1. INTRODUCTION:

1.1 Pharmaceutical Packaging:

Pharmaceutical packaging is a technology that allows the storage of drugs from the time of production to the time of use. We offer life-saving drugs, surgical instruments, blood and blood products, nutritional supplements, powders, poultices, liquids and dosage forms, solid and semi-solid dosage forms. Complex considerations such as establishing good design and communicating with customers, and more pressing concerns such as counterfeiting, promoting patient compliance, ensuring drug integrity, balancing child resistance, and elderly access must be balanced. Packaging is a constantly evolving science that contributes greatly to the success of the pharmaceutical industry^1-3.

1.2. Blistering Process:

Figure 1: Solid Oral Dosage manufacturing (Zhong, L., Gao, L., Li, L., and Zang, H. (2020). Trends-process analytical technology in solid oral dosage manufacturing. European Journal of Pharmaceutics and Biopharmaceutics, 153, 187-199.)

The packaging process is the final step in the production process of oral solid dosage. The blister packaging process depends on the dimensions, shape, properties and materials of the tablet packaging. And also the blister line. This section focuses on the cold form Al/Al blister packaging process⁴.

Blister packs have been widely used in the pharmaceutical sector for packaging solid oral dosage forms for the past 40 years due to their design flexibility and efficiency⁵.

The unique unit dose concept allows patients to easily track their medications by taking oral doses, as the number of doses taken can be visually and tactilely identified. This is one of the main reasons why, for decades, most drugs on the market have been prescribed in pill or capsule form^6-7.

When comparing the company's drug development pipelines to other dosage forms, it is obvious that the absolute numbers and proportion of oral solids in these pipelines are falling. Simultaneously, the number of oral solid medication formulations requiring high to very high barrier protection to maintain stability and satisfy shelf life requirements is increasing significantly⁸. Without a sufficiently high level of protection, developing solid oral dose forms that can be supplied in blister packs will be more challenging than ever⁹.

Key packaging and package design decisions, as discussed in this white paper, can have a substantial influence on drug stakeholders and patients, as well as improve medication development efforts.

2. ORAL DELIVERY TRENDS:

2.1. More advanced drug formulation technology:

Medicinal chemicals must be absorbed by the body in order to be effective. Otherwise, they travel through the digestive tract and are eliminated without having any medical effect. It is challenging to develop effective formulations due to the rising number of poorly soluble medicinal components¹⁰.The first and most important step in increasing the dissolution rate is reducing the size of drug particles to sub-micron level. Efforts to improve solubility include physical modification of certain APIs using less stable polymorphic or amorphous phases. Hydrophilic polymers are commonly used to modulate drug release profiles. Third generation solid dispersion, for example, is made up of finely dispersed drug particles in polymer carriers with the assistance of surfactants^11-12. It is obvious that hydrophilic polymers can gather water during storage and plasticize early if not protected from moisture. This has an impact on the formulation's physical stability and hence its overall performance. Drug particle size reduction significantly enhances the active surface area of all drug particles. As a result, if the medicine molecule contains chemical groups that are susceptible to moisture or oxygen, the danger of chemical breakdown rises¹³. As a result, pharmaceutical and medication delivery businesses are increasingly focused on high-barrier or high-barrier films for blister packing¹⁴.

2.2. An increasing number of life-cycle management (LCM) initiatives:

Many LCM initiatives aim to reduce the frequency of drug prescriptions with the goal of increasing patient compliance and improving treatment outcomes. Fixed-dose combination (FDC) and orally dispersible tablets (ODT) are the most prevalent forms of modified-release (MR) formulations, such as controlled-release (CR) and extended-release (ER). Almost all medications offered in these LCM categories came in blister packets made of high or ultra-high moisture barrier films¹⁵.

2.3. Larger dose sizes result in larger packs:

As the amount of high-performance excipients and APIs required for live formulations increases, tuning drug release profiles often results in larger dose sizes¹⁶. The same is true for any attempt to improve drug dissolution rates by producing submicron drug particles. FDCs and low-power APIs face similar challenges. The dosage and package size have increased significantly¹⁷. Most patients with chronic diseases choose compact packages. On the other hand, a package that is too large may compromise patient compliance (ie, MR) efforts¹⁸.

2.4. Beyond moisture sensitivities:

Several compositions contain APIs that are reactive to oxygen and light as well as moisture. Vitamin-containing medications are frequently packed in blister packs, which are constructed up of multi-layered sheets that serve as an oxygen and moisture barrier or an oxygen, moisture, and light barrier¹⁹.

3. THE INDUSTRY DRIVERS - BLISTER PACKAGING CRITERIA:

3.1 Globalization:

Today, the number of drugs available worldwide is increasing. The primary protective packaging used in temperate climates is often inadequate in hot, dry, and humid locations. As a result, high and ultra-high moisture barrier films are growing in popularity, overtaking the medium and low barrier categories when it comes to solid oral dosage formulation²⁰.

3.2. Simplicity reduction:

Many pharmaceutical companies have adopted the approach of creating a limited number of agreed upon "first goal" key packaging instructions. The ability to stabilize in different climatic zones and meet the objectives of the stakeholders of marketing and packaging operations is a key selection factor for a primary packaging material²¹. Additionally, there is an ongoing effort to minimize complexity by limiting the number of agreed-upon changes to a select few to reduce the cycle time and analysis costs associated with parallel stability testing. Faster turnaround, easier site relocation projects, and increased operational equipment effectiveness (OEE) through general economies of scale are the downstream benefits of packaging operations²².

3.3. Product price reduction:

In addition, the efficiency requirements of the packaging process are becoming more stringent every year. Key motivations include increasing production in current production facilities and funding production with less investment. As an outcome, packing methods and machinery have been selected with the purpose of lowering the cost of goods (CoG) considerably^23-24.

3.4 Improvements in packaging sustainability:

A growing number of pharmaceutical companies, especially in the packaging sector, are developing sustainability strategies to verifiably reduce energy and waste consumption. As a result, intensive efforts are being made to develop smaller and slimmer packages²⁵.

3.5. Prevention of medication errors:

Many solid oral products offer tablets or strength tablets. Appropriate color organization of the exterior container and/or prospective color distinctions in the medicine itself, along with visible blister packing sheets of paper, has been found to aid in the prevention of medication mistakes²⁶.

3.6. Child Resistance:

It is difficult to create a package that is difficult for young people to open, and at the same time to create a simple package for users, especially older people. Despite the fact that there are now several child-resistant (US 16 CFR 1700-F=1 standards) and "elderly-friendly" blister packaging options available, companies are still looking for packages that meet all standards. comply They continue to invest their time and effort. Development from^27-,28.

4. BLISTER PACKAGING CRITERIA – THE PATIENT BENEFITS:

For simple reasons such as patient forgetfulness, a significant percentage of prescribed drug regimens do not produce desirable results. For this reason, drug companies strive to fully utilise the advantages of edible pharmaceuticals in order to more effectively complement the lives of their customers²⁹.

In addition, patients who encounter packing problems during treatment are more likely to not adhere to packing and have poor treatment outcomes, and because of its variability, it has a significant impact on long-term care and from the owner's perspective³⁰. The brand is losing patients ^24-25. On the other hand, Prescription medicine brand managers are increasingly aware that the package design may influence treatment outcomes, leading to better outcomes and greater profits³¹. Pfizer's Z-Pak pocketbook, a prescription drug delivered in a predetermined unit dose design, is a well-known and extremely effective example of this³².

5. OPTIONS FOR HIGH-BARRIER PACKAGING:

There are many package offerings that meet the performance criteria of effective moisture, Protection against oxygen and light³³. Examples include amber bottles made of glass with metal screw tops, HDPE laminating bottles, cold foil blisters (CFF), and blister packs produced from high-barrier the process of thermoforming films^34,35.

Outside of the United States, strong-barrier the thermoforming process and cold forming are the leading packaging methods for humidity-sensitive food products ³⁶. Outside of the United States, the most widely used packaging techniques for moisture-sensitive edible solids are high-barrier thermoforming and cold forming ^37-38.

The most popular polymer films used in thermoforming blister applications are laminated PVC and PVDC-coated PVC films. At every given barriers layer thickness, Aclar film delivers the best moist barrier. Solutions containing additional polymers such as EVOH and PVDC are available if an oxygen barrier is required. The range of high and ultra-high barrier films starts with PVDC coating weight of 120 grams and a clear film thickness of 51 microns^39-40.

The following are the common benefits of all thermoplastic-based the thermoforming films:

· Even with bigger dosage and tablet sizes, the packaging footprint is less than that of CFF. The package's dimension can be decreased by up to 65% (on average around 55%), especially with big capsules or tablets.

· User popularity has increased since it provides for patient freedom of choice, accessibility, and convenience of dosage collection.

· Material consumption up to 60% less from film production to lead stock to cardboard.

· Reduction of energy consumption and carbon footprint - up to 25%.

· Save up to 200% on materials from film forming to lead stock and cartons ⁴¹.

6. CONCLUSION:

Historically, value creation in medical care has been cantered on bringing new approaches to underserved patient requirements. Better treatment outcomes benefit the entire society. Patient and family members live healthier lives and enjoy a better standard of life as a result of the treatment. Social systems can budget for less intensive care and assisted living costs. Less absenteeism benefits employers. It also allows doctors to give their patients superior care and assistance. Pharmaceutical firms are stepping up their efforts to enhance treatment effectiveness and outcomes in contexts outside than controlled clinical trials.

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Received on 06.07.2023 Revised on 12.03.2024

Accepted on 16.08.2024 Published on 20.01.2025

Available online from January 27, 2025

Research J. Pharmacy and Technology. 2025;18(1):445-448.

DOI: 10.52711/0974-360X.2025.00068

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