INTRODUCTION: – In pharmaceutical industry it is vital that package selected preserve the integrity of product. The selection of package begins with determination of products physical & chemical characteristics. Quality control of a packaging component starts at design stage. All the aspects of a pack development may give rise to quality problems. It must be identified & minimized by performing quality control tests.
QUALITY CONTROL TESTING & STANDARDS: – The packaging materials are classified into two classes,
- Primary:- ampoules, vials, plastic bottles, polymer-coated foils.
- Secondary:- cartons, labels, leaflets
PRIMARY COMPONENTS: –
Setting the standards:- Several distinct areas are taken in to concern for setting the standards,
3.Compatability & customer usability
A suitable Acceptable Quality Limit (AQL) is set for the major and minor categories. An AQL must not be set for critical defects since these are unacceptable at any level. A tighter AQL will be set for major defects (eg: 0.65AQL) than for minor defects (eg: 2.5 AQL)
DIMENSIONS: – The dimensions can be separated in to two types: –
The critical dimensions for each compound are as follows
Vial:- Flange depth, flange diameters, bore diameters, vial heights, body diameters, wall thickness, base thickness, & verticality.
Rubber Plug:- Flange depth, flange diameters, & plug diameters.
Aluminum Overseal:- Internal skirt depth, external diameter, and aluminum thickness.
MEASURING COMPOUNDS:- Various measuring equipments used are:-
- Optical Projector
OPTICAL PROJECTOR:- To measure flange depth or neck height an optical projector is the best choice of equipment.
CALIPERS FITTED WITH SPECIAL JAWS:- The jaws must be exactly vertical to the wall surface to obtain an accurate measurement.
MICROMETER:- A different set of jaws will be required for each plug size to be measured. The ideal size of micrometers for this purpose is 25-50mm.
CAPABILITY AND CUSTOMER USABILITY:-
Eye dropper pack:- Nozzle must have good interference fit in to the bottle & allow one drop at a time though nozzle hole when inverted. No leak should be noted. Cap should be capable of begin removed by customers easily.
CHEMICAL TESTING: Glass container
IMPORTANT CHEMICAL TESTS :-
- Hydrolytic resistance test.
- Water attack test.
- Powdered glass test.
- Light transmission test.
- Arsenic test
HYDROLYTIC RESISTANCE TEST:- Determine average overflow volume. Auto clave at 121 ° C for 60 minutes. Combine the liquid from container being examined. To 50ml liquid add 0.15 ml methyl red solution and titrate to 0.01 M HCL. Repeat the same with freshly prepared distilled water. The difference between the two represents 0.01M HCL required by test solutions.
DISTINCTION BETWEEN TYPE I AND TYPE II:- Rinse the container twice in distilled water. Fill completely in 4% v/v solution of hydrofluoric acid, allow to stand for ten minutes. Empty and rinse the container five times in water. Carry out procedure same as hydrolytic resistance. Compare results in limiting values given in table -1.
For type I glass values obtained in HF treated containers are closely similar to type I /type II.
For type II glass values obtained in HF treated containers greatly exceed those given in table for Type I/ Type II similarly to those given in Type III.
Water attack test:- Mainly done for treated soda lime glass.
Light transmission test:- Measure the transmission in reference to air at spectral region of 290nm to 450nm. The observed light transmission for colored glass containers for preparation not for parental use does not exceed 10% at any wavelength. Observed light transmission for colored glass containers for parental preparation does not exceed the limit in the table.
Result is not greater than value stated in table.
TEST FOR ARSENIC:- The absorbance of test solution does not exceed the absorbance obtained by repeating the same with 0.1ml arsenic standard solution (10ppm) in place of test solution (0.1ppm).
OTHER IMPORTANT TEST FOR GLASS CONTAINER:-
Thermal shock test:- The samples are placed in an upright position in a tray which is immersed into hot water for given time, then transferred to cold water bath. Samples are examined before & after the tests for outside surface cracks or breakage.
Internal bursting pressure test:- The test bottle is filled with water & then placed inside the test chamber. A sealing head is applied & the internal pressure automatically raised by series of increments. Each increment is held for a set time. The bottle can either be checked to a pre-selected pressure level or the test continued until the container finally bursts.
Annealing test:- The sample is examined by polarized light in either a polariscope or strain viewer. The strain pattern is compared against standard discs or limit samples.
Vertical load test:- The bottle is placed between a fixed platform & a hydraulic ramp platform which is gradually raised so that a vertical load is applied. The load is registered on pressure gauge.
Autoclaving (121 ° C for 60 min):- Ability of a filled or empty container to withstand autoclaving may be checked.
AMPOULES: – Testing of Ampoules sealing:
- Head space oxygen
- Sealed Ampoules length
- Quality of seal
PLASTIC CONTAINERS:- Plastic containers can be mainly categorized as:-
- Thermosetting plastics (cannot be remelted)
- Thermoplastics (can be reprocessed)
WHO guidelines on selection of plastics on pharmaceutical preparations.
INFUSION AND INJECTIONS:-
- Physicochemical on aqueous extracts
- Nonvolatile residue, heavy metals, buffering capacity, reducing substances
- Biological invivo
- Acute systemic toxicity in mice
- Intra cutaneous test (rabbits), cardiovascular (cat) toxicity infusions
- Biological invitro
- Hemolytic effect of aqueous extracts
AQUEOUS OPHTHALMIC PREPARATION: –
- Physicochemical on aqueous extracts
- Non volatile residue, buffering capacity, reducing substances
- Biological test on aqueous extracts
- Eye irritation in rabbits on repeated instillation (Draize test)
PHYSICOCHEMICAL TEST ON AQUEOUS ON EXTRACT:-
- Light absorption
- Non-volatile matter
- Residue on ignition
- Heavy metals
- Buffering Capacity
- Oxidizable substances
Systemic injection test:- Test animal:- Albino Mice
Inject each of 5 mice in test group with sample or blank observe the animals immediately, again after 4hr & then at 24, 48, 72hrs. If none of animals shows significant greater biological reactivity than the blank the sample meets the requirements. If abnormal behavior such as Convulsion or Prostration occurs or if body weight loss is greater than 2g, the sample does not meet the requirements.
Intra cutaneous test:- Test animal:- Rabbit
Examine the sites of for any tissue reaction like erythema, edema, neurosis at 24, 48, 72 hours after injection.
- Limit:- difference between the scores of sample and blank should be lesser than 1.0.
Eye irritation test on rabbits:- Test animal:- albino rabbits
- Limit:- Sample extract shows no significant irritant response during the observation period with blank extract.
RUBBER CLOSURES:- Rubber closures are used to seal the cartridges, vials and bottles, providing a material soft and elastic enough to permit entry & withdrawal of a hypodermic needle without loss of integrity of sealed container.
QUALITY CONTROL TESTS:-
Fragmentation test:- This test is applicable to closure intended to be pierced by a hypodermic needle & the closures used for aqueous preparation.
Self-sealability test:- This test is applicable to closures intended to be used in multi dose container.
QC TEST FOR COLLAPSIBLE TUBES:
- Leakage Test
- Lacquer Curing Test
- Power of Adhesion
- Flexibility Test
- Lacquer compatibility test
- Product Compatibility
- Lacquer Compatibility
QUALITY CONTROL FOR METALLIC TINS:- Protocols of test:
Limit:- Specimen metallic tins with tolerance 170mm ± 10mm.
- Inner diameter:- Limit:- It should not be less than 98mm.
- Outer diameter:- Limit:- NMT 105mm.
QUALITY CONTROL TEST FOR STRIP & BLISTER PACKAGING:- The strips & blisters were placed inside the desiccator & vacuum was applied. After sometime vacuum was released & strips, blisters were taken out. The water present over the outer surface of the packages was wiped off with tissue paper. The contents of strips & blister packages were removed & the presence of moisture was checked. If there is no leakage, the contents will not be wetted. This indicates the perfect sealing of packages.
Testing of Paper & Board:- The test pieces for paper & board are conditioned for the tests to be carried out in standard conditions. Those conditions are Temperature – 23 ° C ± 1 ° C, Relative humidity – 50% ± 2%.
TEST FOR CARTONS:-
- Compression:- This method is used to assess the strength of erected package.
- Carton opening force:- The method is used to hold the flat carton as delivered, by its creases between thumb & first finger press.
- Coefficient of friction:- Both static & kinetic coefficients of friction are determined by sliding the specimen over itself under specific test conditions.
- Crease stiffness:- This involves testing a carton board piece & folding it through 90 ° . It will then try to recover its former position when bending force is removed.
- Joint shear strength:- This is a method of testing the glued lap seam on the side of a carton for strength of the adhesive using a tensile testing machine.
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