Pharmaceutical technologies | THE CHAPTER 23

The Chapter 23  Technology inektsi Preparations.
 Description the technological circuit of the manufacture realizing Vacuum technology.  Comparative the characteristic of the equipment Lines ÂÎSÑÍ and 3060 and circuits. Clearing of solutions.
Medicinal forms for injections.
LF for injections - group LF, entered into an organism with the help A syringe with infringement of an integrity of integuments or mucous Shells. GF XI: to inektsionnym LF concern sterile water and Not water solutions, suspensions, emulsii and dry firm substances (powders and tablets) which dissolve sterile water Directly ahead of introduction. Inektsionnye solutions V ≥ 100 Ml - infuzionnye.
the Syringe of a modern design has been offered in 1952ã. by the doctor Pravatsem. Depending on a place of introduction injections are applied Different kinds: intraskin, hypodermic, intramuscular Intravenous, spinal, intracranial, vnutribrjushinnye, Intrapleural, intraarticulate, injections in a cardiac musle and Other
Recently it is offered bezygolnyj a painless method Introductions of medical products. He is based on ability Jets of substance with the greater kinetic energy to overcome Resistance and to penetrate into fabrics.

(+) the parties inektsionnogo introductions medicinal substances:
speed of action (in some seconds);
an opportunity of introduction to the patient in a unconsciousness;
medicinal substances are entered, passing such protective barriers An organism, as a gastroenteric path and a liver promoting To destruction of medicinal substance; hence, injections Provide accuracy of batching;
introduction of medical products for which another is impossible A way (insulin, the some people a/b, hormones);
an opportunity of localization of action of medicinal substances;
full snimanie sensations with unpleasant taste and smells Medical products.

(-) the parties:
whereas medicinal substances are entered besides protective A barrier of an organism, there is a serious danger of entering Infections;
at introduction of solutions in blood there is a danger embolii, Owing to hit of firm particles or puzyrkov air, O Which exceeds O fine vessels. At embolii vessels, pit. The oblong brain or heart, is possible a lethal outcome. (embolija - corking).
Introductions infuzionnyh solutions it is direct in a fabric can To call shifts of osmotic pressure, rN, etc. - a sharp pain, Burning, sometimes the feverish phenomena.
Some kinds of injections demand high qualification The medical personnel (spinal, intracranial, etc.)

the Basic requirements to inektsionnym to solutions (see previous Lecture):
sterility - full absence viable microorganisms;
àãèðîãåííîñòü;
äîëæíû to be transparent in comparison with water or others Solvents;
stability at manufacturing and storage. For increase Stability some solutions prepare with stabilizers.
Solvents - water for injections, fat oils, etilomat, spirit etilovyj, glycerin, propilenglikol, polietilenoksid 400, benzilbenzoat, benzilovyj spirit, etc.
Auxiliary substances - preservatives, antioxidants, Stabilizers, emulgatory, soljubilizatory and others specified in FS.
Medical products for vnutripolostnyh, intraintimate, Intraocular injections should not contain some preservatives.

the Technology inektsionnyh preparations represents complex Multiphasic manufacture, include as the basic, and Auxiliary processes.






Now, due to systematic development of technics, for Process ampulirovanija automatic product lines are created. Creation of such lines allow to exclude completely almost Physical work of the person, having left behind it only function of supervision Behind process. Since 50 engineers and inventors of all countries The world, search for the comprehensible decision of construction of lines ampulirovanija.
In the conducting capitalist countries for ampulirovanija use shirokogorlye ampoules that causes shpritsevuju technology. In A domestic production it is applied basically vacuum Filling.

the Description of technological process on automatic transfer lines ampulirovanija f. ÂÎSÑÍ.
Empty cut off and set in special metal The bunker of an ampoule « a throat upwards » move on a loading table The washing machine, it is removed zhaljuzijnaja zaslonka, and ampoules move Under a pressure in a zone of immersing for filling with water and the further Scoring. Special distributive shnekom the machine Provides rjadnoe pozitsionirovannoe an arrangement of ampoules for Further their putting on on syringes of a washing drum, where Their washing by hot distilled water is provided with The subsequent purge of filters. On the termination of process of an ampoule Are blown off from needles and further by a continuous stream « a throat upwards » Go to the sterilizing tunnel, where at t=350? C in The laminated stream of hot sterile air of an ampoule Pass zones of heating and sterilization and further get in a zone Coolings. The sterile cooled ampoules on an output from installation Get on transport system of submission in the machine of filling and zapajki which is closed by the laminated stream sterile Air.
In machine AVR for filling and zapajki the basic are provided Operations:
exact, dosed out filling;
replacements of environment by inert gas (if necessary);
zapajka a capillary of an ampoule a method of a delay mechanical ticks.
the Filled and sealed - in ampoules on the conveyor move « a throat Upwards » on operation of coding. The given operation is An obligatory condition of output, otvevajushchejsja world To standards.
the Basic purpose of coding - provides conformity of filling A solution rendered on an ampoule and further on packing of the information, Exception pereputyvanija and substitutions of solutions in an ampoule on Operations of packing.
In the domestic industry the given operations are absent.
Check of the filled ampoules in technological process passes 2 Stages of the control (except for bakter. prov and on quality of a solution):
on tightness of ampoules;
on presence of mechanical inclusions in a solution.
the Machine supervising on tightness, allows to reveal Microcracks. The way of the control of mechanical inclusions is High-speed also allows to exclude manual skills used at us.
After the control ready ampoules with a solution act on operation Marks or etiketirovki. In the conducting countries marks of ampoules It is carried out by 2 ways:
drawing of the information before otzhigom ampoules (right after Manufacturing) with reception high-quality and fixed Marks.
the Label of labels after operation zapajki with use sticky Transparent plenok.
After that there is an operation of packing.

the Circuit mojki on a line f. "SHtrunk" (Q = 18 thousand - 20 tys./ch)
filling of ampoules with water - 1ñ
scoring by ultrasound - 12ñ
opolaskivanie water 2 ts on 2ñ - 4ñ
blowing off - 2ñ
mojka distilled water - 2ñ
blowing off 3 ts on 2ñ - 6ñ
----------------
only 28 sek

Mariupol line AP - 25Ï 30000 ampoules / ch (1 - 2 ml)
the Line 3060 - for ampoules of 10 and 20 ml
13200 ampoules / ch V = 10ìë and 8600 ampoules / ch V = 20ìë
Service: 2 persons.
Carries out 12 technological operations:
1. mojka an external surface of ampoules (dushir. Hot water);
2. mojka an internal surface of ampoules with scoring Ultrasound from above;
3. mojka an internal surface with scoring by ultrasound From below;
4. opolaskivanie ampoules;
5. drying (without sterilization);
6. cooling of ampoules;
7. filling;
8. revolution of technological cartridges on 180?;
9. prodavlivanie a solution in capillaries of ampoules and gas protection A solution;
10. dushirovanie capillaries of ampoules;
11. zapajka ampoules;
12. movement of cartridges from one operation on another.

the Description of the technological circuit of the manufacture realizing Vacuum technology.
(the line 3060 Mariupol ZMTO)
For realization of a vacuum way of filling of ampoules is intended Robotized, a line 3060 which are carrying out operations mojki - dryings - fillings - zapajki, leaving for the operator of function of the control And managements of process.
For sterilization of ampoules - installation AP 18, however, loading and A unloading of carriages industrial manually. Lack of a line Domestic - absence of the technical decision on continuous Sterilizations. The control of ampoules - visual. After viewing goes Operation of packing.


the Comparative characteristic of the equipment of line ÂÎSÑÍ and 3060 and Circuits.
SHpritsevoj and ultrasonic methods mojki. Ultrasonic and parakondensatsionnaja mojka. Ultrasonic mojka allows "To beat off" Parakondensatsionnaja mojka much more effek-
mechanical pollution - it is often. Glasses. tivnee, than shpritsevaja, That the pain
Presence of system of a water-revolution inside necks of impurity initial speaks drota and low
machines, i.e. used on last quality domestic Technologies izgotov -
operations fresh distilled water lenija ampoules.
it is not dumped, and is going to in collection P/k mojka in known To a measure it is compensated
and the pump it is pumped over through the filter by operation by sterilization Empty ampoules.
sterile kill (f. ÐÀLL) on
the previous operation of washing.


2. Drying and sterilization of empty ampoules.
l. ÂÎSÑÍ l. 3060
Sterilization of empty ampoules abroad - In a line of sterilization not Enters. Necessary
obligatory process. Used la-sterilization to make In through passage it is dry -
minarnye streams of sterile air an air sterilizer at t=180? C τ=60ìèí
ãîðÿ÷åãî, that allows: - to provide Lacks: temperature in Different zones
uniform distribution of temperatures neodinakova.
- effect of removal pirogenov; In a sterilizer gets not Sterile air.
- the big degree of cleanliness.
Air - through the sterile filter.


3. Filling of ampoules (approximately on 10 % more nominal)
l. ÂÎSÑÍ l. 3060
device AVR device AP-4M2
SHpritsevoj the method is carried out with the help the Vacuum way. In The case ukreplena capacity
piston dozatora. Some needles lower with a false bottom and The bottom descent with the valve
inside of ampoules, occurs their filling rast-for an output in A reception tank. The cartridge with an ampoule
the thief, for easily oxidized - by a principle lami capillaries downwards Establish inside
gas protection. In the beginning in shipped in ampu-the device on emphasises, A cover close, sozda -
lu a needle submit inert gas and thus jut vacuum. The valve Close. To capacity submit
air, then a solution and again a solution is superseded from it and Create the vacuum corresponding tre-
inert gas and ampoules immediately submit on zapajku buemomu to volume Fillings. After filling
(+) shpritsevogo a method: ampoules vacuum extinguish submission sterile vozdu-
- high accuracy of batching (yo 2 %); hom. Stayed in capacity A solution merge - capillaries do not become soiled, that is especially important For regeneration by inert gas for gas for dense and viscous Solutions; protection submit instead of air.
- the charge of inert gas in minimal kolichest-(+) vacuum A method:
vah; - high efficiency;
(-): - complexity of orientation of a needle at introduction in (-):- Insufficiency of a dosage of a solution in an ampoule; ampoules;
- small productivity - low % of use of a solution,
(till 10 thousand ampoule / hour) taking place in the device and demanding
re-filtering.

Àñàsåðtiñ.
ë. ÂÎSÑÍ it is completed with special compact installation with A sterile premise - Àñàsåðtic. System Asasertic Represents special boxing which will consist from Locker rooms, zones for putting on of sterile clothes and the worker Premises for filling and zapajki ampoules (a class 100). Ventsistema provides a constant exchange of air and compensates Allocation of heat in sterile premises. Telecommunication with The help of an intercom. Loading and a unloading of ampoules- Outside of sterile premises. System Asasertic will consist from easy Mounted tight elements. The general charges on the organization 1 class of cleanliness (a class 100, a class "And")
system Asasertic a usual variant of a sterile premise
140 % 400 - 600 %
Conclusions: the Analysis of technology and the equipment, issued abroad Shows, that the most modern and automatic is l. ÂÎSÑÍ. However in the country this equipment works for us Unsatisfactorily because of poor quality of initial ampoules. Because of Poor quality stekloampul domestic shpritsevaja technology Does not receive a wide circulation. At the same time provides Sufficient quality of a ready product at high hour Productivity on lines of vacuum filling.

Preparation of solutions. Water solutions inektsionnyh preparations Prepare on apirogennoj to water.
Apirogennuju water receive from water cleared special akvadistilljatorah. The pharmacopoeia the USA XX allows, besides Return is used osmos. Basic aquadistillers sites The evaporator, the condenser and the collection is. And, Application of film evaporators is constructive The decision of a question of improvement of quality of distillate, when not Occurs perebrosa the drop phase, containing pirogeny, from The evaporator in the condenser and the collection. By a principle film The evaporator 3 case installation - akvadistilljator works « Finn - Aqua ».

Clearing of solutions - is carried out in 2 stages:
1-n a stage - rough kill (deletes particles of more than 50 microns) On druk-filters and nutch-filters.
2-n a stage - for the bill membrannogo filtering. On a design A filtering element - disk and cartridge. O por 0,002 - 1 A micron.
Domestic installation ÓÏË-0,6; ÓÏÂ-0,6; ÓÏÂ-6- Ultrafiltering installations on polyh fibres. Polye fibres (a material - aromatic polyamide) are typed in a bunch in Glass cylinders of various height - columns. One column The device dividing is called: AR.
are abroad issued membrannye installations by firms: "Millipor", "Pall", "Sartorius", etc.

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