Kul Csp 2013 Solution
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Transcript of Kul Csp 2013 Solution
8/13/2019 Kul Csp 2013 Solution
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Karakteristik larutan…
Penyusun larutan : solut dan solvent
Keuntungan larutan;
1. Nyaman utk pediatric dan geriatric2. Efek lebih cepat dibandingkan sediaan…
3. lebih homogen dibandingkan suspensi atau
emulsi
4. Mengurangi efek samping obat yg iritatif thdsal cerna jika tdk diberikan dalam btk larutan
(aspirin, KBr)
5. Flexible dose
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1. bulky
2. sulit menutupi rasa/bau yg tidak enak utk
obat tertentu
3. takaran kdg2x sulit utk tepat dosis 4. stabilitas < sediaan padat
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Solvent : aqeous (keuntungan &
kerugiannya ??),
macamnya: (potable water, pharmacopeal
purified water, aromatic water)
non aqeous (fixed oil/vegetable oil, alkohol,
micellaneous: gliserol, propilenglikol)
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Bagaimana larutan bisa terbentuk ?
(solut terion solvated/hidrated
Intermoleculer interaction
Bedakan antara terlarut (dissoloved) dan
terjadinya reaksi……
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Faktor penting yang perlu diperhatikan dlm
pembentukan larutan :
solubility
stability
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dissolution rates generally increase with:
a. smaller particle sizes
b. effective stirring
c. lower viscosities
d. increased temperature.
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1. Buffers
2. Viscosity enhancer
3. Preservative (syarat nya:……
1. effective against a wide spectrum of
microorganisms
2. stable for its shelf life
3. non toxic, non sensitizing4. compatible with the ingredients in the
dosage form
5. free of taste and odour
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1. gol. Alkohol (etanol, propilenglikol)
2. acid (as. Benzoat, as. Sorbat)
3. ester (paraben = ester dari
parahidroksibenzoic acid, metil, etil,propil, butil), perhatikan pH efektifnya…..
4. gol. Ammonium kuarterner (Benzalkonium chloride )
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Agent pH Range
Benzoic acid 2.5-4.0
Sorbic acid 3.0-6.5
Proprionic acid 2.5-5.0
Acetic acid 3.0-5.0
Parabens 3.0-9.0
Sulfites 2.5-5.0
Nitrites 4.0-5.5
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4. Antioxidants (propil &oktil ester dr asam galat,tokoferol, sod sulfit, ascorbic acid)
oksidasi dpt diinisiasi oleh heat, light , heavy metal (solusi……)
5. Sweetening agentsex: Sucrose
Advantages: Colourless, highly water soluble, stable over awide pH range (4-8), increase the viscosity, masks both saltyand bitter taste, has soothing effect on throat.
Polyhydric alcohols (sorbitol, mannitol and glycerol)possess sweetening power and can be used for diabeticpreparations.
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6. Flavours and perfumes
Natural products: fruit juices, aromatic oil
(peppermint, lemon)
Artificial perfumes are cheaper, morereadily available and more stable than
natural products.
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physical and chemical stability
clarity, colour, odour, taste and viscosity over
its shelf life.
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1- Loss of flavour
2- Change in taste
3- Presence of off flavours due to interaction
with plastic bottle 4- Loss of dye
5- Precipitation
6- discoloration
The effect: Change in smell or feel or taste
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COOHO
CH3
OH2
COOH
OHCH
3COOH+
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Dissolved O2 from air
Catalyzed by trace transition metals
Cu, Ni, Fe, Mn, Co, etc.
Contaminants from drug and solutes from which
solution was made
Ex: captopril
Strategies
Purge with inert gas, usually N2
Antioxidants, EDTA (chelates free metal ions)
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NSH
CH3
O
HOOC
N NS
CH3
O
HOOC
S
CH3
O
COOH
O2
Cu2+
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Dapat dicegah dengan:
1- suitable packing in amber coloured bottles
2- cardboard outers
3- aluminium foil over wraps
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1- pHThe acidity or the alkalinity of a solution hasa profound influence on the decomposition
of drug compound.- Aspirin buffered solution is maximum stable
at a pH of 2.4, above a pH of 10 thedecomposition rate rapidly increases.
pH can also influence the rate of oxidation.
- The system is less readily oxidized when thepH is low.
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2- ComplexationComplex formation reduces the rate of
hydrolysis and oxidation.
e.g. caffeine complexes with local anesthetics,such as benzocaine, procaine and tetracaime
to cause a reduction in their rate of
hydrolytic degradation.
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3- SurfactantsNonionic, cationic and anionic surfactants
when added to solutions containing drugs
form micelle and the drug particles becometrapped in the micelle.
The hydrolytic groups such as OH cannot
penetrate this micelle cover and reach thedrug particles, hence hydrolysis rate is
decreased.
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4- Presence of heavy metals
Heavy metals, such as copper, iron, cobalt
and nickel increase the rate of formation of
free radicals and enhance oxidativedecomposition.
5- Light and humidity
Light, especially ultraviolet light enhances
photolysis and humidity enhances hydrolytic
decomposition.
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1- TemperatureAll the drug products are stored at suitable
temperatures to avoid thermal acceleration
of decomposition. Three varieties oftemperatures are suggested for storage ofdrug products. Room temperature, coolstorage and cold storage.
2- LightLight sensitive materials are stored in
ambered colour bottles.
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3- Humidity
Packing materials are chosen (usually glassand plastic) to prevent exposure of drugproducts to high humid condition.
4- Oxygen
Proper packing keeping the oxygen contentof the solution less and leaving very littlehead space in the bottle above the drugproducts are methods to fight againstoxidation.
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5- Chelating AgentsChelating agents form complexes with heavymetal ions and prevent them from catalyzing
oxidative decomposition.e.g. ethylenediamine tetracetic acid (EDTA)derivatives and salts, citric acid and tartaricacid.
6- SolventsBy the addition of a suitable solvent
hydrolysis rate may be decreased
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(1) suitably designing the containers
(2) usually using single dose containers
(3) sticking to proper storage conditions
(4) adding an antimicrobial substance aspreservative.
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1. gelas
2. plastik
Plastics
The problems with plastic are:1.Migration of the drug through the plastic into the
environment.
2.Transfer of environmental moisture, oxygen, and
other elements into the pharmaceutical product.3.Leaching of container ingredients into the drug.
4.Adsorption of the active drug or excipients by
the plastic.
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3. Metals
- Various alloys and aluminium tubes may beutilized as containers for emulsions,ointments, creams and pastes.
- Limitation: They may cause corrosion andprecipitation in the drug product.
- Overcome: Coating the tubes with polymersmay reduce these tendencies.
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4. Rubber
- Rubber also has the problems of extraction of
drug ingredients and leaching of container
ingredients.
- The pretreatment of rubber vial stoppers and
closures with water and steam reduces
potential leaching
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No dissolution phase
Major concern is physicochemical stabilityand interaction with other substances in GIfluid Change in pH
Dilution of cosolvent
Formation of insoluble complexes Ciprofloxacin with Fe2+, Ca2+, Mg2+ etc.
Viscosity of solution may slow absorption Assuming spherical drug molecule
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ƒ 6
kT kT D
r
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1. Simple Solution (by stirring or heating)
2. Solution by Chemical Reaction (by reacting
two or more solutes with each other in a
suitable solvent)3. Solution by Extraction (Plant or animal
products)