Oral pharmaceutical packaging

First, plastic

Plastics are one of the main packaging materials, and the history of plastics used in pharmaceutical packaging is not too long. The many advantages of plastics have determined that plastics will have and will play a major role in drug packaging. These advantages include light weight, unbreakability, ease of use, barrier to gases, ease of compounding of different plastics, plastics and other materials, and mature molding processes.

Plastic resin

Plastic resin is a kind of plastic polymer compound, according to its different structure and nature, can be roughly divided into two major categories of hot solid resin and thermoplastic resin, pharmaceutical plastic packaging most of the use of thermoplastic resin.

2. Additives

Resin is the main component of plastic. In the plastic manufacturing process also need to add a variety of additives, additives generally have plasticizers, antioxidants, antistatic agents, lubricants, colorants, heat stabilizers and so on.

Second, the relationship between plastic packaging materials and drugs

Drugs are a special commodity. As packaging materials (or containers) that are in direct contact with drugs, they must be able to ensure the safety and efficacy of drugs and ensure the stability of drug quality. At the same time, they must meet the convenience needs of patients.

The adaptability between the plastic packaging material (container) and the packaged drug is a problem that the drug manufacturer must solve when selecting the packaging material. Light, heat, humidity, microbes, oxygen, and mechanical impact can all have an adverse effect on the quality of medicines. The purpose of packaging is to prevent the influence of the above external factors on the quality of medicines at a certain intensity. This involves a barrier problem that includes barriers to light, microorganisms, and gases. Plastic bottles made of brown or added titanium dioxide to make white bottles are also designed to block light. The aluminum foil in the composite film not only greatly improves the gas barrier property, but also completely blocks the light.

Drug solid substrates are generally loose materials, so processed into tablets, capsules and other preparations for taking. Many drugs are crystalline or non-crystalline powders before they are made into tablets and capsules, which are prone to hygroscopic deliquescence. Solid preparations are susceptible to changes in quality due to water vapor and oxygen to varying degrees during storage. Reduce the content, change the release and so on.

At present, the solid oral preparations are mostly in the form of bottles (mostly plastic bottles), blister packs, and bar-type packaging. For plastic bottles, in addition to material selection must have a certain degree of thickness and thickness uniformity, excellent sealing of the bottle mouth. For blister packaging, the forming hard sheet must have a certain thickness. If the PVC hard sheet does not meet the temperature resistance requirement, the PET hard sheet or the PVC/PVDC composite hard sheet may be used instead. The other layer of the blister package is aluminum foil for pharmaceutical packaging. The quality of the original foil used is better. It is generally believed that the thickness of 0.025mm or more is pinhole free. The various composite films used in the strip type packaging must be carefully selected according to the characteristics of the drugs. Liquid oral liquid packaging is still based on glass bottles and plastic bottles. Oral liquid plastic bottles are generally made of PP or PET, which can provide enough mechanical strength to avoid mechanical damage, and can provide certain gas barrier properties and barrier properties to microorganisms. Among them, PET bottles are better, and the flavor of the syrup-based oral liquid packaged in the bottle will not be lost through the bottle wall.

Migration is another issue involved in pharmaceutical packaging materials. This kind of migration is often a two-way migration. Possible migration from plastics to packaged drugs includes various functional additives such as monomers and plasticizers, residual solvents, and the like. The migration of the preparation to the plastic may cause loss of flavor, loss of preservatives and affect the stability. The migration of active ingredients of the drug causes the content to fall. In order to ensure the safety of pharmaceutical packaging materials and containers, quality standards have been established at home and abroad. There are also many regulations in the pharmacopoeia, which not only stipulate the gas permeability and sealability, but also limit the toxic substances that may migrate. Such as heavy metals, water-soluble, alcohol-soluble, ester-soluble leachables, as well as the plastic's abnormal toxicity.

Third, drug packaging commonly used plastics

(1) Polyethylene plastic

Polyethylene is polymerized from ethylene monomers. It is a general term for ethylene polymer compounds. Polyethylene resin is generally colorless, odorless, non-toxic, absorbent, and cold-resistant. It is the most commonly used plastic in oral medicine packaging. According to the density of polyethylene raw materials, there are three points: high, medium and low density. Low density polyethylene is the first generation product, characterized by its softness, low temperature resistance, and good heat sealability. However, the strength is relatively low, the acupuncture resistance is poor, and the oil resistance is also poor. In the composite film for SP packaging, it is often used as an inner seal layer.

High density polyethylene is the second generation of polyethylene. Like low-density polyethylene, it has good chemical stability, good cold resistance, abrasion resistance, and moisture resistance. It has higher strength than low density polyethylene and slightly better oil resistance. Medicinal plastic bottles are generally made of high density polyethylene. Due to poor taste resistance of polyethylene and poor oil resistance, plastic bottles made of HDPE are generally not suitable for storing aromatic and oily drugs. It is also not easy to store drugs that are particularly sensitive to oxygen or water vapor.

Even if there is monomer migration in polyethylene, there is no safety problem. As long as the type and quantity of additives used are controlled, there is no problem in terms of safety.

(2) Polypropylene plastics

Polypropylene is colorless, odorless and non-toxic. Both heat resistance and chemical stability are strong, and the tensile strength is greater than that of polyethylene. In common plastics, it is the only plastic that can be boiled in water and disinfected at 130°C. The disadvantages are poor cold resistance and poor transparency. The pharmaceutical packaging can be made into plastic bottles for solid preparations, plastic bottles for oral liquids, and infusion bottles made of biaxial stretching. Polypropylene is often used as a single film in composite membranes. The polypropylene film used in the composite film is a stretched film and a cast film. The biaxially stretched PP film has good transparency and bright appearance. The disadvantage is that the tear strength is greatly reduced and the heat sealability is also not good, so the biaxially stretched PP film is generally used as the outer layer of the composite film. The cast PP film maintains the characteristics of good tear strength and heat sealability, and can generally be used as an inner seal layer of a composite film.

(3) PVC plastic PVC

Polyvinyl chloride is polymerized from vinyl chloride monomer and is one of the earliest plastic varieties in the world to achieve industrial production. The original form of polyvinyl chloride is transparent and hard. Only adding enough plasticizer can make it soft. Polyvinyl chloride is an excellent barrier to oils, volatile and non-volatile alcohols.

Concerns about the safety of polyvinyl chloride use are mostly concentrated on unpolymerized polyethylene monomer VCM (PVC infusion containers and plasticizer migration issues are not discussed here).

PVC packaging materials or containers generally used as medicines or foods and used pellets have relatively strict control over vinyl chloride monomer, and the general control is ≤ 1 ppm.

(4) polyester

Polyester is a generic term for a class of resins. The so-called "polyester" generally refers to one of them, namely polyethylene terephthalate (PET). PET is transparent, strong, heat resistance and low temperature resistance are very good, non-toxic, light weight, excellent chemical stability, good barrier to water vapor and oxygen, good barrier to odor, no pinholes . These are the advantages of PET. The amount of additives in PET plastics is smaller than that of PE and PP, and there is less opportunity to migrate out, which does not pose a problem in terms of safety. PET is a better plastic for making beverages and condiment bottles, and it is also the best plastic type for making oral liquid plastic bottles such as syrups. Solid oral preparation bottle, blister pack molding material, and outer film of strip composite film are often made of PET

(5) Others

In addition to the above-mentioned commonly used plastics, pharmaceutical packaging also uses plastics with special functions, such as polyvinylidene chloride (in fact, vinylidene chloride and 5 to 50% vinyl chloride are used in the packaging material). . Its outstanding advantage is excellent barrier properties to gases. The barrier property to water vapor is several times to several tens of times that of polyethylene, polypropylene, and polyvinyl chloride, and the barrier property to oxygen is several hundred times that of these kinds of plastics.

Polyvinylidene chloride (PVDC) is generally used in pharmaceutical packaging to:

1. Composite PVC hard sheets (PVC/PVDC hard sheets) to improve the barrier properties of PVC hard sheets.

2. The single layer and coating in the composite film used for strip packaging.

In addition, there are reports that PVDC is coated in plastic bottles made of PE or PP to improve its barrier properties.

Fourth, oral preparation of plastic packaging

Before plastic packaging is used in large quantities, almost all tablets, capsules and oral liquids are packed in brown glass bottles (tablets, jars for capsules, and small bottles for oral use). Glass bottles must be washed, dried, and other processes prior to loading. After the charge, the wood wax plug was used for the waxing process. After packaging, the glass is easily broken during transportation. Many processes, poor appearance, high consumption, and many damages have caused glass bottles to be rare in oral solid glass packaging (oral fluids are also used in glass bottles).

At present, there are the following types of packaging for direct contact with oral solid preparations:

(1) plastic bottles

Plastic bottles are one of the most commonly used packaging containers for oral formulations. According to reports, 70% of oral solid preparations abroad use plastic bottles. Since the early 1980s, China began to introduce three-station bottle-making equipment for injection and injection, and the production and quality of medicinal plastic bottles have greatly improved.

The plastic bottle for packaging of solid preparations is generally made of polyolefin (PE or PP). Titanium dioxide is used as a colorant to protect from light. Colorless transparent or brown transparent plastic bottles made of PET are also used. Plastic bottles for liquid oral preparations are generally made of PP or PET.

In recent years, there have been many cases where parafilms are used in medicinal plastic bottles. Sealing membranes may be beneficial for the stability of drug delivery and storage. However, it is impossible to change the bottled medicine once the lid is opened to remove a piece (grain), and the remaining medicine in the bottle will inevitably be affected by the outside air.

Bottle caps are generally equipped with a safety ring. Once the cap is opened, the safety ring falls off on its own, which is conducive to safe drug use. There is also a bottle cap called a safety cap. Ensure that children under the age of 5 do not open their own food and are safe for children. For children's safe packaging requirements and test methods, etc. China is developing national standards (equivalent to adopting international standards).

(2) single dose blister pack

The blister pack refers to a form in which a plastic hard sheet is first heated to form a vesicle, a tablet is filled with a tablet or a capsule, and then sealed with an adhesive-coated aluminum foil as a covering material. It is generally called PTP packaging.

Tablets and capsules have been packaged in PTP for more than thirty years. Their main advantages are:

Single-dose packaging, after removing one tablet (granules), other drugs are still packaged and have a single-piece sealing effect.

2. The contents of the package can be seen through for verification.

3. Lightweight packaging and convenient transportation.

So far, PTP packaging molding material is mainly PVC hard film. PVC hard sheets are easy to form and have good transparency but poor water vapor barrier properties. For this reason, there are now PP, PET hard films come out. At the same time, composite hard sheets such as PVC/PVDC, PVC/CFE (CFE-polychlorotrifluoroethylene), and PVC/PE/PVDC that can retain the advantages of PVC hard sheets and overcome their shortcomings have emerged.

PVDC and CFE have excellent gas barrier properties, and the moisture permeability of a PVC hard sheet with a thickness of 250 μm is 2.5 g/m24·h. After a layer of 30μm PVDC is compounded, the moisture permeability can be reduced to 0.3g/m2·24h. The other side of a single-dose blister pack is aluminum foil for pharmaceutical packaging (commonly referred to as "PTP" aluminum foil). The metallic aluminum, the main material, should be able to completely isolate light and gas. It is generally believed that the thicker the aluminum foil is, the smaller the pinhole may be. Blister packaging is generally put into the paper box, the role of the paper box: 1. Protection; 2. Printing; 3. Block light.

4.SP packaging

There are single-dose strip packaging and single-dose or multi-dose bag-shaped packaging and other forms.

The strip type packaging is a kind of middle layer tablet, capsule or suppository with a strip-shaped SP film, which is heat-sealed inside the second-layer SP film around the medicament, and the tooth marks are pressed between the tablets to form a unit package. When using, gradually tear apart according to tooth marks. The advantage of strip packaging is that it is easy to use. The disadvantage is that it must be operated on a special SP packaging machine. Generally, it needs to be packed in carton.