TLC, HPLC, FTIR, Raman Spek
4. Stabilitas
Larutan Hidrolisis, oksidasi, fotolisis, pH, pengaruh ion
Padatan DSC, DTA, TGA,
6/8/17 27
No Uji Metode, fungsi dan karakterisasi
5. Mikroskopis
Morfologi Mikroskop, karakterisasi fisik
Ukuran partikel Mikroskop, ayakan, sedimentasi, LD, PCS
Bentuk SEM, TEM,
Luas permukaan BET, permeabilitas udara
6. Kristal dan Polimorf
Kristal DSC, PXRD, kristanilitas, kelarutan
Polimorfi DSC, PXRD, metastabil, stabilitas padatan
7. Sifat Fisik-Mekanis
Densitas partikel Bj ruahan, Bj mampat, Bj sejati, true density
Sudut diam Tipe aliran
Kompresibilitas CI carrs, Hausner Ratio
6/8/17 28
No Uji Metode, fungsi dan karakterisasi
6/8/17 29
Matur
Nuhun .
6/8/17 30