Requirements for Pharmaceutical dosage form containers

Every pharmaceutical preparation must comply with the labeling requirements laid down in the WHO guidelines on GMP for pharmaceutical products.

Tablets. 

These should be kept in well-closed containers and protected from light, moisture, crushing and mechanical shock. Any special storage conditions should be stated on the label. Tablets should be able to withstand handling, including packaging and transportation, without losing their integrity. Moisture-sensitive forms, such as effervescent tablets, should be stored in tightly closed containers or moisture-proof packs, and may require the use of separate packages containing water-adsorbent agents, such as silica gel. Additional special recommendations for packaging, storage and transportation are specified in the relevant individual monographs. For effervescent tablets, the label should state “Not to be swallowed directly”.

Capsules.

These should be packaged and stored in a manner that protects them from microbial contamination. Capsules should be kept in well-closed containers. They should be protected from light, excessive moisture, or dryness, and should not be subjected to temperatures above 30°C. Additional special recommendations for packaging, storage and transportation are specified in the relevant individual monographs.

Parenteral preparations.

These are usually supplied in glass ampoules, bottles or vials, plastic bottles or bags, and prefilled syringes, which are colored in the case of light-sensitive substances. Except where otherwise indicated in the relevant individual monographs, the containers for parenteral preparations should be made from a material that is sufficiently transparent to permit the visual inspection of the contents. They should not adversely affect the quality of the preparation, allow diffusion of any kind into or across the container, or release foreign substances into the preparation. Closures for containers for parenteral preparations should be equipped with a firm seal to prevent the entry of microorganisms and other contaminants while permitting the withdrawal of a part or the whole of the contents without removal of the closure. They should not be made of materials that react with the contents, nor should they allow foreign substances to diffuse into the preparation. The elastomers of which the closure is made should be sufficiently firm to allow the passage of a needle with the least possible shedding of particles. Closures for multi-dose containers should be sufficiently elastic to allow the puncture to reseal when the needle is withdrawn and thus protect the contents from airborne contamination. On visual inspection, solutions, reconstituted solutions and intravenous infusions (except dispersions) should be clear and free from visible particulate matter.

Topical semi-solid dosage forms.

Containers for these dosage forms should be made from a material that does not adversely affect the quality of the preparation or allow diffusion of any kind into or across the container into the preparation. Closures for these containers should be of a design that minimizes microbial contamination and be equipped with a device that reveals whether the container has ever been opened. Containers for topical semi-solid dosage forms should protect the preparation from light, moisture, and damage during handling and transportation. The use of suitable metal or plastic flexible tubes is preferred. Preparations for nasal, aural, vaginal or rectal use should be supplied in containers adapted for the appropriate delivery of the product to the site of application, or should be supplied with a suitable applicator. Topical semi-solid dosage forms should be kept in well-closed containers. The preparation should maintain its pharmaceutical integrity throughout the shelf-life when stored at the temperature indicated on the label; this should normally not exceed 25 °C. Special storage recommendations or limitations are indicated in the relevant individual monographs.

High performance liquid chromatography (HPLC)

High performance liquid chromatography (HPLC)

High performance liquid chromatography (HPLC) is a very efficient separation technique, that is, it yields excellent separation in a very little period of time.

The inventors of modern chromatography, Martin and Synge (at 1941), in theory, the stationary phase requires very small particles and hence a high pressure is essential for forcing the mobile phase through the column. As end result, HPLC is also sometimes referred to as high-pressure liquid chromatography.

   

High performance liquid chromatography (HPLC) is a type of column Chromatography and it is used commonly in biochemistry and analytical chemistry’ to separate components of a mixture by using a variety of chemical interactions between the substance being analyzed (sample) and the constituent elements of column of HPLC.

 Fig: High performance liquid chromatography (HPLC)

Principle of HPLC 

The principle of HPLC is to force the sample through the column of the stationary phase by pumping the mobile phase at high pressure. The sample to be analyzed is introduced in small volume to the stream of mobile phase and the sample molecules are retained by specific chemical and physical interactions with the materials of the stationary phase as it travels the length of the column. The amount of retention depends on- (1) the nature of the sample, (2) the nature of the composition of the stationary phase and mobile phase. The time taken by the sample to travel from the point of injection to the end of the column is called the retention time and is considered an unique identifying characteristic of a given sample because no two compounds will have the same retention time (like no two persons can sit in a single seat / No single person can have two heads). The use of pressure increases the linear speed giving the components less time to diffuse within the column, leading to improved resolution in the resulting chromatogram. Common solvents used include any miscible combinations of water and various organic liquids (the most common are methanol and acetonitrile).

In HPLC separation, the compound that tend to reside in the mobile phase, move more quickly than those that prefer to reside in stationary phase. Phase preference can be expressed by distribution co-efficient, K:

         Cstat      

Kx=-------------  

        Cmob         

 Where,

C_stat= Concentration of compound X in the stationary  phase

C_mob= Concentration of X in mobile phase

K= Partition coefficient

Band Broadening

First Cause: Eddy Diffusion- The column is packed with small stationary phase particles. The mobile phase passes through and transports the sample molecules with it . Some molecules are fortunate and leave the column before most others by traveling an almost directly line path. Other sample molecules undergo several diversions along the way.

Second Cause: Flow distribution-The mobile phase passes in a laminar flow between the stationary phase particles (Fig 6). The flow is faster in the channel center than it is near the particle. Eddy diffusion and floe distribution may be reduced by packing the column with evenly sized particles (First remedy).

Third Cause: Sample molecule diffusion- in the mobile phase- It is also called longitudinal diffusion effect. Sample molecules spread out in the solvent without any external influence (Just like salt or sugar dissolves slowly in water). The longitudinal diffusion has a harmful effect if

(I)  Small stationary phase particles (<10 micron)

(ii) Low mobile phase velocity and

(iii) Large sample diffusion co-efficient etc coincide  in the HPLC system. This can be overcome by following Second remedy.

Fourth cause: Mass transfer between mobile, stagnant mobile and stationary phase- Pore structure of a stationary phase particle explain us that the channels are both narrow and wide, some channels pass through the whole of the particle  while others are stopped off (half way open and then closed). Half way open pores are filled with mobile phase and are stagnated. The recovery process may occur in two ways-(a) the molecules may diffuse back to the mobile flux phase .It depends on the size of pores and viscosity of the solvents used. (b) The molecules may interact with stationary phase and is adsorbed and then after sometime desorbed. Hence mass transfer takes place. In both cases band broadening decrease with increaseing mobile phase flow velocity. These effects can be overcome by Third and Fourth  principles.

Remedy:

First remedy: The packing should be composed of particles with as narrow a size distribution as possible (5:7.5=1:1.5)

Second remedy: The mobile phase flow velocity should be selected so that longitudinal diffusion has no adverse effect

Third remedy: Small particles or those with a thin, porous surface layer should be used as the stationary phase

Fourth remedy: Low viscosity solvents should be used

Mathematical expression of principle of HPLC

Mathematically the principle of HPLC is based on van Deemter theory (The rate theory) expressed as van Deemter equation. This theory employs a kinetic approach and explains band broadening in terms of a number of rate factors.

The van Deemter equation is:

                             2γD_G          8        k’              d_f²ū

  HEPT= 2λd_p +  ------------ +   ---     ----------      -------

                                ū              π²     (1+k’)²        D_L

            Eddy     Molecular      Non-equilibrium effect

            diffusion  diffusion

                 Axial diffusion

Where,

HEPT=Height Equivalent to Theoretical Plates

λ = a measure of the packing irregularities

d_p= Particle diameter, γ=Tortuosity (Full of twists and turns) factor

D_G=Coefficient of gaseous diffusion

D_L=Co-efficient of liquid diffusion                                                                                 

ū=Average linear velocity (Flow rate)

K’=ratio of the capacity of the liquid phase to that of the gas phase. For capillaries, k’=2kd_f/r

d_f-=Average film thickness, r=radius of the capillary

A = Eddy-diffusion, B =Longitudinal diffusion, C = Resistance to mass transfer 

POLYMERASE CHAIN REACTION (PCR)

POLYMERASE CHAIN REACTION (PCR)

The polymerase chain reaction (PCR) provides a simple and ingeneous method for exponentially amplification of specific DNA sequences by in vitro DNA synthesis. This technique was developed by Katy Mullis at Cetus Corporation in Emery Ville, California in 1985. Katy Mullis shared the Nobel prize for chemistry in 1993. This technique has made it possible to synthesize large quantities of a DNA fragment without its cloning. It is ideally suited where the quantity of biological specimen available is very low such as a single fragment of hair or a tiny blood stain left at the site of a crime. The details of PCR techniques and its mechanism are described by Erlich (1989) in his edited book 'PCR Technology'. The PCR technique has now been automated and is carried out by a specially designed machine.

Mechanism of PCR

STEP 1: Denaturation (Melting of Target DNA)

The polymerase chain reaction is a method for making many copies of a specific segment of DNA, starting with small amount. The DNA to be amplified is mixed with deoxyribonucleotides, Taq polymerase (a thermal stable DNA polymerase enzyme) and DNA primers (the DNA primers hydrizide to the end of the gene to be amplified & provide a starting point of Taq polymerase)

STEP 2: Primer Annealing

The mixture is heated to break down the hydrogen bond in the DNA Forming single-stranded molecules. The mixture cooled to allow the DNA primer to anneal to each end of the segment to be copied. The Taq polymerase then synthesized the complementary stands of DNA, using the primer as starting point.

STEP 3: Primer Extension (Polymerization) 

The temp. raised again to separate the Dna stands and then lower the temperature to allow the primers to attached. Taq polymerase now synthesis another set of new complementary stands. This process is repeated until enough DNA has been produced to be identified or used for further research.  After 21 cycles, one molecule of DNA can be amplified to over a one million copies. This amount of amplification can be achived by running the reaction in overnight a thermal cycler, and the instrument that automatically raised and lower the temp. appropriate time interval.

 Fig: POLYMERASE CHAIN REACTION (PCR)

Application of PCR

After the discovery of PCR, the modern biology has been revolutionized in each and every aspect. Some of the areas of application of PCR have briefly been discussed herewith.

01. Diagnosis of Pathogens: There are several pathogens that grow slowly. Therefore, their cells are found less in number in the infected cells/tissues. It is difficult to culture them on artificial medium. Hence, for their diagnosis, PCR-based assays have been developed. These detect the presence of certain specific sequences of the pathogens present in the infected cells/tissues. Besides, it is useful in detection of viral infection before they cause symptoms or serious diseases.

02. Diagnosis of Specific Mutation: In humans there are thousands of genetic diseases. Mutations are also related to genetic diseases. Presence of a faulty DNA sequence can be detected before establishment of disease. By using PCR sickle cell anaemia, phenylketonuria and muscular distrophy can also be detected. The other diseases can also be diagnosed by using PCR. For example PCR­based diagnostic tests for AIDS, Chlamydia, tuberculosis, hepatitis, human pappiloma virus, and other infectious agents and diseases are being developed. The tests are rapid, sensitive and specific.

03. In Prenatal Diagnosis: It is useful in prenatal diagnosis of several genetic diseases. If the genetic diseases are not curable, it is recommended to go for abortion.

04. DNA Fingerprinting: In recent years DNA fingerprinting is more successfully used in forensic science to search out criminals, rapists, solving disputed parentage and uniting the lost parentage       uniting children to their parents or relatives by confirming their identity. This is done through making link between the DNA recovered from samples of blood, semen, hairs, etc. at the spot of crime and the DNA of suspected individuals or between child and his/her parents/relatives.

05. In Research: In addition, DNA fingerprinting of new microorganisms isolated from various extreme environment (soil, water, sediments, air, extreme habitats, etc.) is also carried out to confirm their identity by comparin^g with the DNA sequences of known microorganisms. Their DNA and RNA can be amplified. Besides, it is also useful to determine the orientation and location or restriction fragments relative to one another.

06. In Molecular Archaeology (Palaentology): PCR has been used to clone the DNA fragments from the mummified remains of humans and extinct animals such as the woolly mammoth and dinosaurs from the remains of ancient animals as recently epitomized in Michel Crighton's Jurassic Park. DNA from buried humans has been amplified and used to trace the human migration that occurred in ancient time.

07. Diagnosis of Plant Pathogens: It is also applied in diagnosis of plant diseases. A large number of plant pathogens in various hosts or environmental samples are detected by using PCR, for example, viroids (associated with hops, apple, pear, grape, citrus, etc), viruses (such as TMV, cauli­flower mosaic virus, bean yellow mosaic-virus, plum pox virus, potyviruses), mycoplasmas bacteria (Agrobacterium tumifticiens, P,Yeudotiioticis,vol(in(iceartini, Rhizobium legunfinosaritin, Xanthol"onas compestris, etc), fungi (e.g., collectotrichum gloeosporioides, Glomus spp., Laccaria spp., Phvtophthora spp., Verticillium spp), and nematodes (e.g. Meloido,^,,^,vne incoginta, M. javanica, etc) (Henson and French, 1993; Chawla, 1998).

DNA (GENE) LIBRARY

A gene library is the collection of different DNA sequences from an organism where each sequence has been cloned into a vector for ease of purification, storage and analysis. 

A gene library should contain a certain number of recombinants with a high probability of containing any particular sequence. This value can be calculated if you know the genome size.

A genomic library, also clone bank or gene bank, is a set of DNA from a single organism, ideally though not necessarily containing its whole genomic DNA sequence. The DNA from the source organism of interest is divided into multiple fragments and packaged within cloning vectors such that each carries a portion of it. The vector DNA can then be inserted into host organisms - commonly a population of bacteria - for amplification and retrieval. 

Type of Gene Library

There are two categories of libraries on the basis of source of DNA used:

    (i)            Genomic library (where genomic DNA is used), and

  (ii)            cDNA library (where cDNA or complementary DNA is produced using mRNA).

Genomic Library

It is a set of clones that represent the complete genome of an organism. All fragments of DNA inserted into vectors for further propagation into suitable host represent the whole genome of an organism.

For building of a genomic library the entire genomic DNA is Isolated from host cells/tissues, purified and broken
randomly into fragments of correct size for cloning into a suitable vector. There are two fundamental ways of fragmenting genomic DNA randomly: physical shearing (e.g. pipetting, mixing or sonication) and partial restriction enzyme digestion (by using limiting amount of restriction enzyme the DNA is not digested at every recognition sequence). Using these methods genomic DNA is broken randomly into smaller fragments.

Following Fig. shows a total of 6 random DNA fragments obtained after physical shearing. Vector isolated from bacterium is also digested with the restriction enzyme which digests genomic DNA. The fragments of genomic DNA are inserted into the vector. Each vector consists of diff of DNA. The Recombinant DNA molecules are transferred into bacterial cells bacteriophage particles is assembled.

The genomic library for organisms with smaller genome size (e.g. E. coli) can be construe, in plasmid vector. Only 5,000 clones (of the average size of 5,000 bp) results in 99% chance cloning the entire genome of 4.6 x 10 bp. In addition, libraries from organisms with superior genomes are constructed using phase, cosmid, BAC or YAC vectors.

 cDNA Library

The mRNAs are highly processed representatives of genes which express under definite conditions. The mRNAs cannot be directly cloned because they are unstable hence mRNAs

are converted into cDNAs. The library prepared from complementary or copy DNA (cDNA) is called cDNA library. The cDNA library stand for the DNA of only eukaryotic organisms, not the prokaryotic ones. Because genomic DNA of eukaryotes contains introns (A gene segment that is transcribed from DNA which later on is excised from the primary transcript during processing to a functional  RNA molecule and Exon is the coding region of the gene that are present in processed mRNA), regulatory regions, repetitiv The cDNA library can be constructed by using mRNA because mRNAs are the highly processed, intron-free representatives of DNA having only coding  sequence. Keeping in view the aim of the experiment, DNA molecule is either enzymatically fragmented or maybe procured from cDNA or genomic libraries. Getting a cDNA fragment of its Known function or characterizing its sequence is very difficult. A cDNA fragment is prepared directly by using mRNA as template. It follows many biochemical methods.

Therefore, establishment of genomic library of eukaryotes is not meaningful.

Vaccine

Vaccine

A vaccine is a biological preparation that develops immunity to a particular disease. Vaccines can be, prophylactic (example: to prevent or ameliorate the effects of a future infection by any natural or "wild" pathogen), or therapeutic (e.g. vaccines against cancer are also being investigated.

 Stanly A. Plotkin said,“The three greatest discoveries of medicine in the last 200 years are antisepsis, antibiotics and vaccines”

 Vaccines are of 3 types

1. Killed (inactivated) vaccine e.g. Hepatitis B vaccine,(VIRAL)

2. Live attenuated vaccine e .g. Bacillus Calmette guerin(BCG),(BACTERIAL)

3. Toxoids e.g. Triple antigen

 Hepatitis B Vaccine

Hepatitis B vaccine is used against the infection caused by hepatitis B virus or HBV virus. Hepatitis B is a liver disease caused by the hepatitis B virus.

Brand Names of Hepatitis B Vaccines

Engerix-B (GSK)

 Recombivax HB (GSK)

 Elovac B (Human Biologicals Institute, A

 division of Indian Immunologicals

 Limited)

 Genevac B (Serum Institute)

 Shanvac B etc.

Hepatitis B Vaccine Doses

It takes only 3 shots to protect your selves against hepatitis B for a lifetime. In some cases, an accelerated two-dose series for adolescents is recommended. Theschedule is as given below:

¨  First Shot - At any given time

¨  Second Shot - At least one month after the first dose.

¨  Third Shot - Six months after the first dose.

DOSAGE FORMS ANENGERIX-B is a sterile suspension available in the following presentations:

0.5-mL (10 mcg) single-dose vials and prefilled syringes

1-mL (20 mcg) single-dose vials and prefilled syringes

HOW SUPPLIED/STORAGE

¨  ENGERIX-B is available in single-dose vials and prefilled disposable syringes (packaged without needles) (Preservative Free Formulation)

¨  Store at 2°C to 8°C(36° and 46°F) in a refrigerator. Do not dilute to administer.

¨  Do not freeze; discard if vaccine has been frozen.

Dispensing biotech products considering temperature requirements and storage in dosing and administration devices

Pharmaceutical Biotechnology
  Biotechnology refers to the application of biological systems, living organisms, or their derivatives in making or transforming products or processes for specific use.
 Pharmaceutical Biotechnology Products
The common pharmaceutical biotechnology products that are made by the biotech pharmaceutical companies include, 1.Antibodies e.g. monoclonal antibodies 2. Proteins 3.Recombinant DNA Products.
 Dispensing of Biotechnology Products 
Biotechnology products are proteins subject to denaturation and thus require special handling techniques. While (hospital) pharmacists are skilled in handling parenteral products, biotechnology products may provide additional challenges.
 Storage of Biotech products
  Biotech products have particular storage requirements. The shelf life of these products is often considerably shorter than for conventional compounds. Example, Interferon- α 2a is only stable in a refrigerator in the ready-to-use solution for 12 months. Since most of these products need to be kept at refrigerated temperatures.
 Temperature Requirements 
Since biotech products are basically proteins, they are subject to denaturation when exposed to excessive temperatures. In broad-spectrum, most biotech products are to be stored at 2–8 °C under refrigeration . Exceptions to this rule as exemplified by Alteplase (tissue plasminogen activator). Alteplase is stable at room temperature for several years. Aldesleukin (interleukin-2) is stable for 48 hours at room or normal temperature or up to 18 months in a refrigerator. Betaseron (interferon β-1b) must be stored in a refrigerator and should be used within three hours after reconstitution. While a large amount products require refrigeration to maintain stability due to denaturation by elevated temperatures, extreme cold such as freezing. Storage in Dosing and Administration Devices 
 Most biotech products may adhere to either plastic or glass containers such as syringes, polyvinyl chloride (PVC) intravenous bags etc. The effectiveness of the product may be reduced by three or four fold due to adherence. In order to decrease the amount of adherence, Human Serum Albumin (HSA) is usually added to the solutions. Those products requiring the addition of HSA include aldesleukin, erythropoietin and interferon a.

Blister Packaging Compnents

Introduction For well over four decades, the blister pack has offered a cost-effective and practical method of delivering unit dose packaging. It has proved to be one of the most enduring, versatile and adaptable pack forms, and its popularity has continue to rise unabated in the European market, some time assisted – and at other times potentially threatened – by changes in the regulatory environment. History The 1980s was perhaps the fastest period of growth in demand for blister-packed products in Europe, as governments across the continent began to advocate original pack dispensing (OPD) as the preferred means of delivering product to patients. The key benefit of OPD was that the risk of product tampering, contamination or dispensing errors was largely eliminated; since the product is deliver to the customer exactly as it leaves the packaging line, as opposed to the traditional method of pharmacist dispensing the required amount of medication from bulk supplies. In response to this market trends, machine manufacturers began to offer increase outputs: in the early 1980s 420 blister/minute was considered high speed, by the end of the decade this had doubled, and today out puts 1200 blister/minute are unknown. Blister packaging Blister pack is a term for several types of pre-formed plastic packaging used for small consumer goods, foods, and for pharmaceuticals. In other word, the primary component of a blister pack is a cavity or pocket made from a formable web, usually a thermoformed plastic. This usually has a backing of paperboard or a lidding seal of aluminum foil or plastic. A blister that folds onto itself is often called a clam shell. Blister packaging components The four basic components of pharmaceutical blister packages are the forming film, the lidding material, the heat-seal coating, and the printing ink. Forming films account for approximately 80–85% of the blister package, and lidding materials make up15–20% of the total weight of the package. Because the forming film and the lidding material form an integrated package, they must match precisely. Forming film The forming film is the packaging component that receives the product in deepdrawn pockets. One key to package success is selecting the right plastic film forthe blisters in terms of its property type, grade, and thickness. Identification  Plastic forming filmssuch as PVC, polypropylene (PP), andpolyester (PET) can be thermoformed,but support materials containing aluminum are cold-formed.  The formingfilm usually is colorless and transparent,but it can be obscured for use in child resistant packages or to protect light sensitive drugs.  The forming web for blister packs nearly always is PVC, sometimes coated or laminated with additional components that enhance the oxygen and water-vapor barrier. Difference between Thermo forming & cold forming • Thermoforming- the cavity is constructed of clear, thermoformed plastic, and the lid is formed of clear plastic or a combination of plastic, paper, or foil. • Example: Alu-PVC blister pack • Cold forming –The package contains foil as an essential component of both webs, and its cavity is created by cold stretching. • Example: Alu-Alu blister pack Table: Comparison of Forming Films Type & Thickness Of Forming Film(mil) WVTR(g/m2/day) Price Per Unit Area PVC(10) 1.1 1 PVD/PVDC(10/1.2) 0.17 2.1 PVC/CTFE(8/0.76) 0.07 2.1 PP(12) 0.20 1.3 PET(10) 2.6 1.4 PS(12) 6 1.2 OPA/aluminum/PVC(1/1.8/2.4) 0 2.9 Types of forming films Types forming film are: • Polyvinyl chloroide (PVC) • Polyvinylidene chloride (PVdC) • Chlorotrifluoroethylene (CTEF) • Polypropylene (PP) • Polyethylene terepthalate (PET) • Polystyrene (PS) • Oriented polyamide (OPA) • CTFE homopolymer Polyvinyl chloroide (PVC) PVC forming filmis called rigid PVC because it is almost freeof softening agents. Rigid PVC is a very clear, stiff material with a low WVTR. It exhibits excellent thermoformability; a high flexural strength; good chemical resistance; low permeability to oils, fats, and flavoring ingredients; easy tintability; and low cost. These properties make rigid PVC the material of choice for blister packaging, and it essentially has 100% of the market for the plastic component. PVC films that are thermoformed have a thickness of about 10-mil. Advantages  It has high clarity.  It is practically unaffected by sunlight.  It un-plasticized materials are non-toxic.  It is less permeable to gases than polythene.  Its plasticized grades are good oil resistant.  Some grades can be sterilized by autoclaving.  The surface can be printed readily. Disadvantages  It is less flexible, heavier and much more permeable to water vapour.  It adsorbs some drugs.  It require an extended sterilization time due to its heat resistant. Uses: PVC collapsible bags are used to package most infusion fluids. Recycling process of polyvinyl chloroide (PVC) The relatively new mechanical recycling process known as Vinyloop® technology, developed by Solvay Research & Technology, allows the complete separation of PVC material from the non-PVC materials that are often combined with it. The Vinyloop Process 1. Pretreatment 2. Dissolution 3. Separation 4. Precipitation 5. Drying Polyvinylidene chloride (PVdC) Although the volume of PVC in drug packaging is small, PVDC plays a critical role in blister packaging as laminations or coatings on PVC. PVDC is the most common coating in blister packaging because it can reduce the gas and moisture permeability of PVC blister packages by a factor of 5–10. Coated PVC films have a thickness of 8–10 mil; the thickness of the PVDC coat amounts to 1–2 mil.The coating is applied on one side and usually faces the product and the lidding material. Advantages  High levels of transparency offer the most attractive product presentation and display. The PVdC film can be color-toned to reduce exposure.  Excellent barrier qualities extend the shelf life and conservation of foods, while at the same time reducing the need for preservatives, which in turn enhances the appeal of the product to the consumer.  Outstanding heat sealing properties help materials such as paper, cellophane and other plastics to seal themselves effectively. This means that packaging can be easily and rapidly sealed during processing, so that high film speeds and throughputs can be achieved.  Highly flexible characteristics allow the PVdC to perform across a very wide range of applications Disadvantages While extremely useful as a food packaging agent, the major disadvantage of Saran is that it will undergo thermally induced dehydrochlorination at temperatures very near to processing temperatures. Recycling process of Polyvinylidene chloride (PVdC) Due to the fact that you need such a small amount of PVdC to achieve your barrier needs, there is very little in the post consumer stream especially compared to polymers like PET. If PVdC could be easily segregated, it could be easily recycled. Therefore, PVdC typically can only be recycled in a general non-specific plastic recycling program. Chlorotrifluoroethylene (CTFE) Advantages  Films made from PVC and CTFE have the lowest water-vapor permeability of all films used for blister packaging.  When compared with the water-vapor permeability of 10-mil PVC, the permeability of 8-mil PVC/0.76-mil CTFE is lower by a factor of 15.  However, the environmental concerns regarding PVC also apply to PVC/CTFE films. Disadvantages Extremely expensive. Attacked by esters & aromatic hydrocarbons. Polypropylene (PP) There is an increasing trend toward using PP as a support material for blister packages. The water-vapor permeability of uncoated PP is lower than that of PVCand is comparable to that of PVDC-coatedPVC. The thickness of PP films used in the thermoforAdvantages  Easy recyclability,  No release of toxins during incineration, and  Good moisture-barrier properties. Disadvantages PP has some drawbacks. One problem is thermoforming. The temperatures required for thermoforming PP and for the subsequent cooling process must be controlled precisely. Warping also can occur, in which case the packages must be straightened before cartoning. Other difficulties associated with the use of PP include its thermal instability, higher rigidity than PVC, and susceptibility to post processing shrinkage. Polyethylene terepthalate (PET) Advantages  Bottles for beverages such as soft drinks, fruit juices, mineral waters. It is especially suitable for carbonated drinks, cooking and salad oils, sauces and dressings and detergents.  Wide mouth jars and tubs for jams, preserves, fruits & dried foods.  Trays for pre-cooked meals that can be re-heated in either microwave or conventional ovens. Pasta dishes, meats and vegetables.  Foils for 'boil-in-the-bag' pre-cooked meals, snack foods, nuts, sweets, long life confectionery.  Other PET products with an extra oxygen barrier are ideal for containing beer, vacuum packed dairy products e.g., cheese, processed meats, 'Bag in Box' wines, condiments, coffee, cakes, syrups. Disadvantage The disadvantage is that PET becomes increasingly brittle and opaque at increasing crystallization levels. Extremely crystalline PET is effectively white. This can be clearly seen on the neck of some returnable bottles already in the market. ming process ranges from 10 to 12 mil. Recycling process of Polyethylene terepthalate (PET) Mechanical recycling is a method of recovery a material from waste by means of mechanical processing. In order to be recycled, PET bottles have to be collected from astore and baled. Polystyrene (PS) Advantages  It is light and cheap material & easy to mould  It is odorless, tasteless, and available in transparent.  It has excellent dimensional stability that assure to fine limits of accuracy.  It soften at a lower temperature  Good tensile strength Disadvantages  It is hard & rigid material  It is brittle to cold or when dropped or flexed.  It permits the permeability of water vapor than other plastics.  It tends to be electrostatic and very permeable to aromatic flavoring. Uses: As foam or expanded material Recycling process of Polystyrene (PS) The low cost of polystyrene manufacturing deters recycling. Polystyrene recycling is generally similar to other forms of recycling. Large trucks carry polystyrene, collected in various locations, to polystyrene recycling facilities, similar to the Dart recycling operation in Mason, MI. According to the Concord, CA, website, polystyrene takes up more space in these large trucks than is profitable to recycle. Oriented polyamide (OPA) Advantages  OPA are intriguing. With a laminate structure consisting of 1-mil OPA, 1.8-mil aluminum, and 2.4-mil PVC it is possible to eliminate water-vapor permeability almost entirely.  Moreover, because of the large proportion of aluminum in the laminate, recycling this material has become feasible (particularly because most lidding materials also contain aluminum).  Enormous efforts are being made to replace PVC with PP in such laminates to comply with environmental standards. Disadvantages  Like other laminates containing aluminum, the OPA/aluminum/PVC laminate is cold-formed.  Its cost per square meter can stand any critical comparison with PVDC-coated PVC.  Cold-forming, however, requires more packaging material than doe’s thermoforming to package the same number of the same size of tablets or capsules. CTFE homopolymer Recently introduced a 3-mil CTFE homopolymer barrier film (AclarUltRx 3000) that can be thermoformed easily and that exhibits the highest moisture barrier of clear films. This reflects the trend toward the use of higher-barrier materials. Various Aclar products have allowed wider use of blister packaging because they can be thermoformed into clear or tinted blister cavities and exhibit barrier properties close to those of the near-perfect barrier offered by foil. Lidding materials The lidding material provides the base ormain structural component upon whichthe final blister package is built. It mustbe selected according to the size, shape,and weight of the product as well as thestyle of the package to be produced. Lidding materials range in caliper or thickness from 0.36 to 0.76 mm, but 0.46–0.61mm is the most popular range. Characteristics The lidding material canbe clear plastic, but in pharmaceuticalpackaging it is either plain or printed 1-mil foil (for push-through blister types)or paper/foil or paper/PET/foil laminations (for child-resistant peel–push types). Types of lidding materials Hard aluminum Identification Hard aluminum isthe most widely used push-through liddingmaterial. The foil usually has a thickness of 0.8-mil. There are endeavors,however, to reduce the thickness of this foil to 0.6-mil. The hardness of the aluminumfacilitates push-through opening.Usually, only the print primer side features a printed design, but occasionally theside with the heat-sealing coating also canbe printed. Advantages  A double coat of heat-sealingcoating (a heat-sealing primer and the actual heat-sealing coating) has become thestandard for lidding materials.  The heat-sealing primer ensures optimum adhesion of the heat-sealing coatingto the aluminum foil.  If the heat-sealing primers are colored, applying the heat-sealing coating overthe primer can protect the packaged product from coming in contact with the pigments. Soft aluminum Identification Soft aluminum (1 mil) frequently is usedfor child-resistant push-through foils. Withthe exception of the type of aluminumused, the structure of this lidding material corresponds to that of hard aluminum(0.8- mil). Advantages  The softness and thickness ofthis type of aluminum help prevent children from pushing tablets through it.  Thismaterial also is supplied with a perforation along the sealed seams so that it cannot be peeled off the formed film in onepiece. Paper/aluminum Identification In combinations of paper and aluminum, the weight of the paperamounts to 40–50 g/m2. In Europe, thethickness of the aluminum typically is0.28–0.48 pm, but in the United States ithas a thickness of 0.6–1 mil. Characteristics Lidding material made of a paper/PET/aluminum laminate is often called peel off–push through foil. This kind of material is used predominately in the United States. Advantages • In the United States, this type of materialis used as a peel-off foil, so the foil mustbe relatively thick for effective peeling. Because printing is applied to the side withthe paper, no print primer is required. • The concept is to first peel off the paper/PET laminatefrom the aluminum and then to push thetablet through the aluminum. The Recycling Process of Aluminum: Five stage process 1. Collection 2. Sorting 3. Reprocessing 4. Rolling 5. Converting Heat-seal coatings Identification  A successful heat-sealcoating for blister packages must exhibitgood gloss, clarity, abrasion resistance, andhot tack and must seal to various blisterfilms.  Although heat-seal coatings used forblister packaging still are predominantly solvent-based vinyls (because of their superior gloss), water-based products aremaking some inroads.  In addition, the heat-seal coating mustprecisely match the lidding material andthe plastic material of the forming films.  Theheat-seal coating also protects the printedarea and provides a glossy finish. Mostimportantly, the heat-seal coating must comply with FDA recommendations. Printing inks Identification Printing inks must resist heatsealing temperatures as high as 300 8Cwithout showing any discoloration ortackiness (blocking). In addition, they mustsufficiently resist abrasion, bending, andfading and must be safe for use with theintended product. Printing inks should not contain excessive amounts of hydrocarbonlubricants, greases, oils, or release agents. Advantages  Printing inks provide graphics and aesthetic appeal.  They can be applied to thelidding material by letterpress, gravure, offset, flexographic, or silk-screen printingprocesses. Cold-formed foil/foil Identification One element of the foil/foil blister pack comprises a lamination of plastic film (PVC or PE), adhesive,foil, adhesive, and an outer plastic film.The outer film, which can be PET or PVC,supports the thin aluminum layer and actsas the heat-seal layer. The aluminum layerusually consists of several very thin layersrather than a single thick one. Advantages  The multiple layers help ensure that pinholes do not go all the way through the foil.  They also increase the stretch ability of the metal and facilitate the cold-stretching process. Disadvantage  Is that the cavities must bemade larger in the cold-forming processthan during thermoforming, thus increasing the overall area of the packageand often allowing the product to shiftinside the blister.  Even so, the brittleness of cold-formed aluminum means that foil/foil blisters cannot be made as formfitting as plastic ones Conclusion Packaging engineers have been called upon to develop creative solutions for meeting the Consumer Product Safety Commission’s child-resistant and senior-friendly requirements. With additional regulatory developments such as the International Conference of Harmonization’s testing guidelines and FDA’s rule on iron supplements, a large increase in blister packaging use, along with the use of innovative materials and designs, is expected.