Transcript 2 g on 1 l of solution

Injection dosage form
with stabilizers
Author:
as. Yu.Yu. Plaskonis
Injection dosage forms - a specific group of
drugs that require special conditions of
preparation, the strictest adherence to
aseptic,
technological
discipline,
full
responsibility for the preparation, quality
control and design to dispensing drugs.
Injection solutions are prepared in
aseptic unit
Aseptic conditions - defined conditions, and
complex institutional arrangements required
to enable to save the drugs from getting into
these microorganisms.
Technology process of preparation of
solutions for injection consists of the following
stages:
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Preparation of aseptic unit and the organization of work
in aseptic conditions.
Preparation of vessels and auxiliary materials.
Preparation of solvents and drugs.
dissolved drugs.
stabilization or isotones solutions
Quality control solutions.
Filtering solutions to filling bottles, checking the
absence of mechanical inclusions.
closing, leak check, preparation for sterilization
(marking).
Sterilization.
Quality control and design of drugs to leave.
Preparatory work
Solutions
preparing by
volumetric- mass in
which medicines
taken by weight, and
solvent added to
obtain the desired
volume of solution.
Dissolution
Stabilization solutions when necessary
Stability is achieved by adding stabilizers or
use of special methods of preparation.
Analysis
Filtering solutions
Corking bottles
Sterilizationsolutions exposed
within 1,5-2 hours
after manufacture.
The only exception
is glucose, which
sterilized
immediately after
production.
Stability of drug injection is achieved
compliance with the aseptic conditions of
their preparation, choice of optimal conditions
(temperature, time) sterilization, antimicrobial
use valid tools to achieve the effect of
sterilization at lower temperatures and also
the use of stabilizers - substances that
enhance the chemical stability injecting drugs
in the solutions.
Stabilizers can be divided into three
groups:
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substances that provide chemical
stabilization - antioxidants that prevent
oxidation.
substances that prevent the hydrolysis
of salts and esters saponification.
Antiseptics providing microbiological
stabilization.
№
Name of matter which needs to be stabilized
Stabilizator
1
Solutions of salts, formed by weak bases and
strong acids (atropine sulfate, Scopolamine
hydrobromide, cocaine hydrochloride,
pilocarpine hydrochloride, Novocain, Strychnine
nitrate, Dibazol et al)
Acid hydrochloride (HCl) -10 ml a 0,1
M solution on 1 l
Novocain of 0,25% - 3 ml a 0,1 M on 1
l
Novocain of 0,5%- 4 ml a 0,1 M on 1 l
Novocain of 1% - 9 ml a 0,1 M on 1 l
Novocain of 2% - 12 ml a 0,1 M on 1 l
2
Solutions of salts, formed by strong bases and
weak acids (sodium nitrite, caffeine- benzoate of
sodium, sodium thiosulphate, euphillin)
Sodium hydroxide (NaOH) 0.1 M
10%, 20% caffeine- benzoate of
sodium- 4 ml 0.1 M on 1 l
30% caffeine- benzoate of sodium- 20
ml 0.1 M on 1 l
3
Solutions of easily oxidable matters (acid
ascorbic, vicasol, sodium salicylate, streptocide,
adrenalin hydrotartrat)
Streptocide 5%, 10% - sodium sulfit
2 g on 1 l of solution
Sodium salicylate 10% -sodium
metabisulfite- a 1 g on 1 l of solution
Acid ascorbic 5% - sodium
metabisulfite- 2 g on 1 l of solution
4
Solution of glucose
A stabilizator of Weibel (is
composition: sodium chloride- 5,2 g,
acids chloride - 4,4 ml water for the
injections to 1 l. Stabilizator is added
by 5% from the
volume of solution, which needs to be
stabilized.
The main changes in drugs are
chemical processes:
• oxidation
• hydrolysis
• isomerization
Oxidizing substances
Oxidation are medicinal substances of
different chemical structure: - derivatives of
aromatic amines, fenotiazin, many salts of
alkaloids, salts of bases, vitamins and other
substances containing phenolic , alcohol,
carbonyl groups, amino groups mobilize with
hydrogen atoms.
Oxidation process can be slow in ways:
 a) introduce a substance that rapidly
reacts with alkil radicals, resulting in
peroxide will become only part of the
radicals;
 b) enter the compound, which quickly
reacts with peroxide radicals. This will
reduce the rate of formation of peroxides
and radicals regeneration;
 c) enter Substances that Deplete hydro
peroxide RООН.
Pharmacy used antioxidants that
slow oxidation and prevent the formation
of active radicals. The most effective of
them
are
phenols,
naftolum,
aminofenolum, aromatic amines.
Effective antioxidants are substances
that deplete hydro peroxide (sodium sulfit,
sodium meta-bisulfit, tiosechovyna, ronhalit,
unitiol)
But there are other antioxidants, such as
paraaminofenol, ascorbic acid. .
It is known that redox processes
strengthened influenced by several factors
such as the presence of heavy metal ions,
pH value, oxygen, temperature, etc.
Stabilization easily oxidation substances
are holding a set of measures:
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Introduction of antioxidants (for binding
oxygen).
Introduction of chelating agent (for binding
heavy metal ions).
Creating boundaries pH optimum solution with
acids (hydrochloric, citric, ascorbic).
Removal of oxygen in solvent and in the air
above the solution (boiling, filling bottles to the
top, saturating the solution with carbonic acid,
filling bottles in current inert gas).
Rp.: Solutionis Acidi ascorbinici 5% 50 ml
Sterilisa!
Da. Signa
TECHNOLOGY
stabilize ascorbic acid solutions introduction antioxidant
sodium metabisulfitis 1 g per liter or solution or sodium
sulphite anhydrous 2 g per 1 liter. In addition, solutions of
ascorbic acid strongly acidic. In order to neutralize the
environment of the sodium carbonate solution is introduced
23.85 g per 1 liter. Solution of sodium that is formed,
askorbinat is pH 6-7.
In aseptic conditions in sterile volumetric flask dissolve
2.5 g of ascorbic acid, 1.19 sodium hydrogen carbonate and
0.1 g anhydrous sodium sulphite in part freshly prepared
water for injection. After the allocation of gas bubbles make
up the solution to 50 ml, mixed, filtered in sterile bottles and
sterilized at 120 ° C 8 min. Issuing labels "for injection",
"aseptically”.
WPC (front side)
Date
№ рецепта
Natrii sulfitis anhydrici 0,1
Acidi ascorbinici 2,5
Natrii hydrocarbonatis 1,19
Aquae pro injectionibus ad 50 ml
Vобщ = 50 ml
Sterilis
Prepared:
Signature
Checked:
Signature
Hydrolysis - a reaction of ion exchange
between drugs and water. Hydrolysis are
different classes of compounds: alkaloids,
glycoside,
vitamins,
esters,
proteins,
carbohydrates and especially salt. Hydrolysis
are only salt in which one or both
components are weak.
Hydrolysis of salts formed by weak base
and strong acid, and their stabilization.
This group includes salts of
alkaloids containing synthetic nitrogen
bases (solutions of salts of novocaine,
dybazol, strychnine nitrate, etc.)..
This group of salts stabilize adding 0.1 M
solution of hydrochloric acid, since
excess hydroxyl ions (OH +3) reduces the
degree of dissociation of water and
suppresses hydrolysis, causing a shift of
equilibrium to the left.
Recommended stabilize hydrochloric
acid solutions Apomorphini g / h, atropini
sulfate, dybazoli, novocaine, spazmolityni,
strychnine nitrate, cocaine g / s, dykayini.
Stabilization of solution for injection,
representing the salt of weak bases and
strong acids by 0.1 M hydrochloric acid
solutions. Examples are the solution of
novocaine.
Rp.: Solutionis Novocaini 0,5% 100 ml
Sterilisa!
Da. Signa
For stabilization the 0.5% solution
of novocaine 0.1 M hydrochloric acid
solution to pH 3,8-4,5 taking 4 ml per 1 liter of
solution. Sterilizing at 120С 8 min.
Issuing blue label "for injection", which
indicate:
solution of novocaine 0.5% 100 ml for
infiltration anesthesia, aseptically.
WPC (front side)
Date
№ recipe
Aquae pro injectionibus 100 ml
Novocaini 0,5
Solutionis Аcidi hydrocarbonici 0,1 M gtts. VIII
Vобщ = 100 мл
Sterilis
Prepared:
Checked:
Signature
Signature
Hydrolysis of salts formed a strong base
and weak acid
These are solutions of caffeine-sodium
benzoate, sodium thiosulfate, sodium nitrite.
In this case, hydrolytic processes
enhanced in an acidic environment. To
suppress hydrolysis is necessary: a weak
alkaline medium by add-ing 0.1 M sodium
hydroxide and adding sodium hydrogen
carbonate.
For stabilization of 1 liter of 10 and 20%
solutions of caffeine-sodium benzoate SPh
Ukraine X edition recommends adding 4 ml of
0.1 M sodium hydroxide and 30% sodium
thiosulfate as a stabilizer is added sodium
hydrogen carbonate (20 m per 1 liter).
Stabilization of glucose
For stabilization
glucose added
stabilizer Veybelya, prepare for the words:
Natrii chloridi 5.2 ml
Hydrochloric acid divorced 4.4 ml
Water for injection to 1 liter
When preparing glucose, regardless of its
concentration, stabilizer added 5% by
volume solution.