Packaging Incompatibility

Three types- 1. Primary packaging 2. Secondary packaging 3. Tertiary packaging

Pharmaceutical Packaging

SorptionLeachingPermeationInteraction with metals

Interactions with packaging

ABSORPTION +

ADSORPTION

SORPTION

The process by which one substance, such as a solid or liquid, takes up another substance, such as a liquid or gas, through minute pores or spaces between its molecules.

The process by which molecules of a substance, such as a gas or a liquid, collect on the surface of another substance, such as a solid. The molecules are attracted to the surface but do not enter the solid's minute spaces as in absorption.

Drug or some times excipients can be adsorbed and then absorbed in the primary packaging. Example-

Sorption on packaging

Packaging

Material

Incompatible Drug or

Excipients

Glass Proteins,Globulins,Insuline, Chloroquine

Rubber Antimicrobial preservative

Polyvinyl ChlorideWarferin sodium,

Vitamin A, Benzodiazepines

Migration of a substance from packaging material into medicine

Leaching

Packaging Material Leached substances

Soda glass bottles Alkali substances

Rubber clousures Zinc salts

Borosilicate glass Barium ions

Diethylhexylpthalate (DEHP)

Calcium ion

Entry or exit of anything through the packaging materials.

Permeation

Packaging Materials Permeated substance

Rubber clousers Water vapour

Polyethylene container Benzyl alcohol,Chloroxylenol

Metals are frequently used as constituents of packaging materials. Depending on the nature of the drug product this metals reacts with the drug substances.

Interaction with metals

Reacting metals Incompatible drugs

Heavy metals Bacitracin

Iron, Lead, Barium, Silver, Manganese

Benzoyates

Mercury Benzalconium Chloride

Aluminium Cisplatin

Drug – Excipients interaction: Preformulation stage

Dosage form – Packaging interaction: After Preformulation stage

Prediction and detection of incompatibilities

1. Concentration of the reactant2. pH3. Ionic strength4. Temperature5. Physical state6. Nature of the materials used in containers and closures7. Routs of administration8. Frequency of dose9. Clinical uses.

Things to consider during compatibility studies

Examinations:

1.TLC (Thin Layer Chromatography) 2.FTIR (Fourier Transform Infrared

Spectroscopy)

3.DSC (Differential Scanning Calorimetry) 4.DTA (Differential Thermal Analysis)

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