Packaging Material Science

Packaging Systems & Terminology

• Packaging system / Container–closure system

  • Sum of all components and materials that contain & protect the product.
  • Spans from primary contact parts to tertiary / ancillary units.

• Packaging component (examples)

  • Containers: ampules, vials, bottles, syringes, pen-injectors.
  • Closures: screw caps, stoppers, ferrules, overseals.
  • Closure liners, inner seals, administration ports & accessories, labels, overwraps, cartons, shrink-wrap.

• Container = receptacle that directly holds the drug.

• Closure = material that seals the open space of a container.

Layer-Based Classification

• Primary component – direct contact (bottle, blister film, desiccant).
• Secondary component – contacts the primary component; adds extra protection & labeling (carton, overwrap).
• Tertiary component – contacts secondary; protects during $\text{transport / storage}$ (shipping box, stretch-wrapped pallet load).
• Ancillary component – contacts tertiary during distribution (pallets, skids, shrink-wrap).
• Associated component – delivers drug but not stored in continuous contact (dosing cup/spoon, dropper, syringe).

Pallet vs Skid vs Crate

• Pallet
  • Top & bottom deck boards; size $48" \times 40"$ most common.
  • High friction, stable, rack-friendly; forklift moves easily; load up to $1000\,\text{kg}$.
• Skid
  • No bottom deck → lower friction, easier to drag; oldest pallet type; cheap, nestable, often foundation for heavy machines.
• Crate
  • True box (4 walls + floor); secure, holds large volume; stable yet bulky & harder to handle.

Container Performance Definitions

• Child-resistant & Senior-friendly – meet US CPSC criteria.
• Tamper-evident – cannot be accessed without visible destruction; mandatory for OTC + sterile ophthalmic/otic products.
• Non-reclosable – cannot be closed again (blisters, sachets, single-unit strip).
• Reclosable – can be securely reclosed repeatedly.
• Hermetic container – impervious to air / gas.
• Tight container – protects from contamination, loss, efflorescence, deliquescence, evaporation.

Efflorescence vs Deliquescence

• Efflorescence
  • Hydrated compound’s vapor pressure > atmospheric → loses water until equilibrium.
• Deliquescence
  • Reverse: vapor pressure < atmospheric → absorbs water, becomes more hydrated (e.g., $\text{NaOH}$).
  • Prevention: close container promptly, fill fully, add desiccant (silica gel).

Desired Package Attributes

• Protection: light, gases, moisture, solvent loss, sterility.
• Safety: nontoxic, no taste/odor imparted.
• Compatibility: chemically non-reactive.
• Performance: high-speed machinable, tamper-resistant/evident, transit-worthy, economical, eco-friendly.

Special Container Requirements

• Tamper-resistant packaging spotlight: Tylenol cyanide crisis example → multiple safety seals.
• Light-resistant – protect photo-oxidizable drugs (vitamins $A,D,B<em>{12},E,K,\text{folic acid},\text{riboflavin},B</em>{6}$; amino acids; unsat. fats; phospholipids).
  • UV spectrum: $100\,\text{nm} \rightarrow 400\,\text{nm}$ (far/medium/near UV).
  • UVA $400\text{–}320\,\text{nm}$ passes 25-45 % through special bottles.
  • Glass colors: cobalt = blue, iron chromate = green, $\text{SnO}<em>2$ = opaque white, $\text{Fe}</em>2\text{O}_3 + S$ = brown/amber.
• Moisture-sensitive → tight or hermetic containers.
• Well-closed – shields from solids & handling contamination.

Major Packaging Materials

Glass

• Advantages: chemically inert, impermeable, rigid, age-stable, FDA-cleared, elegant, any size/shape; colored (amber) blocks $290\text{–}450\,\text{nm}$.
• Disadvantages: fragile, heavy, costly machining.

Composition

• Base mix: $\text{SiO}<em>2$ (sand) + $\text{Na}</em>2\text{CO}<em>3$ (soda ash) + $\text{CaCO}</em>3$ (limestone) + cullet.
• Modifiers / additives: boron oxide (melting aid), alumina (hardness), lead (clarity, softness).
• Non-bridging oxygen forms when $\text{Na}^+$ breaks $\text{Si–O–Si}$ network.

Manufacture

1. Fusion $1500\text{–}2500^\circ \text{C}$.
2. Molding
   • Blowing (press-and-blow / blow-and-blow).
   • Drawing (tubes, rods, sheets).
   • Pressing.
   • Casting (gravity / centrifugal).
3. Annealing – controlled cooling (lehr flue for large scale; oven for small).

Glass Types & Tests (USP/NF)

• Type I Borosilicate – highest chemical resistance; $\le 1.0\,\text{mL 0.02 N acid}$ in powdered test.
• Type II Treated soda-lime (sulfur-treated) – water attack limits $0.7\,\text{mL}$ (\le$100\,mL$) or $0.2\,\text{mL}$ (>$100\,mL$).
• Type III Soda-lime – $\le 8.5\,\text{mL}$.
• Type IV / NP General purpose – $\le 15.0\,\text{mL}$.
• Tests: Powdered Glass (Types I, III, IV) & Water Attack (Type II).

Chemical Issues

• Leaching of alkali: distilled water in Type III picks up $10\text{–}15\,\text{ppm NaOH/year}$ vs $0.5\,\text{ppm}$ in Type I (\approx$6\%$ B(2)O(3)).
• Delamination / glass flakes: influenced by high-heat cycles, storage temp, aqueous drugs.
  • Mechanism: $\text{H}^+$ ↔ $\text{Na}^+$ ion exchange, hydration → silica-gel layer → cracking → lamellae.
• Surface treatments: sulfur dioxide + steam create $\text{Na}<em>2\text{SO}</em>4$ layer → increased resistance.

Plastics

• Recycling codes & typical resins:
  • #1 PET; #2 HDPE; #3 PVC; #4 LDPE; #5 PP; #6 PS; #7 Other (nylon, polycarbonate, etc.).

Drug–Plastic Interactions

1. Permeation – bidirectional; water/oxygen ingress (penicillin tablets degrade in PS; tetracycline suspension changes in PE).
   • ↑Temperature ↑Permeability; crystallinity ↓Permeability.
   • Hydrophilic plastics (nylon) = poor WV barrier; hydrophobic (PE) = good.
2. Leaching – additives, dyes migrate into product (toxic risk).
3. Sorption – adsorption/absorption of drug/preservative (loss of potency).
4. Chemical reaction – drug or plastic components react → deformation/contamination.
5. Physical property alteration – container warping, brittleness.

Thermoplastics vs Thermosets

• Thermoplastics: soften on heating, reversible (PE, PVC, PP, PS, nylon).
• Thermosets: cure irreversibly (epoxy, bakelite, phenolics, polyesters).

Metal Containers

• Near-perfect gas & moisture barrier, strong, shatterproof, malleable.
• Used for aerosol cans, DPIs, collapsible tubes (tin, Al, Pb).
• Linings: wax, phenolic, epoxy, vinyl; epoxy $\approx 25\%$ cost premium.
  • Phenolics resist acids; epoxies resist alkalis.
• Drawbacks: cost, pinhole defects, risk of metallic contamination (critical for ophthalmic products).

Rubber Closures & Components

• Uses: stoppers, cap liners, dropper bulbs.
• Materials: natural rubber (resists dilute acids/alkalis; attacked by oxidizers, oils, ketones), hard rubber (>$25\%$ S), neoprene, silicone, polyisoprene, polybutadiene.
• Problems: sorption of drug/preservative; leaching of rubber ingredients.
• Mitigation: epoxy or Teflon–coated stoppers ⇒ minimize sorption & extractives.

Summary Flow – From Manufacturing to Patient

1. Product characterization → choose primary material (glass, plastic, metal, rubber).
2. Confirm environmental threats (light, moisture, gas) → select container type (amber, tight, hermetic, tamper-evident).
3. Layer the system: primary → secondary (label/protect) → tertiary (ship/store) → ancillary (pallet, skid).
4. Verify child-resistance, senior-friendliness, regulatory tests (USP glass tests, CPSC, tamper evidence).
5. Control chemical interactions: alkali leach, permeation, sorption, delamination, metal pinholes, rubber extractives.
6. Ensure performance on high-speed packaging lines, cost feasibility, environmental recyclability.