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Pharmaceutical Analysis 2014
Pharmaceutical Analysis 2014
ANALYSIS
Wayan Redja
2014
Fakultas Farmasi Universitas Pancasila
PARMACEUTICAL ANALYSIS
Introduction
Analytical Methods
Pharmacopoeia
Quality Control
Introduction
Definition
Purpose of Pharmaceutical Analysis
Why Pharmaceutical Analysis Needed
How to Perform Pharmaceutical
Analysis
Steps of Analysis
Introduction
Definition
Pharmaceutical analysis is the qualitative and quantitative
analysis of pharmaceuticals using validated analytical
methods for characterization and quality control.
Purpose
The purpose of pharmaceutical analysis is for characterization
and quality control of pharmaceuticals.
Characterization of pharmaceuticals are carried out to identify
or quatify the pharmaceuticals during synthesis or R&D.
Quality control of pharmaceutical is focus to fulfill the quality
requirements as mentioned in the standard specifications
such as that stated in the monograph of pharmacopoeia.
Introduction
Why Pharmaceutical Analysis Needed
- Pharmaceuticals is used as medicines.
- Sub-standard drugs are still available in the market due to
counterfeiting or degradation during production, distribution,
and storage.
- Consuming sub-standard or counterfeit product cause health
hazard that may be fatal.
- There are three criteria of medicines: Quality, Efficacy and
Safety, so pharmaceutical analysis is needed to confirm that
those three criteria are fulfilled.
Introduction
How to Perform Pharmaceutical Analysis
- Follow the PDCA cycle on each activity of the
following steps of analysis.
- Use the validated analytical methods.
- Make decision according to factual approach.
- Take preventive or corrective actions for any
discrepancies.
Introduction
Steps of Analysis
- Sampling
Method of taking a representative sample from the population
(static or dynamic, homogeneous or heterogeneous population).
- Sample Preparation
Grinding, weighing, dissolving, precipitation, filtration, extraction,
chromatographic separation, drying, etc.)
- Measurement
Conventional or Instrumental Methods
- Evaluation
Calculation and decision making
- Reporting
Certificate of Analysis (COA)
Pharmacopoeia
Definition
Famous Pharmacopoeias
Benefit of Pharmacopoeia
General Notice
Monograph
Pharmacopoeial Methods of Analysis
Pharmacopoeial Methods
● Pharmacopeial Methods
Qualitative and / or quantitative analysis of Pharmacopoeia, for
quality control and research of Active Pharmaceutical
Ingredients (API) or Pharmaceutical Products.
● Quality of drugs
The specifications describe in the monograph of pharmacopoeia.
● Pharmacopoeia
Legal reference of drugs quality and the methods of analysis,
officially be effective for particular country.
Pharmacopeial Methods
● Purpose
1. To determine identity, purity, impurities, and assay
of API or pharmaceutical products.
2. To assure the quality of API or pharmaceutical
products.
3. To release or reject the API or pharmaceutical
products.
General Notice
● Weigh accurately about …
Weigh in analytical balance (error ≤0,1%), ± 10% of the weight.
● Solubility
Parts of solvent required for 1 part of solute:
very soluble (<1part), freely soluble (1-10 parts), soluble (10-30
parts), sparingly soluble (30-100 parts), slightly soluble (100-1000
parts), very slightly soluble (1000-10,000), practically insoluble, or
insoluble (≥ 10,000 parts).
● Concentration: %, N, M, ppm, ppb etc.
● Etc.
Examples of Problems
1. Weigh accurately about 100 mg of tablet powder. What kind of balance
should be used and in what range is the acceptable weight?
● Description
● Identification
● Physicochemical Characterization
● Test of Impurities
● Performance Test (Pharm. Products)
● Assay
Monograph
Quality Parameter Raw Pharmaceutical
Material Product
Description -
Solubility -
Identification
Purity -
Impurities
Performance test -
Assay
Description
● Test of Impurities
Limit test (heavy metals, mercury, arsenic, lead, chloride,
sulphate, residue on ignition, etc.), ordinary impurities,
water content, residual solvent (volatile organic substances,
loss on drying).
Ordinary Impurities<481>
TLC method for accessing profile of impurities of raw material.
Test Solution: 10 mg/ml in specified solvent.
Standard Solution (BPFI): 0,01; 0,05; 0,1 and 0,2 mg/ml in
specified solvent.
Stationary Phase: Plate of 0,25 mm silica gel layer
Mobile Phase: As specified in the monograph.
Spotting: 20 µl Under a stream of N2
Development: Solvent front, ¾ X plate height
Detection: Using the visualization technique(s) specified, e.g.
UV 254 nm, 366 nm, H2SO4-ethanol (10:90) heat, etc.
Evaluation: Determine the relative intensity of the spots of
impurities of Test Solution (Requirement: ≤ 2%).
Ordinary Impurities<481>
Solvent Front
20 cm
●
●
15 cm
● ● ●●
●
U = Test Solution 10 mg/ml
S1 = Standard Solution 0,01 mg/ml
• • • • • S2 = Standard Solution 0,05 mg/ml
U S1
u S2 S3 S4
2 cm
Hard - WV CU
AV = M - X + ks
Apllication
The disintegration test is provided for: uncoated tablets, plain
coated tablets, delayed-release (enteric-coated) tablets,
buccal tablets, sublingual tablets, hard gelatin capsules, soft
gelatin capsules, except for troches, chewing tablets, and
modified-release dosage forms.
Disintegration
How to Determine Disintegration
Using Disintegration Tester
- Basket-rack assembly with six open-ended transparent
tubes held in vertical position with two plastic plates,
attached to the under surface of the lower plate is a woven
stainless steel wire cloth which has a plain square weave
with 1.8-2.2mm mesh apertures.
- 1000 mL low-form beaker for immersion fluid, heated by
a thermostatic arrangement 370±20.
- A device for raising and lowering the basket into the
immersion fluid, frequency 29-32 cycles per minutes,
distance 5.3-5.7cm, downward stroke ≥ 2,5 cm from the
bottom of the beaker, upward stroke ≥ 2,5 cm below the
surface of the fluid. .
Disintegration
Procedure for Uncoated Tablets, Plain Coated Tablets,
and Sublingual Tablets
- Place 1 tablet (or capsule) in each of six tubes of the basket,
operate the apparatus, using water as the immersion fluid
maintained at 370±20 unless otherwise specified.
- Lift the basket at the end of time limit as specified in the
individual monograph.
- Observe the tablets (or the capsules): all of the tablets (or the
capsules) have disintegrated completely.
If 1 or 2 tablets (or capsules) fail to disintegrate completely,
repeat the test on 12 additional tablets (or capsules). The
samples pass the test if ≥ 16 units of the total 18 units of
tablets (or capsules) disintegrate completely.
Disintegration
Method Modification for Particular Samples
- Delayed Release (Enteric Coated) Tablets
a. Immerse the basket in water at room temperature for 5
minutes to dissolve water soluble external coating (if exist).
b. Operate 1 hour using simulated gastric fluid TS . No
evidence of disintegration, cracking, or softening.
c. Continue the operation using simulated intestinal fluid TS
similar to the method and acceptance criteria of the
Uncoated Tablets.
- Buccal Tablets Time limit 4 hours
- Hard or Soft Gelatin Capsules
Attach a removable wire cloth to the surface of the upper
plate of the basket-rack assembly. Operate according to
Uncoated Tablets.
Dissolution
Definition
Dissolution is the percentage of the active ingredient of a product
(tablets or capsules) dissolves in the specified dissolution medium
at 370±0,50, after stirring at the specified speed and time limit.
Why Dissolution
Complete Disintegration of tablets or capsules does not always
represent its complete absorption from GI tract. This is due to un-
dissolved active ingredients that still trap inside the small granule
particles that pass trough the wire mesh of the disintegration
apparatus.
So, Dissolution Test is needed to predict in-vivo bioavailability (BA),
for a product with less soluble active ingredient e.g. Paracetamol
Tablet. However, Dissolution Test is not necessarily needed for
a product with soluble active ingredient, e.g. Antalgin Tablet.
Relative Dissolution Test is in-vitro bioavailability test to predict in-
vivo bioequivalence (BE) of a product .
Dissolution
Purpose
Dissolution is needed to predict the Bioavailability or Bioequivalence
(BA/BE) of a product which contains less soluble active ingredients.
Relative Dissolution Test is in-vitro bioequivalence test to predict in-
vivo bioequivalence (BE) of a product relative to its comparator or
innovator product. Dissolution Test is in-vitro bioavailability test to
predict in-vivo bioavailability (BA) of a new product.
Application
Dissolution Test is provided to determine the compliance with the
dissolution requirement where stated in the individual monograph
for a tablet or capsule dosage form.
For enteric-coated tablet Delayed Release Articles under Drug
Release is applied unless otherwise specified.
For gelatin capsules and gelatin-coated tablets that don’t conform
Dissolution specification, purified pepsin (≤ 750,000 Units / 1000
ml) medium) may be used for medium with < pH 6.8 , or for
medium with pH ≥ 6.8, pancreatin (1750 Units of protease
activity/1000 ml medium)can be used.
Dissolution
How to Determine Dissolution
Using Dissolution Tester
Procedure
Capsules, Uncoated Tablets, and Plain Coated Tablets
Conventional Methods
1. Volumetry
2. Gravimetry
Instrumental Methods
1. Spectrophotometry
2. Chromatography
3. Electrochemical Methods
PERTANYAAN
1. Sajikan dalam tabel, parameter mutu mana dari monografi bahan
baku FI IV berikut yang termasuk persyaratan kemurnian, cemaran
dan kadar:
- Parasetamol - Laktosa
- Minyak Permen - Sakarosa
- Minyak Jarak - Air Murni
- Vaselin Kuning - Natrium klorida
- Etambutol Hidroklorida - Pati Singkong
3. Buat gambar atau foto-kopi, tuliskan nama dan uraikan prinsip kerja
dari alat untuk menentukan: suhu lebur, indeks bias, bobot jenis dan
rotasi jenis. Tuliskan urutan prosedur penetapannya.
Titrasi Bebas Air
Pendahuluan
Teori Asam Basa
Kekuatan Asam Basa
Pelarut
Sistem TBA
Larutan Volumetrik
Penetapan Kadar
TITRASI
BEBAS AIR Pendahuluan
(TBA)
Pendahuluan
PENEMU KONSEP ASAM BASA
Teori Asam Donor Donor
Basa Arrhenius
Kekuatan
proton OH-
Asam Basa Donor Akseptor
Pelarut Bronsted & Lowry
proton proton
Sistem TBA
Larutan
Volumetrik Akseptor Donor
Penetapan
Kadar Lewis Pasangan Pasangan
-Contoh Soal elektron elektron
TITRASI
BEBAS AIR Kekuatan Asam - Basa
(TBA)
# FI IV, hal.975
TITRASI Larutan Volumetrik
BEBAS AIR Asam perklorat 0,1N LV
(TBA)
(10,05 g HClO4 /L, BM 100,46 FI IV, hal.1213)
Pendahuluan Pembuatan
Teori Asam Campur asam perklorat P (70%), asam asetat
Basa glasial P, anhidrida asetat P, dinginkan,
Kekuatan tambah asam asetat glasial P ad 1000 ml.
Asam Basa
Tetapkan kadar air dengan titrasi KF
Pelarut
(persyaratan kadar air 0.02-0,05%).
Sistem TBA
Pembakuan
Larutan
Volumetrik Baku primer kalium biftalat P, keringkan 1200
Penetapan 2 jam, pelarut asam asetat glasial P, indikator
Kadar kristal violet LP (ungu hijau kebiruan).
-Contoh Soal
Lakukan titrasi blangko.
F = 2CP/(B-I)
F = Faktor kesetaraan, μg penisilin/ml natrium tiosulfat 0,01N
C = Konsentrasi Larutan baku, mg/ml
P = Potensi, μg (unit)/ mg BPFI
B = Volume natrium tiosulfat 0,01N untuk Penetapan blangko.
I = Volume natrium tiosulfat 0,01N untuk Titrasi setelah Inaktivasi Larutan baku.
Menghitung kadar (%) zat aktif per unit dosis, misalnya tablet
Ditanyakan:
a. Bagan prosedur ekstraksi.
b. Kandungan (mg) C16H19ClN2.C4H4O4 dalam serbuk tablet
yang digunakan, dihitung dengan rumus: C(Au/As).
c. Kadar (%) C16H19ClN2.C4H4O4 dari jumlah yang tertera pada
etiket.
d. Bila persyaratan kadar tablet tersebut menurut FI IV: tidak kurang
dari 93,0% dan tidak lebih dari 107,0% dari jumlah yang tertera
pada etiket, apakah kadar tablet tersebut memenuhi syarat?
Jawaban Soal: Tab. Klorfeniramin Maleat
(Lanjutan)
Catatan, Beckett & Stenlake: Destilat ditampung dalam asam sulfat 0,1N, titrasi dengan natrium
hidroksida 0,1N, indikator merah metil.
Penetapan Kadar Steroid <631>
Steroid dengan gugus α-ketol (-CHOH-CO-)
Prinsip
Steroid dengan gugus α-ketol, dalam suasana basa mereduksi
senyawa tetrazolium membentuk senyawa berwarna formazan
yang ditetapkan secara spektrofotometri.
Senyawa Tetrazolium
- FI IV : BT (Blue Tetrazolium), dengan steroid α-ketol
membentuk diformazan (ungu), diukur pada 485 nm.
- BP 2001: TPTZ (Triphenyl Tetrazolium Chloride), dengan steroid
α-ketol membentuk trifenil formazan (merah), diukur
pada 525 nm.
Penetapan Kadar FI IV
Penetapan Kadar Boraks,
hal.605 (Asidimetri)