GLASS for Pharmaceutical Packaging and Containers

Glass has been widely used as a drug packaging material. For a large number of pharmaceuticals, including medicinal products for oral and local administration, glass containers are usually the first choice (e.g. bottles for tablets, injection syringes for unit- or multidose administration). Different types of glass may be necessary, depending on the characteristics and the intended use of the medicinal products concerned.

Advantages of glass:
• It allows easy inspection of the containers contents
• It is available in variously shaped containers

Disadvantage of glass:
• It is fragile
• It is expensive when compared to the price of plastic

GLASS Composition
  • Silica (SiO2) 59-75 %
  • Calcium oxide (CaO) 5-12 %
  • Sodium oxide (Na2O) 12-17 %
  • Alumina (Al2O3) 0.5-3.0 %
  • Other oxide :
  1. Barium oxide (BaO)
  2. Boric oxide (B2O2)
  3. Potassium oxdie (K2O)
  4. Magnesium oxide (MgO)
Manufacturers should arrange with their suppliers to obtain the appropriate type of glass container for the intended use. Suppliers should provide the raw and packaging materials in conformity with industrial norms.

Glass containers are classified according to their hydrolytic resistance
  • Type I Glass : Neutral glass, with a high hydrolytic resistant due to the chemical composition of the glass itself.
  • Type II Glass : usually of soda-lime-silica glass with a high hydrolytic resistance resulting from suitable treatment of the surface.
  • Type III Glass : Soda-lime glass usually of soda-lime-silica glass with only moderate hydrolytic resistance.
Glass type and recommendation for used
  • Type I glass : suitable for most preparations whether or not for parenteral use, widely used as glass ampoules and vials to package
  • Type II glass : suitable for most acidic & neutral, aqueous preparations whether or not for parenteral use.
  • Type III glass : general suitable for non-aqueous preparations for parenteral use, for powders for parenteral use (except for freeze-dried preparations) and for preparations not for parenteral use.
Glass and recommendation for used
  • Except for type I glass containers, glass containers for pharmaceutical preparation are not to be re-used
  • Containers for human blood and blood components must not be re-used.

Ampoule :
• One point cut ampoules
• Flat Based and constricted neck ampoule
• Flame cut ampoules
• Closed ampoules
• Ampoules with colour break band and identification bands

Used in the dispensary as either amber metric medical bottles or ribbed (fluted oval bottles. Available in sizes from 50 ml to 500 ml
• Amber metric medical bottles are used for packaging a wide range of oral medicine
• Ribbed oval bottle attached are used to package various product that should not be taken orally
• This include liniment, lotionsm inhalations and antiseptic solutions

Droplet bottles
• Eye drop and dropper bottles for ear and nasal use are hexagonal-shaped amber glass container fluted on three sides
• They are fitted with a cap, rubber teat and dropper as the closure. The bottles are used at a capacity of 10 ml or 20 ml

• Powders and semisolid preparations are generally packed in wide mouthed cylindrical jars made of clear ot amber glass
• Jars varies from 15ml to 500 ml
• Jars are used for packing prepared ointments and pastes

Type, Properties and Application of Blister Packaging for Pharmaceutical Product

Film for blister packaging is requiring compliance with shelf-life standards and protection from gas, moisture, chemicals, and extraneous microbiological and particulate contamination. The ability to precisely control film specifications for blister packaging enables this technique to be used to make specialized products such as child-resistant packaging. The technology for creating child-resistant packaging involves using seals, custom plastic banding, and container closures that must be pressed, twisted, or mechanically manipulated for entry. Foil webs require push-through or puncture to gain entry, and complete plastic tubes are used to totally enclose a package. Medical applications of blister packaging include surgical instruments, medical pouches, implantable devices, diagnostic test kits, and disposables.

Blister Packaging Components and Materials for Pharmaceutical Product (Part IV : Printing inks)

The purpose of printing inks in blister packaging is provide graphics and aesthetic appeal. They can be applied to the lidding material by letterpress, gravure, off-set, flexographic, or silk-screen printing processes.

Printing inks requirements for blister packaginf:
  • resist heat- sealing temperatures as high as 300 8C without showing any discoloration or tackiness (blocking).
  • resist abrasion, bending, and fading
  • safe for use with the intended product
  • should not contain excessive amounts of hydrocarbon lubricants, greases, oils, or release agents.
Cold-formed foil/foil
Best known blister package is made from foil, film, paper, or multimaterial backing that is adhered to a sheet of thermoformed plastic blisters. However, a less common type of blister is the foil/foil lamination used for products that are particularly susceptible to moisture and/or light. Unlike all-plastic blisters, these are not thermoformed but instead are cold-pressed into shape. Products that require the highest degree of protection are packed in an all-foil package. Cold-formable foil is finding favor because it is the only material that provides a 100% barrier to moisture, oxygen, and light. This has helped expand the applications in which blisters can be used, allowing the blister packaging of sensitive products.

Blister Packaging Components and Materials for Pharmaceutical Product (Part III : Heat-seal coatings)

The heat-seal coating influence the appearance and physical integrity of the package. Heat-seal coatings provide a bond between the plastic blister and the printed lidding material. These solvent or water based coatings can be applied to rolls or sheets of printed paperboard using roll coaters, gravure or flexographic methods, knives, silk-screening, or sprays. It is essential that the proper coating weight be applied to the lidding material for optimum heat-sealing results.

Blister Packaging Components and Materials for Pharmaceutical Product (Part II :Lidding Materials)

Lidding materials
The lidding material act as the base or main structural component upon which the final blister package is built. Selection for lidding material should consider the size, shape, weight of the product, and the style of the package to be produced. Lidding materials range in caliper or thickness from 0.36 to 0.76 mm (0.46–0.61 mm is the most popular range). The surface of the lidding material must be compatible with the heat-seal coating process. Clay coatings are added to the lidding material to enhance printing.

Lidding material can be clear plastic, but in pharmaceutical packaging 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). The lidding material must guarantee a WVTR that is at least as low as that of the forming films, and it must be suitable for the type of opening appropriate to the package (e.g., push-through or peel-off).

Comparison of Lidding Material
Lidding Material Price per Unit Area Weight*
0.8-mil Aluminum, hard, push-through601
0.8-mil Aluminum, hard, heat seal-coated, side-printed, push through611.25
1-mil Aluminum, soft, child resistant761.15
45 g(m-2)/1-mil Paper/aluminum, peel-off1211.55
45 g(m-2)/0.48-mil Paper/PET/aluminum, peel off-push through1422.00

*Where 1 represents the price per unit area of 0.8-mil, hard, push-through aluminum

Types of lidding materials.

There are several type of lidding material :
1. Hard aluminum
2. Soft aluminum
3. Paper/aluminum
4. Paper/PET/aluminum

Blister Packaging Components and Materials for Pharmaceutical Product (Part I : Forming Film)

The four basic components of pharmaceutical blister packages are :
  1. the forming film (80–85% of the blister package)
  2. the lidding material (15–20% of the total weight of the package)
  3. the heat-seal coating
  4. the printing ink

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 deep drawn pockets. Thing should be consider in selecting plastic film for the blisters are the type, grade, thickness, height and weight of the product, sharp or pointed edges of the final package, and the impact resistance, aging, migration, and cost of the film. The plastic also must be compatible with the product. Factors influencing package production and speed of assembly must be taken into account, including heat- sealing properties and the ease of cutting and trimming formed blisters.

Plastic forming films such as PVC, polypropylene (PP), and polyester (PET) can be thermoformed, but support materials containing aluminum are cold-formed. The forming film 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.

The Benefits of Blister Packs for Pharmaceutical Product and Health Care

Blister packs can help patients follow drug regimens, protect drugs over a long shelf life, and are portable. Five aspects which blister packaging is better than conventional packaging.
  • product integrity
  • product protection
  • tamper evidence
  • reduced possibility of accidental misuse
  • patient compliance
  • Blister packs are very inexpensive to produce.
  • Can be custom fit to help sell/promote products.
  • Protects and holds the product securely.
  • Many sizes available, from small unit-dose pills to large suit-case sized blisters.
  • Allows products to be seen, but not touched, product is very visible.

The Advantages of Blister Packs

Product integrity. Blister packaging helps retain product integrity because drugs that are prepackaged in blisters are shielded from adverse conditions. Furthermore, opportunities for product contamination are minimal, and each dose is identified by product name, lot number, and expiration date. Therefore, blister packaging ensures product integrity from the producer directly through distribution to the consumer.

Product protection. Blister packaging protects pharmaceuticals in the home better than bottles do. Blister packaging, keeps each tablet or capsule hermetically sealed in its own bubble. Drugs that are not taken remain in the original package and are fully protected against external conditions. A blister protects a moisture-sensitive tablet right up to administration. In contrast, the moisture in the headspace of a multiple-unit bottle is replaced each time the bottle is opened.

Tamper evidence. The dosage units are individually sealed in constructions of plastic, foil, and/or paper. The package must be designed so that one must tear the compartment to get at the product, and it must not be possible to separate the backing materials from the blister without leaving evidence. Once a bottle has been opened, whatever tamper-evident mechanism it had is gone. With blister packaging, however, each tablet or capsule is individually protected from tampering until use, so any form of tampering with a blister package is immediately visible.

Possibility of accidental misuse. Blister packaging can be made child resistant. Most child-resistant blister packages contain a paper/film layer with a peelable adhesive. Patients must peel the adhesive away from the foil backing before the pill can be pushed through. Specifying 15-mil polyvinyl chloride (PVC) blister stock provides extra security because it is less likely that children could puncture the package by biting through it. Companies also are experimenting with bitter coatings to deter children from putting packages in their mouths.

Patient compliance. As many as 30% of all prescriptions are not taken properly initially, and as many as 50% are not continued after one year. Such misuse can cause a range of adverse drug reactions, including death.

Blister packs can be bar coded for use in hospitals and nursing homes to prevent errors in distributing medication. Pharmacists have a greater opportunity to communicate with and advise their patients because less time is necessary to fill the prescription.

Primary Packaging for Pharmaeutical Solid Dosage Form

There are two forms of primary packaging for solid pharmaceutical product:
  1. formable (thermoformable or cold-formable) materials
  2. flexible materials.
Formable materials (blisters and trays) can offer a water, oxygen, or UV barrier as well as a physical and mechanical barrier as a primary way to protect a drug and its delivery system against damage before administering.

Thermoformable materials are based on rigid polymer materials (PVC, PETG, APET, CPET, PP or COC) usually combined by coextrusion, coating, or lamination to barrier materials. Typical barrier materials include PCTFE (polychloro-trifluoroethylene, such as Honeywell's Aclar® fluoropolymer film), PVDC (polyvinylidene chloride), aluminum foil, or EVOH (ethylene vinyl alcohol) coextrusions (Honeywell's OxyShield®).

Packaging Materials for Pharmaceutical Suspensions

Packaging Of Suspensions

Packaging is defined as the collection of different components which surround the pharmaceutical product from the time of production until its use. Pharmacist must aware of wide range of packaging material that relates directly to the stability and acceptability of dosage forms. For example, to optimize shelf life industrial pharmacist must understand inter-relationship of material properties, while the retail pharmacist must not compromise with the storage of the dosage forms.

Pharmaceutical suspensions for oral use are generally packed in wide mouth container having adequate air space above the liquid to ensure proper mixing. Parenteral suspensions are packed in either glass ampoules or vials. Suspension should be stored in tight containers protected from freezing and excessive heat and light. Label : “Shake Before Use” to ensure uniform distribution of solid particles and thereby uniform and proper dosage should exist.

Ideal Requirements Of Packaging Material
  • It should be inert.
  • It should effectively preserve the product from light, air, moisture, mechanical damage and other contamination through shelf life.
  • It should be cheap.
  • It should effectively deliver the product without any difficulty.
  • Carry the correct information and identification of the product
  • Tamper evident/child resistance/Anti counterfeiting

Complete Procedure of CAPA for Pharmaceutical Industry (Part II)

1. Identification - clearly define the problem
2. Evaluation - appraise the magnitude and potensial impact
3. Investigation - make a plan to research the problem

Continue from Complete Procedure of CAPA for Pharmaceutical Industry (Part I)

4 - Analysis - perform a thorough assessment
The investigation procedure is used to conduct the investigation into the cause of the problem. The goal of this analysis is primarily to determine the root cause of the problem described, but any contributing causes are also identified.

•Every possible cause is identified and appropriate data collected.
A list of all possible causes is created which then form the basis for collecting relevant information, test data, etc.
The necessary data and other information is collected that will be used to determine the primary cause of the problem.

•The results of the data collection are documented and organized.
Data may come from a variety of sources: testing results and/or a review of records, processes, service information, design controls, operations, and any other information that may lead to a determination of the fundamental cause of the problem.The data collected is organized into a useable form.The resulting documentation should address all of the possible causes previously determined. This information is used to determine the root cause of the problem. The effectiveness of the analysis will depend on the quality and thoroughness of the information available.

Complete Procedure of CAPA for Pharmaceutical Industry (Part I)

7 Steps of CAPA for Pharmaceutical Industry

Implementing an effective corrective or preventive action capable of satisfying quality assurance and regulatory documentation requirements is accomplished in seven basic steps:
  1. Identification - clearly define the problem
  2. Evaluation - appraise the magnitude and potensial impact
  3. Investigation - make a plan to research the problem
  4. Analysis - perform a thorough assessment with documentation
  5. Action Plan - create a list of required tasks
  6. Implementation - execute the action plan
  7. Follow Up - verify and assess the effectiveness

1 - Identification - clearly define the problem

The initial step in the process is to clearly define the problem. It is important to accurately and completely describe the situation as it exists now. This should include the source of the information, a detailed explanation of the problem, the available evidence that a problem exists.

This should include:

• The source of the information

The specific source of the information is documented. There are many possible sources: Service requests, Internal Quality Audit, Customer complaints, Internal quality audits, Staff observations, Trend data, QA inspections, Process monitoring, Risk analysis, Process performance monitoring, Management review, and Failure mode analysis. This information is important for the investigation and action plan, but also useful for effectiveness evaluation and communicating the resolution of the problem.

• Detailed explanation of the problem

A description of the problem is written that is concise - but complete. The description must contain enough information so that the specific problem can be easily understood.

• Documentation of the available evidence that a problem exists.

List the specific information, documents, or data available that demonstrates that the problem does exist. This information will be very important during the investigation into the problem. For example, the evidence for a product defect may be a high percentage of service requests or product returns. The evidence for a potential equipment problem may be steadily increasing downtime.

CAPA : The Difference Between Corrective and Preventive Action

CAPA is a fundamental management tool that should be used in every quality system.

Corrective Actions 
 A corrective action is a term that encompasses the process of reacting to product problems, customer complaints or other nonconformities and fixing them. The process includes:
  • Reviewing and defining the problem or nonconformity
  • Finding the cause of the problem
  • Developing an action plan to correct the problem and prevent a recurrence
  • Implementing the plan
  • Evaluating the effectiveness of the correction.

Preventive Actions
A preventive action is a process for detecting potential problems or nonconformance’s and eliminating them. The process includes:
  • Identify the potential problem or nonconformance
  • Find the cause of the potential problem
  • Develop a plan to prevent the occurrence.
  • Implement the plan
  • Review the actions taken and the effectiveness in preventing the problem.

Differences between Corrective and Preventive Actions 

The process used for corrective actions and preventive actions is very similar and the steps outlined in this document can be used for either. However, it is important to understand the differences and also be aware of the implications involved in performing and documenting each.

Application of CAPA (Corrective action and preventive action) in Pharmaceutical Industry

Corrective action and preventive action (CAPA, also called corrective action / preventive action) are improvements to an organization's processes taken to eliminate causes of non conformities or other undesirable situations. CAPA is a concept within good manufacturing practice(GMP). It focuses on the systematic investigation of the root causes of non-conformities in an attempt to prevent their recurrence (for corrective action) or to prevent occurrence (for preventive action).

Corrective Action is an action taken to eliminate the causes of an existing nonconformity, defect or other undesirable situation in order to prevent recurrences. Correction: Repair, rework or adjustment and relates to the disposition of an existing non-conformity.

Preventive Action is an action taken to eliminate the causes of potential nonconformity, defect or other undesirable situation in order to prevent the occurrence.

These are out come of the investigations or compliance for
  • Market Complaints
  • Deviations
  • Incidents
  • Out of Specification results
  • Audit observation of any internal or
  • external audit
  • Change controls
  • Market returns
  • product recall